2018 Joint Meeting Program

THE PREMIER ANNUAL MEETING FOR PHYSICIAN-SCIENTISTS

APRIL 20 – 22, 2018 This activity is jointly provided by Harvard Medical School. FAIRMONT CHICAGO MILLENNIUM PARK CHICAGO, ILLINOIS www.jointmeeting.org SPECIAL EVENTS AT THE 2018 AAP / ASCI / APSA JOINT MEETING

FRIDAY, APRIL 20 ASCI President’s Reception in Honor of the 20th Anniversary of the Stanley J. Korsmeyer Award 6:00 p.m. – 7:15 p.m. Gold Room

ASCI Dinner & New Member Induction Ceremony (Ticketed event) 7:30 p.m. – 9:30 p.m. Rouge, Lobby Level Invited Speaker: George Q. Daley, MD, PhD, Harvard Medical School

APSA Welcome Reception (Ticketed event, ID required) 9:00 p.m. – Midnight Mid-America Club, Aon Center (Off-site) SATURDAY, APRIL 21 ASCI Food & Science Evening (ID required) 6:30 p.m. – 9:00 p.m. Mid-America Club, Aon Center (Off-site) Featuring Poster Presentations by the ASCI’s 2018 Young Physician-Scientist Awardees

AAP Member and New Member Induction Banquet (Ticketed event, formal attire required) 7:00 p.m. – 9:30 p.m. Imperial Ballroom, Level B2 Data Sharing in the Setting of Clinical Trials Invited Speaker: Jeffrey M. Drazen, MD, Editor-in-Chief, New England Journal of Medicine

APSA Dinner & Founder’s Award Presentation (Ticketed event) 7:30 p.m. – 9:00 p.m. Rouge, Lobby Level Founder’s Award Recipient: Dania Daye, MD, PhD, Massachusetts General Hospital Charting Your Path as a Physician Scientist Dinner Speaker: Juliane Bubeck-Wardenburg, MD, PhD, Washington University School of Medicine

Dessert Reception & Best Poster Awards (Open to all attendees) 9:45 p.m. – 11:30 p.m. Imperial Lobby, Level B2 SUNDAY, APRIL 22 APSA Residency Luncheon 12:30 p.m. – 2:30 p.m. International Ballroom PROGRAM CONTENTS

General Program Information 2 ______Continuing Medical Education Information 3 ______Joint Program Planning Committee & APSA Events Committee 4 ______Scientific Program Schedule 5 ______Speaker Biographies 13 ______Call for Nominations: 2019 Harrington Prize for Innovation in Medicine 19 ______2018 AAP/ASCI/APSA Leadership 20 ______Travel Award Recipients 21 ______Call for Nominations: George M. Kober Medal 23 ______Oral Presentations & Poster Abstracts 24 ______Oral Presentations & Poster Abstracts Author Index 137 ______Hotel Floor Plans 142 ______Joint Meeting Sponsors Inside Back Cover ______Future Joint Meeting Dates Back Cover ______

www.jointmeeting.org 1 GENERAL PROGRAM INFORMATION

Registration Desk Hours Poster Session Schedule Friday, April 20 7:00 a.m. – 6:30 p.m. Friday, April 20 Saturday, April 21 7:00 a.m. – 5:00 p.m. ϭϬ͗ϬϬĂ͘ŵ͘ʹϯ͗ϬϬƉ͘ŵ͘ WŽƐƚĞƌ^ĞƚƵƉ ϲ͗ϭϱƉ͘ŵ͘ʹϵ͗ϯϬƉ͘ŵ͘ /ŶĨŽƌŵĂůsŝĞǁŝŶŐ͗ƉƌĞƐĞŶƚĞƌƐĚŽŶŽƚ Sunday, April 22 7:30 a.m. – 10:00 a.m. ŶĞĞĚƚŽďĞĂƚƉŽƐƚĞƌ Saturday, April 21 Americans with Disabilities Act dtKWŽƐƚĞƌWƌĞƐĞŶƚĂƟŽŶ^ĞƐƐŝŽŶƐ ǀĞŶƚƐƚĂīǁŝůůďĞŐůĂĚƚŽĂƐƐŝƐƚǇŽƵǁŝƚŚĂŶǇƐƉĞĐŝĂůŶĞĞĚƐ ϴ͗ϬϬĂ͘ŵ͘ʹϵ͗ϬϬĂ͘ŵ͘ WŽƐƚĞƌ^ĞƐƐŝŽŶǁŝƚŚ ;ŝ͘Ğ͕͘ ƉŚǇƐŝĐĂů͕ ĚŝĞƚĂƌǇ͕ ĞƚĐ͘Ϳ͘ WůĞĂƐĞ ĐŽŶƚĂĐƚ ƚŚĞ ZĞŐŝƐƚƌĂƟŽŶ ŽŶƟŶĞŶƚĂůƌĞĂŬĨĂƐƚ ĞƐŬĂƚƚŚĞŵĞĞƟŶŐŝĨǇŽƵƌĞƋƵŝƌĞĂŶǇƐƉĞĐŝĂůĂƐƐŝƐƚĂŶĐĞ͘ ODD numbered posters presented Joint Meeting Evaluations ϭϭ͗ϰϱĂ͘ŵ͘ʹϭ͗ϯϬƉ͘ŵ͘ WŽƐƚĞƌ^ĞƐƐŝŽŶǁŝƚŚ>ƵŶĐŚ EVEN numbered posters presented dŚĞWͬ^/ͬW^:ŽŝŶƚDĞĞƟŶŐWůĂŶŶŝŶŐ ŽŵŵŝƩĞĞƌĞůŝĞƐ ϭ͗ϯϬƉ͘ŵ͘ʹϮ͗ϬϬƉ͘ŵ͘ WŽƐƚĞƌŝƐŵĂŶƚůĞ ŽŶ ǇŽƵƌ ŝŶƉƵƚ ƚŽ ĞŶŚĂŶĐĞ ŝƚƐ ŵĞĞƟŶŐƐ͘ &ŽůůŽǁŝŶŐ ƚŚĞ :ŽŝŶƚ DĞĞƟŶŐ͕ĂŶŽŶůŝŶĞŵĞĞƟŶŐĞǀĂůƵĂƟŽŶǁŝůůďĞĞŵĂŝůĞĚƚŽĂůů ϵ͗ϰϱƉ͘ŵ͘ʹϭϭ͗ϯϬƉ͘ŵ͘ ĞƐƚWŽƐƚĞƌǁĂƌĚƐ ĂƩĞŶĚĞĞƐ͘ W^ ĂƩĞŶĚĞĞƐ ǁŝůů ƌĞĐĞŝǀĞ Ă ƐĞƉĂƌĂƚĞ ƐƵƌǀĞǇ ƚŽ ;ĚƵƌŝŶŐĞƐƐĞƌƚZĞĐĞƉƟŽŶŝŶ ŚĞůƉŝƚƐƉůĂŶŶŝŶŐĐŽŵŵŝƩĞĞĞŶŚĂŶĐĞW^ͲƐƉŽŶƐŽƌĞĚĞǀĞŶƚƐ /ŵƉĞƌŝĂů&ŽǇĞƌͿ ĂƚĨƵƚƵƌĞWͬ^/ͬW^:ŽŝŶƚDĞĞƟŶŐƐ͘zŽƵƌƉĂƌƟĐŝƉĂƟŽŶŝŶ WŽƐƚĞƌƉƌĞƐĞŶƚĞƌƐƐŚŽƵůĚƉůĂŶƚŽďĞĂǀĂŝůĂďůĞŽŶ^ĂƚƵƌĚĂǇĨŽƌ ƚŚŝƐƐƵƌǀĞǇŝƐŐƌĞĂƚůǇĂƉƉƌĞĐŝĂƚĞĚ͘ ƚŚĞŝƌĂƉƉŽŝŶƚĞĚƉŽƐƚĞƌƉƌĞƐĞŶƚĂƟŽŶƐĞƐƐŝŽŶĂŶĚƚŚĞƌĞƐƵůƟŶŐ ĂǁĂƌĚƐƉƌŽŐƌĂŵůĂƚĞƌŝŶƚŚĞĞǀĞŶŝŶŐ͘ AAP/ASCI/APSA Joint Meeting Code of Conduct Best Poster Awards tĞǀĂůƵĞǇŽƵƌĂƩĞŶĚĂŶĐĞ͘KƵƌĐŽŶĨĞƌĞŶĐĞŝƐĚĞĚŝĐĂƚĞĚƚŽ ĞƐƚWŽƐƚĞƌǁĂƌĚƐǁŝůůďĞŐŝǀĞŶŝŶƚŚĞĂŵŽƵŶƚŽĨΨϭ͕ϬϬϬĞĂĐŚ͘ ƉƌŽǀŝĚŝŶŐĂŚĂƌĂƐƐŵĞŶƚͲĨƌĞĞĞǆƉĞƌŝĞŶĐĞĨŽƌĞǀĞƌǇŽŶĞ͕ƌĞŐĂƌĚůĞƐƐ DĞŵďĞƌƐ ŽĨ ƚŚĞ W͕ ^/ ĂŶĚ W^ ǁŝůů ũƵĚŐĞ ƉŽƐƚĞƌƐ ŽŶ ŽĨŐĞŶĚĞƌ͕ŐĞŶĚĞƌŝĚĞŶƟƚǇĂŶĚĞǆƉƌĞƐƐŝŽŶ͕ĂŐĞ͕ƐĞǆƵĂůŽƌŝĞŶƚĂƟŽŶ͕ ƐĐŝĞŶƟĮĐŶŽǀĞůƚǇ͕ƋƵĂůŝƚǇĂŶĚĐůĂƌŝƚǇŽĨƉƌĞƐĞŶƚĂƟŽŶ͘ǁĂƌĚƐǁŝůů ĚŝƐĂďŝůŝƚǇ͕ ƉŚǇƐŝĐĂů ĂƉƉĞĂƌĂŶĐĞ͕ ďŽĚǇ ƐŝǌĞ͕ ƌĂĐĞ͕ ĞƚŚŶŝĐŝƚǇ͕ Žƌ ďĞƉƌĞƐĞŶƚĞĚŽŶ^ĂƚƵƌĚĂǇ͕ƉƌŝůϮϭ͕ĨƌŽŵϵ͗ϰϱƉ͘ŵ͘ʹϭϭ͗ϯϬƉ͘ŵ͘ ƌĞůŝŐŝŽƵƐƉƌĞĨĞƌĞŶĐĞ͘Wͬ^/ͬW^ĚŽŶŽƚƚŽůĞƌĂƚĞŚĂƌĂƐƐŵĞŶƚ WŽƐƚĞƌ ƉƌĞƐĞŶƚĞƌƐ ƐŚŽƵůĚ ƉůĂŶ ŽŶ ĂƩĞŶĚŝŶŐ ĨŽƌ ĂǁĂƌĚ ŽĨĐŽŶĨĞƌĞŶĐĞƉĂƌƟĐŝƉĂŶƚƐŝŶĂŶǇĨŽƌŵ͘ƉĂƌƟĐŝƉĂŶƚĞŶŐĂŐŝŶŐ ƉƌĞƐĞŶƚĂƟŽŶ͘ ŝŶŚĂƌĂƐƐŝŶŐďĞŚĂǀŝŽƌǁŝůůďĞǁĂƌŶĞĚĂŶĚŵĂǇďĞĂƐŬĞĚƚŽůĞĂǀĞ ƚŚĞĐŽŶĨĞƌĞŶĐĞǁŝƚŚŶŽƌĞĨƵŶĚ͘/ĨǇŽƵĂƌĞďĞŝŶŐŚĂƌĂƐƐĞĚ͕ŶŽƟĐĞ ƚŚĂƚƐŽŵĞŽŶĞĞůƐĞŝƐďĞŝŶŐŚĂƌĂƐƐĞĚ͕ŽƌŚĂǀĞĂŶǇŽƚŚĞƌĐŽŶĐĞƌŶƐ͕ ƉůĞĂƐĞĐŽŶƚĂĐƚĂŵĞŵďĞƌŽĨĐŽŶĨĞƌĞŶĐĞƐƚĂīĂƚƚŚĞƌĞŐŝƐƚƌĂƟŽŶ ĚĞƐŬŝŵŵĞĚŝĂƚĞůǇ͘ŽŶĨĞƌĞŶĐĞƐƚĂīĂŶĚŽƌŐĂŶŝǌĞƌƐĂƌĞĚĞĚŝĐĂƚĞĚ ƚŽ ŵĂŬŝŶŐ Ăůů ƉĂƌƟĐŝƉĂŶƚƐ ĨĞĞů ƐĂĨĞ ĨŽƌ ƚŚĞ ĚƵƌĂƟŽŶ ŽĨ ƚŚĞ ĐŽŶĨĞƌĞŶĐĞ͘

2 2018 AAP / ASCI / APSA Joint Meeting CONTINUING MEDICAL EDUCATION INFORMATION

Continuing Medical Education (CME) Accreditation Statement Information dŚŝƐĂĐƟǀŝƚǇŚĂƐďĞĞŶƉůĂŶŶĞĚĂŶĚŝŵƉůĞŵĞŶƚĞĚŝŶĂĐĐŽƌĚĂŶĐĞ dŚĞ Wͬ^/ͬW^ :ŽŝŶƚ DĞĞƟŶŐ ĂŶŶƵĂůůǇ ďƌŝŶŐƐ ƚŽŐĞƚŚĞƌ ǁŝƚŚ ƚŚĞ ĂĐĐƌĞĚŝƚĂƟŽŶ ƌĞƋƵŝƌĞŵĞŶƚƐ ĂŶĚ ƉŽůŝĐŝĞƐ ŽĨ ƚŚĞ ƉŚǇƐŝĐŝĂŶͲƐĐŝĞŶƟƐƚƐŽĨĂůůďĂĐŬŐƌŽƵŶĚƐƚŽŚŝŐŚůŝŐŚƚƐŽŵĞŽĨƚŚĞ ĐĐƌĞĚŝƚĂƟŽŶŽƵŶĐŝůĨŽƌŽŶƟŶƵŝŶŐDĞĚŝĐĂůĚƵĐĂƟŽŶ;DͿ ďĞƐƚĞǆĂŵƉůĞƐŽĨƚƌĂŶƐůĂƟŽŶĂůďŝŽŵĞĚŝĐĂůƌĞƐĞĂƌĐŚ͕ƚŽĐĞůĞďƌĂƚĞ ƚŚƌŽƵŐŚƚŚĞũŽŝŶƚƉƌŽǀŝĚĞƌƐŚŝƉŽĨ,ĂƌǀĂƌĚDĞĚŝĐĂů^ĐŚŽŽůĂŶĚ ŶĞǁŵĞŵďĞƌƐĞůĞĐƚĞĚƚŽƚŚĞWĂŶĚ^/ŝŶƌĞĐŽŐŶŝƟŽŶŽĨ ƚŚĞƐƐŽĐŝĂƟŽŶŽĨŵĞƌŝĐĂŶWŚǇƐŝĐŝĂŶƐ͕ƚŚĞŵĞƌŝĐĂŶ^ŽĐŝĞƚǇ ƚŚĞŝƌƌĞƐĞĂƌĐŚĂŶĚůĞĂĚĞƌƐŚŝƉĐŽŶƚƌŝďƵƟŽŶƐ͕ĂŶĚƚŽƌĞĐŽŐŶŝǌĞ ĨŽƌůŝŶŝĐĂů/ŶǀĞƐƟŐĂƟŽŶ͕ĂŶĚƚŚĞŵĞƌŝĐĂŶWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚƐ ƚŚĞĐĂƌĞĞƌƐŽĨƉŚǇƐŝĐŝĂŶͲƐĐŝĞŶƟƐƚƐǁŚŽŚĂǀĞŚĂĚŵĂũŽƌŝŵƉĂĐƚ ƐƐŽĐŝĂƟŽŶ͘dŚĞ,ĂƌǀĂƌĚDĞĚŝĐĂů^ĐŚŽŽůŝƐĂĐĐƌĞĚŝƚĞĚďǇƚŚĞ ŽŶƚŚĞŝƌĮĞůĚƐ͘ DƚŽƉƌŽǀŝĚĞĐŽŶƟŶƵŝŶŐŵĞĚŝĐĂůĞĚƵĐĂƟŽŶĨŽƌƉŚǇƐŝĐŝĂŶƐ͘ Meeting Learning Objectives AMA Credit Designation Statement dŚĞ ,ĂƌǀĂƌĚ DĞĚŝĐĂů ^ĐŚŽŽů ĚĞƐŝŐŶĂƚĞƐ ƚŚŝƐ ůŝǀĞ ĂĐƟǀŝƚǇ ĨŽƌ hƉŽŶĐŽŵƉůĞƟŽŶŽĨƚŚŝƐĂĐƟǀŝƚǇ͕ƉĂƌƟĐŝƉĂŶƚƐǁŝůůďĞĂďůĞƚŽ͗ Ă ŵĂǆŝŵƵŵ ŽĨ ϴ AMA PRA Category 1 CreditsΡ͘ WŚǇƐŝĐŝĂŶƐ x ǀĂůƵĂƚĞŝŵƉŽƌƚĂŶƚƌĞĐĞŶƚĂĚǀĂŶĐĞƐŝŶƚŚĞƐĐŝĞŶƟĮĐďĂƐŝƐŽĨ ƐŚŽƵůĚĐůĂŝŵŽŶůǇƚŚĞĐƌĞĚŝƚĐŽŵŵĞŶƐƵƌĂƚĞǁŝƚŚƚŚĞĞǆƚĞŶƚŽĨ ĚŝƐĞĂƐĞĂŶĚƚŚĞƌĂƉǇ͘ ƚŚĞŝƌƉĂƌƟĐŝƉĂƟŽŶŝŶƚŚĞĂĐƟǀŝƚǇ͘ x ŽŶƐŝĚĞƌ ŶŽǀĞů ƐƚƌĂƚĞŐŝĞƐ ƚŽ ĂĚĚƌĞƐƐ ĐŚĂůůĞŶŐĞƐ ƚŽ ƚŚĞ ƉŚǇƐŝĐŝĂŶͲƐĐŝĞŶƟƐƚ͘ Claiming CME Credit and Obtaining x ĞƚĞƌŵŝŶĞƚŚĞƌŽůĞƐƚŚĂƚŝŵƉƌŽǀĞĚƵŶĚĞƌƐƚĂŶĚŝŶŐŽĨƚŚĞƐĞ Certificates ĂĚǀĂŶĐĞƐĂŶĚƐƚƌĂƚĞŐŝĞƐĐĂŶƉůĂǇŝŶƚŚĞƉŽƚĞŶƟĂůƚƌĞĂƚŵĞŶƚ WĂƌƟĐŝƉĂŶƚƐǁŝůůďĞƐĞŶƚĂůŝŶŬƚŽƚŚĞŽŶůŝŶĞĞǀĂůƵĂƟŽŶďĞĨŽƌĞ ŽĨŚƵŵĂŶĚŝƐĞĂƐĞ͘ ƚŚĞƐƚĂƌƚŽĨƚŚĞŵĞĞƟŶŐĂŶĚǁŝůůďĞƌĞƋƵŝƌĞĚƚŽĐŽŵƉůĞƚĞƚŚĞ ŽŶůŝŶĞĞǀĂůƵĂƟŽŶƚŽƌĞĐĞŝǀĞDĐƌĞĚŝƚ͘KŶĐĞƚŚĞĞǀĂůƵĂƟŽŶ Target Audience ŝƐĐŽŵƉůĞƚĞĚ͕ƉĂƌƟĐŝƉĂŶƚƐŵĂǇƉƌŝŶƚ͕ƐĂǀĞ͕ŽƌĞŵĂŝůƚŚĞŝƌD dŚŝƐ ĂĐƟǀŝƚǇ ŝƐ ƚĂƌŐĞƚĞĚ ƚŽǁĂƌĚƐ ƉŚǇƐŝĐŝĂŶͲƐĐŝĞŶƟƐƚƐ͕ ƚƌĂŝŶĞĞƐ ĐĞƌƟĮĐĂƚĞƐ Žƌ ĐĞƌƟĮĐĂƚĞƐ ŽĨ ĂƩĞŶĚĂŶĐĞ ;ĨŽƌ ŶŽŶͲƉŚǇƐŝĐŝĂŶƐͿ͘ ĂŶĚ ƐƚƵĚĞŶƚƐ ĂĐƌŽƐƐ Ă ďƌŽĂĚ ƌĂŶŐĞ ŽĨ ƐƉĞĐŝĂůƟĞƐ ŝŶĐůƵĚŝŶŐ YƵĞƐƟŽŶƐƌĞůĂƚĞĚƚŽƚŚŝƐĂĐƟǀŝƚǇŽƌŽŶĐŽŵƉůĞƟŶŐƚŚŝƐŽŶůŝŶĞ ďĂƐŝĐ ƌĞƐĞĂƌĐŚ͕ ĐĂƌĚŝŽůŽŐǇͬĐĂƌĚŝŽǀĂƐĐƵůĂƌ ƌĞƐĞĂƌĐŚ͕ ĐĞůů ĂŶĚ ĞǀĂůƵĂƟŽŶŵĂǇďĞĚŝƌĞĐƚĞĚƚŽĐĞƉƌŽŐƌĂŵƐΛŚŵƐ͘ŚĂƌǀĂƌĚ͘ĞĚƵ. ŵŽůĞĐƵůĂƌ ďŝŽůŽŐǇ͕ ĞŶĚŽĐƌŝŶĞ ĂŶĚ ŵĞƚĂďŽůŝƐŵ͕ ŚĞŵĂƚŽůŽŐǇ͕ ŝŵŵƵŶŽůŽŐǇ͕ ŝŶĨĞĐƟŽƵƐ ĚŝƐĞĂƐĞƐ͕ ŶĞƉŚƌŽůŽŐǇ͕ ƉƵůŵŽŶŽůŽŐǇ͕ Disclaimer ĂŶĚŽƚŚĞƌƐ͘ DĂĐƟǀŝƟĞƐƐƉŽŶƐŽƌĞĚďǇ,ĂƌǀĂƌĚDĞĚŝĐĂů^ĐŚŽŽůĂƌĞŽīĞƌĞĚ ƐŽůĞůǇĨŽƌĞĚƵĐĂƟŽŶĂůƉƵƌƉŽƐĞƐĂŶĚĚŽŶŽƚĐŽŶƐƟƚƵƚĞĂŶǇĨŽƌŵ HMS Disclosure Policy ŽĨ ĐĞƌƟĮĐĂƟŽŶ ŽĨ ĐŽŵƉĞƚĞŶĐǇ͘ WƌĂĐƟƟŽŶĞƌƐ ƐŚŽƵůĚ ĂůǁĂǇƐ ,D^ ĂĚŚĞƌĞƐ ƚŽ Ăůů ĐĐƌĞĚŝƚĂƟŽŶ ŽƵŶĐŝů ĨŽƌ ŽŶƟŶƵŝŶŐ ĐŽŶƐƵůƚ ĂĚĚŝƟŽŶĂů ƐŽƵƌĐĞƐ ŽĨ ŝŶĨŽƌŵĂƟŽŶ ĂŶĚ ĞǆĞƌĐŝƐĞ ƚŚĞŝƌ DĞĚŝĐĂůĚƵĐĂƟŽŶ;DͿĐĐƌĞĚŝƚĂƟŽŶƌŝƚĞƌŝĂĂŶĚWŽůŝĐŝĞƐ͘ ďĞƐƚƉƌŽĨĞƐƐŝŽŶĂůũƵĚŐŵĞŶƚďĞĨŽƌĞŵĂŬŝŶŐĐůŝŶŝĐĂůĚĞĐŝƐŝŽŶƐŽĨ /ƚŝƐ,D^͛ƐƉŽůŝĐǇƚŚĂƚƚŚŽƐĞǁŚŽŚĂǀĞŝŶŇƵĞŶĐĞĚƚŚĞĐŽŶƚĞŶƚ ĂŶǇŬŝŶĚ͘dŚĞĐŽŶƚĞŶƚŽĨĞĂĐŚƉƌĞƐĞŶƚĂƟŽŶĚŽĞƐŶŽƚŶĞĐĞƐƐĂƌŝůǇ ŽĨ Ă D ĂĐƟǀŝƚǇ ;Ğ͘Ő͘ ƉůĂŶŶĞƌƐ͕ ĨĂĐƵůƚǇ͕ ĂƵƚŚŽƌƐ͕ ƌĞǀŝĞǁĞƌƐ ƌĞŇĞĐƚƚŚĞǀŝĞǁƐŽĨ,ĂƌǀĂƌĚDĞĚŝĐĂů^ĐŚŽŽů͘ ĂŶĚ ŽƚŚĞƌƐͿ ĚŝƐĐůŽƐĞ Ăůů ƌĞůĞǀĂŶƚ ĮŶĂŶĐŝĂů ƌĞůĂƟŽŶƐŚŝƉƐ ǁŝƚŚ ĐŽŵŵĞƌĐŝĂůĞŶƟƟĞƐƐŽƚŚĂƚ,D^ŵĂǇŝĚĞŶƟĨǇĂŶĚƌĞƐŽůǀĞĂŶǇ ĐŽŶŇŝĐƚƐŽĨŝŶƚĞƌĞƐƚƉƌŝŽƌƚŽƚŚĞĂĐƟǀŝƚǇ͘dŚĞƐĞĚŝƐĐůŽƐƵƌĞƐǁŝůů ďĞƉƌŽǀŝĚĞĚŝŶƚŚĞĂĐƟǀŝƚǇŵĂƚĞƌŝĂůƐĨŽƌƚŚĞůĞĂƌŶĞƌƐĂůŽŶŐǁŝƚŚ ĚŝƐĐůŽƐƵƌĞŽĨĂŶǇĐŽŵŵĞƌĐŝĂůƐƵƉƉŽƌƚƌĞĐĞŝǀĞĚĨŽƌƚŚĞĂĐƟǀŝƚǇ ƉƌŝŽƌƚŽƚŚĞďĞŐŝŶŶŝŶŐŽĨƚŚĞĂĐƟǀŝƚǇ͘ ,D^ ƐƚƌŝǀĞƐ ƚŽ ĞŶƐƵƌĞ ƚŚĂƚ ƚŚĞ ĐŽŶƚĞŶƚ ŽĨ Ăůů ŝƚƐ ĂĐĐƌĞĚŝƚĞĚ ĂĐƟǀŝƟĞƐ ŝƐ ŝŶĚĞƉĞŶĚĞŶƚ ĨƌŽŵ ĂŶǇ ĐŽŵŵĞƌĐŝĂů ŝŶŇƵĞŶĐĞ͕ ƉƌĞƐĞŶƚƐĂďĂůĂŶĐĞŽĨƚŚĞƌĂƉĞƵƟĐŽƉƟŽŶƐ͕ƉƌŽŵŽƚĞƐŝŵƉƌŽǀĞͲ ŵĞŶƚƐŝŶŚĞĂůƚŚĐĂƌĞĂŶĚŝƐŝŶĂůŝŐŶŵĞŶƚǁŝƚŚƚŚĞDŽŶƚĞŶƚ sĂůŝĚĂƟŽŶ WŽůŝĐǇ͘ ĚĚŝƟŽŶĂůůǇ͕ ĨĂĐƵůƚǇ ŵĞŵďĞƌƐ ŚĂǀĞ ďĞĞŶ ŝŶƐƚƌƵĐƚĞĚƚŽĚŝƐĐůŽƐĞĂŶǇůŝŵŝƚĂƟŽŶƐŽĨĚĂƚĂĂŶĚƵŶůĂďĞůĞĚŽƌ ŝŶǀĞƐƟŐĂƟŽŶĂů ƵƐĞƐ ŽĨ ƉƌŽĚƵĐƚƐ͕ ƉŚĂƌŵĂĐĞƵƟĐĂůƐ Žƌ ŵĞĚŝĐĂů ĚĞǀŝĐĞƐĚƵƌŝŶŐƚŚĞŝƌƉƌĞƐĞŶƚĂƟŽŶƐ͘

www.jointmeeting.org 3 JOINT PROGRAM PLANNING COMMITTEE & APSA EVENTS COMMITTEE

Joint Program Planning Committee Members APSA Events Committee From the AAP: WƌĞƐŝĚĞŶƚ Jillian Liu (6th year MD/PhD) WWƌĞƐŝĚĞŶƚ Ohio State University Serpil Erzurum, MD Cleveland Clinic WƌĞƐŝĚĞŶƚͲůĞĐƚ Audra Iness (5th year MD/PhD) WsŝĐĞWƌĞƐŝĚĞŶƚ Virginia Commonwealth Univ. School of Medicine John Carethers, MD University of Michigan ǀĞŶƚƐŽͲŚĂŝƌ Allyson Palmer (8th year MD/PhD) W/ŵŵĞĚŝĂƚĞWĂƐƚWƌĞƐŝĚĞŶƚ Mayo Clinic Linda Fried, MD, MPH Columbia University, ǀĞŶƚƐŽͲŚĂŝƌ Mailman School of Public Health Jason Siu (6th year MD/PhD) Ohio State University From the ASCI: ǀĞŶƚƐsŝĐĞͲŚĂŝƌ ^/WƌĞƐŝĚĞŶƚ Jeremie Lever (5th year MD/PhD) Benjamin L. Ebert, MD, PhD University of Alabama at Birmingham Harvard Medical School, ǀĞŶƚƐsŝĐĞͲŚĂŝƌ ĂŶĂͲ&ĂƌďĞƌĂŶĐĞƌ/ŶƐƟƚƵƚĞ Lillian Zhang (4th year MD/PhD) ^/WƌĞƐŝĚĞŶƚͲůĞĐƚ UC Davis School of Medicine Kieren Marr, MD ǀĞŶƚƐŽŵŵŝƚƚĞĞDĞŵďĞƌ John Hopkins School of Medicine Seemaab Ali (4th year MD/PhD) ^//ŵŵĞĚŝĂƚĞWĂƐƚWƌĞƐŝĚĞŶƚ Ohio State University Vivian G. Cheung, MD ǀĞŶƚƐŽŵŵŝƚƚĞĞDĞŵďĞƌ ,ŽǁĂƌĚ,ƵŐŚĞƐDĞĚŝĐĂů/ŶƐƟƚƵƚĞ͖ Eileen Hu (4th year MD/PhD) University of Michigan Medical School Ohio State University From APSA: ǀĞŶƚƐŽŵŵŝƚƚĞĞDĞŵďĞƌ Rachel Hurley (6th year MD/PhD) W^WƌĞƐŝĚĞŶƚ Mayo Clinic Jillian Liu Ohio State University ǀĞŶƚƐŽŵŵŝƚƚĞĞDĞŵďĞƌ Jose Rodrigues (2nd year MD/PhD) /ŵŵĞĚŝĂƚĞWĂƐƚWƌĞƐŝĚĞŶƚ Michigan State Alexander Adami hŶŝǀĞƌƐŝƚǇŽĨŽŶŶĞĐƟĐƵƚ W^WƌĞƐŝĚĞŶƚͲůĞĐƚ Audra Iness VCU School of Medicine W^ǀĞŶƚƐŽͲŚĂŝƌ Allyson Palmer Mayo Clinic W^ǀĞŶƚƐŽͲŚĂŝƌ Jason Siu Ohio State University

4 2018 AAP / ASCI / APSA Joint Meeting SCIENTIFIC PROGRAM SCHEDULE

Friday, April 20, 2018 Time Event Location 8:30 a.m. – 11:00 a.m. W^ƵƐŝŶĞƐƐDĞĞƟŶŐ ZŽƵŐĞ (Open to all APSA members) APSA Session I 11:00 a.m. – 11:45 a.m. ^ĞůĞĐƟǀĞƵƚŽƉŚĂŐǇĂŶĚŐĞͲƌĞůĂƚĞĚŝƐĞĂƐĞƐ͗ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ Making a Career out of Cellular Waste Managing /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗ Ana Maria Cuervo, MD, PhD Albert Einstein College of Medicine

12:00 p.m. – 12:45 p.m. ,ŽǁƌĞĂŵƐŽŵĞdƌƵĞ͗ZĞŇĞĐƟŽŶƐŽŶĂ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ WŚǇƐŝĐŝĂŶͲ^ĐŝĞŶƟƐƚĂƌĞĞƌ /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Levi Garraway, MD, PhD Eli Lilly

1:00 p.m. – 3:00 p.m. Poster Setup /ŵƉĞƌŝĂůĂůůƌŽŽŵ WůĞŶĂƌǇ^ĞƐƐŝŽŶ/͗ŐŝŶŐĂŶĚ,ĞĂůƚŚ>ŝǀŝŶŐ/ DŽĚĞƌĂƚŽƌƐ͗Vivian Cheung, Linda Fried, and Jillian Liu /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ 1:00 p.m. – 1:30 p.m. ĂƚĂůǇǌŝŶŐ/ŶŶŽǀĂƟŽŶĂŶĚŚĂƌƟŶŐĂWĂƚŚĨŽƌƚŚĞ&ƵƚƵƌĞ ŽĨ,ĞĂůƚŚǇ>ŽŶŐĞǀŝƚǇ͗dŚĞZŽůĞŽĨƚŚĞEĂƟŽŶĂůĐĂĚĞŵǇ of Medicine /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Victor Dzau, MD EĂƟŽŶĂůĐĂĚĞŵǇŽĨDĞĚŝĐŝŶĞ

1:30 p.m. – 2:00 p.m. ^ĞĂƌĐŚŝŶŐĨŽƌƚŚĞŽŵŵŽŶZŽŽƚŽĨDƵůƟDŽƌďŝĚŝƚǇĂŶĚ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ &ƵŶĐƟŽŶĂůĞĐůŝŶĞŝŶŐŝŶŐ͗dŚĞ'ĞƌŽƐĐŝĞŶĐĞ/ŶŝƟĂƟǀĞ /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Luigi Ferrucci, MD, PhD EĂƟŽŶĂů/ŶƐƟƚƵƚĞƐŽĨ,ĞĂůƚŚͬEĂƟŽŶĂů/ŶƐƟƚƵƚĞŽŶŐŝŶŐ

^/ĂŶĚWEĞǁDĞŵďĞƌWƌĞƐĞŶƚĂƟŽŶƐ 2:00 p.m. – 2:15 p.m. hŶĚĞƌƐƚĂŶĚŝŶŐĂŶĚdĂƌŐĞƟŶŐDƵƚĂƟŽŶƐŝŶZE^ƉůŝĐŝŶŐ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ Factors in Cancer ^/EĞǁDĞŵďĞƌ͗KŵĂƌďĚĞůͲtĂŚĂď͕D͕WŚ DĞŵŽƌŝĂů^ůŽĂŶ<ĞƩĞƌŝŶŐĂŶĐĞƌĞŶƚĞƌ Recipient, 2017 Seldin-Smith Award

2:15 p.m. – 2:30 p.m. dŚĞZŝƐŝŶŐ/ŶĐŝĚĞŶĐĞŽĨ/ŝŶ/ŵŵŝŐƌĂŶƚƐ͗ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ Is it All in the Genes? WEĞǁDĞŵďĞƌ͗Maria T. Abreu, MD University of Miami Miller School of Medicine

2:30 p.m. – 2:45 p.m. KƵƌZĞĚYƵĞĞŶ͛ƐZĂĐĞ͗dŚĞŽŶŇŝĐƚƚŚĂƚƌĞĂƚĞƐ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ Genones and its Roles in Disease ^/EĞǁDĞŵďĞƌ͗Kathleen H. Burns, MD, PhD John Hopkins University School of Medicine

2:45 p.m. – 3:00 p.m. Clonal Hematopoiesis, Aging, and Human Disease /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ WEĞǁDĞŵďĞƌ͗ Ross L. Levine, MD DĞŵŽƌŝĂů^ůŽĂŶ<ĞƩĞƌŝŶŐĂŶĐĞƌĞŶƚĞƌ

3:00 p.m. – 3:30 p.m. Break

www.jointmeeting.org 5 SCIENTIFIC PROGRAM SCHEDULE

Friday, April 20, 2018 ;ĐŽŶƟŶƵĞĚͿ Time Event Location DŽĚĞƌĂƚŽƌƐ͗Serpil Erzurum, Kieren Marr, and Allyson Palmer 3:30 p.m. – 4:00 p.m. ASCI Harrington Prize Lecture /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ ZĞĐŝƉŝĞŶƚ͗Helen H. Hobbs, MD University of Texas Southwestern Medical Center

4:00 p.m. – 4:30 p.m. W^>ĂƐŬĞƌǁĂƌĚtŝŶŶĞƌ>ĞĐƚƵƌĞ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ ůƵĐŝĚĂƟŽŶŽĨĞůůƵůĂƌKǆǇŐĞŶ^ĞŶƐŝŶŐWĂƚŚǁĂǇƐ͗ /ŵƉůŝĐĂƟŽŶƐĨŽƌDĞĚŝĐŝŶĞ ^ŝƌWĞƚĞƌ:͘ZĂƚĐůŝīĞ͕&Z^ University of Oxford

4:30 p.m. – 5:00 p.m. ^/WƌĞƐŝĚĞŶƟĂůĚĚƌĞƐƐ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ dŚĞEĞǆƚ'ĞŶĞƌĂƟŽŶŽĨWŚǇƐŝĐŝĂŶͲ^ĐŝĞŶƟƐƚƐ Benjamin L. Ebert, MD, PhD ĂŶĂͲ&ĂƌďĞƌĂŶĐĞƌ/ŶƐƟƚƵƚĞ

5:00 p.m. – 5:30 p.m. ^/ͬ^ƚĂŶůĞǇ:͘<ŽƌƐŵĞǇĞƌǁĂƌĚ>ĞĐƚƵƌĞ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ Natural Product Drug Targets are Conserved from Model and Pathogenic Yeasts to Humans Joseph Heitman, MD, PhD Duke University Medical Center

5:30 p.m. – 5:45 p.m. ^ƉĞĐŝĂů^ĞƌǀŝĐĞǁĂƌĚĨŽƌWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ tŽƌŬĨŽƌĐĞtŽƌŬŝŶŐ'ƌŽƵƉ͗ David Ginsburg, Sherry Mills, Susan Shurin WƌĞƐĞŶƚĞĚďǇBenjamin Ebert and Serpil Erzurum

5:45 p.m. – 7:00 p.m. APSA Diversity Working Group ^ƚĂƚĞZŽŽŵ 6:00 p.m. – 7:15 p.m. ^/WƌĞƐŝĚĞŶƚ͛ƐZĞĐĞƉƟŽŶŝŶ,ŽŶŽƌŽĨƚŚĞϮϬƚŚŶŶŝǀĞƌƐĂƌǇ 'ŽůĚZŽŽŵ of the Stanley J. Korsmeyer Award &ĞĂƚƵƌŝŶŐƌĞŵĂƌŬƐĨƌŽŵ͗ Benjamin L. Ebert, MD, PhD Susan Korsmeyer ^ĐŽƩ͘ƌŵƐƚƌŽŶŐ͕D͕WŚ Timothy J. Ley, MD

6:15 p.m. – 9:30 p.m. Poster Viewing Only /ŵƉĞƌŝĂůĂůůƌŽŽŵ 7:00 p.m. – 9:00 p.m. WKīƐŝƚĞWƌĞƐŝĚĞŶƚ͛ƐŝŶŶĞƌ DŝĚͲŵĞƌŝĐĂůƵď ;ǇŝŶǀŝƚĂƟŽŶŽŶůǇĂŶĚ/ƌĞƋƵŝƌĞĚͿ

7:30 p.m. – 9:30 p.m. ^/ŝŶŶĞƌΘEĞǁDĞŵďĞƌ/ŶĚƵĐƟŽŶĞƌĞŵŽŶǇ ZŽƵŐĞ Speaker: George Q. Daley, MD, PhD Harvard Medical School ƫƌĞ͗ƵƐŝŶĞƐƐ (Ticketed event)

ϵ͗ϬϬƉ͘ŵ͘ʹDŝĚŶŝŐŚƚ W^tĞůĐŽŵĞZĞĐĞƉƟŽŶ DŝĚͲŵĞƌŝĐĂůƵď ;dŝĐŬĞƚĞĚĞǀĞŶƚ͕/ƌĞƋƵŝƌĞĚͿ

6 2018 AAP / ASCI / APSA Joint Meeting SCIENTIFIC PROGRAM SCHEDULE

Saturday, April 21, 2018 Time Event Location 7:00 a.m. – 8:00 a.m. WŽƵŶĐŝůDĞĞƟŶŐ ^ƚĂƚĞZŽŽŵ͕ϮŶĚ>ĞǀĞů 7:00 a.m. – 8:00 a.m. DĞŶƚŽƌŝŶŐƌĞĂŬĨĂƐƚ͗EĂǀŝŐĂƟŶŐƚŚĞWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚĂƌĞĞƌ ZŽƵŐĞ (Ticketed event) 8:00 a.m. – 9:00 a.m. W^ŽĂƌĚŽĨŝƌĞĐƚŽƌƐDĞĞƟŶŐ ŵďĂƐƐǇZŽŽŵ 8:00 a.m. – 9:00 a.m. WŽƐƚĞƌ^ĞƐƐŝŽŶĂŶĚŽŶƟŶĞŶƚĂůƌĞĂŬĨĂƐƚ /ŵƉĞƌŝĂůĂůůƌŽŽŵ ODD number posters will be presented/judged. 9:00 a.m. – 9:30 a.m. WůĞŶĂƌǇ^ĞƐƐŝŽŶ//͗ŐŝŶŐĂŶĚ,ĞĂůƚŚ>ŝǀŝŶŐ// DŽĚĞƌĂƚŽƌƐ͗Serpil Erzurum, W. Kimryn Rathmell, and Jason Siu /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ Frailty and Resilience in Aging /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Linda Fried, MD, MPH Columbia University, Mailman School of Public Health

9:30 a.m. – 9:45 a.m. W^dƌĂŝŶĞĞKƌĂůďƐƚƌĂĐƚWƌĞƐĞŶƚĂƟŽŶ͗ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ hƐŝŶŐ>ϭǀtŽŵĂŝŶƚŽĐƟǀĂƚĞůƚĞƌŶĂƚĞŶŝŽŶ ƵƌƌĞŶƚƐŝŶǇƐƟĐ&ŝďƌŽƐŝƐŝƌǁĂǇ /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Kayla Berry Washington University School of Medicine APSA Travel Awardee

9:45 a.m. – 10:15 a.m. ŝŐŝƟǌŝŶŐ,ĞĂůƚŚƐƉĂŶ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Eric Topol, MD ^ĐƌŝƉƉƐZĞƐĞĂƌĐŚ/ŶƐƟƚƵƚĞ

10:15 a.m. – 10:30 a.m. Break DŽĚĞƌĂƚŽƌƐ͗Hossein Ardehali, Mitchell Lazar, and Lillian Zhang 10:30 a.m. – 11:00 a.m. dŚĞdĞůŽŵĞƌĞ^ǇŶĚƌŽŵĞƐ͗ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ A Paradigm for Molecular Medicine /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Mary Y. Armanios, MD John Hopkins Medicine

11:00 a.m. – 11:30 a.m. ZĞǀŝƐŝƟŶŐĂůĂƐƐŝĐ͗EнDĞƚĂďŽůŝƐŵĂŶĚŐŝŶŐW^ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗ Eric M. Verdin, MD dŚĞƵĐŬ/ŶƐƟƚƵƚĞĨŽƌZĞƐĞĂƌĐŚŽŶŐŝŶŐ

11:30 a.m. – 11:45 a.m. ^/^ĞůĚŝŶͲ^ŵŝƚŚǁĂƌĚĨŽƌWŝŽŶĞĞƌŝŶŐZĞƐĞĂƌĐŚ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ ZĞĐŽŐŶŝƟŽŶŽĨƚŚĞϮϬϭϴZĞĐŝƉŝĞŶƚƐ͗

Anna Greka, MD, PhD Harvard Medical School

Deepak Nijhawan, MD, PhD UT Southwestern Medical Center

www.jointmeeting.org 7 SCIENTIFIC PROGRAM SCHEDULE

Saturday, April 21, 2018 ;ĐŽŶƟŶƵĞĚͿ Time Event Location 11:45 a.m. – 1:30 p.m. Poster Session with Lunch /ŵƉĞƌŝĂůĂůůƌŽŽŵ EVEN number posters will be presented/judged. 12:45 p.m. – 1:30 p.m. WŽƐƚĞƌZĞǀŝĞǁĞƌDĞĞƟŶŐ ZŽǇĂůZŽŽŵ͕>ĞǀĞůϮ 1:30 p.m. – 2:00 p.m. WůĞŶĂƌǇ^ĞƐƐŝŽŶ///͗,ƵŵĂŶ'ĞŶĞƟĐƐĂŶĚ,ĞĂůƚŚǇ>ŽŶŐĞǀŝƚǇ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ DŽĚĞƌĂƚŽƌƐ͗Benjamin Ebert, Mary Klotman, and Jeremie Lever The Genome(s) and Epigenome(s) of Acute Myeloid Leukemia /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Timothy J. Ley, MD Washington University School of Medicine

2:00 p.m. – 2:15 p.m. W^dƌĂŝŶĞĞKƌĂůďƐƚƌĂĐƚWƌĞƐĞŶƚĂƟŽŶ͗ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ ŚĂƌĂĐƚĞƌŝǌĂƟŽŶĂŶĚDĞƚĂďŽůŝĐ^ǇŶƚŚĞƟĐ>ĞƚŚĂů dĞƐƟŶŐŝŶĂEĞǁDŽĚĞůŽĨ^,Ͳ>ŽƐƐ&ĂŵŝůŝĂů Pheochromocytoma and Paraganglioma /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗John Smestad Mayo Clinic AAP/ASCI Travel Awardee 2:15 p.m. – 2:45 p.m. EŽƌŵĂůĂŶĚEĞŽƉůĂƐƟĐ^ƚĞŵĞůůƐ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Irving L. Weissman, MD Stanford University

2:45 p.m. – 3:15 p.m. Break DŽĚĞƌĂƚŽƌƐ͗John Carethers, Benjamin Ebert, and Audra Iness 3:15 p.m. – 3:45 p.m. Genes, Genomes and Future of Medicine /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗ZŝĐŚĂƌĚW͘>ŝŌŽŶ͕D͕WŚ Rockefeller University

3:45 p.m. – 4:15 p.m. Science, Serendipity and the Single Degree /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ <ŽďĞƌ>ĞĐƚƵƌĞƌ͗Helen H. Hobbs, MD University of Texas Southwestern Medical Center

4:15 p.m. – 4:45 p.m. WWƌĞƐŝĚĞŶƟĂůĚĚƌĞƐƐ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ dŚĞŵĞƌŝĐĂŶWŚǇƐŝĐŝĂŶͲ^ĐŝĞŶƟƐƚ͗ϲϬŝƐƚŚĞŶĞǁϰϬ Serpil Erzurum, MD Cleveland Clinic

4:45 p.m. – 5:15 p.m. <ŽďĞƌDĞĚĂůWƌĞƐĞŶƚĂƟŽŶ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ

ZĞĐŝƉŝĞŶƚ͗ Stuart H. Orkin, MD ĂŶĂ&ĂƌďĞƌĂŶĐĞƌ/ŶƐƟƚƵƚĞ

WƌĞƐĞŶƚĞƌ͗ Leonard I. Zon, MD ,ŽǁĂƌĚ,ƵŐŚĞƐDĞĚŝĐĂů/ŶƐƟƚƵƚĞ͕ Harvard Medical School, Boston Children’s Hospital

5:15 p.m. – 5:30 p.m. WƵƐŝŶĞƐƐDĞĞƟŶŐ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ

8 2018 AAP / ASCI / APSA Joint Meeting SCIENTIFIC PROGRAM SCHEDULE

Saturday, April 21, 2018 ;ĐŽŶƟŶƵĞĚͿ Time Event Location 5:45 p.m. – 7:00 p.m. W^WĂŶĞů͗WŽůŝĐǇĂŶĚĚǀŽĐĂĐǇtŽƌŬƐŚŽƉ ƌǇƐƚĂůZŽŽŵ DŽĚĞƌĂƚŽƌ͗ Samantha Spellicy WĂŶĞůŝƐƚƐ͗

Michael Coburn Research!America

Ryan Murray, BS American Society of Nephrology

Benjamin Krinsky, PhD &ĞĚĞƌĂƟŽŶŽĨŵĞƌŝĐĂŶ^ŽĐŝĞƟĞƐĨŽƌǆƉĞƌŝŵĞŶƚĂůŝŽůŽŐǇ

Sharon K. Inouye, MD, MPH Hebrew SeniorLife/Harvard Medical School

5:45 p.m. – 7:00 p.m. W^WĂŶĞů͗ƌŝƟĐĂůĂŶĚ^ŽĐŝĂůWĞƌƐƉĞĐƟǀĞƐŽŶŐŝŶŐ ŵďĂƐƐĂĚŽƌZŽŽŵ DŽĚĞƌĂƚŽƌ͗ Josh Franklin WĂŶĞůŝƐts:

Janelle Taylor, PhD University of Washington

Greg A. Sachs, MD Indiana University

Carla Keirns, MD, PhD Kansas University Medical Center

6:30 p.m. – 9:00 p.m. ASCI Food & Science Evening DŝĚͲŵĞƌŝĐĂůƵď &ĞĂƚƵƌŝŶŐWŽƐƚĞƌWƌĞƐĞŶƚĂƟŽŶƐďǇƚŚĞ^/͛ƐϮϬϭϴ zŽƵŶŐWŚǇƐŝĐŝĂŶͲ^ĐŝĞŶƟƐƚǁĂƌĚĞĞƐ ;/ƌĞƋƵŝƌĞĚͿ 7:00 p.m. – 9:30 p.m. WDĞŵďĞƌĂŶĚEĞǁDĞŵďĞƌ/ŶĚƵĐƟŽŶĂŶƋƵĞƚ͗ /ŵƉĞƌŝĂůĂůůƌŽŽŵ ĂƚĂ^ŚĂƌŝŶŐŝŶƚŚĞ^ĞƫŶŐŽĨůŝŶŝĐĂůdƌŝĂůƐ /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗:ĞīƌĞǇD͘ƌĂǌĞŶ͕D Editor-in-Chief, New England Journal of Medicine ƫƌĞ͗&ŽƌŵĂůZĞƋƵŝƌĞĚ (Ticketed event)

www.jointmeeting.org 9 SCIENTIFIC PROGRAM SCHEDULE

Saturday, April 21, 2018 ;ĐŽŶƟŶƵĞĚͿ Time Event Location 7:30 p.m. – 9:00 p.m. W^ŝŶŶĞƌΘ&ŽƵŶĚĞƌ͛ƐǁĂƌĚWƌĞƐĞŶƚĂƟŽŶ(Ticketed event) ZŽƵŐĞ

&ŽƵŶĚĞƌ͛ƐǁĂƌĚZĞĐŝƉŝĞŶƚ͗Dania Daye, MD, PhD DĂƐƐĂĐŚƵƐĞƩƐ'ĞŶĞƌĂů,ŽƐƉŝƚĂů

ŚĂƌƟŶŐzŽƵƌWĂƚŚĂƐĂWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚ Dinner Speaker: :ƵůŝĂŶĞƵďĞĐŬͲtĂƌĚĞŶďƵƌŐ͕D͕WŚ Washington University School of Medicine

9:45 p.m. – 11:30 p.m. ĞƐƐĞƌƚZĞĐĞƉƟŽŶĂŶĚĞƐƚWŽƐƚĞƌǁĂƌĚƐ;KƉĞŶƚŽĂůůĂƩĞŶĚĞĞƐͿ /ŵƉĞƌŝĂů>ŽďďǇ

Sunday, April 22, 2018 Time Event Location 8:00 a.m. – 12:00 p.m. APSA Session II 8:00 a.m. – 9:30 am DĞŶƚŽƌŝŶŐƌĞĂŬĨĂƐƚ͗DĞĚŝĐĂů^ƉĞĐŝĂůƚǇǆƉůŽƌĂƟŽŶ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ 8:30 a.m. – 9:30 a.m. ^ŽĐŝĞƚǇ>ĞĂĚĞƌƐŚŝƉtƌĂƉhƉDĞĞƟŶŐ ^ƚĂƚĞZŽŽŵ 9:30 a.m. – 10:00 a.m. ĞůŝƌŝƵŵŝŶKůĚĞƌĚƵůƚƐ͗DǇ/ŶǀĞƐƟŐĂƟǀĞ:ŽƵƌŶĞǇ 'ŽůĚZŽŽŵ /ŶǀŝƚĞĚ^ƉĞĂŬĞƌ͗Sharon Inouye, MD, MPH Hebrew SeniorLife/Harvard Medical School

10:00 a.m. – 11:00 a.m. W^WĂŶĞů͗ůƚĞƌŶĂƟǀĞĂƌĞĞƌƐ 'ŽůĚZŽŽŵ DŽĚĞƌĂƚŽƌ͗ Eileen Hu WĂŶĞůŝƐƚƐ͗

Daryll C. Dykes, PhD, MD, JD Medical and Surgical Spine Consultants of Minnesota

Anna Fisher, MD hŶŝǀĞƌƐŝƚǇŽĨZŽĐŚĞƐƚĞƌ^ĐŚŽŽůŽĨDĞĚŝĐŝŶĞΘĞŶƟƐƚƌǇ

Andrew Chan, MD, PhD 'ĞŶĞŶƚĞĐŚ͕/ŶĐ͘

10:00 a.m. – 12:00 p.m. W^ZĞƐĞĂƌĐŚWĂƚŚǁĂǇZĞƐŝĚĞŶĐǇWƌŽŐƌĂŵŝƌĞĐƚŽƌƐDĞĞƟŶŐ ^ƚĂƚĞZŽŽŵ

10 2018 AAP / ASCI / APSA Joint Meeting SCIENTIFIC PROGRAM SCHEDULE

Sunday, April 22, 2018 ;ĐŽŶƟŶƵĞĚͿ Time Event Location 11:00 a.m. – 12:00 p.m. W^WĂŶĞů͗ZĞƐŝůŝĞŶĐĞtŽƌŬƐŚŽƉ 'ŽůĚZŽŽŵ DŽĚĞƌĂƚŽƌ͗ Audra Iness WĂŶĞůŝƐƚƐ͗

Kay Lund, PhD EĂƟŽŶĂů/ŶƐƟƚƵƚĞƐŽĨ,ĞĂůƚŚ

Dani Dumitriu, MD, PhD Icahn School of Medicine at Mount Sinai

Michael Helmrath, MD, MS ŝŶĐŝŶŶĂƟŚŝůĚƌĞŶ͛Ɛ,ŽƐƉŝƚĂůDĞĚŝĐĂůĞŶƚĞƌ

11:00 a.m. – 12:00 p.m. W^WĂŶĞů͗dŚĞŽ͛ƐĂŶĚŽŶ͛ƚƐŽĨD^dWĚŵŝƐƐŝŽŶƐ ŵďĂƐƐĂĚŽƌZŽŽŵ DŽĚĞƌĂƚŽƌ͗ Jose Rodrigues WĂŶĞůŝƐƚƐ͗

ŶĚƌĞĂŵĂůĮƚĂŶŽ͕K͕WŚ Michigan State University

Dianna Milewicz, MD, PhD University of Texas Medical School at Houston

Paul Utz, MD Stanford University School of Medicine

12:30 p.m. – 2:30 p.m. APSA Residency Luncheon /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ 1 ĞƚŚ/ƐƌĂĞůĞĂĐŽŶĞƐƐDĞĚŝĐĂůĞŶƚĞƌ/ŶƚĞƌŶĂůDĞĚŝĐŝŶĞWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚdƌĂĐŬ Director: Steven Freedman, MD, PhD 2 hŶŝǀĞƌƐŝƚǇŽĨWĞŶŶƐǇůǀĂŶŝĂ/ŶƚĞƌŶĂůDĞĚŝĐŝŶĞWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚWĂƚŚǁĂǇWƌŽŐƌĂŵ Director: Peter Klein, MD, PhD 3 DĂƐƐĂĐŚƵƐĞƩƐ'ĞŶĞƌĂů,ŽƐƉŝƚĂů/ŶƚĞƌŶĂůDĞĚŝĐŝŶĞZĞƐŝĚĞŶĐǇWƌŽŐƌĂŵ ŝƌĞĐƚŽƌ͗:ĂƟŶsǇĂƐ͕D͕WŚ͘ƐƐŽĐŝĂƚĞŝƌĞĐƚŽƌ͗ĂƌŽůŝŶĞ^ŽŬŽů͕D͕WŚ 4 ŝŶĐŝŶŶĂƟŚŝůĚƌĞŶ͛Ɛ,ŽƐƉŝƚĂůWĞĚŝĂƚƌŝĐ^ĐŝĞŶƟƐƚĞǀĞůŽƉŵĞŶƚWƌŽŐƌĂŵ ŚĂŝƌŽĨ,ĞŵĂƚŽůŽŐǇdƌĂŶƐůĂƟŽŶĂůZĞƐĞĂƌĐŚ͗ZƵƐƐĞůůtĂƌĞ͕D͕WŚ 5 ƌŝŐŚĂŵĂŶĚtŽŵĞŶ͛Ɛ,ŽƐƉŝƚĂů/ŶƚĞƌŶĂůDĞĚŝĐŝŶĞZĞƐŝĚĞŶĐǇWƌŽŐƌĂŵ Director: Joel Katz, MD. Assoc. Program Director: Rebecca Baron, MD 6 sĂŶĚĞƌďŝůƚhŶŝǀĞƌƐŝƚǇ^ĐŚŽŽůŽĨDĞĚŝĐŝŶĞWŚǇƐŝĐŝĂŶͲ^ĐŝĞŶƟƐƚdƌĂŝŶŝŶŐWƌŽŐƌĂŵ Director: Patrick Hu, MD, PhD 7 KŚŝŽ^ƚĂƚĞhŶŝǀĞƌƐŝƚǇWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚdƌĂŝŶŝŶŐWƌŽŐƌĂŵ Director: Robert Baiocchi, MD, PhD 8 ĂǇůŽƌWĞĚŝĂƚƌŝĐWĞĚŝĂƚƌŝĐŝĂŶͲ^ĐŝĞŶƟƐƚdƌĂŝŶŝŶŐΘĞǀĞůŽƉŵĞŶƚWƌŽŐƌĂŵ Assoc. Director: Audrea Burns, PhD

www.jointmeeting.org 11 SCIENTIFIC PROGRAM SCHEDULE

Sunday, April 22, 2018 ;ĐŽŶƟŶƵĞĚͿ Time Event Location 12:30 p.m. – 2:30 p.m. APSA Residency Luncheon ;ĐŽŶƟŶƵĞĚͿ /ŶƚĞƌŶĂƟŽŶĂůĂůůƌŽŽŵ 9 hŶŝǀĞƌƐŝƚǇŽĨůĂďĂŵĂĂƚŝƌŵŝŶŐŚĂŵ/DZĞƐĞĂƌĐŚWĂƚŚǁĂǇWƌŽŐƌĂŵ Director: Sonya Heath, MD 10 ŚŝůĚƌĞŶ͛Ɛ,ŽƐƉŝƚĂůŽĨ>ŽƐŶŐĞůĞƐ'ĞŽƌŐĞŽŶŶĞůů^ŽĐŝĞƚǇĨŽƌWĞĚŝĂƚƌŝĐ^ĐŝĞŶƟƐƚƐ Director: Lee Helman, MD 11 hŶŝǀĞƌƐŝƚǇŽĨDŝŶŶĞƐŽƚĂ/ŶƚĞƌŶĂůDĞĚŝĐŝŶĞWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚdƌĂŝŶŝŶŐWƌŽŐƌĂŵ ŝƌĞĐƚŽƌ͗ůŝīŽƌĚ^ƚĞĞƌ͕D 12 hŶŝǀĞƌƐŝƚǇŽĨ/ŽǁĂDƵůƟĚŝƐĐŝƉůŝŶĂƌǇWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚdƌĂŝŶŝŶŐWƌŽŐƌĂŵ Director: Joel Kline, MD 13 hŶŝǀĞƌƐŝƚǇŽĨŝŶĐŝŶŶĂƟ/ŶƚĞƌŶĂůDĞĚŝĐŝŶĞWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚdƌĂŝŶŝŶŐWƌŽŐƌĂŵ Director: Jack Rubinstein, MD, Dept. of Medicine. Research Manager: Yolanda Wess, MEd, BSN 14 EĂƟŽŶĂů/ŶƐƟƚƵƚĞƐŽĨ,ĞĂůƚŚůŝŶŝĐĂůĞŶƚĞƌZĞƐŝĚĞŶĐǇĂŶĚ&ĞůůŽǁƐŚŝƉWƌŽŐƌĂŵƐ Director: Robert Lembo, MD 15 hŶŝǀĞƌƐŝƚǇŽĨZŽĐŚĞƐƚĞƌDĞĚŝĐĂůĞŶƚĞƌ/DZĞƐĞĂƌĐŚWĂƚŚǁĂǇ Director: Jason Mendler, MD, PhD 16 hŶŝǀĞƌƐŝƚǇŽĨhƚĂŚWŚǇƐŝĐŝĂŶ^ĐŝĞŶƟƐƚdƌĂŝŶŝŶŐWƌŽŐƌĂŵ ƐƐŽĐŝĂƚĞŚĂŝƌŽĨZĞƐĞĂƌĐŚ͗'ƵǇŝŵŵĞƌŵĂŶ͕D

12 2018 AAP / ASCI / APSA Joint Meeting SPEAKER BIOGRAPHIES

KŵĂƌ/͘ďĚĞůͲtĂŚĂď͕D ƚĞůŽŵĞƌĂƐĞŝŶĚŝƐĞĂƐĞ͘ƌ͘ƌŵĂŶŝŽƐĞĂƌŶĞĚŚĞƌŵĞĚŝĐĂůĚĞŐƌĞĞ ƌ͘ďĚĞůͲtĂŚĂďŝƐƐƐŽĐŝĂƚĞDĞŵďĞƌŝŶƚŚĞ,ƵŵĂŶKŶĐŽůŽŐǇ ĂƚƚŚĞKŚŝŽ^ƚĂƚĞhŶŝǀĞƌƐŝƚǇ͕ǁŚĞƌĞƐŚĞǁĞŶƚŽŶƚŽĐŽŵƉůĞƚĞĂ ĂŶĚ WĂƚŚŽŐĞŶĞƐŝƐ WƌŽŐƌĂŵ ĂŶĚ ĂŶ ƚƚĞŶĚŝŶŐ WŚǇƐŝĐŝĂŶ ŽŶ ƚŚĞ ĐŽŵďŝŶĞĚ ŝŶƚĞƌŶĂů ŵĞĚŝĐŝŶĞ ĂŶĚ ƉĞĚŝĂƚƌŝĐƐ ƌĞƐŝĚĞŶĐǇ͘ ^ŚĞ ƚŚĞŶ >ĞƵŬĞŵŝĂ ^ĞƌǀŝĐĞ ŝŶ ƚŚĞ ĞƉĂƌƚŵĞŶƚ ŽĨ DĞĚŝĐŝŶĞ Ăƚ DĞŵŽƌŝĂů ŵŽǀĞĚ ƚŽ :ŽŚŶƐ ,ŽƉŬŝŶƐ ƚŽ ĐŽŵƉůĞƚĞ ŚĞƌ ŵĞĚŝĐĂů ŽŶĐŽůŽŐǇ ^ůŽĂŶ<ĞƚƚĞƌŝŶŐĂŶĐĞƌĞŶƚĞƌ;D^<Ϳ͘,ĞĂůƐŽƐĞƌǀĞƐĂƐĐŽͲĚŝƌĞĐƚŽƌ ĨĞůůŽǁƐŚŝƉ͘^ŚĞŝƐĐƵƌƌĞŶƚůǇƚŚĞůŝŶŝĐĂůŝƌĞĐƚŽƌŽĨƚŚĞdĞůŽŵĞƌĞ ŽĨƚŚĞ,ĞŵĂƚŽůŽŐǇͬDĞĚŝĐĂůKŶĐŽůŽŐǇĨĞůůŽǁƐŚŝƉƉƌŽŐƌĂŵĂƚD^< ĞŶƚĞƌĂƚ:ŽŚŶƐ,ŽƉŬŝŶƐĂŶĚŽǀĞƌƐĞĂƐƚŚĞƚĞůŽŵĞƌĞĚŝĂŐŶŽƐƚŝĐƐ ĂŶĚĐŽͲĚŝƌĞĐƚŽƌŽĨƚŚĞĞŶƚĞƌĨŽƌ,ĞŵĂƚŽůŽŐŝĐDĂůŝŐŶĂŶĐŝĞƐ͘,ŝƐ ůĂďĂƚ:ŽŚŶƐ,ŽƉŬŝŶƐ,ŽƐƉŝƚĂů͘ƌ͘ƌŵĂŶŝŽƐŝƐĂŵĞŵďĞƌŽĨƚŚĞ ƌĞƐĞĂƌĐŚ ĨŽĐƵƐĞƐ ŽŶ ƵŶĚĞƌƐƚĂŶĚŝŶŐ ƚŚĞ ĨƵŶĐƚŝŽŶĂů ŝŵƉůŝĐĂƚŝŽŶƐ ŵĞƌŝĐĂŶ^ŽĐŝĞƚǇĨŽƌůŝŶŝĐĂů/ŶǀĞƐƚŝŐĂƚŝŽŶĂŶĚƐĞƌǀĞƐĂƐƐƐŽĐŝĂƚĞ ŽĨ ƐŽŵĂƚŝĐ ŵƵƚĂƚŝŽŶƐ ĨŽƵŶĚ ŝŶ ƉĂƚŝĞŶƚƐ ǁŝƚŚ ŚĞŵĂƚŽƉŽŝĞƚŝĐ ĚŝƚŽƌŽĨƚŚĞJournal of Clinical Investigation. ŵĂůŝŐŶĂŶĐŝĞƐ ǁŝƚŚ ƚŚĞ ŚŽƉĞƐ ŽĨ ŝŵƉƌŽǀŝŶŐ ŽƵƌ ƵŶĚĞƌƐƚĂŶĚŝŶŐ Kathleen H. Burns, MD, PhD ŽĨ ĚŝƐĞĂƐĞ ďŝŽůŽŐǇ ĂŶĚ ĚĞǀĞůŽƉ ŶŽǀĞů ƚŚĞƌĂƉŝĞƐ͘ ƵƌƌĞŶƚůǇ͕ ŚŝƐ ƌ͘ƵƌŶƐŝƐĂƉŚǇƐŝĐŝĂŶͲƐĐŝĞŶƚŝƐƚĂŶĚƉƌĂĐƚŝĐŝŶŐŚĞŵĂƚŽƉĂƚŚŽůŽŐŝƐƚ ůĂďŽƌĂƚŽƌǇ ŝƐ ĐĞŶƚĞƌĞĚ ŽŶ ƚŚĞ ƌŽůĞ ŽĨ ŵƵƚĂƚŝŽŶƐ ĂĨĨĞĐƚŝŶŐ ƚŚĞ ĂƚƚŚĞ:ŽŚŶƐ,ŽƉŬŝŶƐhŶŝǀĞƌƐŝƚǇ^ĐŚŽŽůŽĨDĞĚŝĐŝŶĞ͘,ĞƌƌĞƐĞĂƌĐŚ ƚƌĂŶƐĐƌŝƉƚŝŽŶĂůƌĞŐƵůĂƚŝŽŶŝŶůĞƵŬĞŵŝĂƐ͘dŚŝƐŝŶĐůƵĚĞƐŵƵƚĂƚŝŽŶƐ ůĂďŽƌĂƚŽƌǇƐƚƵĚŝĞƐƌŽůĞƐŵŽďŝůĞŐĞŶĞƚŝĐĞůĞŵĞŶƚƐƉůĂǇŝŶŚƵŵĂŶ ŝŶ ĞƉŝŐĞŶĞƚŝĐ ŵŽĚŝĨŝĞƌƐ ŝŶ ůĞƵŬĞŵŝĂ ƉĂƚŚŽŐĞŶĞƐŝƐ ĂƐ ǁĞůů ĂƐ ĚŝƐĞĂƐĞ͘,ĞƌůĂďǁĂƐŽŶĞŽĨƚŚĞĨŝƌƐƚƚŽĚĞǀĞůŽƉĂƚĂƌŐĞƚĞĚŵĞƚŚŽĚ ŵƵƚĂƚŝŽŶƐŝŶĐŽŵƉŽŶĞŶƚƐŽĨƚŚĞZEƐƉůŝĐŝŶŐĨĂĐƚŽƌŵĂĐŚŝŶĞƌǇ͘ ƚŽĂŵƉůŝĨǇŵŽďŝůĞEŝŶƐĞƌƚŝŽŶƐŝƚĞƐŝŶƚŚĞŚƵŵĂŶŐĞŶŽŵĞĨŽƌ ,ŝƐůĂďŽƌĂƚŽƌǇŚĂƐŐĞŶĞƌĂƚĞĚƐƵďƐƚĂŶƚŝĂůƌĞĂŐĞŶƚƐƚŽƐƚƵĚǇƚŚĞƌŽůĞ ĐŽŵƉƌĞŚĞŶƐŝǀĞ ŝŶƐĞƌƚŝŽŶ ŵĂƉƉŝŶŐ͘ dŚĞŝƌ ƐƚƵĚŝĞƐ ŚĂǀĞ ƐŚŽǁŶ ŽĨŵƵƚĂƚĞĚƐƉůŝĐĞŽƐŽŵĂůĨĂĐƚŽƌƐŝŶŚĞŵĂƚŽƉŽŝĞƚŝĐŵĂůŝŐŶĂŶĐŝĞƐ ƚŚĂƚŵŽďŝůĞĞůĞŵĞŶƚŝŶƐĞƌƚŝŽŶƐƌĞƉƌĞƐĞŶƚĂƐŝŐŶŝĨŝĐĂŶƚƐŽƵƌĐĞ ĂŶĚƐŽůŝĚƚƵŵŽƌƐ͕ŝŶĐůƵĚŝŶŐƐĞǀĞƌĂůŵƵƌŝŶĞŵŽĚĞůƐŽĨŵƵƚĂƚŝŽŶƐ ŽĨ ŝŶŚĞƌŝƚĞĚ ƐƚƌƵĐƚƵƌĂů ǀĂƌŝĂƚŝŽŶ ŝŶ ŚƵŵĂŶ ƉŽƉƵůĂƚŝŽŶƐ͕ ĂŶĚ ƚŚĞ ŝŶƚŚĞŐĞŶĞ^ƌƐĨϮ͕^Ĩϯďϭ͕ĂŶĚƌƐƌϮ͘,ŝƐůĂďŽƌĂƚŽƌǇƵƚŝůŝǌĞƐƚŚĞƐĞ ŐƌŽƵƉ ŚĂƐ ŝĚĞŶƚŝĨŝĞĚ ŶƵŵĞƌŽƵƐ ƉŽƚĞŶƚŝĂůůǇ ĨƵŶĐƚŝŽŶĂů ŝŶƐĞƌƚŝŽŶ ŵŽĚĞůƐƚŽĐƌĞĂƚĞŶŽǀĞůŵƵƌŝŶĞŵŽĚĞůƐŽĨŵǇĞůŽŝĚŵĂůŝŐŶĂŶĐŝĞƐ ǀĂƌŝĂŶƚƐĂƚůŽĐŝĂƐƐŽĐŝĂƚĞĚǁŝƚŚŚƵŵĂŶĚŝƐĞĂƐĞƌŝƐŬ͘,ĞƌůĂďĂůƐŽ ĨŽƌ ĞƉŝŐĞŶŽŵŝĐ͕ ĨƵŶĐƚŝŽŶĂů͕ ĂŶĚ ƉƌĞĐůŝŶŝĐĂů ƚŚĞƌĂƉĞƵƚŝĐ ƐƚƵĚŝĞƐ͘ ƐƚƵĚŝĞƐ ƚŚĞ ĞǆƉƌĞƐƐŝŽŶ ĂŶĚ ĂĐƚŝǀŝƚǇ ŽĨ ŵŽďŝůĞ EƐ ŝŶ ŚƵŵĂŶ &ŝŶĂůůǇ͕ ŚŝƐ ůĂďŽƌĂƚŽƌǇ ŝƐ ĂůƐŽ ŝŶƚĞƌĞƐƚĞĚ ŝŶ ŚĞŵĂƚŽůŽŐŝĐĂů ĐĂŶĐĞƌƐ͘ dŚĞ ůĂď ŚĂƐ ĚĞǀĞůŽƉĞĚ ƌĞĂŐĞŶƚƐ ƚŽ ĚĞƚĞĐƚ ƉƌŽƚĞŝŶƐ ŵĂůŝŐŶĂŶĐŝĞƐ ĚƌŝǀĞŶ ďǇ DW ŬŝŶĂƐĞ ƉĂƚŚǁĂǇ ĂůƚĞƌĂƚŝŽŶƐ͘ ,ŝƐ ĞŶĐŽĚĞĚďǇĂĐƚŝǀĞƌĞƚƌŽƚƌĂŶƐƉŽƐŽŶƐ͕ŶĂŵĞůǇ͕>ŽŶŐ/EƚĞƌƐƉĞƌƐĞĚ ůĂďŽƌĂƚŽƌǇ͛ƐƌĞƐĞĂƌĐŚŝƐƐƵƉƉŽƌƚĞĚďǇƚŚĞE/,͕EĂƚŝŽŶĂůĂŶĐĞƌ ůĞŵĞŶƚͲϭ;>/EͲϭͿŽƉĞŶƌĞĂĚŝŶŐĨƌĂŵĞϭƉ;KZ&ϭƉͿĂŶĚKZ&ϮƉ͘ /ŶƐƚŝƚƵƚĞ͕EĂƚŝŽŶĂů,ĞĂƌƚ͕>ƵŶŐ͕ĂŶĚůŽŽĚ/ŶƐƚŝƚƵƚĞƐ͕ƚŚĞ>ĞƵŬĞŵŝĂ dŚĞǇ ŚĂǀĞ ƐŚŽǁŶ ĂďĞƌƌĂŶƚ ĞǆƉƌĞƐƐŝŽŶ ŽĨ KZ&ϭƉ ŝŶ Ă ǁŝĚĞ Θ >ǇŵƉŚŽŵĂ ^ŽĐŝĞƚǇ͕ ƚŚĞ ĞƉƚ͘ ŽĨ ĞĨĞŶƐĞ͕ ƚŚĞ ŵĞƌŝĐĂŶ ǀĂƌŝĞƚǇŽĨŚƵŵĂŶĐĂŶĐĞƌƐ͘dŚŝƐĂĐƚŝǀĂƚŝŽŶŽĨ>/EͲϭŝƐĂƐƐŽĐŝĂƚĞĚ ^ŽĐŝĞƚǇ ŽĨ ,ĞŵĂƚŽůŽŐǇ͕ ĂŶĚ ŶƵŵĞƌŽƵƐ ĂĚĚŝƚŝŽŶĂů ƉŚŝůĂŶƚŚƌŽƉŝĐ ǁŝƚŚ ƐŽŵĂƚŝĐ ĂĐƚŝǀŝƚǇ͕ĂŶĚ ƚŚĞ ƵƌŶƐ ůĂď ŚĂƐ ŵĂƉƉĞĚ ŝŶƐĞƌƚŝŽŶƐ ŽƌŐĂŶŝǌĂƚŝŽŶƐ͘ƌ͘ďĚĞůͲtĂŚĂď͛ƐǁŽƌŬŚĂƐďĞĞŶƌĞĐŽŐŶŝǌĞĚďǇ ŽĨ >/EͲϭ ƐĞƋƵĞŶĐĞƐ ĂĐƋƵŝƌĞĚ ĚƵƌŝŶŐ ƚŚĞ ĐůŽŶĂů ĞǀŽůƵƚŝŽŶ ŽĨ ĂϮϬϭϳ^/^ĞůĚŝŶͲ^ŵŝƚŚǁĂƌĚĨŽƌWŝŽŶĞĞƌŝŶŐZĞƐĞĂƌĐŚĂŶĚƚŚĞ ŐĂƐƚƌŽŝŶƚĞƐƚŝŶĂůĂŶĚŽǀĂƌŝĂŶĐĂŶĐĞƌƐ͘dŚĞůĂďŚĂƐŽŶŐŽŝŶŐƉƌŽũĞĐƚƐ ϮϬϭϲ:ŽĂŶŶĞ>ĞǀǇDĞŵŽƌŝĂůǁĂƌĚĨŽƌKƵƚƐƚĂŶĚŝŶŐĐŚŝĞǀĞŵĞŶƚ ƚŽ ĚŝƐĐĞƌŶ ƚŚĞ ĨƵŶĐƚŝŽŶĂů ĐŽŶƐĞƋƵĞŶĐĞƐ ŽĨ ƐŽŵĂƚŝĐĂůůǇͲĂĐƋƵŝƌĞĚ ĨƌŽŵƚŚĞŵĞƌŝĐĂŶ^ŽĐŝĞƚǇŽĨ,ĞŵĂƚŽůŽŐǇ͘ ŵŽďŝůĞĞůĞŵĞŶƚŝŶƐĞƌƚŝŽŶƐ͕ĂƐǁĞůůĂƐŽƚŚĞƌĞĨĨĞĐƚƐŽĨKZ&ϭƉĂŶĚ Maria T. Abreu, MD KZ&ϮƉĞǆƉƌĞƐƐŝŽŶŝŶŵĂůŝŐŶĂŶĐǇ͘ƌ͘ƵƌŶƐƌĞĐĞŶƚůǇƐĞƌǀĞĚĂƐĐŽͲ ƌ͘ďƌĞƵŝƐĂƉŚǇƐŝĐŝĂŶͲƐĐŝĞŶƚŝƐƚŝŶŐĂƐƚƌŽĞŶƚĞƌŽůŽŐǇǁŝƚŚĂĨŽĐƵƐ ŚĂŝƌŽĨĂƐƚƌĂƚĞŐŝĐǁŽƌŬƐŚŽƉĂƚƚŚĞEĂƚŝŽŶĂůĂŶĐĞƌ/ŶƐƚŝƚƵƚĞŽŶ ŝŶŝŶĨůĂŵŵĂƚŽƌǇďŽǁĞůĚŝƐĞĂƐĞ;/Ϳ͘^ŚĞĐŽŵƉůĞƚĞĚŚĞƌŵĞĚŝĐĂů ƌŽůĞƐŽĨŵŽďŝůĞŐĞŶĞƚŝĐĞůĞŵĞŶƚƐŝŶĐĂŶĐĞƌ͕ĂŶĚĂƐƚŚĞKƌŐĂŶŝǌĞƌ ĚĞŐƌĞĞ Ăƚ ƚŚĞ hŶŝǀĞƌƐŝƚǇ ŽĨ DŝĂŵŝ͕ DŝůůĞƌ ^ĐŚŽŽů ŽĨ DĞĚŝĐŝŶĞ͕ ĨŽƌĂ&^ŵĞĞƚŝŶŐŽŶDŽďŝůĞEƐŝŶƚŚĞDĂŵŵĂůŝĂŶ'ĞŶŽŵĞ͘ ŚĞƌ ƌĞƐŝĚĞŶĐǇ ŝŶ ŵĞĚŝĐŝŶĞ Ăƚ ƌŝŐŚĂŵ ĂŶĚ tŽŵĞŶ͛Ɛ ,ŽƐƉŝƚĂů͕ ^ŚĞ ŚĂƐ ĂƵƚŚŽƌĞĚ ŶƵŵĞƌŽƵƐ ƉƌŝŵĂƌǇ ĂƌƚŝĐůĞƐ ĂŶĚ ƌĞǀŝĞǁƐ ŽŶ ĂŶĚƌĞƐĞĂƌĐŚĨĞůůŽǁƐŚŝƉŝŶŐĂƐƚƌŽĞŶƚĞƌŽůŽŐǇĂƚƚŚĞhŶŝǀĞƌƐŝƚǇŽĨ ŚƵŵĂŶ ƚƌĂŶƐƉŽƐŽŶƐ ĂŶĚ ƚŚĞŝƌ ƌŽůĞƐ ŝŶ ĚŝƐĞĂƐĞ͘ ƌ͘ ƵƌŶƐ ĂůƐŽ ĂůŝĨŽƌŶŝĂ͕ >ŽƐ ŶŐĞůĞƐ ;h>Ϳ͘ ^ŚĞ ŝƐ ĐƵƌƌĞŶƚůǇ ƚŚĞ ŝƌĞĐƚŽƌ ŽĨ ƐĞƌǀĞƐĂƐsŝĐĞŚĂŝƌĨŽƌZĞƐĞĂƌĐŚĨŽƌƚŚĞĞƉĂƌƚŵĞŶƚŽĨWĂƚŚŽůŽŐǇ ƚŚĞƌŽŚŶ͛ƐĂŶĚŽůŝƚŝƐĞŶƚĞƌĂƚhD͕WƌŽĨĞƐƐŽƌŽĨDĞĚŝĐŝŶĞĂŶĚ Ăƚ:ŽŚŶƐ,ŽƉŬŝŶƐ͕ĂŶĚĂƐƚŚĞŝŶĂƵŐƵƌĂůŝƌĞĐƚŽƌŽĨƚŚĞŝŶƐƚŝƚƵƚŝŽŶ͛Ɛ WƌŽĨĞƐƐŽƌŽĨDŝĐƌŽďŝŽůŽŐǇĂŶĚ/ŵŵƵŶŽůŽŐǇ͘ WŚǇƐŝĐŝĂŶ^ĐŝĞŶƚŝƐƚdƌĂŝŶŝŶŐWƌŽŐƌĂŵ;W^dWͿ͘ ƌ͘ ďƌĞƵ ǁĂƐ ĞůĞĐƚĞĚ ƚŽ ƚŚĞ ŵĞƌŝĐĂŶ ^ŽĐŝĞƚǇ ĨŽƌ ůŝŶŝĐĂů Ana Maria Cuervo, MD, PhD /ŶǀĞƐƚŝŐĂƚŝŽŶŝŶϮϬϭϬ͘^ŚĞŝƐƚŚĞĐƵƌƌĞŶƚŚĂŝƌŽĨƚŚĞŵĞƌŝĐĂŶ ƌ͘ƵĞƌǀŽŝƐƚŚĞZ͘Z͘ĞůĨĞƌŚĂŝƌĨŽƌEĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞŝƐĞĂƐĞƐ͕ 'ĂƐƚƌŽĞŶƚĞƌŽůŽŐŝĐĂů ƐƐŽĐŝĂƚŝŽŶ ;'Ϳ /ŶƐƚŝƚƵƚĞ ŽƵŶĐŝů͘ ,Ğƌ WƌŽĨĞƐƐŽƌ ŝŶ ƚŚĞ ĞƉĂƌƚŵĞŶƚƐ ŽĨ ĞǀĞůŽƉŵĞŶƚĂů ĂŶĚ DŽůĞĐƵůĂƌ ƌĞƐĞĂƌĐŚŚĂƐĨŽĐƵƐĞĚŽŶŝŶŶĂƚĞŝŵŵƵŶŝƚǇĂŶĚŝƚƐĐŽŶƚƌŝďƵƚŝŽŶƚŽ ŝŽůŽŐǇĂŶĚŽĨDĞĚŝĐŝŶĞŽĨƚŚĞůďĞƌƚŝŶƐƚĞŝŶŽůůĞŐĞŽĨDĞĚŝĐŝŶĞ /͘ ƌ͘ďƌĞƵ͛Ɛ ůĂďŽƌĂƚŽƌǇͲďĂƐĞĚ E/,ͲĨƵŶĚĞĚ ƌĞƐĞĂƌĐŚ ĨŽĐƵƐĞƐ ĂŶĚ ĐŽͲĚŝƌĞĐƚŽƌ ŽĨ ƚŚĞ ŝŶƐƚĞŝŶ /ŶƐƚŝƚƵƚĞ ĨŽƌ ŐŝŶŐ ^ƚƵĚŝĞƐ͘ ^ŚĞ ŽŶ ĐŽůŝƚŝƐͲĂƐƐŽĐŝĂƚĞĚ ĐĂŶĐĞƌ͕ ƐƚĞŵ ĐĞůůƐ͕ ĂŶĚ ƚŚĞ ŵŝĐƌŽďŝŽŵĞ͘ ŽďƚĂŝŶĞĚ ŚĞƌ D͘͘ ĂŶĚ Ă WŚ͘͘ ŝŶ ŝŽĐŚĞŵŝƐƚƌǇ ĂŶĚ DŽůĞĐƵůĂƌ ^ŝŶĐĞ ƌĞƚƵƌŶŝŶŐ ƚŽ DŝĂŵŝ͕ ƌ͘ ďƌĞƵ͛Ɛ ƚƌĂŶƐůĂƚŝŽŶĂů ƌĞƐĞĂƌĐŚ ďŝŽůŽŐǇ ĨƌŽŵ ƚŚĞ hŶŝǀĞƌƐŝƚǇ ŽĨ sĂůĞŶĐŝĂ ;^ƉĂŝŶͿ ĂŶĚ ƌĞĐĞŝǀĞĚ ĨŽĐƵƐĞƐŽŶƚŚĞƌŝƐŝŶŐŝŶĐŝĚĞŶĐĞŽĨ/ŝŶŝŵŵŝŐƌĂŶƚƐĨƌŽŵ>ĂƚŝŶ ƉŽƐƚĚŽĐƚŽƌĂů ƚƌĂŝŶŝŶŐ Ăƚ dƵĨƚƐ hŶŝǀĞƌƐŝƚǇ͕ ŽƐƚŽŶ͘ /Ŷ ϮϬϬϮ͕ ƐŚĞ ŵĞƌŝĐĂĂŶĚŝŶ,ŝƐƉĂŶŝĐͲŵĞƌŝĐĂŶƐ͘^ŚĞĂŶĚŚĞƌĐŽůůĞĂŐƵĞƐŚĂǀĞ ƐƚĂƌƚĞĚŚĞƌůĂďŽƌĂƚŽƌǇĂƚƚŚĞůďĞƌƚŝŶƐƚĞŝŶŽůůĞŐĞŽĨDĞĚŝĐŝŶĞ͕ ĚĞƐĐƌŝďĞĚƚŚĞƉŚĞŶŽƚǇƉĞĂŶĚŐĞŶŽƚǇƉĞŽĨ,ŝƐƉĂŶŝĐƉĂƚŝĞŶƚƐŝŶ ǁŚĞƌĞƐŚĞĐŽŶƚŝŶƵĞƐŚĞƌƐƚƵĚŝĞƐŝŶƚŚĞƌŽůĞŽĨƉƌŽƚĞŝŶͲĚĞŐƌĂĚĂƚŝŽŶ DŝĂŵŝĚĞǀĞůŽƉŝŶŐ/͘ ŝŶŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞĚŝƐĞĂƐĞƐĂŶĚĂŐŝŶŐ͘ Mary Armanios, MD ƌ͘ƵĞƌǀŽŚĂƐƌĞĐĞŝǀĞĚƉƌĞƐƚŝŐŝŽƵƐĂǁĂƌĚƐƐƵĐŚĂƐƚŚĞW͘ĞŶƐŽŶ ƌ͘ƌŵĂŶŝŽƐŝƐWƌŽĨĞƐƐŽƌŽĨKŶĐŽůŽŐǇĂŶĚ'ĞŶĞƚŝĐDĞĚŝĐŝŶĞĂƚ ĂŶĚƚŚĞ<ĞŝƚŚWŽƌƚĞƌŝŶĞůůŝŽůŽŐǇ͕ƚŚĞEĂƚŚĂŶ^ŚŽĐŬDĞŵŽƌŝĂů ƚŚĞ :ŽŚŶƐ ,ŽƉŬŝŶƐ hŶŝǀĞƌƐŝƚǇ ^ĐŚŽŽů ŽĨ DĞĚŝĐŝŶĞ͘ ,Ğƌ ƌĞƐĞĂƌĐŚ >ĞĐƚƵƌĞ͕ƚŚĞsŝŶĐĞŶƚƌŝƐƚŽĨĂůŽĂŶĚƚŚĞĞŶŶĞƚƚ:͘ŽŚĞŶŝŶďĂƐŝĐ ŝŶƚĞƌĞƐƚƐŚĂǀĞĨŽĐƵƐĞĚŽŶƵŶĚĞƌƐƚĂŶĚŝŶŐƚŚĞƌŽůĞŽĨƚĞůŽŵĞƌĞƐĂŶĚ ĂŐŝŶŐďŝŽůŽŐǇĂŶĚƚŚĞDĂƌƐŚĂůů,ŽƌǁŝƚǌĂŶĚƚŚĞ^ĂƵů<ŽƌĞǇWƌŝǌĞĨŽƌ

www.jointmeeting.org 13 SPEAKER BIOGRAPHIES

ĞǆĐĞůůĞŶĐĞŝŶƌĞƐĞĂƌĐŚĂŶĚŝŶdƌĂŶƐůĂƚŝŽŶĂůDĞĚŝĐŝŶĞ͘^ŚĞĚĞůŝǀĞƌĞĚ ,ĞƐĞƌǀĞƐŽŶƚŚĞEĂƚŝŽŶĂůĐĂĚĞŵǇŽĨDĞĚŝĐŝŶĞ͛Ɛ&ŽƌƵŵŽŶƌƵŐ ƉƌŽŵŝŶĞŶƚůĞĐƚƵƌĞƐƐƵĐŚĂƐƚŚĞZŽďĞƌƚZ͘<ŽŶŚ͕ƚŚĞE/,ŝƌĞĐƚŽƌ͛Ɛ͕ ŝƐĐŽǀĞƌǇ͕ĞǀĞůŽƉŵĞŶƚ͕ĂŶĚdƌĂŶƐůĂƚŝŽŶ͘ ƚŚĞ ZŽǇ tĂůĨŽƌĚ͕ ƚŚĞ &ĞŽĚŽƌ >ǇŶĞŶ͕ ƚŚĞ DĂƌŐĂƌĞƚ WŝƚƚŵĂŶ͕ ƚŚĞ Ŷ ĂĐƚŝǀĞ ƌĞƐĞĂƌĐŚĞƌ ŝŶ ƚŚĞ ĨŝĞůĚ ŽĨ ƉƵůŵŽŶĂƌǇ ŵĞĚŝĐŝŶĞ͕ ƌ͘ /hD ǁĂƌĚ͕ ƚŚĞ ĂǀŝĚ ,͘ DƵƌĚŽǆŬ͕ ƚŚĞ 'ĞƌƌǇ ƵƌďĂĐŚ ĂŶĚ ƌĂǌĞŶĚĞĨŝŶĞĚƚŚĞƌŽůĞŽĨŶŽǀĞůĞŶĚŽŐĞŶŽƵƐĐŚĞŵŝĐĂůĂŐĞŶƚƐŝŶ ƚŚĞ,ĂƌǀĞǇ^ŽĐŝĞƚǇ>ĞĐƚƵƌĞ͘^ŚĞŝƐĐƵƌƌĞŶƚůǇĐŽͲĚŝƚŽƌͲŝŶͲŚŝĞĨŽĨ ĂƐƚŚŵĂ͕ůĞĂĚŝŶŐƚŽĨŽƵƌůŝĐĞŶƐĞĚƉŚĂƌŵĂĐĞƵƚŝĐĂůƐĨŽƌĂƐƚŚŵĂ͕ŶŽǁ ŐŝŶŐĞůůĂŶĚŚĂƐďĞĞŶŵĞŵďĞƌŽĨƚŚĞE/^ĐŝĞŶƚŝĨŝĐŽƵŶĐŝůĂŶĚ ƵƐĞĚďǇƚĞŶƐŽĨŵŝůůŝŽŶƐŽĨƉĞŽƉůĞǁŽƌůĚǁŝĚĞ͘,ĞŚĂƐƉƵďůŝƐŚĞĚ ŽĨƚŚĞE/,ŽƵŶĐŝůŽĨŽƵŶĐŝůƐ͘ ŽǀĞƌϱϬϬƉĂƉĞƌƐ͕ĞĚŝƚŽƌŝĂůƐĂŶĚƌĞǀŝĞǁĂƌƚŝĐůĞƐĂŶĚŚĂƐĞĚŝƚĞĚƚĞŶ George Q. Daley, MD, PhD ďŽŽŬƐ͕ŝŶĐůƵĚŝŶŐ'ŽůĚŵĂŶͲĞĐŝůDĞĚŝĐŝŶĞand Asthma and COPD. ƌ͘ĂůĞǇŝƐĚĞĂŶŽĨ,ĂƌǀĂƌĚDĞĚŝĐĂů^ĐŚŽŽů;,D^ͿĂŶĚƚŚĞĂƌŽůŝŶĞ /Ŷ ϮϬϬϬ͕ ƌ͘ƌĂǌĞŶ ďĞĐĂŵĞ ĞĚŝƚŽƌͲŝŶͲĐŚŝĞĨ ŽĨ ƚŚĞ New England ^ŚŝĞůĚƐ tĂůŬĞƌ WƌŽĨĞƐƐŽƌ ŽĨ DĞĚŝĐŝŶĞ Ăƚ ,D^͘ ,Ğ ŚĂƐ ďĞĞŶ Journal of Medicine͘^ŝŶĐĞƚŚĞŶ͕ƚŚĞJournalŚĂƐƉƵďůŝƐŚĞĚŵĂũŽƌ ƉƌŽĨĞƐƐŽƌ ŽĨ ďŝŽůŽŐŝĐĂů ĐŚĞŵŝƐƚƌǇ ĂŶĚ ŵŽůĞĐƵůĂƌ ƉŚĂƌŵĂĐŽůŽŐǇ ƉĂƉĞƌƐ ĂĚǀĂŶĐŝŶŐ ƚŚĞ ƐĐŝĞŶĐĞ ŽĨ ŵĞĚŝĐŝŶĞ͕ ŝŶĐůƵĚŝŶŐ ƚŚĞ ĨŝƌƐƚ Ăƚ ,D^ ƐŝŶĐĞ ϮϬϭϬ ĂŶĚ ĂŶ ŝŶǀĞƐƚŝŐĂƚŽƌ ŽĨ ƚŚĞ ,ŽǁĂƌĚ ,ƵŐŚĞƐ ĚĞƐĐƌŝƉƚŝŽŶƐŽĨ^Z^͕ƚŝŵĞůǇĐŽǀĞƌĂŐĞŽĨƚŚĞďŽůĂĂŶĚŝŬĂǀŝƌƵƐ DĞĚŝĐĂů/ŶƐƚŝƚƵƚĞƐŝŶĐĞϮϬϬϴ͘/Ŷ:ƵůǇϮϬϭϲ͕ŚĞďĞĐĂŵĞƚŚĞZŽďĞƌƚ ĞƉŝĚĞŵŝĐƐ͕ĂŶĚĂĚǀĂŶĐĞƐŝŶƚŚĞƚƌĞĂƚŵĞŶƚŽĨĐĂŶĐĞƌ͕ŚĞĂƌƚĚŝƐĞĂƐĞ ͘ ^ƚƌĂŶĂŚĂŶ WƌŽĨĞƐƐŽƌ ŽĨ WĞĚŝĂƚƌŝĐƐ ĂŶĚ WƌŽĨĞƐƐŽƌ ŽĨ ŝŽůŽŐŝĐĂů ĂŶĚůƵŶŐĚŝƐĞĂƐĞ͘/ƚŚĂƐďĞĞŶĂƚƚŚĞĨŽƌĞĨƌŽŶƚŽĨǁŽƌůĚǁŝĚĞĞĨĨŽƌƚƐ ŚĞŵŝƐƚƌǇ ĂŶĚ DŽůĞĐƵůĂƌ WŚĂƌŵĂĐŽůŽŐǇ Ăƚ ,D^͘ ,Ğ ƉƌĞǀŝŽƵƐůǇ ƚŽ ƌĞŐŝƐƚĞƌ Ăůů ĐůŝŶŝĐĂů ƚƌŝĂůƐ ĂŶĚ ƚŽ ƐŚĂƌĞ ĐůŝŶŝĐĂů ƚƌŝĂů ĚĂƚĂ͘ dŚĞ ŚĞůĚ͕ĂƐŝƚƐŝŶĂƵŐƵƌĂůŝŶĐƵŵďĞŶƚ͕ƚŚĞ^ĂŵƵĞů͘>Ƶǆ͕/sŚĂŝƌŝŶ JournalŶŽǁŚĂƐŽǀĞƌĂŚĂůĨĂŵŝůůŝŽŶƌĞĂĚĞƌƐĞǀĞƌǇǁĞĞŬĂŶĚƚŚĞ ,ĞŵĂƚŽůŽŐǇͬKŶĐŽůŽŐǇĂƚŽƐƚŽŶŚŝůĚƌĞŶ͛Ɛ,ŽƐƉŝƚĂů͘ĨŽƌŵĞƌĐŚŝĞĨ ŚŝŐŚĞƐƚŝŵƉĂĐƚĨĂĐƚŽƌŽĨĂŶǇũŽƵƌŶĂůƉƵďůŝƐŚŝŶŐŽƌŝŐŝŶĂůƌĞƐĞĂƌĐŚ͘ ƌĞƐŝĚĞŶƚŝŶŵĞĚŝĐŝŶĞĂƚDĂƐƐĂĐŚƵƐĞƚƚƐ'ĞŶĞƌĂů,ŽƐƉŝƚĂů;ϭϵϵϰͲϵϱͿ͕ Victor J. Dzau, MD ĂůĞǇ ŵĂŝŶƚĂŝŶĞĚ ĂŶ ĂĐƚŝǀĞ ĐůŝŶŝĐĂů ƉƌĂĐƚŝĐĞ ŝŶ ŚĞŵĂƚŽůŽŐǇͬ ƌ͘ǌĂƵ ŝƐ ƚŚĞ WƌĞƐŝĚĞŶƚ ŽĨ ƚŚĞ EĂƚŝŽŶĂů ĐĂĚĞŵǇ ŽĨ DĞĚŝĐŝŶĞ ŽŶĐŽůŽŐǇ Ăƚ DĂƐƐĂĐŚƵƐĞƚƚƐ 'ĞŶĞƌĂů ,ŽƐƉŝƚĂů ;D',Ϳ ĂŶĚ ƚŚĞŶ ;EDͿ͕ĨŽƌŵĞƌůǇƚŚĞ/ŶƐƚŝƚƵƚĞŽĨDĞĚŝĐŝŶĞ;/KDͿ͘/ŶĂĚĚŝƚŝŽŶ͕ŚĞ Ăƚ ŽƐƚŽŶ ŚŝůĚƌĞŶ͛Ɛ͕ ƵŶƚŝů ĂƐƐƵŵŝŶŐ ŚŝƐ ĂĚŵŝŶŝƐƚƌĂƚŝǀĞ ƌŽůĞ ĂƐ ƐĞƌǀĞƐ ĂƐ sŝĐĞ ŚĂŝƌ ŽĨ ƚŚĞ EĂƚŝŽŶĂů ZĞƐĞĂƌĐŚ ŽƵŶĐŝů͘ ƌ͘ǌĂƵ ĚŝƌĞĐƚŽƌ ŽĨ ƚŚĞ WĞĚŝĂƚƌŝĐ ^ƚĞŵ Ğůů dƌĂŶƐƉůĂŶƚĂƚŝŽŶ WƌŽŐƌĂŵ Ăƚ ŝƐŚĂŶĐĞůůŽƌŵĞƌŝƚƵƐĂŶĚ:ĂŵĞƐ͘ƵŬĞWƌŽĨĞƐƐŽƌŽĨDĞĚŝĐŝŶĞ ĂŶĂͲ&ĂƌďĞƌͬŽƐƚŽŶ ŚŝůĚƌĞŶ͛Ɛ ĂŶĐĞƌ ĂŶĚ ůŽŽĚ ŝƐŽƌĚĞƌƐ ĂƚƵŬĞhŶŝǀĞƌƐŝƚǇĂŶĚƚŚĞƉĂƐƚWƌĞƐŝĚĞŶƚĂŶĚKŽĨƚŚĞƵŬĞ ĞŶƚĞƌ͕ĂƉŽƐƚŚĞŚĞůĚƵŶƚŝů:ĂŶ͘ϮϬϭϳ͘ƌ͘ĂůĞǇĞĂƌŶĞĚŚŝƐWŚ hŶŝǀĞƌƐŝƚǇ ,ĞĂůƚŚ ^ǇƐƚĞŵ͘ WƌĞǀŝŽƵƐůǇ͕ ƌ͘ ǌĂƵ ǁĂƐ ƚŚĞ ,ĞƌƐĞǇ ŝŶďŝŽůŽŐǇ;ϭϵϴϵͿĂƚD/d͕ǁŽƌŬŝŶŐŝŶĂǀŝĚĂůƚŝŵŽƌĞ͛ƐůĂďŽƌĂƚŽƌǇ WƌŽĨĞƐƐŽƌ ŽĨ dŚĞŽƌǇ ĂŶĚ WƌĂĐƚŝĐĞ ŽĨ DĞĚŝĐŝŶĞ ĂŶĚ ŚĂŝƌŵĂŶ ŽĨ ĂƚƚŚĞD/dͲĂĨĨŝůŝĂƚĞĚtŚŝƚĞŚĞĂĚ/ŶƐƚŝƚƵƚĞĨŽƌŝŽŵĞĚŝĐĂůZĞƐĞĂƌĐŚ͕ DĞĚŝĐŝŶĞ Ăƚ ,ĂƌǀĂƌĚ DĞĚŝĐĂů ^ĐŚŽŽů͛Ɛ ƌŝŐŚĂŵ ĂŶĚ tŽŵĞŶ͛Ɛ ĂŶĚŚŝƐDĨƌŽŵ,D^ŝŶϭϵϵϭ͘,ĞƚŚĞŶƉƵƌƐƵĞĚĐůŝŶŝĐĂůƚƌĂŝŶŝŶŐ ,ŽƐƉŝƚĂů͕ĂƐǁĞůůĂƐŚĂŝƌŵĂŶŽĨƚŚĞĞƉĂƌƚŵĞŶƚŽĨDĞĚŝĐŝŶĞĂƚ ŝŶŝŶƚĞƌŶĂůŵĞĚŝĐŝŶĞĂƚD',ĂŶĚǁĂƐĂĐůŝŶŝĐĂůĨĞůůŽǁĂƚƌŝŐŚĂŵ ^ƚĂŶĨŽƌĚhŶŝǀĞƌƐŝƚǇ͘ ĂŶĚtŽŵĞŶ͛ƐĂŶĚŽƐƚŽŶŚŝůĚƌĞŶ͛ƐŚŽƐƉŝƚĂůƐ͘ƌ͘ĂůĞǇǁĂƐĂŶ ŝŶĂƵŐƵƌĂů ǁŝŶŶĞƌ ŽĨ ƚŚĞ EĂƚŝŽŶĂů /ŶƐƚŝƚƵƚĞƐ ŽĨ ,ĞĂůƚŚ ŝƌĞĐƚŽƌ͛Ɛ ƌ͘ ǌĂƵ ŝƐ ĂŶ ŝŶƚĞƌŶĂƚŝŽŶĂůůǇ ĂĐĐůĂŝŵĞĚ ůĞĂĚĞƌ ĂŶĚ ƐĐŝĞŶƚŝƐƚ WŝŽŶĞĞƌǁĂƌĚĨŽƌŚŝŐŚůǇŝŶŶŽǀĂƚŝǀĞƌĞƐĞĂƌĐŚ;ϮϬϬϰͿ͘KƚŚĞƌŚŽŶŽƌƐ ǁŚŽƐĞǁŽƌŬŚĂƐŝŵƉƌŽǀĞĚŚĞĂůƚŚĐĂƌĞŝŶƚŚĞhŶŝƚĞĚ^ƚĂƚĞƐĂŶĚ ŝŶĐůƵĚĞƚŚĞŵĞƌŝĐĂŶWŚŝůŽƐŽƉŚŝĐĂů^ŽĐŝĞƚǇ͛Ɛ:ƵĚƐŽŶĂůĂŶĚWƌŝǌĞ ŐůŽďĂůůǇ͘ ^ŝŶĐĞ ĂƌƌŝǀŝŶŐ Ăƚ ƚŚĞ EĂƚŝŽŶĂů ĐĂĚĞŵŝĞƐ͕ ƌ ǌĂƵ ŚĂƐ ĨŽƌ ĂĐŚŝĞǀĞŵĞŶƚ ŝŶ ƉĂƚŝĞŶƚͲŽƌŝĞŶƚĞĚ ƌĞƐĞĂƌĐŚ͕ ƚŚĞ ŵĞƌŝĐĂŶ ůĞĚ ŝŵƉŽƌƚĂŶƚ ŝŶŝƚŝĂƚŝǀĞƐ ƐƵĐŚ ĂƐ ƚŚĞ ŽŵŵŝƐƐŝŽŶ ŽŶ Ă 'ůŽďĂů WĞĚŝĂƚƌŝĐ ^ŽĐŝĞƚǇ͛Ɛ ͘ DĞĂĚ :ŽŚŶƐŽŶ ǁĂƌĚ ĨŽƌ ĐŽŶƚƌŝďƵƚŝŽŶƐ ,ĞĂůƚŚ ZŝƐŬ &ƌĂŵĞǁŽƌŬ͖ ƚŚĞ ,ƵŵĂŶ 'ĞŶĞ ĚŝƚŝŶŐ /ŶŝƚŝĂƚŝǀĞ͖ ƚŽ ƐƚĞŵ ĐĞůů ƌĞƐĞĂƌĐŚ͕ ƚŚĞ ŵĞƌŝĐĂŶ ^ŽĐŝĞƚǇ ŽĨ ,ĞŵĂƚŽůŽŐǇ͛Ɛ ͘ ĂŶĚ sŝƚĂů ŝƌĞĐƚŝŽŶƐ ĨŽƌ ,ĞĂůƚŚ ĂŶĚ ,ĞĂůƚŚ ĂƌĞ͕ ĂŶĚ ƚŚĞ ED ŽŶŶĂůůdŚŽŵĂƐWƌŝǌĞĨŽƌĂĚǀĂŶĐĞƐŝŶŚƵŵĂŶͲŝŶĚƵĐĞĚƉůƵƌŝƉŽƚĞŶƚ 'ƌĂŶĚŚĂůůĞŶŐĞƐŝŶ,ĞĂůƚŚǇ>ŽŶŐĞǀŝƚǇ͘,ŝƐŽǁŶƌĞƐĞĂƌĐŚůĂŝĚƚŚĞ ƐƚĞŵ ĐĞůůƐ ĂŶĚ ƚŚĞ /ŶƚĞƌŶĂƚŝŽŶĂů ŚƌŽŶŝĐ DǇĞůŽŝĚ >ĞƵŬĞŵŝĂ ĨŽƵŶĚĂƚŝŽŶĨŽƌĚĞǀĞůŽƉŵĞŶƚŽĨƚŚĞĐůĂƐƐŽĨůŝĨĞƐĂǀŝŶŐĚƌƵŐƐŬŶŽǁŶ &ŽƵŶĚĂƚŝŽŶ͛Ɛ :ĂŶĞƚ ZŽǁůĞǇ WƌŝǌĞ ĨŽƌ ŽƵƚƐƚĂŶĚŝŶŐ ůŝĨĞƚŝŵĞ ĂƐ ŝŶŚŝďŝƚŽƌƐ͕ ƵƐĞĚ ŐůŽďĂůůǇ ƚŽ ƚƌĞĂƚ ŚŝŐŚ ďůŽŽĚ ƉƌĞƐƐƵƌĞ ĐŽŶƚƌŝďƵƚŝŽŶƐ ƚŽ ƚŚĞ ƵŶĚĞƌƐƚĂŶĚŝŶŐ ĂŶĚͬŽƌ ƚƌĞĂƚŵĞŶƚ ŽĨ ƚŚĞ ĂŶĚ ĐŽŶŐĞƐƚŝǀĞ ŚĞĂƌƚ ĨĂŝůƵƌĞ͘ ,Ğ ƉŝŽŶĞĞƌĞĚ ŐĞŶĞ ƚŚĞƌĂƉǇ ĂŶĚ ĚŝƐĞĂƐĞ͘ ,Ğ ŝƐ ĂŶ ĞůĞĐƚĞĚ ŵĞŵďĞƌ ŽĨ ƚŚĞ EĂƚŝŽŶĂů ĐĂĚĞŵǇ ŽĨ ƌĞŐĞŶĞƌĂƚŝǀĞŵĞĚŝĐŝŶĞĨŽƌĐĂƌĚŝŽǀĂƐĐƵůĂƌĚŝƐĞĂƐĞƐ͘ DĞĚŝĐŝŶĞĂŶĚƚŚĞ^/͕ĂŵŽŶŐŽƚŚĞƌƉƌŽĨĞƐƐŝŽŶĂůƐŽĐŝĞƚŝĞƐ͘ /ŶŚŝƐƌŽůĞĂƐĂůĞĂĚĞƌŝŶŚĞĂůƚŚĐĂƌĞ͕ƌ͘ǌĂƵŚĂƐůĞĚĞĨĨŽƌƚƐŝŶ ŝŶŶŽǀĂƚŝŽŶƚŽŝŵƉƌŽǀĞŚĞĂůƚŚ͕ŝŶĐůƵĚŝŶŐƚŚĞĚĞǀĞůŽƉŵĞŶƚŽĨƚŚĞ Jeffrey M. Drazen, M.D. ƵŬĞ dƌĂŶƐůĂƚŝŽŶĂů DĞĚŝĐŝŶĞ /ŶƐƚŝƚƵƚĞ͕ ƚŚĞ ƵŬĞ 'ůŽďĂů ,ĞĂůƚŚ ƌ͘ƌĂǌĞŶǁĂƐďŽƌŶĂŶĚƌĂŝƐĞĚŝŶůĂǇƚŽŶ͕DŝƐƐŽƵƌŝ͕ƌ͘ƌĂǌĞŶ /ŶƐƚŝƚƵƚĞ͕ ƚŚĞ ƵŬĞͲEĂƚŝŽŶĂů hŶŝǀĞƌƐŝƚǇ ŽĨ ^ŝŶŐĂƉŽƌĞ 'ƌĂĚƵĂƚĞ ŵĂũŽƌĞĚŝŶĂƉƉůŝĞĚƉŚǇƐŝĐƐĂƚdƵĨƚƐhŶŝǀĞƌƐŝƚǇĂŶĚŐƌĂĚƵĂƚĞĚĨƌŽŵ DĞĚŝĐĂů^ĐŚŽŽů͕ĂŶĚƚŚĞƵŬĞ/ŶƐƚŝƚƵƚĞĨŽƌ,ĞĂůƚŚ/ŶŶŽǀĂƚŝŽŶ͘Ɛ ,ĂƌǀĂƌĚDĞĚŝĐĂů^ĐŚŽŽůŝŶϭϵϳϮ͘,ĞĐƵƌƌĞŶƚůǇŚŽůĚƐƚŚĞƉŽƐŝƚŝŽŶƐ ŽŶĞ ŽĨ ƚŚĞ ǁŽƌůĚ͛Ɛ ƉƌĞĞŵŝŶĞŶƚ ŚĞĂůƚŚ ůĞĂĚĞƌƐ͕ ƌ͘ǌĂƵ ĂĚǀŝƐĞƐ ŽĨ ƐĞŶŝŽƌ ƉŚǇƐŝĐŝĂŶ Ăƚ ƚŚĞ ƌŝŐŚĂŵ ĂŶĚ tŽŵĞŶ͛Ɛ ,ŽƐƉŝƚĂů͕ ŐŽǀĞƌŶŵĞŶƚƐ͕ ĐŽƌƉŽƌĂƚŝŽŶƐ͕ ĂŶĚ ƵŶŝǀĞƌƐŝƚŝĞƐ ǁŽƌůĚǁŝĚĞ͘ ,Ğ ŚĂƐ ŝƐƚŝŶŐƵŝƐŚĞĚWĂƌŬĞƌ͘&ƌĂŶĐŝƐWƌŽĨĞƐƐŽƌŽĨDĞĚŝĐŝŶĞĂƚ,ĂƌǀĂƌĚ ƐĞƌǀĞĚĂƐĂŵĞŵďĞƌŽĨƚŚĞĚǀŝƐŽƌǇŽŵŵŝƚƚĞĞƚŽƚŚĞŝƌĞĐƚŽƌ DĞĚŝĐĂů^ĐŚŽŽů͕ƉƌŽĨĞƐƐŽƌŽĨƉŚǇƐŝŽůŽŐǇĂƚƚŚĞ,ĂƌǀĂƌĚ^ĐŚŽŽůŽĨ ŽĨƚŚĞEĂƚŝŽŶĂů/ŶƐƚŝƚƵƚĞƐŽĨ,ĞĂůƚŚ;E/,ͿĂŶĚĂƐŚĂŝƌŽĨƚŚĞE/, WƵďůŝĐ ,ĞĂůƚŚ ĂŶĚ ĂĚũƵŶĐƚ ƉƌŽĨĞƐƐŽƌ ŽĨ ŵĞĚŝĐŝŶĞ Ăƚ ƚŚĞ ŽƐƚŽŶ ĂƌĚŝŽǀĂƐĐƵůĂƌ ŝƐĞĂƐĞ ĚǀŝƐŽƌǇ ŽŵŵŝƚƚĞĞ͘ ƵƌƌĞŶƚůǇ ŚĞ ŝƐ Ă hŶŝǀĞƌƐŝƚǇ ^ĐŚŽŽů ŽĨ DĞĚŝĐŝŶĞ͘ ,Ğ ŝƐ ƚŚĞ ƌĞĐŝƉŝĞŶƚ ŽĨ ŚŽŶŽƌĂƌǇ ŵĞŵďĞƌŽĨƚŚĞŽĂƌĚŽĨƚŚĞ^ŝŶŐĂƉŽƌĞ,ĞĂůƚŚ^ǇƐƚĞŵ͕ŵĞŵďĞƌŽĨ ĚĞŐƌĞĞƐĨƌŽŵƚŚĞhŶŝǀĞƌƐŝƚǇŽĨ&ĞƌƌĂƌĂ͕ƚŚĞhŶŝǀĞƌƐŝƚǇŽĨƚŚĞŶƐ ƚŚĞ,ĞĂůƚŚŝŽŵĞĚŝĐĂů^ĐŝĞŶĐĞƐƚŚĞ/ŶƚĞƌŶĂƚŝŽŶĂůĚǀŝƐŽƌǇŽƵŶĐŝů ĂŶĚƚŚĞhŶŝǀĞƌƐŝƚǇŽĨDŽĚĞŶĂ͘ ŽĨ^ŝŶŐĂƉŽƌĞĂŶĚĚǀŝƐŽƌǇŽƵŶĐŝůŽĨƚŚĞ/ŵƉĞƌŝĂůŽůůĞŐĞ,ĞĂůƚŚ ƌ͘ƌĂǌĞŶŝƐĂŶĞůĞĐƚĞĚŵĞŵďĞƌŽĨƚŚĞŵĞƌŝĐĂŶ^ŽĐŝĞƚǇĨŽƌ WĂƌƚŶĞƌƐ͕ h<͘ ,Ğ ǁĂƐ ŽŶ ƚŚĞ ŽĂƌĚ ŽĨ ,ĞĂůƚŚ 'ŽǀĞƌŶŽƌƐ ŽĨ ƚŚĞ ůŝŶŝĐĂů/ŶǀĞƐƚŝŐĂƚŝŽŶ͕ƚŚĞƐƐŽĐŝĂƚŝŽŶŽĨŵĞƌŝĐĂŶWŚǇƐŝĐŝĂŶƐ͕ƚŚĞ tŽƌůĚĐŽŶŽŵŝĐ&ŽƌƵŵĂŶĚĐŚĂŝƌĞĚŝƚƐ'ůŽďĂůŐĞŶĚĂŽƵŶĐŝůŽŶ /ŶƚĞƌƵƌďĂŶůŝŶŝĐĂůůƵďĂŶĚƚŚĞEĂƚŝŽŶĂůĐĂĚĞŵǇŽĨDĞĚŝĐŝŶĞ͘ WĞƌƐŽŶĂůŝǌĞĚĂŶĚWƌĞĐŝƐŝŽŶDĞĚŝĐŝŶĞ͘

14 2018 AAP / ASCI / APSA Joint Meeting SPEAKER BIOGRAPHIES

ŵŽŶŐ ŚŝƐ ŵĂŶǇ ŚŽŶŽƌƐ ĂŶĚ ƌĞĐŽŐŶŝƚŝŽŶƐ ĂƌĞ ƚŚĞ 'Ƶstav Luigi Ferrucci, MD, PhD EǇůŝŶ DĞĚĂů ĨƌŽŵ ƚŚĞ ^ǁĞĚŝƐŚ ZŽǇĂů ŽůůĞŐĞ ŽĨ DĞĚŝĐŝŶĞ͕ ƌ͘&ĞƌƌƵĐĐŝŝƐĂŐĞƌŝĂƚƌŝĐŝĂŶĂŶĚĂŶĞƉŝĚĞŵŝŽůŽŐŝƐƚǁŚŽĐŽŶĚƵĐƚƐ ƚŚĞ ŝƐƚŝŶŐƵŝƐŚĞĚ ^ĐŝĞŶƚŝƐƚ ǁĂƌĚ ĨƌŽŵ ƚŚĞ ŵĞƌŝĐĂŶ ,ĞĂƌƚ ƌĞƐĞĂƌĐŚŽŶƚŚĞĐĂƵƐĂůƉĂƚŚǁĂǇƐůĞĂĚŝŶŐƚŽƉƌŽŐƌĞƐƐŝǀĞƉŚǇƐŝĐĂů ƐƐŽĐŝĂƚŝŽŶ͕ ůůŝƐ /ƐůĂŶĚ DĞĚĂů ŽĨ ,ŽŶŽƌ͕ĂŶĚ ƚŚĞ ,ĞŶƌǇ &ƌĞŝƐĞŶ ĂŶĚ ĐŽŐŶŝƚŝǀĞ ĚĞĐůŝŶĞ ŝŶ ŽůĚĞƌ ƉĞƌƐŽŶƐ͘ ,Ğ ŚĂƐ ŵĂĚĞ ŵĂũŽƌ /ŶƚĞƌŶĂƚŝŽŶĂůWƌŝǌĞ͘/ŶϮϬϭϰ͕ŚĞƌĞĐĞŝǀĞĚƚŚĞWƵďůŝĐ^ĞƌǀŝĐĞDĞĚĂů ĐŽŶƚƌŝďƵƚŝŽŶƐ ŝŶ ƚŚĞ ĚĞƐŝŐŶ ŽĨ ŵĂŶǇ ĞƉŝĚĞŵŝŽůŽŐŝĐĂů ƐƚƵĚŝĞƐ ĨƌŽŵƚŚĞWƌĞƐŝĚĞŶƚŽĨ^ŝŶŐĂƉŽƌĞ͘,ĞŝƐĂŵĞŵďĞƌŽĨƚŚĞ/ŶƐƚŝƚƵƚĞ ĐŽŶĚƵĐƚĞĚ ŝŶ ƚŚĞ h͘^͘ ĂŶĚ ŝŶ ƵƌŽƉĞ͕ ŝŶĐůƵĚŝŶŐ ƚŚĞ European ŽĨDĞĚŝĐŝŶĞŽĨƚŚĞEĂƚŝŽŶĂůĐĂĚĞŵǇŽĨ^ĐŝĞŶĐĞƐ͕ƚŚĞŵĞƌŝĐĂŶ Longitudinal Study on Aging, the “ICare Dicomano Study,”ƚŚĞ ĐĂĚĞŵǇ ŽĨ ƌƚƐ ĂŶĚ ^ĐŝĞŶĐĞƐ ĂŶĚ ƚŚĞ ƵƌŽƉĞĂŶ ĐĂĚĞŵǇ ŽĨ <ƐƚƵĚǇŽĨĞŶƚĞŶĂƌŝĂŶƐŝŶ^ĂƌĚŝŶŝĂĂŶĚƚŚĞWomen’s Health ^ĐŝĞŶĐĞƐĂŶĚƌƚƐ͘ and Aging Study͘ ,Ğ ǁĂƐ ĂůƐŽ ƚŚĞ WƌŝŶĐŝƉĂů /ŶǀĞƐƚŝŐĂƚŽƌ ŽĨ ƚŚĞ Benjamin L. Ebert, MD, PhD InCHIANTI ƐƚƵĚǇ͕ Ă ůŽŶŐŝƚƵĚŝŶĂů ƐƚƵĚǇ ĐŽŶĚƵĐƚĞĚ ŝŶ ƚŚĞ ŚŝĂŶƚŝ ƌ͘ďĞƌƚ͕ϮϬϭϳͲϮϬϭϴWƌĞƐŝĚĞŶƚŽĨƚŚĞŵĞƌŝĐĂŶ^ŽĐŝĞƚǇĨŽƌůŝŶŝĐĂů 'ĞŽŐƌĂƉŚŝĐĂů ĂƌĞĂ ;dƵƐĐĂŶǇ͕ /ƚĂůǇͿ ůŽŽŬŝŶŐ Ăƚ ƌŝƐŬ ĨĂĐƚŽƌƐ ĨŽƌ /ŶǀĞƐƚŝŐĂƚŝŽŶ͕ŝƐĐŚĂŝƌŽĨDĞĚŝĐĂůKŶĐŽůŽŐǇĂƚĂŶĂͲ&ĂƌďĞƌĂŶĐĞƌ ŵŽďŝůŝƚǇĚŝƐĂďŝůŝƚǇŝŶŽůĚĞƌƉĞƌƐŽŶƐ͘ƌ͘&ĞƌƌƵĐĐŝƌĞĐĞŝǀĞĚĂDĞĚŝĐĂů /ŶƐƚŝƚƵƚĞ͕ ŝƐ ƉƌŽĨĞƐƐŽƌ ŽĨ DĞĚŝĐŝŶĞ Ăƚ ,ĂƌǀĂƌĚ DĞĚŝĐĂů ^ĐŚŽŽů͕ ĞŐƌĞĞ ĂŶĚ ŽĂƌĚ ĞƌƚŝĨŝĐĂƚŝŽŶ ŝŶ ϭϵϴϬ͕ ŽĂƌĚ ĞƌƚŝĨŝĐĂƚŝŽŶ ŝŶ ĂŶŝŶƐƚŝƚƵƚĞŵĞŵďĞƌŽĨƚŚĞƌŽĂĚ/ŶƐƚŝƚƵƚĞ͕ĂŶĚůĞĂĚĞƌŽĨƚŚĞ 'ĞƌŝĂƚƌŝĐƐ ŝŶ ϭϵϴϮ ĂŶĚ WŚ͘͘ ŝŶ ŝŽůŽŐǇ ĂŶĚ WĂƚŚŽƉŚǇƐŝŽůŽŐǇ ŽĨ >ĞƵŬĞŵŝĂ WƌŽŐƌĂŵ ĨŽƌ ƚŚĞ ĂŶĂͲ&ĂƌďĞƌͬ,ĂƌǀĂƌĚ ĂŶĐĞƌ ĞŶƚĞƌ͘ ŐŝŶŐŝŶϭϵϵϴĂƚƚŚĞhŶŝǀĞƌƐŝƚǇŽĨ&ůŽƌĞŶĐĞ͕/ƚĂůǇ͘,ĞƐƉĞŶƚĂϮͲǇĞĂƌ ,ŝƐ ƌĞƐĞĂƌĐŚ ĨŽĐƵƐĞƐ ŽŶ ƚŚĞ ŐĞŶĞƚŝĐƐ͕ ďŝŽůŽŐǇ͕ ĂŶĚ ƚŚĞƌĂƉǇ ŽĨ ŝŶƚĞƌŶƐŚŝƉĂƚƚŚĞ/ŶƚĞŶƐŝǀĞĂƌĞhŶŝƚŽĨƚŚĞ&ůŽƌĞŶĐĞ/ŶƐƚŝƚƵƚĞŽĨ ŵǇĞůŽŝĚ ŵĂůŝŐŶĂŶĐŝĞƐ͘ dŚŝƐ ǁŽƌŬ ŚĂƐ ůĞĚ ƚŽ ƚŚĞ ĐŚĂƌĂĐƚĞƌŝǌĂƚŝŽŶ 'ĞƌŽŶƚŽůŽŐǇ ĂŶĚ 'ĞƌŝĂƚƌŝĐƐ͕ ĂŶĚ ǁĂƐ ĨŽƌ ŵĂŶǇ ǇĞĂƌƐ ƐƐŽĐŝĂƚĞ ŽĨĐůŽŶĂůŚĞŵĂƚŽƉŽŝĞƐŝƐĂƐĂƉƌĞͲŵĂůŝŐŶĂŶƚƐƚĂƚĞĨŽƌŚĞŵĂƚŽůŽŐŝĐ WƌŽĨĞƐƐŽƌ ŽĨ ŝŽůŽŐǇ͕ ,ƵŵĂŶ WŚǇƐŝŽůŽŐǇ ĂŶĚ ^ƚĂƚŝƐƚŝĐƐ Ăƚ ƚŚĞ ŵĂůŝŐŶĂŶĐŝĞƐ͕ ĂŶĚ ĞůƵĐŝĚĂƚŝŽŶ ŽĨ ƚŚĞ ŵĞĐŚĂŶŝƐŵ ŽĨ ĂĐƚŝŽŶ ŽĨ hŶŝǀĞƌƐŝƚǇŽĨ&ůŽƌĞŶĐĞ͘ĞƚǁĞĞŶϭϵϴϱĂŶĚϮϬϬϮŚĞǁĂƐŚŝĞĨŽĨ ůĞŶĂůŝĚŽŵŝĚĞ ĂŶĚ ƌĞůĂƚĞĚ ŵŽůĞĐƵůĞƐ ƚŚĂƚ ŝŶĚƵĐĞ ĚĞŐƌĂĚĂƚŝŽŶ ŽĨ 'ĞƌŝĂƚƌŝĐZĞŚĂďŝůŝƚĂƚŝŽŶĂƚƚŚĞĞƉĂƌƚŵĞŶƚŽĨ'ĞƌŝĂƚƌŝĐDĞĚŝĐŝŶĞ ƐƉĞĐŝĨŝĐ ƉƌŽƚĞŝŶƐ͘ ƌ͘ ďĞƌƚ ƌĞĐĞŝǀĞĚ Ă ďĂĐŚĞůŽƌ͛Ɛ ĚĞŐƌĞĞ ĨƌŽŵ ĂŶĚ ŝƌĞĐƚŽƌ ŽĨ ƚŚĞ >ĂďŽƌĂƚŽƌǇ ŽĨ ůŝŶŝĐĂů ƉŝĚĞŵŝŽůŽŐǇ Ăƚ ƚŚĞ tŝůůŝĂŵƐŽůůĞŐĞ͕ĂĚŽĐƚŽƌĂƚĞĨƌŽŵKǆĨŽƌĚhŶŝǀĞƌƐŝƚǇŽŶĂZŚŽĚĞƐ /ƚĂůŝĂŶEĂƚŝŽŶĂů/ŶƐƚŝƚƵƚĞŽĨŐŝŶŐ͘/Ŷ^ĞƉƚĞŵďĞƌϮϬϬϮ͕ŚĞďĞĐĂŵĞ ^ĐŚŽůĂƌƐŚŝƉ͕ĂŶĚĂŶDĨƌŽŵ,ĂƌǀĂƌĚDĞĚŝĐĂů^ĐŚŽŽů͘,ĞĐŽŵƉůĞƚĞĚ ƚŚĞŚŝĞĨŽĨƚŚĞ>ŽŶŐŝƚƵĚŝŶĂů^ƚƵĚŝĞƐ^ĞĐƚŝŽŶĂƚE/͘&ƌŽŵϮϬϬϮƚŽ ĂƌĞƐŝĚĞŶĐǇŝŶŝŶƚĞƌŶĂůŵĞĚŝĐŝŶĞĂƚDĂƐƐĂĐŚƵƐĞƚƚƐ'ĞŶĞƌĂů,ŽƐƉŝƚĂů ϮϬϭϰŚĞǁĂƐƚŚĞŝƌĞĐƚŽƌŽĨƚŚĞĂůƚŝŵŽƌĞ>ŽŶŐŝƚƵĚŝŶĂů^ƚƵĚǇŽŶ ĂŶĚĂĨĞůůŽǁƐŚŝƉŝŶŚĞŵĂƚŽůŽŐǇͬŽŶĐŽůŽŐǇĂƚĂŶĂͲ&ĂƌďĞƌ͘ ŐŝŶŐ͘ƌ͘&ĞƌƌƵĐĐŝŝƐĐƵƌƌĞŶƚůǇƚŚĞ^ĐŝĞŶƚŝĨŝĐŝƌĞĐƚŽƌŽĨE/͕ƐŝŶĐĞ DĂǇϮϬϭϭ͘ Serpil Erzurum, MD Linda P. Fried, MD, MPH ƌ͘ ƌǌƵƌƵŵ ŝƐ ƚŚĞ ůĨƌĞĚ >ĞƌŶĞƌ ŚĂŝƌ ŽĨ ƚŚĞ >ĞƌŶĞƌ ZĞƐĞĂƌĐŚ /ŶƐƚŝƚƵƚĞĂŶĚĂƐƚĂĨĨƉŚǇƐŝĐŝĂŶĂƚƚŚĞůĞǀĞůĂŶĚůŝŶŝĐ͘ƌ͘ƌǌƵƌƵŵ ƌ͘&ƌŝĞĚ͕ĞĂŶŽĨƚŚĞDĂŝůŵĂŶ^ĐŚŽŽůŽĨWƵďůŝĐ,ĞĂůƚŚŝƐĂƉƵďůŝĐ ĞĂƌŶĞĚŚĞƌŵĞĚŝĐĂůĚĞŐƌĞĞĨƌŽŵEŽƌƚŚĞĂƐƚĞƌŶKŚŝŽhŶŝǀĞƌƐŝƚŝĞƐ ŚĞĂůƚŚůĞĂĚĞƌŝŶƚŚĞĨŝĞůĚƐŽĨĞƉŝĚĞŵŝŽůŽŐǇĂŶĚŐĞƌŝĂƚƌŝĐƐ͘^ŚĞŚĂƐ ŽůůĞŐĞŽĨDĞĚŝĐŝŶĞĂŶĚĐŽŵƉůĞƚĞĚƌĞƐŝĚĞŶĐǇƚƌĂŝŶŝŶŐŝŶ/ŶƚĞƌŶĂů ĚĞĚŝĐĂƚĞĚŚĞƌĐĂƌĞĞƌƚŽƚŚĞƐĐŝĞŶĐĞŽĨŚĞĂůƚŚǇĂŐŝŶŐĂŶĚĚĞĨŝŶŝŶŐ DĞĚŝĐŝŶĞ Ăƚ ĂǇůŽƌ ŽůůĞŐĞ ŽĨ DĞĚŝĐŝŶĞ ǁŚĞƌĞ ƐŚĞ ǁĂƐ ŶĂŵĞĚ ŚŽǁ ƚŽ ƚƌĂŶƐŝƚŝŽŶ ƚŽ Ă ǁŽƌůĚ ǁŚĞƌĞ ŐƌĞĂƚĞƌ ůŽŶŐĞǀŝƚǇ ďĞŶĞĨŝƚƐ ƚŚĞ DĂĐ/ŶƚŽƐŚ ŽƵƚƐƚĂŶĚŝŶŐ ƌĞƐŝĚĞŶƚ͘ &ŽůůŽǁŝŶŐ ĐŽŵƉůĞƚŝŽŶ ŽĨ ƉĞŽƉůĞŽĨĂůůĂŐĞƐ͘ŶŝŶƚĞƌŶĂƚŝŽŶĂůůǇƌĞŶŽǁŶĞĚƐĐŝĞŶƚŝƐƚ͕ƐŚĞŚĂƐ ƌĞƐŝĚĞŶĐǇ͕ ƐŚĞ ƉƌĂĐƚŝĐĞĚ ŝŶ ƚŚĞ /ŶĚŝĂŶ ,ĞĂůƚŚ ƐĞƌǀŝĐĞ ŝŶ ^ŽƵƚŚ ĚŽŶĞƐĞŵŝŶĂůǁŽƌŬŝŶĚĞĨŝŶŝŶŐĨƌĂŝůƚǇĂƐĂĐůŝŶŝĐĂůƐǇŶĚƌŽŵĞĂŶĚ ĂŬŽƚĂ͕ ƐĞƌǀŝŶŐ ĂƐ d ŽĨĨŝĐĞƌ ĨŽƌ ƚŚĞ ǁĞƐƚĞƌŶ ƉĂƌƚ ŽĨ ƚŚĞ ƐƚĂƚĞ͘ ŝůůƵŵŝŶĂƚŝŶŐďŽƚŚŝƚƐĐĂƵƐĞƐĂŶĚƚŚĞƉŽƚĞŶƚŝĂůĨŽƌƉƌĞǀĞŶƚŝŽŶĂƐ ^ƵďƐĞƋƵĞŶƚůǇ͕ƐŚĞĞŶƚĞƌĞĚƉƵůŵŽŶĂƌǇĂŶĚĐƌŝƚŝĐĂůĐĂƌĞĨĞůůŽǁƐŚŝƉ ŬĞǇƐƚŽŽƉƚŝŵŝǌŝŶŐŚĞĂůƚŚĨŽƌŽůĚĞƌĂĚƵůƚƐ͘,ĞƌƐĐŝĞŶƚŝĨŝĐĚŝƐĐŽǀĞƌŝĞƐ ƚƌĂŝŶŝŶŐĂƚƚŚĞhŶŝǀĞƌƐŝƚǇŽĨŽůŽƌĂĚŽͬEĂƚŝŽŶĂů:ĞǁŝƐŚĞŶƚĞƌĂŶĚ ŚĂǀĞƚƌĂŶƐĨŽƌŵĞĚŵĞĚŝĐĂůĐĂƌĞĂŶĚƉƵďůŝĐŚĞĂůƚŚŐůŽďĂůůǇ͕ĂŶĚŽƵƌ ƚŚĞŶƉŽƐƚĚŽĐƚŽƌĂůƌĞƐĞĂƌĐŚƚƌĂŝŶŝŶŐĂƚƚŚĞEĂƚŝŽŶĂů,ĞĂƌƚ͕>ƵŶŐ ƵŶĚĞƌƐƚĂŶĚŝŶŐŽĨŚŽǁƚŽďƵŝůĚƐƵĐĐĞƐƐĨƵůƐŽĐŝĞƚŝĞƐŽĨůŽŶŐĞƌůŝǀĞƐ͘ ĂŶĚůŽŽĚ/ŶƐƚŝƚƵƚĞ͘ƌ͘ƌǌƵƌƵŵ͛ƐƐĐŝĞŶƚŝĨŝĐĂĐĐŽŵƉůŝƐŚŵĞŶƚƐŽǀĞƌ hŶĚĞƌ&ƌŝĞĚ͛ƐǀŝƐŝŽŶĂƌǇůĞĂĚĞƌƐŚŝƉ͕ƚŚĞDĂŝůŵĂŶ^ĐŚŽŽůĐŽŶƚŝŶƵĞƐ ƚŚĞƉĂƐƚϯϬǇĞĂƌƐŚĂǀĞďĞĞŶďƌŽĂĚĂŶĚĨĂƌͲƌĞĂĐŚŝŶŐŝŶŝŵƉĂĐƚĨŽƌ ƚŽďĞĂůĞĂĚĞƌŝŶƚƌĂŶƐĨŽƌŵŝŶŐƚŚĞŚĞĂůƚŚŽĨƉŽƉƵůĂƚŝŽŶƐĂŶĚŝƐŽŶĞ ƌĞƐƉŝƌĂƚŽƌǇŵĞĚŝĐŝŶĞ͘,ĞƌƐĐŝĞŶƚŝĨŝĐĐŽŶƚƌŝďƵƚŝŽŶƐĂŶĚůĞĂĚĞƌƐŚŝƉ ŽĨƚŚĞƚŽƉĨŝǀĞE/,ͲĨƵŶĚĞĚƐĐŚŽŽůƐŽĨƉƵďůŝĐŚĞĂůƚŚ͘&ƌŝĞĚůĞĚƚŚĞ ŝŶ ƉƵůŵŽŶĂƌǇ ƌĞƐĞĂƌĐŚ ŚĂǀĞ ůĞĚ ƚŽ ĚŝĂŐŶŽƐƚŝĐ ĂŶĚ ƚŚĞƌĂƉĞƵƚŝĐ ^ĐŚŽŽůƚŽďƵŝůĚƚŚĞŶĂƚŝŽŶ͛ƐĨŝƌƐƚƉƌŽŐƌĂŵŽŶĐůŝŵĂƚĞĂŶĚŚĞĂůƚŚ ĂĚǀĂŶĐĞƐ ŝŶ ĂƐƚŚŵĂ ĂŶĚ ůƵŶŐ ǀĂƐĐƵůĂƌ ĚŝƐĞĂƐĞƐ͕ ĂŶĚ ŚĞůƉĞĚ ƚŽ ĂŶĚĂŵƵůƚŝĚŝƐĐŝƉůŝŶĂƌǇƉƌŽŐƌĂŵƚŚĂƚĚĞůŝǀĞƌƐĞĐŽŶŽŵŝĐĞǀŝĚĞŶĐĞ ŝĚĞŶƚŝĨǇ ŚƵŵĂŶ ƉŚǇƐŝŽůŽŐŝĐ ĂĚĂƉƚŝǀĞ ƌĞƐƉŽŶƐĞƐ ƚŽ ŚŝŐŚͲĂůƚŝƚƵĚĞ ŽŶƚŚĞǀĂůƵĞŽĨƉƌĞǀĞŶƚŝŽŶ͘&ƌŝĞĚŽƉĞŶĞĚƚŚĞŽůƵŵďŝĂĞŶƚĞƌĨŽƌ ŚǇƉŽǆŝĂ͘^ŚĞŚĂƐƉƵďůŝƐŚĞĚŵŽƌĞƚŚĂŶϮϱϬƉĞĞƌͲƌĞǀŝĞǁĞĚĂƌƚŝĐůĞƐ ŐŝŶŐĂŶĚĞůĞǀĂƚĞĚŽůƵŵďŝĂ͛ƐůĞĂĚĞƌƐŚŝƉƌŽůĞŝŶƌĞƐĞĂƌĐŚ͕ƉŽůŝĐǇ ĂŶĚŚĞƌƌĞƐĞĂƌĐŚŝƐĨƵŶĚĞĚďǇĂǁŝĚĞǀĂƌŝĞƚǇŽĨŐƌĂŶƚƐĨƌŽŵƚŚĞ ĂŶĚƉƌŽŐƌĂŵŵŝŶŐƚŽƐƵƉƉŽƌƚŚĞĂůƚŚǇĐŝƚŝĞƐ͘ƐĂůĞĂĚĞƌŝŶƉƵďůŝĐ EĂƚŝŽŶĂů/ŶƐƚŝƚƵƚĞƐŽĨ,ĞĂůƚŚ͘^ŚĞŚĂƐĞĂƌŶĞĚŶƵŵĞƌŽƵƐĂǁĂƌĚƐ͕ ŚĞĂůƚŚ ĞĚƵĐĂƚŝŽŶ͕ ƐŚĞ ŝŶŝƚŝĂƚĞĚ ŽůƵŵďŝĂͬDĂŝůŵĂŶ͛Ɛ ŝŶŶŽǀĂƚŝǀĞ ŝŶĐůƵĚŝŶŐƚŚĞDZ/dĂǁĂƌĚĨƌŽŵE,>/͕ĞůĞĐƚŝŽŶƚŽƚŚĞŵĞƌŝĐĂŶ ŝŶƚĞƌĚŝƐĐŝƉůŝŶĂƌǇƉƵďůŝĐŚĞĂůƚŚĐƵƌƌŝĐƵůƵŵƚŚĂƚĞŵƉŚĂƐŝǌĞƐĂůŝĨĞͲ ^ŽĐŝĞƚǇĨŽƌůŝŶŝĐĂů/ŶǀĞƐƚŝŐĂƚŝŽŶ;^/Ϳ͕ĞůĞĐƚŝŽŶƚŽƚŚĞƐƐŽĐŝĂƚŝŽŶ ĐŽƵƌƐĞĂƉƉƌŽĂĐŚƚŽƉƌĞǀĞŶƚŝŽŶŽĨĚŝƐĞĂƐĞĂŶĚĚŝƐĂďŝůŝƚǇ͘&ƌŝĞĚŝƐ ŽĨ ŵĞƌŝĐĂŶ WŚǇƐŝĐŝĂŶƐ͕ ĞůĞĐƚŝŽŶ ƚŽ ƚŚĞ EĂƚŝŽŶĂů ĐĂĚĞŵǇ ŽĨ ĂŶĞůĞĐƚĞĚŵĞŵďĞƌŽĨƚŚĞh͘^͘EĂƚŝŽŶĂůĐĂĚĞŵǇŽĨDĞĚŝĐŝŶĞ͕ĂƐ DĞĚŝĐŝŶĞ͕ ĂŶĚ ƚŚĞ ůŝǌĂďĞƚŚ ZŝĐŚ ǁĂƌĚ ĨƌŽŵ ƚŚĞ ŵĞƌŝĐĂŶ ǁĞůůĂƐƚŚĞWƌĞƐŝĚĞŶƚŽĨƚŚĞƐƐŽĐŝĂƚŝŽŶŽĨŵĞƌŝĐĂŶWŚǇƐŝĐŝĂŶƐ͕ dŚŽƌĂĐŝĐ^ŽĐŝĞƚǇĨŽƌŚĞƌǁŽƌŬŝŶĂĚǀĂŶĐŝŶŐƚŚĞĐĂƌĞĞƌƐŽĨǁŽŵĞŶ ƚŚĞĞůĞĐƚĞĚƐŽĐŝĞƚǇŽĨƚŚĞh͘^͘ůĞĂĚŝŶŐƉŚǇƐŝĐŝĂŶƐĐŝĞŶƚŝƐƚƐ͘^ŚĞ ŝŶŵĞĚŝĐŝŶĞĂŶĚƐĐŝĞŶĐĞ͘/ŶĂĚĚŝƚŝŽŶƚŽŚĞƌůĞĂĚĞƌƐŚŝƉĂƚůĞǀĞůĂŶĚ ŝƐƚŚĞĨŝƌƐƚĞĂŶŽĨĂ^ĐŚŽŽůŽĨWƵďůŝĐ,ĞĂůƚŚƚŽďĞWƌĞƐŝĚĞŶƚŽĨ ůŝŶŝĐ͕ ƌ͘ ƌǌƵƌƵŵ ƐĞƌǀĞƐ ƚŚĞ ƉƌŽĨĞƐƐŝŽŶ ĂƐ ŵĞŵďĞƌ ŽĨ ƚŚĞ W͘^ŚĞŝƐĂůƐŽŽͲŚĂŝƌŽĨƚŚĞtŽƌůĚĐŽŶŽŵŝĐ&ŽƌƵŵ͛Ɛ'ůŽďĂů ĚǀŝƐŽƌǇ ŽƵŶĐŝů ƚŽ ƚŚĞ E,>/͕ ŚĂŝƌ ŽĨ ƚŚĞ ŵĞƌŝĐĂŶ ŽĂƌĚ ŽĨ ŽƵŶĐŝů ŽŶ ƚŚĞ &ƵƚƵƌĞ ŽĨ ,ƵŵĂŶ ŶŚĂŶĐĞŵĞŶƚ ĂŶĚ ŽŶ ƚŚĞ /ŶƚĞƌŶĂůDĞĚŝĐŝŶĞWƵůŵŽŶĂƌǇŝƐĞĂƐĞ^ƵďƐƉĞĐŝĂůƚǇŽĂƌĚ͕ĂŶĚŝƐ ^ƚĞĞƌŝŶŐŽŵŵŝƚƚĞĞĨŽƌƚŚĞŝƌŽƵŶĐŝůŽŶ,ƵŵĂŶĞŶƚƌŝĐ,ĞĂůƚŚ͘ ĐƵƌƌĞŶƚůǇƚŚĞWƌĞƐŝĚĞŶƚŽĨƚŚĞƐƐŽĐŝĂƚŝŽŶŽĨŵĞƌŝĐĂŶWŚǇƐŝĐŝĂŶƐ͘

www.jointmeeting.org 15 SPEAKER BIOGRAPHIES

Levi A. Garraway, MD, PhD Helen Hobbs, MD ƌ͘'ĂƌƌĂǁĂǇƌĞĐĞŝǀĞĚŚŝƐ͕D͕ĂŶĚWŚĚĞŐƌĞĞƐĨƌŽŵ,ĂƌǀĂƌĚ ƌ͘ ,ŽďďƐ ƌĞĐĞŝǀĞĚ ŚĞƌ ƵŶĚĞƌŐƌĂĚƵĂƚĞ ĚĞŐƌĞĞ ĨƌŽŵ ^ƚĂŶĨŽƌĚ DĞĚŝĐĂů^ĐŚŽŽů͘dŚĞƌĞĂĨƚĞƌ͕ŚĞĚŝĚĂŶŝŶƚĞƌŶƐŚŝƉĂŶĚƌĞƐŝĚĞŶĐǇŝŶ hŶŝǀĞƌƐŝƚǇ ĂŶĚ ŚĞƌ ŵĞĚŝĐĂů ĚĞŐƌĞĞ ĨƌŽŵ ĂƐĞ tĞƐƚĞƌŶ ZĞƐĞƌǀĞ ŝŶƚĞƌŶĂůŵĞĚŝĐŝŶĞĂƚƚŚĞDĂƐƐĂĐŚƵƐĞƚƚƐ'ĞŶĞƌĂů,ŽƐƉŝƚĂů͕ǁŚĞƌĞ hŶŝǀĞƌƐŝƚǇ ^ĐŚŽŽů ŽĨ DĞĚŝĐŝŶĞ͘ ĨƚĞƌ ŽďƚĂŝŶŝŶŐ ŚĞƌ ĐůŝŶŝĐĂů ĂŶĚ ŚĞ ĂůƐŽ ƐĞƌǀĞĚ ĂƐ DĞĚŝĐĂů ŚŝĞĨ ZĞƐŝĚĞŶƚ ŝŶ ϮϬϬϯ͘ 'ĂƌƌĂǁĂǇ ƉŽƐƚͲĚŽĐƚŽƌĂů ƚƌĂŝŶŝŶŐ Ăƚ ŽůƵŵďŝĂͲWƌĞƐďǇƚĞƌŝĂŶ ,ŽƐƉŝƚĂů ĂŶĚ ĐŽŵƉůĞƚĞĚ ŚŝƐ ĨĞůůŽǁƐŚŝƉ ƚƌĂŝŶŝŶŐ ŝŶ ŵĞĚŝĐĂů ŽŶĐŽůŽŐǇ Ăƚ ƚŚĞ hŶŝǀĞƌƐŝƚǇŽĨdĞǆĂƐ;hdͿ^ŽƵƚŚǁĞƐƚĞƌŶDĞĚŝĐĂůĞŶƚĞƌĂůůĂƐ͕ƐŚĞ ĂŶĂͲ&ĂƌďĞƌĂŶĐĞƌ/ŶƐƚŝƚƵƚĞ͘,ĞƌĞĐĞŝǀĞĚďŽĂƌĚĐĞƌƚŝĨŝĐĂƚŝŽŶŝŶ ũŽŝŶĞĚƚŚĞĨĂĐƵůƚǇŽĨhd^ŽƵƚŚǁĞƐƚĞƌŶ͘^ŚĞŝƐĐƵƌƌĞŶƚůǇWƌŽĨĞƐƐŽƌ ŝŶƚĞƌŶĂůŵĞĚŝĐŝŶĞĂŶĚŵĞĚŝĐĂůŽŶĐŽůŽŐǇ͘ ŽĨ/ŶƚĞƌŶĂůDĞĚŝĐŝŶĞĂŶĚDŽůĞĐƵůĂƌ'ĞŶĞƚŝĐƐ͕ĂƐǁĞůůĂƐŝƌĞĐƚŽƌ WƌŝŽƌ ƚŽ ũŽŝŶŝŶŐ ůŝ >ŝůůǇ ĂŶĚ ŽŵƉĂŶǇ͕ 'ĂƌƌĂǁĂǇ ƐĞƌǀĞĚ ĂƐ ĂŶ ŽĨƚŚĞDĐĞƌŵŽƚƚĞŶƚĞƌĨŽƌ,ƵŵĂŶ'ƌŽǁƚŚĂŶĚĞǀĞůŽƉŵĞŶƚ ŝŶǀĞƐƚŝŐĂƚŽƌ ŽĨ ƚŚĞ ,ŽǁĂƌĚ ,ƵŐŚĞƐ DĞĚŝĐĂů /ŶƐƚŝƚƵƚĞ ĂŶĚ ĂŶ Ăƚhd^ŽƵƚŚǁĞƐƚĞƌŶDĞĚŝĐĂůĞŶƚĞƌŝŶĂůůĂƐ͘^ŝŶĐĞϮϬϬϮ͕ƐŚĞŚĂƐ ƐƐŽĐŝĂƚĞ WƌŽĨĞƐƐŽƌ ŽĨ DĞĚŝĐŝŶĞ Ăƚ ƚŚĞ ĂŶĂͲ&ĂƌďĞƌ ĂŶĐĞƌ ďĞĞŶĂŶ/ŶǀĞƐƚŝŐĂƚŽƌŽĨƚŚĞ,ŽǁĂƌĚ,ƵŐŚĞƐDĞĚŝĐĂů/ŶƐƚŝƚƵƚĞ͘/Ŷ /ŶƐƚŝƚƵƚĞ͕,ĂƌǀĂƌĚDĞĚŝĐĂů^ĐŚŽŽůĂŶĚĂŶ/ŶƐƚŝƚƵƚĞDĞŵďĞƌŽĨƚŚĞ ƉĂƌƚŶĞƌƐŚŝƉǁŝƚŚ:ŽŶĂƚŚĂŶŽŚĞŶ͕ƐŚĞŚĂƐŝĚĞŶƚŝĨŝĞĚŐĞŶĞƐĂŶĚ ƌŽĂĚ/ŶƐƚŝƚƵƚĞ͘,ĞǁĂƐƚŚĞŝŶĂƵŐƵƌĂůŝƌĞĐƚŽƌŽĨƚŚĞ:ŽŝŶƚĞŶƚĞƌ ƐĞƋƵĞŶĐĞǀĂƌŝĂƚŝŽŶƐĐŽŶƚƌŝďƵƚŝŶŐƚŽŵĞƚĂďŽůŝĐĂŶĚĐĂƌĚŝŽǀĂƐĐƵůĂƌ ĨŽƌ ĂŶĐĞƌ WƌĞĐŝƐŝŽŶ DĞĚŝĐŝŶĞ͕ ǁŚŝĐŚ ƐƉĂŶƐ ƚŚĞ ĂŶĂͲ&ĂƌďĞƌ͕ ĚŝƐŽƌĚĞƌƐǁŝƚŚĂĨŽĐƵƐŽŶůŝƉŝĚƐĂŶĚůŝƉŽƉƌŽƚĞŝŶƐ͘dŽŐĞƚŚĞƌƚŚĞǇ ƌŝŐŚĂŵ ĂŶĚ tŽŵĞŶ͛Ɛ ,ŽƐƉŝƚĂů͕ ŽƐƚŽŶ ŚŝůĚƌĞŶ͛Ɛ ,ŽƐƉŝƚĂů ĂŶĚ ƐŚŽǁĞĚƚŚĂƚƌĂƌĞŐĞŶĞƚŝĐǀĂƌŝĂƚŝŽŶƐĐŽŶƚƌŝďƵƚĞƚŽĐŽŵƉůĞǆƚƌĂŝƚƐ ƚŚĞƌŽĂĚ/ŶƐƚŝƚƵƚĞŽĨD/dĂŶĚ,ĂƌǀĂƌĚ͘'ĂƌƌĂǁĂǇůĞĚĂƌĞƐĞĂƌĐŚ ŝŶ ƚŚĞ ŐĞŶĞƌĂů ƉŽƉƵůĂƚŝŽŶ͘ Ǉ ĐŽŶĐĞŶƚƌĂƚŝŶŐ ŽŶ ĂůůĞůĞƐ ŽĨ ůŽǁ ŐƌŽƵƉ ƚŚĂƚ ƐƚƵĚŝĞĚ ĐĂŶĐĞƌ ŐĞŶŽŵŝĐƐ͕ ĚƌƵŐ ƌĞƐŝƐƚĂŶĐĞ͕ ĂŶĚ ĨƌĞƋƵĞŶĐǇĂŶĚůĂƌŐĞƉŚĞŶŽƚǇƉŝĐĞĨĨĞĐƚƐŝǌĞ͕ƚŚĞǇŚĂǀĞĚŝƐĐŽǀĞƌĞĚ ĐĂŶĐĞƌ ƉƌĞĐŝƐŝŽŶ ŵĞĚŝĐŝŶĞ͘ ,ŝƐ ƌĞƐĞĂƌĐŚ ŝŶĨŽƌŵĞĚ ƐĞǀĞƌĂů ŐĞŶĞ ŶĞǁƚŚĞƌĂƉĞƵƚŝĐƚĂƌŐĞƚƐĨŽƌƚŚĞƉƌĞǀĞŶƚŝŽŶĂŶĚƚƌĞĂƚŵĞŶƚŽĨŚĞĂƌƚ ƚĂƌŐĞƚƐ ĂŶĚ ͞ĚƌƵŐŐĂďůĞ͟ ƉĂƚŚǁĂǇƐ ƌĞůĞǀĂŶƚ ƚŽ ƚŚĞ ŐĞŶĞƐŝƐ ĂŶĚ ĚŝƐĞĂƐĞ͕ ŝŶĐůƵĚŝŶŐ W^<ϵ͘ DŽƐƚ ƌĞĐĞŶƚůǇ͕ ƚŚĞǇ ŚĂǀĞ ŝĚĞŶƚŝĨŝĞĚ ƚŚĞƌĂƉĞƵƚŝĐ ǀƵůŶĞƌĂďŝůŝƚŝĞƐ ŽĨ ŵĞůĂŶŽŵĂ͕ ƉƌŽƐƚĂƚĞ ĐĂŶĐĞƌ͕ ĂŶĚ ŐĞŶĞƚŝĐǀĂƌŝĂŶƚƐƚŚĂƚĐŽŶƚƌŝďƵƚĞƚŽƚŚĞĨƵůůƐƉĞĐƚƌƵŵŽĨĨĂƚƚǇůŝǀĞƌ ŽƚŚĞƌ ŵĂůŝŐŶĂŶĐŝĞƐ͘ 'ĂƌƌĂǁĂǇ ŚĂƐ ƌĞĐĞŝǀĞĚ ŶƵŵĞƌŽƵƐ ĂǁĂƌĚƐ ĚŝƐĞĂƐĞ͕ĞǆƚĞŶĚŝŶŐĨƌŽŵŚĞƉĂƚŝĐƐƚĞĂƚŽƐŝƐƚŽĐŝƌƌŚŽƐŝƐ͘,ŽďďƐǁĂƐ ŝŶĐůƵĚŝŶŐ ƚŚĞ WĂƵů DĂƌŬƐ WƌŝǌĞ ĨŽƌ ĂŶĐĞƌ ZĞƐĞĂƌĐŚ͕ ƚŚĞ :ĂŶĞ ĞůĞĐƚĞĚƚŽƚŚĞ/ŶƐƚŝƚƵƚĞŽĨDĞĚŝĐŝŶĞ͕ŵĞƌŝĐĂŶĐĂĚĞŵǇŽĨƌƚƐ ĂŶĚ^ĐŝĞŶĐĞƐ͕ĂŶĚƚŚĞEĂƚŝŽŶĂůĐĂĚĞŵǇŽĨ^ĐŝĞŶĐĞƐ͘^ŚĞŚĂƐďĞĞŶ ŽŽŬĞtƌŝŐŚƚǁĂƌĚĨƌŽŵZ͕ƚŚĞEĞǁ/ŶŶŽǀĂƚŽƌǁĂƌĚĨƌŽŵ ĂǁĂƌĚĞĚƉƌŝǌĞƐĨŽƌŚĞƌǁŽƌŬĨƌŽŵƚŚĞŵĞƌŝĐĂŶ,ĞĂƌƚƐƐŽĐŝĂƚŝŽŶ ƚŚĞE/,ĂŶĚĂŶKƵƚƐƚĂŶĚŝŶŐ/ŶǀĞƐƚŝŐĂƚŽƌǁĂƌĚĨƌŽŵƚŚĞEĂƚŝŽŶĂů ΀ƚŚĞ ůŝŶŝĐĂů ZĞƐĞĂƌĐŚ WƌŝǌĞ ;ϮϬϬϱͿ ĂŶĚ ƚŚĞ ŝƐƚŝŶŐƵŝƐŚĞĚ ĂŶĐĞƌ/ŶƐƚŝƚƵƚĞ͘ ^ĐŝĞŶƚŝƐƚ ǁĂƌĚ ;ϮϬϬϳͿ΁͕ ƚŚĞ /ŶĂƵŐƵƌĂů /ŶƚĞƌŶĂƚŝŽŶĂů ^ŽĐŝĞƚǇ ŽĨ Joseph Heitman, MD, PhD ƚŚĞƌŽƐĐůĞƌŽƐŝƐ WƌŝǌĞ ;ϮϬϭϮͿ͕ ƚŚĞ WĂƐĂƌŽǁ &ŽƵŶĚĂƚŝŽŶ ǁĂƌĚ ŝŶ ƌ͘,ĞŝƚŵĂŶŝƐĂ:ĂŵĞƐ͘ƵŬĞWƌŽĨĞƐƐŽƌŝŶƚŚĞĞƉĂƌƚŵĞŶƚƐŽĨ ĂƌĚŝŽǀĂƐĐƵůĂƌ ZĞƐĞĂƌĐŚ ;ϮϬϭϯͿ͕ ƚŚĞ WĞĂƌů DĞŝƐƚĞƌ 'ƌĞĞŶŐĂƌĚ DŽůĞĐƵůĂƌ'ĞŶĞƚŝĐƐĂŶĚDŝĐƌŽďŝŽůŽŐǇ͕WŚĂƌŵĂĐŽůŽŐǇĂŶĚĂŶĐĞƌ WƌŝǌĞ;ϮϬϭϱͿ͕ƚŚĞϮϬϭϲƌĞĂŬƚŚƌŽƵŐŚWƌŝǌĞŝŶ>ŝĨĞ^ĐŝĞŶĐĞƐĂŶĚƚŚĞ ŝŽůŽŐǇ͕ĂŶĚDĞĚŝĐŝŶĞĂƚƵŬĞhŶŝǀĞƌƐŝƚǇDĞĚŝĐĂůĞŶƚĞƌĂŶĚŚĂŝƌ WĂƐƐĂŶŽǁĂƌĚ;ϮϬϭϲͿ͘ ŽĨƚŚĞĞƉĂƌƚŵĞŶƚŽĨDŽůĞĐƵůĂƌŝŽůŽŐǇĂŶĚŝƌĞĐƚŽƌŽĨƚŚĞƵŬĞ Sharon K. Inouye, MD, MPH ĞŶƚĞƌĨŽƌDŝĐƌŽďŝĂůWĂƚŚŽŐĞŶĞƐŝƐ͘,ĞƐĞƌǀĞĚĂƐĚŝƌĞĐƚŽƌŽĨƚŚĞƵŬĞ ƌ͘ /ŶŽƵǇĞ ŝƐ ĂŶ ŝŶƚĞƌŶĂƚŝŽŶĂůůǇ ƌĞĐŽŐŶŝǌĞĚ ůĞĂĚĞƌ ŝŶ ŐĞƌŝĂƚƌŝĐ hŶŝǀĞƌƐŝƚǇ WƌŽŐƌĂŵ ŝŶ 'ĞŶĞƚŝĐƐ ĂŶĚ 'ĞŶŽŵŝĐƐ ĨƌŽŵ ϮϬϬϮͲϮϬϬϵ͘ ŵĞĚŝĐŝŶĞ ĂŶĚ ĂŐŝŶŐ ƌĞƐĞĂƌĐŚ͘ ^ŚĞ ŝƐ ĂŶ ĞůĞĐƚĞĚ ŵĞŵďĞƌ ŽĨ ƚŚĞ ƌ͘,ĞŝƚŵĂŶƌĞĐĞŝǀĞĚŚŝƐƵŶĚĞƌŐƌĂĚƵĂƚĞƚƌĂŝŶŝŶŐĂƚƚŚĞhŶŝǀĞƌƐŝƚǇ EĂƚŝŽŶĂů ĐĂĚĞŵǇ ŽĨ DĞĚŝĐŝŶĞ͕ ĐŚĂŝƌĞĚ ƚŚĞ ĞůŝƌŝƵŵ ůŝŶŝĐĂů ŽĨŚŝĐĂŐŽŝŶĐŚĞŵŝƐƚƌǇĂŶĚďŝŽĐŚĞŵŝƐƚƌǇ͕ĂƐĂŶDͲWŚƐƚƵĚĞŶƚ 'ƵŝĚĞůŝŶĞƐWĂŶĞůĨŽƌƚŚĞŵĞƌŝĐĂŶ'ĞƌŝĂƚƌŝĐƐ^ŽĐŝĞƚǇ͕ĂŶĚƐĞƌǀĞƐ Ăƚ ŽƌŶĞůů ĂŶĚ ZŽĐŬĞĨĞůůĞƌ hŶŝǀĞƌƐŝƚŝĞƐ͕ ǁŚĞƌĞ ŚĞ ǁŽƌŬĞĚ ǁŝƚŚ ĂƐĂŶƐƐŽĐŝĂƚĞĚŝƚŽƌŽĨƚŚĞ:ŽƵƌŶĂůŽĨƚŚĞŵĞƌŝĐĂŶ'ĞƌŝĂƚƌŝĐƐ WĞƚĞƌ DŽĚĞů ĂŶĚ EŽƌƚŽŶ ŝŶĚĞƌ ŽŶ ŚŽǁ ƌĞƐƚƌŝĐƚŝŽŶ ĞŶǌǇŵĞƐ ^ŽĐŝĞƚǇ͘ ,Ğƌ ƌĞƐĞĂƌĐŚ ĨŽĐƵƐĞƐ ŽŶ ƉƌĞǀĞŶƚŝŽŶ ŽĨ ĚĞůŝƌŝƵŵ ĂŶĚ ƌĞĐŽŐŶŝǌĞ ƐƉĞĐŝĨŝĐ E ƐĞƋƵĞŶĐĞƐ ĂŶĚ ŚŽǁ ďĂĐƚĞƌŝĂ ƌĞƐƉŽŶĚ ĐŽŐŶŝƚŝǀĞ ĚĞĐůŝŶĞ ǁŝƚŚ ĂŐŝŶŐ͕ ƉƌŽŵŽƚŝŶŐ ŚĞĂůƚŚǇ ĂŐŝŶŐ ĂŶĚ ƚŽĂŶĚƌĞƉĂŝƌEďƌĞĂŬƐĂŶĚŶŝĐŬƐ͘ƌ͘,ĞŝƚŵĂŶǁĂƐĂŶDK ŝŶĚĞƉĞŶĚĞŶĐĞĨŽůůŽǁĂĐƵƚĞŝůůŶĞƐƐ͕ĂŶĚŝŵƉƌŽǀĞŵĞŶƚŽĨŚĞĂůƚŚĐĂƌĞ ůŽŶŐͲƚĞƌŵ ĨĞůůŽǁ Ăƚ ƚŚĞ ŝŽĐĞŶƚĞƌ ŝŶ ĂƐĞů͕ ^ǁŝƚǌĞƌůĂŶĚ ƉƌŝŽƌ ƚŽ ƐǇƐƚĞŵƐƚŚƌŽƵŐŚƉŽůŝĐǇ͘ ŵŽǀŝŶŐƚŽƵŬĞŝŶϭϵϵϮ͘ƌ͘,ĞŝƚŵĂŶĂŶĚĐŽůůĞĂŐƵĞƐĨŽĐƵƐŽŶƚŚĞ ŵŽĚĞůǇĞĂƐƚSaccharomyces cerevisiaeĂŶĚƚŚĞƉĂƚŚŽŐĞŶŝĐĨƵŶŐŝ ŽŶƚŝŶƵŽƵƐůǇE/,ͲĨƵŶĚĞĚƐŝŶĐĞϭϵϴϵǁŝƚŚŽǀĞƌϱϬŐƌĂŶƚƐĂŶĚŽǀĞƌ Cryptococcus neoformans and Candida albicans͘dŚĞŝƌƐƚƵĚŝĞƐŚĂǀĞ ϮϱϬƉƵďůŝĐĂƚŝŽŶƐ͕ƌ͘/ŶŽƵǇĞĚĞǀĞůŽƉĞĚƚŚĞŽŶĨƵƐŝŽŶƐƐĞƐƐŵĞŶƚ ƌĞǀĞĂůĞĚƚŚĞĐŽŶƐĞƌǀĞĚƚĂƌŐĞƚƐĨŽƌŝŵŵƵŶŽƐƵƉƉƌĞƐƐŝǀĞĂŶƚŝĨƵŶŐĂů DĞƚŚŽĚ ;DͿͶƚŚĞ ŵŽƐƚ ǁŝĚĞůǇ ƵƐĞĚ ŵĞƚŚŽĚ ĨŽƌ ĚĞůŝƌŝƵŵ ĚƌƵŐƐĂŶĚĚĞůŝŶĞĂƚĞĚĐĂůĐŝŶĞƵƌŝŶĂŶĚdŽƌƐŝŐŶĂůŝŶŐƉĂƚŚǁĂǇƐ͘ƌ͘ ŝĚĞŶƚŝĨŝĐĂƚŝŽŶ͕ƵƐĞĚŝŶŽǀĞƌϰϬϬϬƉƵďůŝĐĂƚŝŽŶƐĂŶĚƚƌĂŶƐůĂƚĞĚŝŶƚŽ ,ĞŝƚŵĂŶŝƐĂƌĞĐŝƉŝĞŶƚŽĨƚŚĞƵƌƌŽƵŐŚƐtĞůĐŽŵĞ^ĐŚŽůĂƌǁĂƌĚ ϮϬůĂŶŐƵĂŐĞƐͶĂůŽŶŐǁŝƚŚƚŚĞ,ŽƐƉŝƚĂůůĚĞƌ>ŝĨĞWƌŽŐƌĂŵ;,>WͿ ŝŶ DŽůĞĐƵůĂƌ WĂƚŚŽŐĞŶŝĐ DǇĐŽůŽŐǇ͕ ƚŚĞ ϮϬϬϮ ^D D'E ĨŽƌĚĞůŝƌŝƵŵƉƌĞǀĞŶƚŝŽŶ͕ĂĐŽƐƚͲĞĨĨĞĐƚŝǀĞŵŽĚĞůŽĨƉĂƚŝĞŶƚͲĐĞŶƚĞƌĞĚ ĂǁĂƌĚĨŽƌƐŝŐŶŝĨŝĐĂŶƚĐŽŶƚƌŝďƵƚŝŽŶƐƵƐŝŶŐŵŽůĞĐƵůĂƌďŝŽůŽŐǇƚŽŽƵƌ ĐĂƌĞƚŚĂƚŚĂƐďĞĞŶĚŝƐƐĞŵŝŶĂƚĞĚƚŽŽǀĞƌϮϬϬŚŽƐƉŝƚĂůƐǁŽƌůĚǁŝĚĞ͘ ƵŶĚĞƌƐƚĂŶĚŝŶŐŽĨŚƵŵĂŶĚŝƐĞĂƐĞ͕ĂŶĚƚŚĞϮϬϬϯ^ƋƵŝďďǁĂƌĚĨƌŽŵ ^ŚĞǁĂƐƌĞĐĞŶƚůǇĂǁĂƌĚĞĚĂŶZϮϰĞůŝƌŝƵŵEĞƚǁŽƌŬŐƌĂŶƚďǇƚŚĞ ƚŚĞ/ŶĨĞĐƚŝŽƵƐŝƐĞĂƐĞƐ^ŽĐŝĞƚǇŽĨŵĞƌŝĐĂ;/^ͿĨŽƌŽƵƚƐƚĂŶĚŝŶŐ EĂƚŝŽŶĂů /ŶƐƚŝƚƵƚĞƐ ŽĨ ,ĞĂůƚŚ͘ ^ŚĞ ŝƐ ĐŽŵŵŝƚƚĞĚ ƚŽ ƚƌĂŶƐůĂƚŝŶŐ ĐŽŶƚƌŝďƵƚŝŽŶƐƚŽŝŶĨĞĐƚŝŽƵƐĚŝƐĞĂƐĞƌĞƐĞĂƌĐŚ͘ƌ͘,ĞŝƚŵĂŶŚĂƐďĞĞŶ ƌĞƐĞĂƌĐŚŝŶƚŽƉƌĂĐƚŝĐĞĂŶĚƉŽůŝĐǇĐŚĂŶŐĞƐ͘ ĂŶŝŶƐƚƌƵĐƚŽƌƐŝŶĐĞϭϵϵϴĂƚƚŚĞtŽŽĚƐ,ŽůĞDŽůĞĐƵůĂƌDǇĐŽůŽŐǇ Ross Levine, MD ŽƵƌƐĞ͕ŝƐĂŶĞĚŝƚŽƌŽĨƵŬĂƌǇŽƚŝĐĞůů͕ŝƐĂŵĞŵďĞƌŽĨƚŚĞ^/ ƌ͘>ĞǀŝŶĞŝƐĂDĞŵďĞƌŽĨƚŚĞ,ƵŵĂŶKŶĐŽůŽŐǇĂŶĚWĂƚŚŽŐĞŶĞƐŝƐ ;ĞůĞĐƚĞĚ ϮϬϬϯͿ͕ Ă ĨĞůůŽǁ ŽĨ ƚŚĞ /^ ŝŶ ϮϬϬϯ͕ Ă ĨĞůůŽǁ ŽĨ ƚŚĞ WƌŽŐƌĂŵ ĂŶĚ ĂŶ ƚƚĞŶĚŝŶŐ WŚǇƐŝĐŝĂŶ ŽŶ ƚŚĞ >ĞƵŬĞŵŝĂ ^ĞƌǀŝĐĞ͕ ŵĞƌŝĐĂŶĐĂĚĞŵǇŽĨDŝĐƌŽďŝŽůŽŐǇŝŶϮϬϬϰ͕ĂŶĚĂĨĞůůŽǁŽĨƚŚĞ ĞƉĂƌƚŵĞŶƚ ŽĨ DĞĚŝĐŝŶĞ͘ ,Ğ ŝƐ ƚŚĞ >ĂƵƌĞŶĐĞ :ŽƐĞƉŚ ŝŶĞĞŶ ŵĞƌŝĐĂŶƐƐŽĐŝĂƚŝŽŶĨŽƌƚŚĞĚǀĂŶĐĞŵĞŶƚŽĨ^ĐŝĞŶĐĞ;ϮϬϬϱͿ͘ ŚĂŝƌ ŝŶ >ĞƵŬĞŵŝĂ ZĞƐĞĂƌĐŚ͕ Ă WƌŽĨĞƐƐŽƌ ŽĨ DĞĚŝĐŝŶĞ Ăƚ tĞŝůů

16 2018 AAP / ASCI / APSA Joint Meeting SPEAKER BIOGRAPHIES

ŽƌŶĞůůDĞĚŝĐĂůŽůůĞŐĞ͕ĂŶĚŝƐƚŚĞŝƌĞĐƚŽƌŽĨƚŚĞD^<ĞŶƚĞƌĨŽƌ ůĞǀĞůƐĞƋƵĞŶĐŝŶŐ͘ ,ĞŵĂƚŽůŽŐŝĐDĂůŝŐŶĂŶĐŝĞƐ͘ƌ͘>ĞǀŝŶĞǁĂƐďŽƌŶĂŶĚƌĂŝƐĞĚŝŶƚŚĞ ,ĞŝƐĂŵĞŵďĞƌŽĨƚŚĞEĂƚŝŽŶĂůĐĂĚĞŵǇŽĨ^ĐŝĞŶĐĞƐ͕ƚŚĞEĂƚŝŽŶĂů EĞǁ zŽƌŬĂƌĞĂ͕ ĂŶĚ ƚŚĞŶ ƌĞĐĞŝǀĞĚ ŚŝƐ ĨƌŽŵ ,ĂƌǀĂƌĚ ŽůůĞŐĞ ĐĂĚĞŵǇ ŽĨ DĞĚŝĐŝŶĞ ĂŶĚ ƚŚĞ ŵĞƌŝĐĂŶ ĐĂĚĞŵǇ ŽĨ ƌƚƐ ĂŶĚ ĂŶĚĂD͘͘ĨƌŽŵ:ŽŚŶƐ,ŽƉŬŝŶƐ͘ƌ͘>ĞǀŝŶĞƐĞƌǀĞĚĂƐĂZĞƐŝĚĞŶƚŝŶ ^ĐŝĞŶĐĞƐ͘ ,Ğ ĨŽƌŵĞƌůǇ ƐĞƌǀĞĚ ŽŶ ƚŚĞ 'ŽǀĞƌŶŝŶŐ ŽƵŶĐŝůƐ ŽĨ ƚŚĞ /ŶƚĞƌŶĂůDĞĚŝĐŝŶĞĂƚƚŚĞD',ĂŶĚƐƵďƐĞƋƵĞŶƚůǇĂƐĂ,ĞŵĂƚŽůŽŐǇͲ EĂƚŝŽŶĂů ĐĂĚĞŵǇ ŽĨ ^ĐŝĞŶĐĞƐ ĂŶĚ ƚŚĞ /ŶƐƚŝƚƵƚĞ ŽĨ DĞĚŝĐŝŶĞ͕ KŶĐŽůŽŐǇ &ĞůůŽǁ Ăƚ &/ͬ,ĂƌǀĂƌĚ͘ /Ŷ ^ĞƉƚĞŵďĞƌ ϮϬϬϳ͕ ŚĞ ǁĂƐ ĂŶĚŝƐĐƵƌƌĞŶƚůǇŽŶƚŚĞĚǀŝƐŽƌǇŽƵŶĐŝůƚŽƚŚĞE/,ŝƌĞĐƚŽƌ͕ƚŚĞ ƌĞĐƌƵŝƚĞĚ ƚŽ D^< ƚŽ ƚŚĞ ,ƵŵĂŶ KŶĐŽůŽŐǇ ĂŶĚ WĂƚŚŽŐĞŶĞƐŝƐ ^ĐŝĞŶƚŝĨŝĐĚǀŝƐŽƌǇŽĂƌĚƐŽĨDĂƐƐĂĐŚƵƐĞƚƚƐ'ĞŶĞƌĂů,ŽƐƉŝƚĂů͕ƚŚĞ WƌŽŐƌĂŵ͕ǁŚŝůĞŚĞĂůƐŽƐĞĞƐƉĂƚŝĞŶƚƐŽŶƚŚĞD^<>ĞƵŬĞŵŝĂ^ĞƌǀŝĐĞ͘ tŚŝƚĞŚĞĂĚ/ŶƐƚŝƚƵƚĞ͕ƚŚĞƌŽĂĚ/ŶƐƚŝƚƵƚĞ͕ƚŚĞ^ŝŵŽŶƐ&ŽƵŶĚĂƚŝŽŶ Timothy J. Ley, MD ĨŽƌ ƵƚŝƐŵ ZĞƐĞĂƌĐŚ͕ ĂŶĚ ƚŚĞ ŽĂƌĚ ŽĨ ŝƌĞĐƚŽƌƐ ŽĨ ZŽĐŚĞ ĂŶĚ 'ĞŶĞŶƚĞĐŚ͘ ,Ğ ƌĞĐĞŶƚůǇ ƐĞƌǀĞĚ ĂƐ ŽͲŚĂŝƌ ŽĨ ƚŚĞ WůĂŶŶŝŶŐ ƌ͘ >ĞǇ ƌĞĐĞŝǀĞĚ ŚŝƐ ĨƌŽŵ ƌĂŬĞ hŶŝǀĞƌƐŝƚǇ͕ ŚŝƐ D ĚĞŐƌĞĞ ŽŵŵŝƚƚĞĞĨŽƌƚŚĞWƌĞƐŝĚĞŶƚ͛ƐWƌĞĐŝƐŝŽŶDĞĚŝĐŝŶĞ/ŶŝƚŝĂƚŝǀĞ͘ ĨƌŽŵtĂƐŚŝŶŐƚŽŶhŶŝǀĞƌƐŝƚǇDĞĚŝĐĂů^ĐŚŽŽů͕ĂŶĚƉĞƌĨŽƌŵĞĚŚŝƐ ŝŶƚĞƌŶĂů ŵĞĚŝĐŝŶĞ ƌĞƐŝĚĞŶĐǇ Ăƚ DĂƐƐĂĐŚƵƐĞƚƚƐ 'ĞŶĞƌĂů ,ŽƐƉŝƚĂů͘ ,ĞŚĂƐƌĞĐĞŝǀĞĚƚŚĞŚŝŐŚĞƐƚƐĐŝĞŶƚŝĨŝĐĂǁĂƌĚƐŽĨƚŚĞŵĞƌŝĐĂŶ ,Ğ ĐŽŵƉůĞƚĞĚ ĨĞůůŽǁƐŚŝƉƐ ŝŶ ,ĞŵĂƚŽůŽŐǇ ĂŶĚ KŶĐŽůŽŐǇ Ăƚ ƚŚĞ ,ĞĂƌƚ ƐƐŽĐŝĂƚŝŽŶ͕ ƚŚĞ ŵĞƌŝĐĂŶ ^ŽĐŝĞƚǇ ŽĨ EĞƉŚƌŽůŽŐǇ͕ ƚŚĞ E/, ĂŶĚ Ăƚ tĂƐŚŝŶŐƚŽŶ hŶŝǀĞƌƐŝƚǇ͕ ĂŶĚ ũŽŝŶĞĚ ƚŚĞ ĨĂĐƵůƚǇ Ăƚ ŽƵŶĐŝůĨŽƌ,ŝŐŚůŽŽĚWƌĞƐƐƵƌĞZĞƐĞĂƌĐŚ͕ƚŚĞŵĞƌŝĐĂŶ^ŽĐŝĞƚǇŽĨ tĂƐŚŝŶŐƚŽŶ hŶŝǀĞƌƐŝƚǇ ŝŶ ^ƚ͘ >ŽƵŝƐ ŝŶ ϭϵϴϲ͘ ,Ğ ŶŽǁ ŚŽůĚƐ ƚŚĞ ,ǇƉĞƌƚĞŶƐŝŽŶ͕ƚŚĞ/ŶƚĞƌŶĂƚŝŽŶĂů^ŽĐŝĞƚǇŽĨ,ǇƉĞƌƚĞŶƐŝŽŶ͕ĂŶĚƚŚĞ >ĞǁŝƐd͘ĂŶĚZŽƐĂůŝŶĚ͘ƉƉůĞŚĂŝƌŝŶKŶĐŽůŽŐǇ͕ŝƐWƌŽĨĞƐƐŽƌŽĨ /ŶƚĞƌŶĂƚŝŽŶĂů^ŽĐŝĞƚǇŽĨEĞƉŚƌŽůŽŐǇ͘,ĞƌĞĐĞŝǀĞĚƚŚĞϮϬϬϴtŝůĞǇ DĞĚŝĐŝŶĞĂŶĚŽĨ'ĞŶĞƚŝĐƐĂƚtĂƐŚŝŶŐƚŽŶhŶŝǀĞƌƐŝƚǇ͕ĂŶĚƐĞƌǀĞƐ WƌŝǌĞĨŽƌŝŽŵĞĚŝĐĂů^ĐŝĞŶĐĞƐĂŶĚƚŚĞϮϬϭϰƌĞĂŬƚŚƌŽƵŐŚWƌŝǌĞŝŶ ĂƐŝƌĞĐƚŽƌŽĨƚŚĞ^ƚĞŵĞůůŝŽůŽŐǇ^ĞĐƚŝŽŶŝŶƚŚĞĞƉĂƌƚŵĞŶƚ >ŝĨĞ^ĐŝĞŶĐĞƐ͘ ŽĨDĞĚŝĐŝŶĞ͘>ĞǇŝƐĂƉĂƐƚƉƌĞƐŝĚĞŶƚŽĨƚŚĞŵĞƌŝĐĂŶ^ŽĐŝĞƚǇĨŽƌ Dr. Stuart H Orkin, MD ůŝŶŝĐĂů/ŶǀĞƐƚŝŐĂƚŝŽŶ͕ƉĂƐƚƚƌĞĂƐƵƌĞƌŽĨƚŚĞŵĞƌŝĐĂŶƐƐŽĐŝĂƚŝŽŶ ƌ͘KƌŬŝŶŝƐƚŚĞĂǀŝĚ'͘EĂƚŚĂŶŝƐƚŝŶŐƵŝƐŚĞĚWƌŽĨĞƐƐŽƌŽĨWĞĚŝĂƚƌŝĐƐ ŽĨ WŚǇƐŝĐŝĂŶƐ͕ Ă ĨĞůůŽǁ ŽĨ ^ ĂŶĚ ƚŚĞ ŵĞƌŝĐĂŶ ĐĂĚĞŵǇ ŽĨ Ăƚ ,ĂƌǀĂƌĚ DĞĚŝĐĂů ^ĐŚŽŽů͕ ĂŶĚ ĂŶ /ŶǀĞƐƚŝŐĂƚŽƌ ŽĨ ƚŚĞ ,ŽǁĂƌĚ ƌƚƐ ĂŶĚ ^ĐŝĞŶĐĞƐ͕ ĂŶĚ Ă ŵĞŵďĞƌ ŽĨ ƚŚĞ EĂƚŝŽŶĂů ĐĂĚĞŵǇ ŽĨ ,ƵŐŚĞƐ DĞĚŝĐĂů /ŶƐƚŝƚƵƚĞ͘ ƌ͘ KƌŬŝŶ͛Ɛ ƉŝŽŶĞĞƌŝŶŐ ĞĨĨŽƌƚƐ ĚĞĨŝŶĞĚ DĞĚŝĐŝŶĞ͘,ĞǁĂƐĂƉƉŽŝŶƚĞĚďǇWƌĞƐŝĚĞŶƚKďĂŵĂƚŽƚŚĞEĂƚŝŽŶĂů ƚŚĞ ŵŽůĞĐƵůĂƌ ďĂƐŝƐ ŽĨ ŚƵŵĂŶ ďůŽŽĚ ĚŝƐŽƌĚĞƌƐ ĂŶĚ ŵĞĐŚĂŶŝƐŵƐ ĂŶĐĞƌĚǀŝƐŽƌǇŽĂƌĚŝŶϮϬϭϱ͘ ŐŽǀĞƌŶŝŶŐďůŽŽĚĐĞůůĚĞǀĞůŽƉŵĞŶƚ͘,ŝƐĞĂƌůǇĂĐĐŽŵƉůŝƐŚŵĞŶƚƐůĞĚ >ĞǇ ŚĂƐ ĚĞǀĞůŽƉĞĚ ĂƉƉƌŽĂĐŚĞƐ ƚŽ ƌĞĂĐƚŝǀĂƚĞ ĨĞƚĂů ŚĞŵŽŐůŽďŝŶ ƚŽ ƚŚĞ ĨŝƌƐƚ ĐŽŵƉƌĞŚĞŶƐŝǀĞ ŵŽůĞĐƵůĂƌ ĚŝƐƐĞĐƚŝŽŶ ŽĨ ĂŶ ŝŶŚĞƌŝƚĞĚ ƐǇŶƚŚĞƐŝƐĨŽƌƉĂƚŝĞŶƚƐǁŝƚŚŚĞŵŽŐůŽďŝŶŽƉĂƚŚŝĞƐ͕ĚĞĨŝŶĞĚƚŚĞƌŽůĞ ĚŝƐŽƌĚĞƌ ;ƚŚĞ ƚŚĂůĂƐƐĞŵŝĂ ƐǇŶĚƌŽŵĞƐͿ͘ ,Ğ ĐŚĂƌĂĐƚĞƌŝǌĞĚ ŐĞŶĞƐ ŽĨƚŚĞƉĞƌĨŽƌŝŶͬŐƌĂŶǌǇŵĞƐǇƐƚĞŵĨŽƌƚŚĞĨƵŶĐƚŝŽŶŽĨĐǇƚŽƚŽǆŝĐĂŶĚ ƌĞƐƉŽŶƐŝďůĞ ĨŽƌ ŽƚŚĞƌ ŚƵŵĂŶ ďůŽŽĚ ĚŝƐŽƌĚĞƌƐ͕ ŝŶĐůƵĚŝŶŐ yͲůŝŶŬĞĚ ƌĞŐƵůĂƚŽƌǇdĐĞůůƐ͕ĂŶĚŚĂƐƉĞƌĨŽƌŵĞĚƉŝŽŶĞĞƌŝŶŐƐƚƵĚŝĞƐƚŚĂƚŚĂǀĞ ĐŚƌŽŶŝĐ ŐƌĂŶƵůŽŵĂƚŽƵƐ ĚŝƐĞĂƐĞ ;ƚŚĞ ĨŝƌƐƚ ƉŽƐŝƚŝŽŶĂů ĐůŽŶŝŶŐͿ͘ ƌ͘ ƉƌĞĐŝƐĞůǇĚĞĨŝŶĞĚƚŚĞŐĞŶŽŵŝĐƐŽĨĂĐƵƚĞŵǇĞůŽŝĚůĞƵŬĞŵŝĂ͘,ĞŚĂƐ KƌŬŝŶƚŚĞŶƚƌĂŶƐĨŽƌŵĞĚƚŚĞƐƚƵĚǇŽĨďůŽŽĚƐƚĞŵĐĞůůĚĞǀĞůŽƉŵĞŶƚďǇ ǁƌŝƚƚĞŶĞǆƚĞŶƐŝǀĞůǇĂďŽƵƚƚŚĞƉŚǇƐŝĐŝĂŶͲƐĐŝĞŶƚŝƐƚĐĂƌĞĞƌƉĂƚŚ͕ĂŶĚ ŝĚĞŶƚŝĨǇŝŶŐĂŶĚĐŚĂƌĂĐƚĞƌŝǌŝŶŐƚŚĞĨŝƌƐƚŚĞŵĂƚŽƉŽŝĞƚŝĐƚƌĂŶƐĐƌŝƉƚŝŽŶ ǁĂƐĂŶĂĚǀŽĐĂƚĞĨŽƌĞƐƚĂďůŝƐŚŝŶŐƚŚĞĞǆƚƌĂŵƵƌĂů>ŽĂŶZĞƉĂǇŵĞŶƚ ĨĂĐƚŽƌƐ ;ƚŚĞ 'd ĨĂŵŝůǇͿ ĂŶĚ ƚŚĞŝƌ ĐƌŝƚŝĐĂů ĐŽͲĂĐƚŝǀĂƚŽƌƐ͘ ,ŝƐ WƌŽŐƌĂŵƐĂƚƚŚĞE/,͘,ĞŚĂƐŵĞŶƚŽƌĞĚŵŽƌĞƚŚĂŶϱϬƉƌĞͲĂŶĚƉŽƐƚͲ ƌĞĐĞŶƚ ůĂŶĚŵĂƌŬ ƐƚƵĚŝĞƐ ŽŶ >ϭϭ͕ Ă ĐƌŝƚŝĐĂů ƌĞƉƌĞƐƐŽƌ ŽĨ ĨĞƚĂů ĚŽĐƚŽƌĂůĨĞůůŽǁƐŝŶŚŝƐůĂďŽƌĂƚŽƌǇ͖ŵŽƐƚŚŽůĚƌĞƐĞĂƌĐŚƉŽƐŝƚŝŽŶƐŝŶ ŚĞŵŽŐůŽďŝŶ;,ď&Ϳ͕ŚĂǀĞŝůůƵŵŝŶĂƚĞĚƌĞŐƵůĂƚŝŽŶŽĨƚŚĞĨĞƚĂůͲƚŽͲĂĚƵůƚ ĂĐĂĚĞŵŝĐŵĞĚŝĐŝŶĞŽƌƉŚĂƌŵĂĐĞƵƚŝĐĂůĐŽŵƉĂŶŝĞƐ͘ ƐǁŝƚĐŚ ĂŶĚ ŝŵƉƌŽǀĞĚ ƉƌŽƐƉĞĐƚƐ ĨŽƌ ,ď& ƌĞĂĐƚŝǀĂƚŝŽŶ ĂƐ ŐĞŶĞƚŝĐ Richard P. Lifton, MD, PhD Žƌ ƉŚĂƌŵĂĐŽůŽŐŝĐĂů ƚŚĞƌĂƉǇ ŽĨ ƚŚĞ ƚŚĂůĂƐƐĞŵŝĂƐ ĂŶĚ ƐŝĐŬůĞ ĐĞůů ĚŝƐĞĂƐĞ͘dŚĞƐĞĐŽŶƚƌŝďƵƚŝŽŶƐƚŽŚƵŵĂŶŐĞŶĞƚŝĐƐĂŶĚŵĞĚŝĐŝŶĞĂƌĞ ƌ͘>ŝĨƚŽŶŝƐWƌĞƐŝĚĞŶƚŽĨdŚĞZŽĐŬĞĨĞůůĞƌhŶŝǀĞƌƐŝƚǇǁŚĞƌĞŚĞŝƐ ƵŶŵĂƚĐŚĞĚĨŽƌƚŚĞŝƌďƌĞĂĚƚŚ͕ĨŽĐƵƐ͕ĂŶĚďƌŽĂĚŝŵƉĂĐƚ͘,ĞŝƐĂůƐŽ ĂůƐŽ ŚĞĂĚ ŽĨ ƚŚĞ ůĂďŽƌĂƚŽƌǇ ŽĨ ,ƵŵĂŶ 'ĞŶĞƚŝĐƐ ĂŶĚ 'ĞŶŽŵŝĐƐ͘ ĂŶĞůĞĐƚĞĚŵĞŵďĞƌŽĨƚŚĞEĂƚŝŽŶĂůĐĂĚĞŵǇŽĨ^ĐŝĞŶĐĞƐ;E^Ϳ͕ ,ĞŐƌĂĚƵĂƚĞĚsumma cum laudeĨƌŽŵĂƌƚŵŽƵƚŚ͕ĂŶĚƌĞĐĞŝǀĞĚ /ŶƐƚŝƚƵƚĞ ŽĨ DĞĚŝĐŝŶĞ͕ ŵĞƌŝĐĂŶ ĐĂĚĞŵǇ ŽĨ ƌƚƐ ĂŶĚ ^ĐŝĞŶĐĞƐ͕ DĂŶĚWŚĚĞŐƌĞĞƐĨƌŽŵ^ƚĂŶĨŽƌĚ͘,ĞƚŚĞŶǁĂƐZĞƐŝĚĞŶƚĂŶĚ ĂŶĚ ƚŚĞ ŵĞƌŝĐĂŶ WŚŝůŽƐŽƉŚŝĐĂů ^ŽĐŝĞƚǇ͕ ĂŶĚ ƌĞĐŝƉŝĞŶƚ ŽĨ ƚŚĞ ͘ ŚŝĞĨZĞƐŝĚĞŶƚŝŶDĞĚŝĐŝŶĞĂƚƌŝŐŚĂŵĂŶĚtŽŵĞŶ͛Ɛ,ŽƐƉŝƚĂů͕ĂŶĚ DĞĂĚ:ŽŚŶƐŽŶǁĂƌĚŽĨƚŚĞŵĞƌŝĐĂŶĐĂĚĞŵǇŽĨWĞĚŝĂƚƌŝĐƐ͕ ĐŽŶƚŝŶƵĞĚ ŽŶ ƚŚĞ ,ĂƌǀĂƌĚ DĞĚŝĐĂů ^ĐŚŽŽů ĨĂĐƵůƚǇ ďĞĨŽƌĞ ďĞŝŶŐ ƚŚĞtĂƌƌĞŶůƉĞƌƚWƌŝǌĞ͕ƚŚĞ,ĞůŵƵƚ,ŽƌƚĞŶ&ŽƵŶĚĂƚŝŽŶWƌŝǌĞ͕ƚŚĞ ƌĞĐƌƵŝƚĞĚƚŽzĂůĞŝŶϭϵϵϯ͕ǁŚĞƌĞŚĞƐĞƌǀĞĚĂƐ^ƚĞƌůŝŶŐWƌŽĨĞƐƐŽƌ ŝƐƚŝŶŐƵŝƐŚĞĚZĞƐĞĂƌĐŚǁĂƌĚĨƌŽŵƚŚĞƐƐŽĐŝĂƚŝŽŶŽĨŵĞƌŝĐĂŶ ĂŶĚ ŚĂŝƌ ŽĨ 'ĞŶĞƚŝĐƐ ĨƌŽŵ ϭϵϵϴ ƚŽ ϮϬϭϲ ďĞĨŽƌĞ ŵŽǀŝŶŐ ƚŽ DĞĚŝĐĂů ŽůůĞŐĞƐ ;DͿ͕ ƚŚĞ ͘ ŽŶŶĂůů dŚŽŵĂƐ͕ ĂŵĞƐŚĞŬ ZŽĐŬĞĨĞůůĞƌ͘ƚzĂůĞ͕ŚĞǁĂƐĂůƐŽ&ŽƵŶĚĞƌĂŶĚǆĞĐƵƚŝǀĞŝƌĞĐƚŽƌŽĨ ĂŶĚ ĂƐŝĐ ^ĐŝĞŶĐĞ DĞŶƚŽƌ ǁĂƌĚƐ ŽĨ ƚŚĞ ŵĞƌŝĐĂŶ ^ŽĐŝĞƚǇ ŽĨ ƚŚĞzĂůĞĞŶƚĞƌĨŽƌ'ĞŶŽŵĞŶĂůǇƐŝƐ͘ ,ĞŵĂƚŽůŽŐǇ;^,Ϳ͕ƚŚĞDĞƚĐĂůĨǁĂƌĚŽĨƚŚĞ/ŶƚĞƌŶĂƚŝŽŶĂů^ŽĐŝĞƚǇ ƌ͘ >ŝĨƚŽŶ ŚĂƐ ƵƐĞĚ ŚƵŵĂŶ ŐĞŶĞƚŝĐƐ ĂŶĚ ŐĞŶŽŵŝĐƐ ƚŽ ŝĚĞŶƚŝĨǇ ŽĨǆƉĞƌŝŵĞŶƚĂů,ĞŵĂƚŽůŽŐǇ;/^,Ϳ͕ĂŶĚƚŚĞtŝůůŝĂŵ͘ůůĂŶǁĂƌĚ ŵƵƚĂƚŝŽŶƐ ƚŚĂƚ ŝĚĞŶƚŝĨǇ ŬĞǇ ŐĞŶĞƐ ĂŶĚ ƉĂƚŚǁĂǇƐ ƵŶĚĞƌůǇŝŶŐ ŽĨƚŚĞŵĞƌŝĐĂŶ^ŽĐŝĞƚǇŽĨ,ƵŵĂŶ'ĞŶĞƚŝĐƐ͘/ŶϮϬϭϯ͕ŚĞƌĞĐĞŝǀĞĚ ŚǇƉĞƌƚĞŶƐŝŽŶ͕ ŵǇŽĐĂƌĚŝĂů ŝŶĨĂƌĐƚŝŽŶ͕ ŽƐƚĞŽƉŽƌŽƐŝƐ͕ ĐĞƌĞďƌĂů :ĞƐƐŝĞ ^ƚĞǀĞŶƐŽŶ <ŽǀĂůĞŶŬŽ DĞĚĂů ŽĨ ƚŚĞ E^ ĨŽƌ ͞ŝŵƉŽƌƚĂŶƚ ŚĞŵŽƌƌŚĂŐĞ͕ ĐŽŶŐĞŶŝƚĂů ŚĞĂƌƚ ĚŝƐĞĂƐĞ ĂŶĚ ŶĞŽƉůĂƐŝĂ͘ ,ŝƐ ǁŽƌŬ ĐŽŶƚƌŝďƵƚŝŽŶƐƚŽƚŚĞŵĞĚŝĐĂůƐĐŝĞŶĐĞƐ͘͟ ŽŶŚǇƉĞƌƚĞŶƐŝŽŶ͕ǁŚŝĐŚĂĨĨĞĐƚƐŽŶĞďŝůůŝŽŶƉĞŽƉůĞǁŽƌůĚǁŝĚĞ͕ŚĂƐ ĚĞŵŽŶƐƚƌĂƚĞĚƚŚĞŬĞǇƌŽůĞƐŽĨƌĞŶĂůƐĂůƚĂŶĚƉŽƚĂƐƐŝƵŵŚĂŶĚůŝŶŐ Sir Peter Ratcliffe, FRS ŝŶ ďůŽŽĚ ƉƌĞƐƐƵƌĞ ƌĞŐƵůĂƚŝŽŶ͕ ůĞĂĚŝŶŐ ƚŽ ŶĞǁ ĂƉƉƌŽĂĐŚĞƐ ƚŽ ƌ͘ ZĂƚĐůŝĨĨĞ ŝƐ Ă ƉŚǇƐŝĐŝĂŶ ƐĐŝĞŶƚŝƐƚ ǁŚŽ ƚƌĂŝŶĞĚ ŝŶ ŵĞĚŝĐŝŶĞ Ăƚ ƚƌĞĂƚŵĞŶƚĂŶĚƉƌĞǀĞŶƚŝŽŶƚŚĂƚŚĂǀĞďĞĞŶĂƉƉůŝĞĚƚŽƚŚĞŐĞŶĞƌĂů 'ŽŶǀŝůůĞ ĂŶĚ ĂŝƵƐ ŽůůĞŐĞ͕ ĂŵďƌŝĚŐĞ ĂŶĚ ^ƚ͘ ĂƌƚŚŽůŽŵĞǁ͛Ɛ ƉŽƉƵůĂƚŝŽŶ ǁŽƌůĚͲǁŝĚĞ͘ /Ŷ ϮϬϬϵ͕ ŚŝƐ ŐƌŽƵƉ ĚĞǀĞůŽƉĞĚ ĞǆŽŵĞ ,ŽƐƉŝƚĂů͕>ŽŶĚŽŶ͕ďĞĨŽƌĞŵŽǀŝŶŐƚŽKǆĨŽƌĚƚŽƐƉĞĐŝĂůŝǌĞŝŶƌĞŶĂů ƐĞƋƵĞŶĐŝŶŐĂŶĚƉĞƌĨŽƌŵĞĚƚŚĞĨŝƌƐƚĐůŝŶŝĐĂůĚŝĂŐŶŽƐŝƐďǇŐĞŶŽŵĞͲ medŝĐŝŶĞ͘ ,ŝƐ ǁŽƌŬ ŽŶ ŽǆǇŐĞŶ ƐĞŶƐŝŶŐ ŚĂƐ ǁŽŶ Ă ŶƵŵďĞƌ ŽĨ

www.jointmeeting.org 17 SPEAKER BIOGRAPHIES

ĂǁĂƌĚƐŝŶĐůƵĚŝŶŐƚŚĞ>ŽƵŝƐͲ:ĞĂŶƚĞƚWƌŝǌĞŝŶDĞĚŝĐŝŶĞ͕ƚŚĞĂŶĂĚĂ ƚŚĞŵĞƌŝĐĂŶƐƐŽĐŝĂƚŝŽŶĨŽƌƚŚĞĚǀĂŶĐĞŵĞŶƚŽĨ^ĐŝĞŶĐĞĂŶĚĂŶ 'ĂŝƌĚŶĞƌ /ŶƚĞƌŶĂƚŝŽŶĂů ǁĂƌĚ͕ ĂŶĚ ƚŚĞ >ĂƐŬĞƌ ǁĂƌĚ ĨŽƌ ĂƐŝĐ ĞůĞĐƚĞĚŵĞŵďĞƌŽĨƚŚĞŵĞƌŝĐĂŶ^ŽĐŝĞƚǇĨŽƌůŝŶŝĐĂů/ŶǀĞƐƚŝŐĂƚŝŽŶ ŝŽŵĞĚŝĐĂůZĞƐĞĂƌĐŚ͘WĞƚĞƌǁĂƐĞůĞĐƚĞĚƚŽƚŚĞ&ĞůůŽǁƐŚŝƉŽĨƚŚĞ ĂŶĚƚŚĞƐƐŽĐŝĂƚŝŽŶŽĨŵĞƌŝĐĂŶWŚǇƐŝĐŝĂŶƐ͘,ĞĂůƐŽƐĞƌǀĞƐŽŶƚŚĞ ZŽǇĂů^ŽĐŝĞƚǇĂŶĚƚŽƚŚĞĐĂĚĞŵǇŽĨDĞĚŝĐĂů^ĐŝĞŶĐĞƐŝŶϮϬϬϮ͘ ĚǀŝƐŽƌǇŽƵŶĐŝůŽĨE/ĂƚƚŚĞEĂƚŝŽŶĂů/ŶƐƚŝƚƵƚĞƐŽĨ,ĞĂůƚŚ͘ ,ĞŝƐĂŵĞŵďĞƌŽĨDKĂŶĚĂĨŽƌĞŝŐŶŚŽŶŽƌĂƌǇŵĞŵďĞƌŽĨƚŚĞ Irving L. Weissman, MD ŵĞƌŝĐĂŶ ĐĂĚĞŵǇ ŽĨ ƌƚƐ ĂŶĚ ^ĐŝĞŶĐĞƐ͘ ,Ğ ǁĂƐ ŬŶŝŐŚƚĞĚ ĨŽƌ ƐĞƌǀŝĐĞƐƚŽŵĞĚŝĐŝŶĞŝŶƚŚĞEĞǁzĞĂƌ͛Ɛ,ŽŶŽƵƌƐ͕ϮϬϭϰ͘ ƌ͘tĞŝƐƐŵĂŶŝƐƚŚĞŝƌĞĐƚŽƌŽĨƚŚĞ^ƚĂŶĨŽƌĚ/ŶƐƚŝƚƵƚĞĨŽƌ^ƚĞŵĞůů ŝŽůŽŐǇĂŶĚZĞŐĞŶĞƌĂƚŝǀĞDĞĚŝĐŝŶĞĂŶĚŝƌĞĐƚŽƌŽĨƚŚĞ^ƚĂŶĨŽƌĚ /ŶϮϬϬϰ͕ŚĞǁĂƐĂƉƉŽŝŶƚĞĚEƵĨĨŝĞůĚWƌŽĨĞƐƐŽƌŽĨůŝŶŝĐĂůDĞĚŝĐŝŶĞ >ƵĚǁŝŐĞŶƚĞƌĨŽƌĂŶĐĞƌ^ƚĞŵĞůůZĞƐĞĂƌĐŚ͘ Ăƚ ƚŚĞ hŶŝǀĞƌƐŝƚǇ ŽĨ KǆĨŽƌĚ ĂŶĚ ƐĞƌǀĞĚ ĂƐ ,ĞĂĚ ŽĨ ƚŚĞ EƵĨĨŝĞůĚ ĞƉĂƌƚŵĞŶƚŽĨůŝŶŝĐĂůDĞĚŝĐŝŶĞĨƌŽŵϮϬϬϰͲϮϬϭϲ͘/ŶDĂǇϮϬϭϲŚĞ ƌ͘tĞŝƐƐŵĂŶǁĂƐĂŵĞŵďĞƌŽĨƚŚĞĨŽƵŶĚŝŶŐ^ĐŝĞŶƚŝĨŝĐĚǀŝƐŽƌǇ ǁĂƐĂƉƉŽŝŶƚĞĚŝƌĞĐƚŽƌŽĨůŝŶŝĐĂůZĞƐĞĂƌĐŚĂƚƚŚĞ&ƌĂŶĐŝƐƌŝĐŬ ŽĂƌĚƐ ŽĨ ŵŐĞŶ ;ϭϵϴϭͲϭϵϴϵͿ͕ Ey ;ϭϵϴϭͲϭϵϵϮͿ͕ ĂŶĚ dͲĞůů /ŶƐƚŝƚƵƚĞ͕ƌĞƚĂŝŶŝŶŐĂƉŽƐŝƚŝŽŶĂƚKǆĨŽƌĚĂƐŵĞŵďĞƌŽĨƚŚĞ>ƵĚǁŝŐ ^ĐŝĞŶĐĞƐ;ϭϵϴϴͲϭϵϵϮͿ͘,ĞĐŽͲĨŽƵŶĚĞĚ͕ǁĂƐĂŝƌĞĐƚŽƌ͕ĂŶĚĐŚĂŝƌĞĚ /ŶƐƚŝƚƵƚĞ ŽĨ ĂŶĐĞƌ ZĞƐĞĂƌĐŚ ĂŶĚ ŝƌĞĐƚŽƌ ŽĨ KǆĨŽƌĚ͛Ɛ dĂƌŐĞƚ ƚŚĞ^ĐŝĞŶƚŝĨŝĐĚǀŝƐŽƌǇŽĂƌĚĂƚ^Ǉ^ƚĞŵŝǆϭϵϴϴͲϭϵϵϲ͕^ƚĞŵĞůůƐŝŶ ŝƐĐŽǀĞƌǇ/ŶƐƚŝƚƵƚĞ͘ ϭϵϵϲͲƉƌĞƐĞŶƚ͕ĂŶĚĞůůĞƌĂŶƚŝŶϮϬϬϭͲϵ͘,ĞĨŽƵŶĚĞĚ&ŽƌƚǇ^ĞǀĞŶ /ŶĐ͘ŝŶϮϬϭϱ͕ĂŶĚŝƐĂŝƌĞĐƚŽƌŽĨƚŚĞŽŵƉĂŶǇ͘ Eric Topol, MD ,ŝƐƌĞƐĞĂƌĐŚĞŶĐŽŵƉĂƐƐĞƐƚŚĞďŝŽůŽŐǇĂŶĚĞǀŽůƵƚŝŽŶŽĨƐƚĞŵĐĞůůƐ ƌ͘dŽƉŽůŝƐƚŚĞ&ŽƵŶĚĞƌĂŶĚŝƌĞĐƚŽƌŽĨƚŚĞ^ĐƌŝƉƉƐdƌĂŶƐůĂƚŝŽŶĂů ĂŶĚ ƉƌŽŐĞŶŝƚŽƌ ĐĞůůƐ͕ ŵĂŝŶůǇ ďůŽŽĚͲĨŽƌŵŝŶŐ ĂŶĚ ďƌĂŝŶͲĨŽƌŵŝŶŐ͘ ^ĐŝĞŶĐĞ /ŶƐƚŝƚƵƚĞ ;^d^/Ϳ͕ WƌŽĨĞƐƐŽƌ͕ DŽůĞĐƵůĂƌ DĞĚŝĐŝŶĞ͕ ĂŶĚ ,ĞŝƐĂůƐŽĞŶŐĂŐĞĚŝŶŝƐŽůĂƚŝŶŐĂŶĚĐŚĂƌĂĐƚĞƌŝǌŝŶŐƚŚĞƌĂƌĞĐĂŶĐĞƌ ǆĞĐƵƚŝǀĞsŝĐĞͲWƌĞƐŝĚĞŶƚŽĨdŚĞ^ĐƌŝƉƉƐZĞƐĞĂƌĐŚ/ŶƐƚŝƚƵƚĞ;d^Z/Ϳ͘ ĂŶĚ ůĞƵŬĞŵŝĂ ƐƚĞŵ ĐĞůůƐ ĂƐ ƚŚĞ ŽŶůǇ ĚĂŶŐĞƌŽƵƐ ĐĞůůƐ ŝŶ ƚŚĞƐĞ Ɛ Ă ƌĞƐĞĂƌĐŚĞƌ͕ ŚĞ ŚĂƐ ƉƵďůŝƐŚĞĚ ŽǀĞƌ ϭϭϬϬ ƉĞĞƌͲƌĞǀŝĞǁĞĚ ŵĂůŝŐŶĂŶĐŝĞƐ͕ ĞƐƉĞĐŝĂůůǇ ǁŝƚŚ ŚƵŵĂŶ ĐĂŶĐĞƌƐ͘ ,Ğ ĚŝƐĐŽǀĞƌĞĚ ĂƌƚŝĐůĞƐ͕ǁŝƚŚŵŽƌĞƚŚĂŶϭϴϱ͕ϬϬϬĐŝƚĂƚŝŽŶƐ͕ĞůĞĐƚĞĚƚŽƚŚĞEĂƚŝŽŶĂů ƚŚĂƚĂůůĐĂŶĐĞƌƐƚĞŵĐĞůůƐĞǆƉƌĞƐƐϰϳ͕ƚŚĞ͚ĚŽŶ͛ƚĞĂƚŵĞ͛ƐŝŐŶĂů͕ ĐĂĚĞŵǇ ŽĨ DĞĚŝĐŝŶĞ͕ ĂŶĚ ŝƐ ŽŶĞ ŽĨ ƚŚĞ ƚŽƉ ϭϬ ŵŽƐƚ ĐŝƚĞĚ ƚŽ ŽǀĞƌĐŽŵĞ ƉƌŽƉŚĂŐŽĐǇƚŝĐ ƐŝŐŶĂůƐ ƚŚĂƚ ĂƌŝƐĞ ĚƵƌŝŶŐ ĐĂŶĐĞƌ ƌĞƐĞĂƌĐŚĞƌƐ ŝŶ ŵĞĚŝĐŝŶĞ ;dŚŽŵƐŽŶ ZĞƵƚĞƌƐ /^/͕ ͞ŽĐƚŽƌ ŽĨ ƚŚĞ ĚĞǀĞůŽƉŵĞŶƚ͕ĂŶĚŚĂƐƐŚŽǁŶƚŚĂƚďůŽĐŬŝŶŐĂŶƚŝďŽĚŝĞƐƚŽϰϳŚĂǀĞ ĞĐĂĚĞ͟Ϳ͘,ŝƐƉƌŝŶĐŝƉĂůƐĐŝĞŶƚŝĨŝĐĨŽĐƵƐŚĂƐďĞĞŶŽŶƚŚĞŐĞŶŽŵŝĐ ƚŚĞƌĂƉĞƵƚŝĐƉŽƚĞŶƚŝĂůĨŽƌĂůůƚĞƐƚĞĚŚƵŵĂŶĐĂŶĐĞƌƐ͘&ŝŶĂůůǇ͕ŚĞŚĂƐ ĂŶĚĚŝŐŝƚĂůƚŽŽůƐƚŽŝŶĚŝǀŝĚƵĂůŝǌĞŵĞĚŝĐŝŶĞͶĂŶĚƚŚĞƉŽǁĞƌƚŚĂƚ ĂůŽŶŐͲƚĞƌŵƌĞƐĞĂƌĐŚŝŶƚĞƌĞƐƚŝŶƚŚĞƉŚǇůŽŐĞŶǇĂŶĚĚĞǀĞůŽƉŵĞŶƚĂů ďƌŝŶŐƐƚŽŝŶĚŝǀŝĚƵĂůƐƚŽĚƌŝǀĞƚŚĞĨƵƚƵƌĞŽĨŵĞĚŝĐŝŶĞ͘ ďŝŽůŽŐǇŽĨƚŚĞĐĞůůƐƚŚĂƚŵĂŬĞƵƉƚŚĞďůŽŽĚͲĨŽƌŵŝŶŐĂŶĚŝŵŵƵŶĞ /ŶϮϬϭϲ͕dŽƉŽůǁĂƐĂǁĂƌĚĞĚĂΨϮϬϳDŐƌĂŶƚĨƌŽŵƚŚĞE/,ƚŽůĞĂĚĂ ƐǇƐƚĞŵƐ͘,ŝƐůĂďŽƌĂƚŽƌǇǁĂƐĨŝƌƐƚƚŽŝĚĞŶƚŝĨǇĂŶĚŝƐŽůĂƚĞƚŚĞďůŽŽĚͲ ƐŝŐŶŝĨŝĐĂŶƚƉĂƌƚŽĨƚŚĞWƌĞĐŝƐŝŽŶDĞĚŝĐŝŶĞ/ŶŝƚŝĂƚŝǀĞ͕ĂƉƌŽƐƉĞĐƚŝǀĞ ĨŽƌŵŝŶŐƐƚĞŵĐĞůůĨƌŽŵŵŝĐĞ͕ĂŶĚŚĂƐƉƵƌŝĨŝĞĚĞĂĐŚƉƌŽŐĞŶŝƚŽƌŝŶ ƌĞƐĞĂƌĐŚƉƌŽŐƌĂŵƚŚĂƚĂŝŵƐƚŽĞŶƌŽůůϭŵŝůůŝŽŶƉĂƌƚŝĐŝƉĂŶƚƐŝŶƚŚĞ ƚŚĞƐƚĂŐĞƐŽĨĚĞǀĞůŽƉŵĞŶƚďĞƚǁĞĞŶƚŚĞƐƚĞŵĐĞůůƐĂŶĚŵĂƚƵƌĞ h^͘WƌŝŽƌƚŽĐŽŵŝŶŐƚŽůĞĂĚ^ĐƌŝƉƉƐ^d^/ŝŶϮϬϬϳ͕ĨŽƌǁŚŝĐŚŚĞŝƐ ƉƌŽŐĞŶǇ ;ŐƌĂŶƵůŽĐǇƚĞƐ͕ ŵĂĐƌŽͲƉŚĂŐĞƐ͕ ĞƚĐ͘Ϳ͘ ƚ ^Ǉ^ƚĞŵŝǆ ŚĞ ĐŽͲ ƚŚĞƉƌŝŶĐŝƉĂůŝŶǀĞƐƚŝŐĂƚŽƌŽĨĂĨůĂŐƐŚŝƉΨϯϯDE/,ŐƌĂŶƚ͕ŚĞůĞĚƚŚĞ ĚŝƐĐŽǀĞƌĞĚƚŚĞŚƵŵĂŶŚĞŵĂƚŽƉŽĞƚŝĐƐƚĞŵĐĞůůĂŶĚĂƚ^ƚĞŵĞůůƐ͕ ůĞǀĞůĂŶĚůŝŶŝĐƚŽďĞĐŽŵĞƚŚĞηϭĐĞŶƚĞƌĨŽƌŚĞĂƌƚĐĂƌĞĂŶĚǁĂƐ ŚĞ ĐŽͲĚŝƐĐŽǀĞƌĞĚ Ă ŚƵŵĂŶ ĐĞŶƚƌĂů ŶĞƌǀŽƵƐ ƐǇƐƚĞŵ ƐƚĞŵ ĐĞůů͘ /Ŷ ƚŚĞĨŽƵŶĚĞƌŽĨĂŶĞǁŵĞĚŝĐĂůƐĐŚŽŽůƚŚĞƌĞ͘,ĞŚĂƐďĞĞŶǀŽƚĞĚ ĂĚĚŝƚŝŽŶ͕ƚŚĞtĞŝƐƐŵĂŶůĂďŽƌĂƚŽƌǇŚĂƐƉŝŽŶĞĞƌĞĚƚŚĞƐƚƵĚǇŽĨƚŚĞ ĂƐƚŚĞηϭŵŽƐƚ/ŶĨůƵĞŶƚŝĂůƉŚǇƐŝĐŝĂŶůĞĂĚĞƌŝŶƚŚĞhŶŝƚĞĚ^ƚĂƚĞƐŝŶ ŐĞŶĞƐĂŶĚƉƌŽƚĞŝŶƐŝŶǀŽůǀĞĚŝŶĐĞůůĂĚŚĞƐŝŽŶĞǀĞŶƚƐƌĞƋƵŝƌĞĚĨŽƌ ĂŶĂƚŝŽŶĂůƉŽůůĐŽŶĚƵĐƚĞĚďǇModern Healthcare͘ĞƐŝĚĞƐĞĚŝƚŝŶŐ ůǇŵƉŚŽĐǇƚĞŚŽŵŝŶŐƚŽůǇŵƉŚŽŝĚŽƌŐĂŶƐŝŶǀŝǀŽ͕ĞŝƚŚĞƌĂƐĂŶŽƌŵĂů ƐĞǀĞƌĂů ƚĞǆƚďŽŽŬƐ͕ ŚĞ ŚĂƐ ƉƵďůŝƐŚĞĚ Ϯ ďĞƐƚƐĞůůĞƌ ďŽŽŬƐ ŽŶ ƚŚĞ ĨƵŶĐƚŝŽŶŽƌĂƐĞǀĞŶƚƐŝŶǀŽůǀĞĚŝŶŵĂůŝŐŶĂŶƚůĞƵŬĞŵŝĐŵĞƚĂƐƚĂƐĞƐ͘ ĨƵƚƵƌĞŽĨŵĞĚŝĐŝŶĞ͗The Creative Destruction of Medicine and The WƌŽĨĞƐƐŽƌ tĞŝƐƐŵĂŶ ŝƐ Ă ŵĞŵďĞƌ ŽĨ ƚŚĞ EĂƚŝŽŶĂů ĐĂĚĞŵǇ ŽĨ Patient Will See You Now. ^ĐŝĞŶĐĞƐ͕ ƚŚĞ /ŶƐƚŝƚƵƚĞ ŽĨ DĞĚŝĐŝŶĞ Ăƚ ƚŚĞ EĂƚŝŽŶĂů ĐĂĚĞŵǇ͕ Eric Verdin, MD ĂŶĚ ƚŚĞ ŵĞƌŝĐĂŶ ƐƐŽĐŝĂƚŝŽŶ ŽĨ ƌƚƐ ĂŶĚ ^ĐŝĞŶĐĞƐ͘ ,Ğ ŚĂƐ ƌĞĐĞŝǀĞĚŵĂŶǇĂǁĂƌĚƐ͕ŝŶĐůƵĚŝŶŐƚŚĞ<ĂŝƐĞƌǁĂƌĚĨŽƌǆĐĞůůĞŶĐĞ ƌ͘ sĞƌĚŝŶ ŝƐ ƚŚĞ WƌĞƐŝĚĞŶƚ ĂŶĚ K ŽĨ ƚŚĞ ƵĐŬ /ŶƐƚŝƚƵƚĞ ĨŽƌ ŝŶWƌĞĐůŝŶŝĐĂůdĞĂĐŚŝŶŐ͕ƚŚĞWĂƐĂƌŽǁǁĂƌĚŝŶĂŶĐĞƌZĞƐĞĂƌĐŚ͕ ZĞƐĞĂƌĐŚŽŶŐŝŶŐ͘ŶĂƚŝǀĞŽĨĞůŐŝƵŵ͕ƌ͘sĞƌĚŝŶƌĞĐĞŝǀĞĚŚŝƐ ƚŚĞ ĂůŝĨŽƌŶŝĂ ^ĐŝĞŶƚŝƐƚ ŽĨ ƚŚĞ zĞĂƌ͕ƚŚĞ Ğ sŝůůŝĞƌƐ /ŶƚĞƌŶĂƚŝŽŶĂů ŽĐƚŽƌĂƚĞ ŽĨ DĞĚŝĐŝŶĞ ;DͿ ĨƌŽŵ ƚŚĞ hŶŝǀĞƌƐŝƚǇ ŽĨ >ŝĞŐĞ ĂŶĚ ĐŚŝĞǀĞŵĞŶƚ ǁĂƌĚ ŽĨ ƚŚĞ >ĞƵŬĞŵŝĂ ^ŽĐŝĞƚǇ ŽĨ ŵĞƌŝĐĂ͕ ƚŚĞ ĂĚĚŝƚŝŽŶĂů ĐůŝŶŝĐĂů ĂŶĚ ƌĞƐĞĂƌĐŚ ƚƌĂŝŶŝŶŐ Ăƚ ,ĂƌǀĂƌĚ DĞĚŝĐĂů ZŽďĞƌƚ <ŽĐŚ ǁĂƌĚ͕ ƚŚĞ ZŽƐĞŶƐƚŝĞů ǁĂƌĚ͕ dŚĞ ŵĂǆ ĞůďƌƵĐŬ ^ĐŚŽŽů͘,ĞŚĂƐŚĞůĚĨĂĐƵůƚǇƉŽƐŝƚŝŽŶƐĂƚƚŚĞhŶŝǀĞƌƐŝƚǇŽĨƌƵƐƐĞůƐ͕ DĞĚĂů͕ĂŶĚƚŚĞ:ĞƐƐŝĞ^ƚĞǀĞŶƐŽŶ<ŽǀĂůĞŶŬŽǁĂƌĚŽĨƚŚĞEĂƚŝŽŶĂů ƚŚĞEĂƚŝŽŶĂů/ŶƐƚŝƚƵƚĞƐŽĨ,ĞĂůƚŚ;E/,Ϳ͕ƚŚĞWŝĐŽǁĞƌ/ŶƐƚŝƚƵƚĞĨŽƌ ĐĂĚĞŵǇŽĨ^ĐŝĞŶĐĞƐ͘,ĞŝƐĂůƐŽƚŚĞϮϬϬϰEĞǁzŽƌŬĐĂĚĞŵǇŽĨ DĞĚŝĐĂůZĞƐĞĂƌĐŚĂŶĚƚŚĞ'ůĂĚƐƚŽŶĞ/ŶƐƚŝƚƵƚĞƐ͘ƌ͘sĞƌĚŝŶŝƐĂůƐŽ DĞĚŝĐŝŶĞ ǁĂƌĚ ĨŽƌ ĚŝƐƚŝŶŐƵŝƐŚĞĚ ĐŽŶƚƌŝďƵƚŝŽŶƐ ƚŽ ďŝŽŵĞĚŝĐĂů ĂWƌŽĨĞƐƐŽƌŽĨDĞĚŝĐŝŶĞĂƚhŶŝǀĞƌƐŝƚǇŽĨĂůŝĨŽƌŶŝĂ͕^ĂŶ&ƌĂŶĐŝƐĐŽ͘ ƌĞƐĞĂƌĐŚ͕ĂŶĚŚĂƐƐĞǀĞƌĂůŚŽŶŽƌĂƌǇĚŽĐƚŽƌĂƚĞƐ͘ ƌ͘sĞƌĚŝŶ͛ƐůĂďŽƌĂƚŽƌǇĨŽĐƵƐĞƐŽŶƚŚĞƌŽůĞŽĨĞƉŝŐĞŶĞƚŝĐƌĞŐƵůĂƚŽƌƐ ŝŶƚŚĞĂŐŝŶŐƉƌŽĐĞƐƐ͘,ŝƐůĂďŽƌĂƚŽƌǇǁĂƐĨŝƌƐƚƚŽĐůŽŶĞĂĨĂŵŝůǇ Leonard I. Zon, MD ŽĨ ĞŶǌǇŵĞƐ͕ ĐĂůůĞĚ ,Ɛ͕ ǁŚŝĐŚ ƌĞŐƵůĂƚĞ ŚŝƐƚŽŶĞ ĂĐĞƚǇůĂƚŝŽŶ͘ ƌ͘ ŽŶ ŝƐƚŚĞ'ƌŽƵƐďĞĐŬWƌŽĨĞƐƐŽƌŽĨWĞĚŝĂƚƌŝĐDĞĚŝĐŝŶĞĂƚ ƌ͘ sĞƌĚŝŶ ƐƚƵĚŝĞƐ ŚŽǁ ŵĞƚĂďŽůŝƐŵ͕ ĚŝĞƚ ĂŶĚ ƐŵĂůů ŵŽůĞĐƵůĞƐ ,ĂƌǀĂƌĚ DĞĚŝĐĂů ^ĐŚŽŽů͕ ĂŶ /ŶǀĞƐƚŝŐĂƚŽƌ Ăƚ ,ŽǁĂƌĚ ,ƵŐŚĞƐ ƌĞŐƵůĂƚĞƚŚĞĂĐƚŝǀŝƚǇŽĨ,ƐĂŶĚ^ŝƌƚƵŝŶƐĂŶĚƚŚĞƌĞďǇƚŚĞĂŐŝŶŐ DĞĚŝĐĂů /ŶƐƚŝƚƵƚĞ͕ ĂŶĚ ƚŚĞ ŝƌĞĐƚŽƌ ŽĨ ƚŚĞ ^ƚĞŵ Ğůů WƌŽŐƌĂŵ Ăƚ ƉƌŽĐĞƐƐĂŶĚŝƚƐĂƐƐŽĐŝĂƚĞĚĚŝƐĞĂƐĞƐ͕ŝŶĐůƵĚŝŶŐůǌŚĞŝŵĞƌ͛Ɛ͘,ĞŚĂƐ ŽƐƚŽŶ ŚŝůĚƌĞŶ͛Ɛ ,ŽƐƉŝƚĂů͘ ,Ğ ŝƐ ŝŶƚĞƌŶĂƚŝŽŶĂůůǇͲƌĞĐŽŐŶŝǌĞĚ ĨŽƌ ƉƵďůŝƐŚĞĚŵŽƌĞƚŚĂŶϮϭϬƐĐŝĞŶƚŝĨŝĐƉĂƉĞƌƐĂŶĚŚŽůĚƐŵŽƌĞƚŚĂŶ ŚŝƐƉŝŽŶĞĞƌŝŶŐǁŽƌŬŝŶƐƚĞŵĐĞůůďŝŽůŽŐǇĂŶĚĐĂŶĐĞƌŐĞŶĞƚŝĐƐ͕ĂŶĚ ϭϱƉĂƚĞŶƚƐ͘,ĞŚĂƐďĞĞŶƌĞĐŽŐŶŝǌĞĚĨŽƌŚŝƐƌĞƐĞĂƌĐŚǁŝƚŚĂ'ůĞŶŶ ŚĂƐ ďĞĞŶ ƚŚĞ ƉƌĞĞŵŝŶĞŶƚ ĨŝŐƵƌĞ ŝŶ ĞƐƚĂďůŝƐŚŝŶŐ ǌĞďƌĂĨŝƐŚ ĂƐ ĂŶ ǁĂƌĚĨŽƌZĞƐĞĂƌĐŚŝŶŝŽůŽŐŝĐĂůDĞĐŚĂŶŝƐŵƐŽĨŐŝŶŐĂŶĚĂƐĞŶŝŽƌ ŝŶǀĂůƵĂďůĞŐĞŶĞƚŝĐŵŽĚĞůĨŽƌƚŚĞƐƚƵĚǇŽĨďůŽŽĚĂŶĚŚĞŵĂƚŽƉŽŝĞƚŝĐ ƐĐŚŽůĂƌƐŚŝƉĨƌŽŵƚŚĞůůŝƐŽŶDĞĚŝĐĂů&ŽƵŶĚĂƚŝŽŶ͘,ĞŝƐĂĨĞůůŽǁŽĨ ĚĞǀĞůŽƉŵĞŶƚ͘

18 2018 AAP / ASCI / APSA Joint Meeting The Harrington Prize for Innovation in Medicine

NOW ACCEPTING NOMINATIONS FOR 2019

The Harrington Prize for Innovation in Medicine, presented by the American Society for Clinical Investigation (ASCI) and the Harrington Discovery Institute at University Hospitals in Cleveland, Ohio, honors a physician-scientist who has moved the ﬁeld forward through innovation, creativity and potential to impact human health.

Applications are now being accepted for the 2019 Harrington Prize – an international award open to those holding an MD or equivalent degree. This annual prize includes:

- An unrestricted $20,000 honorarium - The Harrington Prize Lecture, delivered at the 2019 AAP/ASCI/APSA Joint Meeting - Participation at the annual Harrington Discovery Institute Symposium - A personal essay, published in the Journal of Clinicall Investigation

Nominations accepted through August 28, 2018. To learn more or to apply, visit HarringtonDiscoveryy.org/ThePrize.

ACCELERATING BREAKTHROUGH DISCOVERIES INTO MEDICINES

www.jointmeeting.org 19 2018 AAP/ASCI/APSA LEADERSHIP

AAP Council Officers ASCI Council Officers APSA Board of Directors WƌĞƐŝĚĞŶƚ WƌĞƐŝĚĞŶƚ ŚĂŝƌ Serpil Erzurum, MD Benjamin L. Ebert, MD, PhD Moshe Levi, MD Cleveland Clinic Harvard Medical School, 'ĞŽƌŐĞƚŽǁŶhŶŝǀĞƌƐŝƚǇ sŝĐĞͲWƌĞƐŝĚĞŶƚ Dana-Farber Cancer Institute /ŵŵĞĚŝĂƚĞWĂƐƚͲŚĂŝƌ John Carethers, MD WƌĞƐŝĚĞŶƚͲůĞĐƚ Jaimo Ahn, MD, PhD University of Michigan Kieren Marr, MD University of Pennsylvania ^ĞĐƌĞƚĂƌǇ Johns Hopkins School of Medicine ŝƌĞĐƚŽƌ Mitchell Lazar, MD, PhD sŝĐĞWƌĞƐŝĚĞŶƚ Lawrence ;^ŬŝƉͿ Brass, MD, PhD Perelman School of Medicine, W. Kimryn Rathmell, MD, PhD University of Pennsylvania University of Pennsylvania Vanderbilt University ŝƌĞĐƚŽƌ Treasurer ^ĞĐƌĞƚĂƌǇͲdƌĞĂƐƵƌĞƌ Dania Daye, MD, PhD Robert Brown, DPhil, MD Hossein Ardehali, MD, PhD DĂƐƐĂĐŚƵƐĞƚƚƐ'ĞŶĞƌĂů,ŽƐƉŝƚĂů University of Mass. Medical School Northwestern University Medical Center ŝƌĞĐƚŽƌ ĚŝƚŽƌ͕dŚĞ:ŽƵƌŶĂůŽĨůŝŶŝĐĂů/ŶǀĞƐƚŝŐĂƚŝŽŶ ^ŚǁĂǇƚĂ<ƵŬƌĞƟ͕D͕WŚ AAP Councilors Gordon F. Tomaselli, MD UCLA Nancy Davidson, MD Johns Hopkins University ŝƌĞĐƚŽƌ Fred Hutchinson Cancer Research Center ĚŝƚŽƌ͕://ŶƐŝŐŚƚ Jillian Liu (6th-year MD/PhD) Betty Diamond, MD Howard A. Rockman, MD Ohio State University The Feinstein Institute for Medical Research Duke University School of Medicine ŝƌĞĐƚŽƌ Maurizio Fava, MD /ŵŵĞĚŝĂƚĞWĂƐƚWƌĞƐŝĚĞŶƚ Robin Lorenz, MD, PhD DĂƐƐĂĐŚƵƐĞƚƚƐ'ĞŶĞƌĂů,ŽƐƉŝƚĂů Vivian G. Cheung, MD University of Alabama at Birmingham ,ŽǁĂƌĚ,ƵŐŚĞƐDĞĚŝĐĂů/ŶƐƚŝƚƵƚĞ͖ ŝƌĞĐƚŽƌ David Ginsburg, MD University of Michigan Medical School Life Sciences Institute, Univ. of Michigan David Markovitz, MD University of Michigan Todd Golub, MD ASCI Councilors Broad Institute of MIT and Harvard, ŝƌĞĐƚŽƌ Dana Farber Cancer Institute Clara Abraham, MD <ŽĮDĞŶƐĂŚ͕D͕WŚ Yale University School of Medicine Yale University Peter Igarashi, MD University of Minnesota Medical School Andrew P. Fontenot, MD ŝƌĞĐƚŽƌ University of Colorado Denver Evan Noch, MD, PhD John Ioannidis, MD New York Presbyterian Hospital-Cornell Stanford University Jay D. Horton, MD UT Southwestern Medical Center ŝƌĞĐƚŽƌ Daniel Kelly, MD Donna M. Martin, MD, PhD Kerry O’Banion, MD, PhD Perelman School of Medicine, University of Rochester University of Pennsylvania University of Michigan ŝƌĞĐƚŽƌ Mary Klotman, MD Ben Z. Stanger, MD, PhD University of Pennsylvania Aylin Rodan, MD, PhD Duke University School of Medicine University of Utah Warren Leonard, MD Sohail F. Tavazoie, MD, PhD National Institutes of Health Rockefeller University APSA Executive Council Elizabeth McNally, MD, PhD WƌĞƐŝĚĞŶƚ Northwestern Feinberg School of Medicine Jillian Liu (6th year MD/PhD) David Thomas, MD, MPH Ohio State University Johns Hopkins University /ŵŵĞĚŝĂƚĞWĂƐƚͲWƌĞƐŝĚĞŶƚ Alexander Adami (8th year MD/PhD) University of Connecticut

20 2018 AAP / ASCI / APSA Joint Meeting 2018 AAP/ASCI/APSA LEADERSHIP

APSA Executive Council (continued) WƌĞƐŝĚĞŶƚͲůĞĐƚ DĞŵďĞƌƐŚŝƉŚĂŝƌ dĞĐŚŶŽůŽŐǇŚĂŝƌ Audra Iness (5th year MD/PhD) Abhik Banerjee (6th year MD/PhD) Tim Kennell (4th year MD/PhD) Virginia Commonwealth University USC/Caltech University of Alabama at Birmingham School of Medicine WĂƌƚŶĞƌƐŚŝƉƐŚĂŝƌ D>DͬK sŝĐĞͲWƌĞƐŝĚĞŶƚ Daniel Barnett (7th year DO-PhD) Siyu Shi (1st year MD) Hanna Erickson (5th year MD/PhD) Michigan State University Stanford School of Medicine University of Illinois at Urbana-Champaign WŽůŝĐǇŽͲŚĂŝƌ D>KͲDͬWŚ ǀĞŶƚƐŽͲŚĂŝƌ Shinnyi “Cindy” Chou;W'zϭWƐǇĐŚŝĂƚƌǇ Teddy Mamo (7th year MD/PhD) Allyson Palmer (8th year MD/PhD) Resident) Mayo Clinic Mayo Clinic University of Pittsburgh ŽͲD>^^, ǀĞŶƚƐŽͲŚĂŝƌ WŽůŝĐǇŽͲŚĂŝƌ Tyler Zahrli (7th year MD/PhD) Jason Siu (6th year MD/PhD) Mariam Bonyadi (5th year MD/PhD) Saint Louis University Ohio State University University of Illinois at Urbana-Champaign ŽͲD>^^, &ƵŶĚƌĂŝƐŝŶŐŽͲŚĂŝƌ WƵďůŝĐZĞůĂƚŝŽŶƐŚĂŝƌ Joshua Franklin (5th year MD-PhD) Karen Doersch (8th year MD/PhD) Vadim Yerokhin (5th year DO/PhD) University of Pennsylvania Texas A&M Health Science Center Oklahoma State University Center for &ƵŶĚƌĂŝƐŝŶŐŽͲŚĂŝƌ Health Sciences Nadav Weinstock (6th-year MD/PhD) SUNY Buffalo

TRAVEL AWARD RECIPIENTS

2018 AAP/ASCI Travel Award Recipients Amanda Garfinkel Lindsay Kozek Samantha Spellicy Harvard Medical School Vanderbilt University DĞĚŝĐĂůŽůůĞŐĞŽĨ'ĞŽƌŐŝĂĂŶĚƚŚĞ Meghan Green Haney Daniel Leonard hŶŝǀĞƌƐŝƚǇŽĨ'ĞŽƌŐŝĂ University of Kentucky Cleveland Clinic Lerner College of Alexander Tereshchenko Lauren Harasymiw Medicine at Case Western Reserve University of Iowa University of Minnesota University Priya Umapathi Paishiun Hsieh Evan Lynch :ŽŚŶƐ,ŽƉŬŝŶƐDĞĚŝĐĂů/ŶƐƟƚƵƟŽŶƐ Case Western Reserve University University of Kentucky College of Natalie Vandeven Medicine Eric Irons University of Washington hŶŝǀĞƌƐŝƚǇĂƚƵīĂůŽ Beth Neilsen John Walker University of Nebraska Medical Center Anjali Jacob Vanderbilt University Boston University School of Medicine Anjan Saha Lillian Zhang University of Michigan Sunil Joshi University of California, Davis <ŶŝŐŚƚĂŶĐĞƌ/ŶƐƟƚƵƚĞ͕KƌĞŐŽŶ,ĞĂůƚŚΘ John Smestad Science University Mayo Clinic Kunio Kawanishi Jaclyn Souder University of California, San Diego University of Alabama at Birmingham

www.jointmeeting.org 21 TRAVEL AWARD RECIPIENTS

2018 APSA Travel Award Recipients Adewunmi Adelaja Nelson Gil ^ĂŵƵĞů:ĞĂŶͲĂƉƚŝƐƚĞ UCLA Albert Einstein College of Medicine University of Pennsylvania Damian Almiron Bonnin :ŽƐĞ'ƌĂũĂůĞƐͲZĞǇĞƐ Jeremie Lever 'ĞŝƐĞů^ĐŚŽŽůŽĨDĞĚŝĐŝŶĞ Washington Univ. School of Medicine University of Alabama at Birmingham Kayla Berry >ĞDŽǇŶĞ,ĂďŝŵĂŶĂͲ'ƌŝĨĨŝŶ Rachel Levy Washington Univ. School of Medicine Washington University in Saint Louis University of Florida Michelle Corkrum Jonathan Herrera Aaron Gabriel Sandoval University of Minnesota University of Michigan University of Florida Kow Essuman Gabriel Heymann Ashley Scott Washington Univ. School of Medicine University of Washington Mayo Clinic Nicholas Eustace Donovan Inniss Emile Vieta Ferrer University of Alabama at Birmingham Saint John’s University/The College of ^ĂŶ:ƵĂŶĂƵƟƐƚĂ^ĐŚŽŽůŽĨDĞĚŝĐŝŶĞ Guillermo Flores St. Benedict Michigan St. College of Human Medicine/ Bianca Islam sĂŶŶĚĞů/ŶƐƟƚƵƚĞ'ƌĂĚƵĂƚĞ^ĐŚŽŽů Augusta University

2018 American Association of Immunologists Travel Award Recipients Joshua Alinger John Klement Alfonso Tan Garcia Washington University in St. Louis Augusta University Duke-NUS Medical School Aaron Fan Megan Maurano Augusta University University of Washington

2018 American Society of Nephrology (ASN) Travel Award Recipients Emily Groopman Aaron Lim Hannah Turbeville Columbia University Vanderbilt University School of Medicine University of Mississippi Medical Center

2018 Society for Academic Emergency Medicine Travel Award Recipients Anshul Dhingra Monica Lieng DĞĂŐŚĂŶZŽǇͲK͛ZĞŝůůǇ Case Western Reserve University University of California, Davis University of Texas Health Sciences Uriel Kim Mohamad Fadhli Masri Center at Houston Case Western Reserve University Duke-NUS Medical School

2018 APSA Undergraduate Travel Award Recipients Melanie Barbini Yifan Mao Sinibaldo Romero Arocha Northeastern University The University of Chicago DĂǇŽůŝŶŝĐ'ƌĂĚƵĂƚĞ^ĐŚŽŽůŽĨ Jordy Botello Kimberly Meza Biomedical Sciences University of Florida Barnard College/Columbia University Caroline Haoud Rochelle Hall Nadine Ramirez Columbia University Brooklyn College-CUNY University of Denver Andy Tang Carlos Jeronimo Valeria Rodriguez Alfaro North Seattle College CUNY Lehman College New York University Jennifer Jung Princeton University

22 2018 AAP / ASCI / APSA Joint Meeting Call for Nomination for the George M. Kober Medal

This is a Call for Nomination for the George M. Kober Medal Recipient for 2020.

He was active in the early days as a leader of several national organizations including the Association of American Physicians – an early organization founded in the 1885 by seven Physicians (including William Osler) an organization which promotes:

“the pursuit of medical knowledge, and the advancement through experimentation and discovery of basic and clinical science and their application to clinical medicine…”

Please provide a brief cover letter highlighting the major accomplishments of the nominee along with an updated CV and submit by December 1, 2018 to Lori Ennis at [email protected]

George M. Kober Medal The Association of American Physicians honors Kober and continues to honor him by giving their highest award to an honoree every year. This award is given to an AAP member whose lifetime efforts have had an enormous impact on the field of Internal Medicine (or the specific member’s discipline) through the scientific discipline they have brought to the field and the many outstanding scientists that they have trained.

To view a list of past recipients go to: http://aap-online.org/kober

www.jointmeeting.org 23 ORAL PRESENTATIONS & POSTER ABSTRACTS

www.jointmeeting.org

24 2018 AAP / ASCI / APSA Joint Meeting ORAL PRESENTATIONS

APSA Trainee Oral Presentations

1 Using CLCA1 vWA Domain to Activate Alternate Anion 2 Characterization and metabolic synthetic lethal testing Currents in Cystic Fibrosis Airway in a new model of SDH-loss familial pheochromocytoma and Kayla Berry paraganglioma Washington University School of Medicine, St. Louis, USA John A. Smestad In the airway, proper activity of the anion channel CFTR contributes Mayo Clinic, Rochester, USA to innate immune defense by maintaining a hydrated and alkaline 6XFFLQDWH GHK\GURJHQDVH 6'+ ORVV SKHRFKURPRF\WRPD DQG mucus layer. This allows potentially pathogenic microorganisms to SDUDJDQJOLRPD 33*/ DUHWXPRUVGULYHQE\WULFDUER[F\OLFDFLG be trapped, quickly killed, and cleared via mucociliary clearance, 7&$ F\FOH PHWDEROLF GHUDQJHPHQW %LDOOHOLF ORVV RI IXQFWLRQ LQ WKXVSUHYHQWLQJPLFURELDOFRORQL]DWLRQRIWKHOXQJV,QF\VWLF¿EURVLV 6'+VXEXQLWVOHDGVWRDFFXPXODWLRQRILQWUDFHOOXODUVXFFLQDWHZKLFK (CF), this activity is impaired, resulting in repeated pulmonary competitively inhibits dioxygenase enzymes, causing activation infections that damage the lung and, if severe and prolonged of pseudohypoxic signaling and hypermethylation of histones enough, lead to early death without lung transplantation. Available DQG'1$7KHPHFKDQLVPVE\ZKLFKWKHVHDOWHUDWLRQVOHDGWR therapies remain focused on targeted rescue of the CFTR mutation. WXPRULJHQHVLVDUHXQFOHDUKRZHYHU,QDQHႇRUWWRIXQGDPHQWDOO\ However, given the thousands of mutations found in this patient XQGHUVWDQGKRZ6'+ORVVUHSURJUDPVFHOOELRORJ\ZHGHYHORSHGDQ SRSXODWLRQ LQGLYLGXDOL]HG UHVFXH RI HDFK ZRXOG EH GLႈFXOW $Q LPPRUWDOL]HGPRXVHHPEU\RQLF¿EUREODVWFHOOOLQHZLWKFRQGLWLRQDO alternative and potentially universal strategy may involve activation genetic disruption of SdhcIRUXVHLQV\VWHPDWLFPXOWLRPLF RIDGLႇHUHQWFKORULGHFKDQQHOLQOXQJHSLWKHOLXPWRE\SDVV&)75 VWXGLHV WR H[DPLQH KRZ WKLV VSHFL¿F SHUWXUEDWLRQ DႇHFWV ELRORJ\ dysfunction. Toward that end, we recently demonstrated that DWPXOWLSOHOHYHOV:H¿UVWYDOLGDWHWKHGHULYHGPRGHOE\WUDFNLQJ the vWA domain of CLCA1 (calcium activated chloride channel the kinetics of SdhcJHQHUHDUUDQJHPHQW6'+&SURWHLQORVVDQG regulator 1) directly engages the calcium activated chloride channel subsequent intracellular succinate accumulation. We then perform TMEM16A and stabilizes its surface expression on the order of global transcriptomic, epigenomic, and proteomic characterization minutes, thereby increasing anion currents through the channel. RIFKDQJHVUHVXOWLQJIURP6'+&ORVVLGHQWLI\LQJVSHFL¿F )XUWKHUVXSSRUWLQJDWUDႈFNLQJPHFKDQLVPZH¿QGWKDW&/&$ perturbations at multiple biological levels. In the transcriptome, rescues TMEM16A from a late endosomal fate. We are currently we observe strong activation of antiviral response genes, along pursuing a structural model of this interaction, which would be with increased expression of extracellular matrix genes that has used to inform future design of therapies based on the CLCA1/ EHHQUHSRUWHGSUHYLRXVO\IRURWKHU6'+ORVVV\VWHPV([DPLQDWLRQ 70(0$LQWHUDFWLRQ:HKDYHPDGHVLJQL¿FDQWSURJUHVVE\ RI'1$PHWK\ODWLRQSDWWHUQVYLDUHYHUVHGUHSUHVHQWDWLRQELVXO¿WH determining the structure of the CLCA1 vWA domain to 2.05 Å, the sequencing reveals that observed transcriptomic perturbations ¿UVWVWUXFWXUHRIDQ\SDUWRI&/&$6LQFH&/&$GLUHFWO\HQJDJHV are weakly correlated with altered patterns of gene promoter TMEM16A, we hypothesized that this molecular recognition PHWK\ODWLRQ DOWKRXJK WKH WRS JHQH RQWRORJLHV DႇHFWHG E\ FRXOG EH XWLOL]HG WR VSHFL¿FDOO\ DFWLYDWH DQLRQ FXUUHQWV LQ DLUZD\ WUDQVFULSWLRQDO SHUWXUEDWLRQV ZHUH QRW UHÀHFWHG LQ JHQH RQWRORJ\ epithelia through TMEM16A to compensate for dysfunctional CFTR DQDO\VLVRISURPRWHUGLႇHUHQWLDOPHWK\ODWLRQ$WWKH&S*VLWHOHYHO channels. In whole cell patch clamp experiments, we demonstrate two distinctive patterns of methylation change were observed: that CLCA1, and in particular its vWA domain, is able to activate hypermethylation of loci with initially low methylation values, and TMEM16A currents in primary CF airway epithelial cells from three hypomethylation of loci with initially high methylation values. This GLVWLQFW &) JHQRW\SHV ǻ)*!$ ǻ)ǻ) DQG REVHUYDWLRQ FKDOOHQJHV WKH VLPSOH PRGHO RI VXFFLQDWHPHGLDWHG ǻ)LQV$ :HIXUWKHUPRUHVKRZWKDWSXUL¿HGY:$GRPDLQ LQKLELWLRQRI7(7'1$GHPHWK\ODVHVUHVXOWLQJLQJOREDO'1$ is able to sustain currents through TMEM16A in polarized CF K\SHUPHWK\ODWLRQ *OREDO SURWHRPLF DQDO\VLV UHYHDOV JHQHUDO DLUZD\HSLWKHOLDRIDQRWKHUJHQRW\SH ǻ)*!7 LQ8VVLQJ GRZQUHJXODWLRQRIFRPSRQHQWVRIWKHF\WRVROLFULERVRPHDQG chamber studies. Together, these studies highlight the exciting YDULDEOHXSDQGGRZQUHJXODWLRQRIVSHFL¿FPLWRFKRQGULDO potential for universal CF treatment modeled after the CLCA1 vWA SURWHLQV ,Q SDUWLFXODU REVHUYHG FKDQJHV LQFOXGH XSUHJXODWLRQ domain/TMEM16A interaction, and future work will examine the of mitochondrial solute transport, antioxidant defense, fatty acid ability of the interaction to restore healthy mucous properties. FDWDEROLVP DQG IHUPHQWDWLRQ SDWKZD\V DQG GRZQUHJXODWLRQ RI FRPSOH[,)LQDOO\ZHSHUIRUPDQDO\VLVRI6'+&V\QWKHWLFOHWKDOLW\ ZLWKODFWDWHGHK\GURJHQDVH$ /'+$ DQGS\UXYDWHFDUER[\ODVH 3&; ZKLFKDUHEHOLHYHGWREHLPSRUWDQWIRUUHJHQHUDWLRQRI1$' DQGDVSDUWDWHELRV\QWKHVLVUHVSHFWLYHO\2XUGDWDVKRZWKDW6'+ ORVVFHOOVDUHVHOHFWLYHO\YXOQHUDEOHWR/'+JHQHWLFNQRFNGRZQ RUFKHPLFDOLQKLELWLRQVXJJHVWLQJWKDW/'+LQKLELWLRQPD\EHDQ HႇHFWLYHWKHUDSHXWLFVWUDWHJ\IRU6'+ORVV33*/

www.jointmeeting.org 25 POSTER ABSTRACTS

1 Characterization of external globus pallidus neurons from RI ,ț%V ZKLFK DOVR SURYLGH QHJDWLYH IHHGEDFN 6HYHUDO VWXGLHV RI the Dbx1 lineage H[DPLQHG1)ț%VLJQDOLQJE\H[RJHQRXVH[SUHVVLRQRIDÀXRUHVFHQW Zachary A. Abecassis 1)ț%IXVLRQSURWHLQUHSRUWHULQFHOOOLQHVEXWKRZ1)ț%VLJQDOLQJ Northwestern University, USA is controlled in primary macrophages and how polarizing cytokines PD\DႇHFW1)ț%FRQWUROUHPDLQVXQNQRZQ 3DUNLQVRQ¶VGLVHDVH 3' LVDSUHYDOHQWQHXURGHJHQHUDWLYHGLVHDVH WKDWDႇHFWVWKHFHQWUDOQHUYRXVV\VWHP(DUO\VWDJHVRIWKHGLVHDVH 8VLQJ ERQHPDUURZGHULYHG PDFURSKDJH %0'0V GHULYHG IURP include symptoms of resting tremor, muscle rigidity, bradykinesia, 5HO$9HQXVNQRFNLQPLFHVLQJOHFHOODQDO\VLVRI1)ț%VLJQDOLQJLQ and gait instability that often lead to other complications, such as macrophages revealed oscillatory dynamics in response to cytokine GHPHQWLD RU GHSUHVVLRQ '\VIXQFWLRQ ZLWKLQ WKH EDVDO JDQJOLD VWLPXOLVXFKDV71)DQGODUJHO\QRQRVFLOODWRU\G\QDPLFVUHVSRQVH SDUWLFXODUO\WKHH[WHUQDOJOREXVSDOOLGXV *3H KDVEHHQLPSOLFDWHG WR0\GPHGLDWHGSDWKRJHQOLJDQGV7KLVIXQGDPHQWDOGLVWLQFWLRQ LQWKHPRWRUPDQLIHVWDWLRQVRIWKHGLVHDVH7KH*3HPRVWQRWDEO\ between friend vs foe signaling contributed to a large mutual projects to other areas within the basal ganglia circuit, primarily the information score of more than 2.1 bits. GRUVDOVWULDWXPDQGVXEWKDODPLFQXFOHXV 671 ,WVFRPPXQLFDWLRQ ,QWHUHVWLQJO\ ,)1ȖSRODUL]HG PDFURSKDJHV PRGHOLQJ WKRVH IRXQG with other areas of the brain, such as the cortex and thalamus, LQ LQÀDPPDWRU\ OHVLRQV VKRZHG D GUDPDWLFDOO\ UHGXFHG FDSDFLW\ UHPDLQV ODUJHO\ XQNQRZQ :H UHFHQWO\ LGHQWL¿HG D VXEW\SH RI WRGLVWLQJXLVK71)IURP3$03OLJDQGVLQWHUPVRI1)ț%G\QDPLFV *3H QHXURQV WKDW RULJLQDWH IURP SURJHQLWRU FHOOV H[SUHVVLQJ WKH )UHTXHQF\GRPDLQ DQDO\VLV UHYHDOHG WKDW ,)1Ȗ HQKDQFHV QRQ SURWHLQFRGLQJJHQHGHYHORSLQJEUDLQKRPHRER[ 'E[ GXULQJ RVFLOODWRU\1)ț%G\QDPLFVWKXVGLPLQLVKLQJWKHPXWXDOLQIRUPDWLRQ HPEU\RORJLFGHYHORSPHQW&RQWUDU\WRWKHPDMRULW\RIWKH*3HWKDW JHQHUDWHGE\71)RU3$03VWLPXODWLRQ originates from the medial and lateral ganglionic eminences, these We are currently examining the molecular mechanism by which neurons originate from the preoptic area. The objective of this ,)1ȖDOWHUVWKH1)ț%,ț%VLJQDOLQJPRGXOHWRGLPLQLVKLWVDELOLW\WR VWXG\ ZDV WR FRPSUHKHQVLYHO\ SUR¿OH WKHVH QHXURQV WR GHWHUPLQH GLVWLQJXLVKIULHQGYVIRHOLNHOLJDQGV whether they possess any unique qualities as compared to the NQRZQVXEW\SHVRI*3HQHXURQVLHSDUYDOEXPLQ 39 DQG1SDV 3 Dietary protein load, stone type and stone procedures WUDQVFULSWLRQ IDFWRUH[SUHVVLQJ QHXURQV %\ FURVVLQJ D 'E[&UH predict albuminuria in kidney stone formers WUDQVJHQLF PRXVH ZLWK D ÀR[HGVWRS WG7RPDWR $L PRXVH ZH Omar Al Dhaybi KDYHEHHQDEOHWRLGHQWLI\QHXURQVRULJLQDWLQJIURPWKH'E[OLQHDJH University of Chicago, Chicago, USA 'E[ ZLWK WG7RPDWR ÀXRUHVFHQFH ,PPXQRKLVWRFKHPLVWU\ ZDV There is evidence that kidney stones may cause chronic kidney SHUIRUPHGIRUNQRZQ*3HSURWHLQVDQGLQWULQVLFFHOOSURSHUWLHVZHUH GLVHDVH &.' DQGNLGQH\VWRQHSDWLHQWVGHYHORSHQGVWDJHUHQDO FDSWXUHGXVLQJFHOODWWDFKHGDQGZKROHFHOOSDWFKFODPSUHFRUGLQJV failure at rates higher than the general population. However, we )LQDOO\UHWURJUDGH WUDFHUV ÀXRURJROG DQG FKROHUD WR[LQ VXEXQLW % do not yet know what aspects of stone disease give rise to the were injected into various brain regions, including the subthalamic well known association between having stones and losing kidney nucleus, cortex, and parafascicular nucleus of the thalamus IXQFWLRQ 8ULQH DOEXPLQ LV DQ DFFHSWHG ELRPDUNHU IRU SURJUHVVLYH 3) LQ RUGHU WR HYDOXDWH SRWHQWLDO SURMHFWLRQ VLWHV RI 'E[ *3H &.'WKDWPD\EHFRPHHYLGHQWSULRUWRORVVRIJORPHUXODU¿OWUDWLRQ QHXURQV,PPXQRKLVWRFKHPLVWU\UHYHDOHGWKDW'E[*3HQHXURQV UDWH *)5 DQGPLJKWLGHQWLI\SDWLHQWVZKRDUHDWULVNIRUSURJUHVVLRQ FRQVWLWXWHSHUFHQWRI*3HQHXURQV7KHVHQHXURQVZHUHKHDYLO\ 39 a ZLWK VRPH H[SUHVVLQJ 1SDV a &RQWUDU\ WR :HPHDVXUHGXULQHDOEXPLQLQSDWLHQWVHYDOXDWHGE\WKH.LGQH\ WZRWKLUGV RI 1SDV QHXURQV WKH 1SDV 'E[ QHXURQV GLG QRW 6WRQH3UHYHQWLRQ3URJUDPDWWKH8QLYHUVLW\RI&KLFDJRVLQFH H[SUHVV )R[S D VXEVHW RI 1SDV QHXURQV NQRZQ WR SURMHFW (DFK SDWLHQW FROOHFWV WKUHH KRXU XULQHV ZLWK D PDWFKLQJ EORRG exclusively to the striatum. Electrophysiological analysis revealed RႇPHGLFDWLRQVWKDWDႇHFWPLQHUDOPHWDEROLVPZKLFKDUHDQDO\]HG WKDW 'E[ *3H QHXURQV DSSHDU WR PDWFK WKH UHVXOWV VHHQ LQ WKH IRUVWRQHULVNIDFWRUVSULRUWRWKH¿UVWFOLQLFYLVLW2QO\XULQHVWHVWLQJ LPPXQRKLVWRFKHPLVWU\ UHSUHVHQWLQJ D VXEVHW RI ERWK 39 DQG negative for blood with a standard dipstick were used in this analysis. 1SDVQHXURQV5HWURJUDGHWUDFLQJUHYHDOHGSURMHFWLRQVWRERWKWKH All patients gave consent for use of their data, and the protocol was 671 DQG 3) (OHFWURSK\VLRORJ\ DQG LPPXQRKLVWRFKHPLVWU\ UHYHDO DSSURYHGE\WKH,QVWLWXWLRQDO5HYLHZ%RDUG'DWDDQDO\]HGLQFOXGHG WKDW*3HQHXURQVRI'E[OLQHDJHDSSHDUWREHUHSUHVHQWDWLYHRIWKH laboratory and demographic data, stone analyses, history of stone JUHDWHUQHXURQDOSRSXODWLRQRIWKH*3H+RZHYHUWKHSURMHFWLRQWR events and procedures, past medical history, and number of stones the PF represents a novel projection site of these neurons, not seen on radiographs. Our aim in this study was to determine whether E\DQ\RWKHUELRPDUNHUVZLWKLQWKH*3H7KHUHIRUHWKHXQLTXHRULJLQ VSHFL¿F VWRQH W\SHV RU DVVRFLDWHG FRQGLWLRQV QXPEHU RI VWRQH of these neurons presents an opportunity to leverage this transgenic episodes, or procedures for stone removal were associated with mouse to further explore this anatomical projection. SDWKRORJLFDOEXPLQXULD:HDOVRH[SORUHGWKHHႇHFWRIWKHH[FUHWLRQ rate of various urine analytes on albuminuria in separate analyses. 6LQJOHFHOO DQDO\VLV RI 1)ț% VLJQDOLQJ LQ SULPDU\ 2 ,QRXUVDPSOHRINLGQH\VWRQHIRUPHUVF\VWLQXULD OHDVWVTXDUHV macrophages PHDQ DOEXPLQXULD GLႇHUHQFH RI PJJ S DQG XULQDU\ Adewunmi O. Adelaja sulfate were strongly correlated with pathologic albuminuria. Calcium UCLA, Los Angeles, USA phosphate and uric acid stones were not associated with worsening Macrophages are the primary initiators and coordinators of immune DOEXPLQXULD$OEXPLQXULDZDVQRWDႇHFWHGE\WKHQXPEHURIVWRQH responses. They exhibit highly heterogenous phenotypes to regulate episodes, or none of the procedures performed, except percutaneous innate defense, initiation and coordination of adaptive immunity QHSKUROLWKRWRPLHV OHDVWVTXDUHVPHDQDOEXPLQXULDLQFUHDVHE\ and tissue repair. These phenotypes are a function of the tissue PJJLQSDWLHQWVZKRXQGHUZHQWWKUHHRUPRUHSURFHGXUHVS PLFURHQYLURQPHQWGHWHUPLQHGE\F\WRNLQHV,QÀDPPDWRU\UHVSRQVHV $OEXPLQXULD ZDV JUHDWO\ DPSOL¿HG LQ &.' ,99 SDWLHQWV ZLWK KLJK in macrophages are dependent on the activity of the transcription SURWHLQLQWDNH OHDVWVTXDUHVPHDQDOEXPLQXULDLQFUHDVHE\! IDFWRU 1)ț% ZKLFK LV UHJXODWHG E\ VWLPXOXVLQGXFHG GHJUDGDWLRQ IRULQWHUDFWLRQRI&.',99±SURWHLQFDWDEROLFUDWHS 7KLV

26 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

HႇHFW ZDV QRW VHHQ LQ SDWLHQWV ZLWK &.' ,,, ,Q D PDWFKHG &.' SUHVHQWLQJ ZLWK +69 VXVFHSWLELOLW\ DQG DXWRLPPXQLW\ .LQGUHG FRKRUWWKHVORSHRIVXOIDWH¶VHႇHFWRQDOEXPLQXULDZDVHYHQVWHHSHU % FRQVLVWHG RI RQH SDWLHQW ZLWK VHYHUH &09 P\RFDUGLWLV DQG Our study suggests that cystine stone formers have increased DGHQRYLUDO KHSDWLWLV %RWK NLQGUHGV ZHUH HYDOXDWHG IRU 1. FHOO urine albumin excretion compared to other stone formers. Higher function and showed reductions in target killing in spite of normal GLHWDU\SURWHLQORDGVDUHDOVRVLJQL¿FDQWO\UHODWHGWRKLJKHUULVNRI cytotoxic granule degranulation against the same target. Microscopy DOEXPLQXULDSURJUHVVLRQLQNLGQH\VWRQHIRUPHUVZLWKDGYDQFHG&.' analysis suggested that granule mobility was reduced in at least RQHNLQGUHG&\72)UHYHDOHGUHGXFWLRQVLQ3/&*SKRVSKRU\ODWLRQ 4 Sulfasalazine as a treatment for acquired epilepsy DIWHU UHFHSWRU FURVVOLQNLQJ LQ WKH 1. FHOOV RI ERWK NLQGUHGV Oscar B. Alcoreza Kindred A also presented with a reduction in naïve B cells without Virginia Tech Carilion School of Medicine and Research perturbations in immunoglobulin output, B cell memory formation Institute, USA or class switching. Trio whole exome sequencing was performed and revealed rare heterozygous PLCG2 mutations in both kindreds. (SLOHSV\DႇHFWVDSSUR[LPDWHO\PLOOLRQ$PHULFDQVZLWK )XQFWLRQDODQDO\VLVDVZHOODVPRXVHDQG&5,635PRGHOVVXSSRUW QHZ FDVHV EHLQJ GLDJQRVHG HDFK \HDU 'HVSLWH VRPH VXFFHVV DIXQFWLRQDOKDSORLQVXႈFLHQF\DVDFDXVHIRU1.'LQWKHVHSDWLHQWV PDQDJLQJ HSLOHSV\ FXUUHQW WKHUDSHXWLFV RႇHU QR EHQH¿W WR LQ +HWHUR]\JRXVORVVRIIXQFWLRQSRLQWPXWDWLRQVLQPLCG2 have not patients. Previous studies from our lab revealed that primary brain EHHQ SUHYLRXVO\ LQYHVWLJDWHG DV D FDXVH RI 1. FHOO GH¿FLHQF\ RU tumors release glutamate and induce electroencephalographic recurrent Herpesvirus infection. Thus, these patients represent a ((* FRQ¿UPHG EHKDYLRUDO VHL]XUHV LQ DGXOW PLFH LPSODQWHG ZLWK QRYHO LPPXQRGH¿FLHQF\ LQYROYLQJ PLCG2 KDSORLQVXႈFLHQF\ 1. KXPDQGHULYHG JOLRPD FHOOV 7KHVH VWXGLHV LGHQWL¿HG LQFUHDVHG cell dysfunction, and Herpesvirus susceptibility. H[SUHVVLRQRIV\VWHP[F 6;& DF\VWHLQHJOXWDPDWHH[FKDQJHURQ glioma cells as a major contributor to elevated glutamate levels in 6 Characterization of the heterogeneity in 5-aminolevulinic WXPRULPSODQWHGPLFH,QKLELWLRQRI6;&YLDVXOIDVDOD]LQH 6$6 DQ DFLGLQGXFHGÀXRUHVFHQFHLQ*%0 )'$DSSURYHGDQWLLQÀDPPDWRU\GUXJGHFUHDVHGJOXWDPDWHUHOHDVH Damian A. Almiron Bonnin DQG((*FRQ¿UPHGEHKDYLRUDOVHL]XUHV Geisel School of Medicine, Lebanon, USA 6;&LVQRUPDOO\H[SUHVVHGRQJOLDOFHOOVDQGJOLRVLVLVDSURPLQHQW $PLQROHYXOLQLFDFLG $/$ LQGXFHGÀXRUHVFHQFHLVDQLQQRYDWLYH feature of many forms of epilepsy. Additionally, recent studies DQGHႇHFWLYHVXUJLFDODSSURDFKIRUWKHLQWUDRSHUDWLYHLGHQWL¿FDWLRQRI revealed that astroglial dysfunction, leading to pathological changes WXPRUWLVVXHIRUUHVHFWLRQ)OXRUHVFHQFHJXLGHGQHXURVXUJHU\XVLQJ in the extracellular environment and neuronal metabolism, may $/$ KDV UHFHQWO\ EHHQ VKRZQ WR LPSURYH JOLREODVWRPD *%0 play a critical role in the initiation of seizures and development UHVHFWLRQDQGFRQVHTXHQWO\SURORQJVXUYLYDOLQ*%0ZKLFKLVWKH of epilepsy. We therefore hypothesize that gliosis may cause an most common and most aggressive primary brain tumor of adults. LQFUHDVHLQ6;&H[SUHVVLRQOHDGLQJWRHQKDQFHGJOXWDPDWHUHOHDVH 7KH HႇHFWLYHQHVV RI WKLV DSSURDFK LQ *%0 KRZHYHU KDV EHHQ LQDFTXLUHGHSLOHSVLHVDQGWKDWWUHDWPHQWZLWK6$6FDQGHFUHDVH FRPSURPLVHGE\WKHKHWHURJHQHLW\RI$/$LQGXFHGÀXRUHVFHQFH seizure occurrence in mouse models of epilepsy. To test this, we REVHUYHG GXULQJ VXUJHU\ :KLOH VRPH UHJLRQV ZLWKLQ *%0 UHDGLO\ XVHGWKHNDLQLFDFLG .$ LQGXFHGPRGHORIDFTXLUHGHSLOHSV\ZKLFK ÀXRUHVFH DIWHU $/$ DGPLQLVWUDWLRQ RWKHU UHJLRQV RI WKH WXPRU present with gliosis, to characterize changes in the expression ZKLFK DUH KLVWRORJLFDOO\ LQGLVWLQJXLVKDEOH IURP WKH ÀXRUHVFHQW RI6;&2XUSUHOLPLQDU\GDWDUHYHDOWKDWDQLPDOVWUHDWHGZLWK.$ tissues, do not. VKRZHGLQFUHDVHSURWHLQH[SUHVVLRQRI6;&LQWKHKLSSRFDPSXVDQG WKDWWUHDWPHQWZLWK6$6GHFUHDVHVWKHH[SUHVVLRQRI6;&8VLQJ 7RXQGHUVWDQG WKLV KHWHURJHQHLW\ LQ $/$LQGXFHG ÀXRUHVFHQFH, WKHEHWDLQWHJULQNQRFNRXWPRXVHPRGHOZKLFKLVFKDUDFWHUL]HG ZHFROOHFWHGERWKÀXRUHVFHQWDQGQRQÀXRUHVFHQW*%0VSHFLPHQV by widespread chronic astrogliosis and spontaneous seizures, our from a total of fourteen surgical patients and examined their gene SUHOLPLQDU\ UHVXOWV VXJJHVW WKDW WUHDWPHQW ZLWK 6$6 GHFUHDVHV H[SUHVVLRQ SUR¿OHV :H H[DPLQHG DSSUR[LPDWHO\ ¿IW\ WKRXVDQG ((*FRQ¿UPHGEHKDYLRUDOVHL]XUHV GLႇHUHQW JHQHV LQ HDFK VSHFLPHQ DQG IRXQG WKDW ÀXRUHVFHQW DQG QRQÀXRUHVFHQW *%0 WLVVXHV ZHUH FKDUDFWHUL]HG E\ GLVWLQFW JHQH 7KHVHUHVXOWVVXJJHVWWKDW6;&PD\SOD\DUROHLQWKHSDWKRJHQHVLV H[SUHVVLRQVLJQDWXUHV:KLOHQRQÀXRUHVFHQWWXPRUWLVVXHWHQGHG RIDFTXLUHGHSLOHSVLHVDQGWKDWIXUWKHUVWXGLHVRQ6;&DQGWKHHႇHFWV WRUHVHPEOHWKHQHXUDOVXEW\SHRI*%0ÀXRUHVFHQWWXPRUWLVVXHGLG RI 6$6 LV ZDUUDQWHG DV D SRWHQWLDO QRYHO WKHUDSHXWLF PRGDOLW\$V not exhibit a prominent pattern corresponding to known subtypes of most treatments for epilepsy involves modifying neuronal excitatory *%0&RQVLVWHQWZLWKWKLVREVHUYDWLRQQHXUDO*%0VDPSOHVIURP RULQKLELWRU\PHFKDQLVPV6;&SURYLGHVDQXQH[SORUHGJOLDOWDUJHW WKH&DQFHU*HQRPH$WODVGDWDEDVHH[KLELWHGDVLJQL¿FDQWO\ORZHU for decreasing glutamate release in acquired epilepsies. ÀXRUHVFHQFHVFRUHWKDQQRQQHXUDO*%0VDPSOHVDVGHWHUPLQHG 5 +XPDQ 3/&* +DSORLQVXI¿FLHQF\ 5HVXOWV LQ 1. &HOO E\ RXU ÀXRUHVFHQFH VLJQDWXUH :H DOVR GLVFRYHUHG WKDW QRQ ,PPXQRGH¿FLHQF\DQG+HUSHVYLUXV6XVFHSWLELOLW\ ÀXRUHVFHQW *%0 WLVVXH H[SUHVVHG D SDWWHUQ RI JHQHV VXJJHVWLYH RI KLJK SKRVSKRP\RLQRVLWRO SDWKZD\ DFWLYLW\ ,Q RXU SUHOLPLQDU\ Joshua Alinger VWXGLHVWUHDWLQJ*%0GHULYHGFHOOOLQHVZLWKYDOSURLFDFLGDZHOO Washington University in St. Louis, St. Louis, USA NQRZQ LQKLELWRU RI P\RLQRVLWRO V\QWKHVLV VLJQL¿FDQWO\ LQFUHDVHG 1DWXUDO .LOOHU 1. FHOOV DUH LQQDWH F\WRWR[LF O\PSKRF\WHV FULWLFDO $/$LQGXFHGWXPRUFHOOÀXRUHVFHQFH7KHVH¿QGLQJVFKDUDFWHUL]H IRUWKHFRQWURORI'1$YLUXVHV1.FHOOGH¿FLHQF\ 1.' LVDSRRUO\ WKHPROHFXODUGLႇHUHQFHVEHWZHHQÀXRUHVFHQWDQGQRQÀXRUHVFHQW understood disorder that results in severe or recurrent infections *%0WLVVXHVGXULQJÀXRUHVFHQFHJXLGHGVXUJHU\ZLWK$/$DQG ZLWK +HUSHVYLUXVHV VXFK DV +HUSHV 6LPSOH[ 9LUXV +69 DQG WKH\SURYLGHDUDWLRQDOHIRUWKHHYDOXDWLRQRIP\RLQRVLWROV\QWKHVLV &\WRPHJDORYLUXV &09 +RZHYHU WKH JHQHWLF FDXVHV RI GLVHDVH LQKLELWRUVVXFKDVYDOSURLFDFLGLQÀXRUHVFHQFHJXLGHGVXUJHU\ZLWK DUH XQNQRZQ LQ PRVW 1.' SDWLHQWV +HUHLQ ZH LQYHVWLJDWH WKUHH $/$ patients from two kindreds presenting with severe or recurrent +HUSHVYLUXV LQIHFWLRQV DQG 1.' XVLQJ PDVV F\WRPHWU\ &\72) and whole exome sequencing. Kindred A consisted of two patients

www.jointmeeting.org 27 POSTER ABSTRACTS

7 $OFRKRO8VH'LVRUGHU6\PSWRPDWRORJ\LV5HODWHGWR'LVUXSWHG H[SUHVVLRQ DQG QRUPDO FRFR H[SUHVVLRQ &RQYHUVHO\ ULJKWVLGHG 5HZDUG1HXURFLUFXLWU\5HVSRQVLYHQHVVLQ$GROHVFHQWV injected embryos had no LR patterning defects. Together, our data Joseph Aloi suggests MYRF plays a role in LR patterning, possibly by acting University of Nebraska Medical Center, Boys Town, USA as a midline protein regulating transcription of nodal gene xnr1, as nodal signaling occurs between coco and pitx2 expression in the LR ,QRIDGXOWVLQWKH86ZHUHGLDJQRVHGZLWKDVXEVWDQFH SDWWHUQLQJFDVFDGH:HFRQFOXGHWKDWSDWLHQWGULYHQJHQHGLVFRYHU\ XVH GLVRUGHU LQFOXGLQJ DOFRKRO XVH GLVRUGHU $8' DQGRU from patients with congenital heart disease can provide new insights FDQQDELVXVHGLVRUGHU &8' $OFRKRODQGRUFDQQDELVXVHGXULQJ into the molecular mechanisms that drive cardiac patterning and LR DGROHVFHQFH LV DVVRFLDWHG ZLWK LQFUHDVHG ULVN RI GHYHORSLQJ$8' axis formation. 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These data WR FKURQLF $&' LQLWLDWLQJ WXPRUSURPRWLQJ W\SH LQÀDPPDWLRQ VXJJHVW WKDW LPSDLUHG IXQFWLRQLQJ RI UHZDUG SURFHVVLQJ QHXUR LQ FKURQLF $&' 0LFH ODFNLQJ ,/ RU ,/ UHFHSWRU 67 ZHUH FLUFXLWU\LQDGROHVFHQWVLVUHODWHGWR$8'V\PSWRPDWRORJ\EXWQRW SURWHFWHG IURP $&'LQGXFHG VNLQ FDQFHU FRPSDUHG ZLWK ZLOGW\SH &8'V\PSWRPDWRORJ\)XWXUHZRUNVKRXOGH[DPLQHZKHWKHUWKHVH FRQWUROVDQG,/ZDVUHTXLUHGIRUWKHSURJUHVVLRQRILQÀDPPDWRU\ DOWHUHGQHXUDOUHVSRQVHVDUHULVNIDFWRUVIRURURXWFRPHVRI$8' ERZHO GLVHDVHLQGXFHG FRORUHFWDO FDQFHU 1RWDEO\ ,/¶V GLUHFW LQDGROHVFHQWV$GGLWLRQDOO\VLQFH$8'DQGRU&8'LQDGROHVFHQWV HႇHFW RQ 7 UHJXODWRU\ FHOOV ZDV UHTXLUHG IRU WKH GHYHORSPHQW RID DUHRIWHQFRPRUELGZLWK$WWHQWLRQ'H¿FLW+\SHUDFWLYLW\'LVRUGHUDQG FDQFHUSURPRWLQJ LPPXQH HQYLURQPHQW LQ WKH VNLQ DQG FRORQ 2XU RU 'LVUXSWLYH %HKDYLRU 'LVRUGHUV IXWXUH ZRUN VKRXOG H[DPLQH WKH ¿QGLQJVHOXFLGDWHDPHFKDQLVPXQGHUO\LQJWKHIRUPDWLRQRIDWXPRU QHXUDOUHODWLRQVKLSVEHWZHHQWKHVHGLVRUGHUVDQG$8'DQGRU&8' LQLWLDWLQJLPPXQHHQYLURQPHQWLQFKURQLFLQÀDPPDWRU\GLVHDVHVDQG symptomatology. yield novel targets for cancer treatment and prevention in chronic 8 The congenital heart disease candidate gene myelin LQÀDPPDWRU\FRQWH[WV regulatory factor plays an unexpected role in left right 10 Personal neoantigen vaccine for glioblastoma stimulates patterning QHRHSLWRSHVSHFL¿FLQWUDWXPRUDO7FHOOUHVSRQVHV Sarah K. Amalraj Annabelle J. Anandappa Yale University School of Medicine, USA Dana-Farber Cancer Institute, USA &RQJHQLWDO KHDUW GLVHDVH &+' LV WKH PRVW FRPPRQ PDMRU ELUWK Recent studies have demonstrated that therapies targeting GHIHFW DႇHFWLQJ QHDUO\ RI FKLOGUHQ $OWKRXJK WKH FDXVHV RI QHRDQWLJHQVFDQHOLFLWHႇHFWLYHDQWLWXPRULPPXQLW\7KHVHDQWLJHQV &+' DUH QRW ZHOO XQGHUVWRRG DEQRUPDOLWLHV LQ OHIWULJKW /5 arise from somatic tumor mutations, and are attractive targets for patterning (known as heterotaxy [Htx]) are associated with severe LPPXQRWKHUDS\JLYHQWKHLUH[TXLVLWHWXPRUVSHFL¿FLW\DQGH[HPSWLRQ IRUPV RI &+' $ UHFHQW DQDO\VLV RI +W[&+' SDWLHQWV LGHQWL¿HG from central tolerance. Personalized neoantigen vaccines have numerous candidate genes, including the gene myelin regulatory been shown to be feasible, safe, and immunogenic in highly mutated factor (MYRF). The protein MYRF is known to be a transcription cancers, such as melanoma, but have not been tested in tumors with factor for the generation of myelin in the central nervous system lower mutation rate. during development; however, its role in LR patterning and heart GHYHORSPHQW LV XQGH¿QHG +HUH ZH VKRZ WKDW GHSOHWLRQ RI P\UI A phase I/Ib trial of personal neoantigen vaccines for glioblastoma XVLQJ &5,635EDVHG JHQH PRGL¿FDWLRQ LQ ;HQRSXV WURSLFDOLV *%0 DWXPRUZLWKWHQIROGORZHUPXWDWLRQEXUGHQWKDQPHODQRPD causes midline heart looping defects phenocopying our patient. ZDVFRQGXFWHG)ROORZLQJVWDQGDUGRIFDUHVXUJHU\DQGUDGLDWLRQ We then analyzed the LR patterning markers pitx2 and coco and eight patients received vaccine consisting of up to 20 synthetic long found abnormal bilateral expression of pitx2, but normal expression SHSWLGHV PHGLDQUDQJH WKDWHQFRGHSUHGLFWHGQHRHSLWRSHV RI FRFR LQ P\UIGHSOHWHG HPEU\RV $GGLWLRQDOO\ ZH GHSOHWHG P\UI DQG SRO\,&/& DGMXYDQW &KDQJHV LQ WKH WXPRU PLFURHQYLURQPHQW LQ RQH FHOO RI D WZRFHOO HPEU\R DQG IRXQG WKDW OHIWVLGHG LQMHFWHG ZHUH DVVHVVHG LQ SRVWYDFFLQDWLRQ VXUJLFDO UHVHFWLRQ VSHFLPHQV embryos resulted in heart looping defects, abnormal bilateral pitx2 IURP ¿YH SDWLHQWV 9DFFLQDWLRQ LQGXFHG GH QRYR FLUFXODWLQJ

28 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

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Continuing studies will examine the subcellular location of WKHVHSDWLHQWVLQ¿OWUDWLQJ&'7FHOOVLQFUHDVHGVLJQL¿FDQWO\IURP 06+IRUHDFKFRQVWUXFWHYDOXDWHGWKURXJKLPPXQRÀXRUHVFHQFH DEDVHOLQHRIWRFHOOVPP 3 DIWHUYDFFLQDWLRQ PLFURVFRS\ ,)0 XVLQJDQ06+DQWLERG\LQFHOOVZLWKDQGZLWKRXW ZLWKDVLJQL¿FDQWLQFUHDVHLQWKH&'3'VXEVHW,QFRQWUDVWDOO ,/WUHDWPHQW7KLVDSSURDFKPD\SURYLGHLPSRUWDQWGHWDLOVDERXW three patients who received dexamethasone during vaccine priming WKHPHFKDQLVPVRI06+VKXWWOLQJZLWKSRWHQWLDOLPSOLFDWLRQVIRU IDLOHGWRJHQHUDWHFLUFXODWLQJLPPXQHUHVSRQVHVZLWKQRVLJQL¿FDQW SUHYHQWLRQ DQG WUHDWPHQW RI (0$67DVVRFLDWHG FRORUHFWDO FDQFHU FKDQJHLQ7FHOOLQ¿OWUDWH in patients. :H K\SRWKHVL]HG WKDW SRVWYDFFLQDWLRQ 7,/V ZHUH VSHFL¿F IRU 12 &LUFXODWLQJH[RVRPDOPLFUR51$DVDQRQLQYDVLYH LPPXQL]LQJ QHRDQWLJHQV 6LQJOHFHOO 7 FHOO UHFHSWRU 7&5 biomarker for pediatric medulloblastoma DQDO\VLVRI&'7,/VDQGSHULSKHUDO7FHOOVLQYLWURH[SDQGHG Sydney N. Ariagno against immunizing peptides was performed from one patient with Weill Cornell Medicine, USA FLUFXODWLQJQHRDQWLJHQVSHFL¿F7FHOOV)RXU&'DQGWZR&'7 cell clonotypes in peripheral blood were identical to TILs. In order Medulloblastoma (MB) is the most common malignant pediatric brain WR SUREH WKHLU VSHFL¿FLW\ ZH DSSOLHG D SLSHOLQH GHYHORSHG LQ RXU WXPRUDQGRYHURQHWKLUGRIFKLOGUHQZLWKWKLVFHUHEHOODUWXPRUGLH laboratory to clone and express TCR sequences of interest and ZLWKLQ¿YH\HDUVRIGLDJQRVLV&OLQLFLDQVDUHFXUUHQWO\OLPLWHGLQWKHLU VFUHHQWKHPDJDLQVWFDQGLGDWHDQWLJHQV:HLGHQWL¿HGD7&5 abilities to diagnose this tumor without surgical biopsy and identify VKDUHGLQ&'7FHOOVLQSHULSKHUDOEORRGDQG7,/VVSHFL¿FIRU metastatic or recurrent disease at early stages. The development $5+*$3 D QHRDQWLJHQ WDUJHWHG E\ YDFFLQDWLRQ DQG FDSDEOH of a noninvasive biomarker could help address these problems. RI GLVFULPLQDWLQJ EHWZHHQ WKH PXWDQW DQG ZLOGW\SH SHSWLGH 7KH Exosomes are microvesicles that are secreted from tumors intratumoral TCR repertoire was probed further using an algorithm FRQVWLWXWLYHO\ DQG FRQWDLQ FHOO W\SHVSHFL¿F SURWHLQV DQG JHQHWLF called grouping of lymphocyte interactions by paratope hotspots PDWHULDO LQFOXGLQJ PLFUR51$V PL5V ,Q DGGLWLRQ H[RVRPHV DUH */,3+ WRFOXVWHU7&5VE\VLPLODULW\5HSUHVHQWDWLYH7&5V easily isolated from plasma and provide an unexplored reserve for IURPHDFKFOXVWHUDUHEHLQJWHVWHGIRUQHRDQWLJHQVSHFL¿FLW\DQG noninvasive biomarkers. reactivity against autologous tumor. 8VLQJ D VSRUDGLF 6RQLF +HGJHKRJ 6++ GULYHQ PRXVH PRGHO Our observations demonstrate that neoantigen vaccines favorably RI 0% ZH DVVHVVHG H[RVRPDO SUR¿OHV IURP WXPRU WLVVXH H[SODQW DOWHUWKHLPPXQHPLOLHXRI*%0DQGWKDWQHRHSLWRSHVSHFL¿F7FHOOV cultures and plasma at early and late tumor stages. Exosomes from FDQWUDႈFIURPWKHSHULSKHU\LQWRLQWUDFUDQLDOWXPRUV7KHVHUHVXOWV cerebellar tissue explants and plasma were similarly collected from are particularly promising in a tumor with relatively low mutation DJHPDWFKHG FRQWURO PLFH 7LVVXH H[SODQWV ZHUH FXOWXUHG IRU EXUGHQDQGORZLPPXQHLQ¿OWUDWHVDWEDVHOLQH+RZHYHUWKHUHUHPDLQ KRXUVLQH[RVRPHGHSOHWHGPHGLD&RQGLWLRQHGPHGLDIURPH[SODQWV VLJQL¿FDQWLPPXQRVXSSUHVVLYHIDFWRUVWRRYHUFRPHIRUQHRDQWLJHQ DQGSODVPDVDPSOHVWKHQXQGHUZHQWGLႇHUHQWLDOXOWUDFHQWULIXJDWLRQ VSHFL¿F7FHOOVWRJHQHUDWHFOLQLFDOO\VLJQL¿FDQWDQWLWXPRUDFWLYLW\:H WRLVRODWHH[RVRPHVDQGH[RVRPDOSURWHLQDPRXQWZDVTXDQWL¿HG anticipate that combination therapy with checkpoint blockade may 7LVVXH DQG SODVPDGHULYHG H[RVRPHV WKHQ XQGHUZHQW PL5 EHPRUHHႇHFWLYHLQDXJPHQWLQJDQWLWXPRULPPXQLW\DQGLPSURYLQJ sequencing. Exosomal protein amount and miR expression were outcomes to therapy. FRPSDUHGEHWZHHQHDUO\VWDJHSUHQHRSODVWLFDQGODWHWXPRUVWDJHV as well as between tissue and plasma samples at each stage. &KDUDFWHUL]DWLRQ RI D SRO\PRUSKLF UHJLRQ RI 06+ D 11 :HIRXQGWKDWH[RVRPDOSURWHLQDEXQGDQFHIURPODWHVWDJHWXPRU mismatch repair protein associated with colorectal cancer WLVVXHZDVVLJQL¿FDQWO\KLJKHUWKDQHDUO\VWDJHSUHQHRSODVWLFWLVVXH Bianca Arao YV ȝJPJ 3 DIWHU QRUPDOL]DWLRQ IRU University of California Davis, Davis, USA explant brain weight. Additionally, exosomal protein amount from (OHYDWHG 0LFURVDWHOOLWH $OWHUDWLRQV DW 6HOHFWHG 7HWUDQXFOHRWLGH ODWHVWDJHWXPRUWLVVXHZDVVLJQL¿FDQWO\KLJKHUWKDQWKDWRIODWH UHSHDWV (0$67 LV D JHQHWLF VLJQDWXUH DVVRFLDWHG ZLWK FDQFHU VWDJHFRQWUROFHUHEHOOXP YVȝJPJ 3 metastasis and recurrence in colorectal cancers. It is caused by A similar trend was seen with exosomal plasma samples, although DGH¿FLHQF\LQ06+D'1$PLVPDWFKUHSDLU 005 SURWHLQWKDW VWDWLVWLFDOVLJQL¿FDQFHZDVQRWUHDFKHG YVȝJPJ contains a ERQD¿GHQXFOHDUORFDOL]DWLRQVLJQDO 1/6 DQGWZRQXFOHDU P YVȝJPJ3 :LWKUHJDUGWRWXPRU H[SRUWVLJQDOV 1(6V 7KH1/6DQG1(6VDOORZIRU06+VKXWWOLQJ exosomal content, miR sequencing revealed the presence of the EHWZHHQWKHQXFOHXVDQGWKHF\WRVROXQGHUFHOOXODUVWUHVV7KHSUR PL5aFOXVWHUZKLFKLVVSHFL¿FDOO\DVVRFLDWHGZLWKWKHKXPDQ LQÀDPPDWRU\F\WRNLQH,QWHUOHXNLQ ,/ DOWHUV06+ORFDOL]DWLRQ 6++GULYHQ0%VXEW\SHT3&5YDOLGDWLRQRIPL5H[SUHVVLRQ FDXVLQJGHIHFWVLQ'1$PLVPDWFKUHSDLU6KXWWOLQJRI06+DSSHDUV LQ FLUFXODWLQJ H[RVRPHV FRQ¿UPHG WKDW PL5 E D DQG WR EH DႇHFWHG E\ D SRO\PRUSKLVP QHDU WKH 1/6 WKDW FRQWDLQV D DOOPHPEHUVRIWKHaFOXVWHU ZHUHDSSUR[LPDWHO\WZLFH GHOHWLRQ RI EDVH SDLUV 06+ǻES ZKLFK LQFUHDVHV WKH as prevalent in exosomes from tumor mice as compared with F\WRVROLFSUHVHQFHRI06+WKHUHE\LQFUHDVLQJ(0$672XUDLPLV control mice. WRH[SORUHKRZVSHFL¿FVHTXHQFHVZLWKLQWKHǻESSRO\PRUSKLVP In conclusion, our data suggest that tumor exosomes may be a DႇHFW 06+ VKXWWOLQJ IXQFWLRQ 7KH SRO\PRUSKLF UHJLRQ KDV D potential noninvasive biomarker for monitoring disease status in SRO\DODQLQH WUDFW 3RO\$OD DQG D 3UROLQHULFK GRPDLQ 3UR :H children with MB. Tumor tissue explant and plasma exosomal protein K\SRWKHVL]HWKDW3RO\$ODDQG3URUHJLRQVDUHFULWLFDOLQUHJXODWLQJ DPRXQWLQRXU6++0%PRXVHPRGHOFRUUHODWHVZLWKWXPRUVWDJH WKH1/6IXQFWLRQDQGWKDWWKH\KDYHGLႇHUHQWUROHVLQWKLVUHJXODWLRQ Exosomal miR sequencing shows upregulation of components of ,IWKLVK\SRWKHVLVLVWUXHZHSUHGLFWWKDWGHOHWLRQVLQWKHSHUL1/6 WKHPL5aFOXVWHUWKDWDUHVSHFL¿FIRUWKH6++0%VXEJURXS UHJLRQRI06+ZLOOOHDGWRGLႇHUHQFHVLQORFDOL]DWLRQRI06+7R $GGLWLRQDOVWXGLHVZLOOEHQHHGHGWRYDOLGDWHWKHVHSUHFOLQLFDO¿QGLQJV begin to test this prediction, we successfully generated reporter in human MB tissue and plasma samples.

www.jointmeeting.org 29 POSTER ABSTRACTS

13 An Unusual Etiology For Acute Fulminant Liver Failure D XQLTXH UROH LQ PRGXODWLQJ SKHQRW\SLF WUDLWV ,Q FDQFHUV +63 C. Edmond Awah gene expression is frequently up regulated and has been linked to University of Illinois at Chicago, Urbana Campus, Champaign, USA D SRRU RYHUDOO SURJQRVLV$GGLWLRQDOO\ +63¶V UROH LQ VXSSRUWLQJ protein function and stability in almost every hallmark of cancer ,QWURGXFWLRQ $FXWH IXOPLQDQW OLYHU IDLOXUH LV D OLIHWKUHDWHQLQJ PDNHV LW D OXFUDWLYH WKHUDSHXWLF WDUJHW WR HႇHFWLYHO\ VKXW GRZQ condition characterized by elevated transaminases and prothrombin multiple oncogenic signaling networks simultaneously. We focus our WLPHLQWHUQDWLRQDO QRUPDOL]HG UDWLR ,15 7KH SRRU SURJQRVLV LQYHVWLJDWLRQRQWKHHႇHFWRIFOLQLFDOO\UHOHYDQW+63LQKLELWRUVRQ necessitates treatment in an intensive care unit capable of performing the emergence of aggressive cancer phenotypes as they undergo liver transplants. Wide ranges of etiologies from congenital to HSLWKHOLDOWRPHVHQFK\PDOWUDQVLWLRQ (07 LQYLWUR:HVXEMHFW$ infections have been reported in the literature. Acute fulminant liver OXQJFDQFHUFHOOVWRPXOWLSOHURXQGVRI+63LQKLELWLRQSURYLGHD failure typically presents secondary to shock liver, acute hepatitis, rest and recovery period, and induce EMT via transforming growth and Tylenol toxicity. We present a case of a young female who IDFWRUEHWD 7*)ȕ WUHDWPHQW:HXVHÀRZF\WRPHWU\WRFRPSDUH presented with an unusual etiology for acute fulminant liver failure. changes in distribution of classic EMT markers, cancer stem cell &OLQLFDO&DVH6XPPDU\$\HDUROGIHPDOHZLWKDKLVWRU\RIQRQ markers, and multidrug resistant transporters between our treated ischemic heart failure secondary to methamphetamine abuse and DQGXQWUHDWHGVDPSOHV6LJQL¿FDQWFKDQJHVDUHVHHQDWWUHDWPHQW &23'SUHVHQWHGWRDQRXWVLGHKRVSLWDOZLWKGD\VRIHPHVLVDQG levels far below clinically recommended doses. This work may shed GLDUUKHD (PHVLV LV QRQEORRG\ DQG QRQELOLRXV 6WRROV DUH ORRVH light on mechanisms associated with the development of aggressive ZLWK QR IUDQN EORRG 6KH UHSRUWV ULJKW XSSHU TXDGUDQW DEGRPLQDO cancer traits as well as generate a discussion on strategic use of SDLQ PRGHUDWH LQ LQWHQVLW\ QRQUDGLDWLQJ DQG QR DJJUDYDWLQJ RU +63LQKLELWRUVWRWDUJHWFDQFHUHYROXWLRQ UHOLHYLQJIDFWRUV6KHDOVRUHSRUWHGZRUVHQLQJVKRUWQHVVRIEUHDWK ZLWK RUWKRSQHD DQG SDUR[\VPDO QRFWXUQDO G\VSQHD 8ULQH GUXJ 15 7KH.FQTRW/RQJ1RQ&RGLQJ51$5HJXODWHV*HQHWLF VFUHHQ ZDV SRVLWLYH IRU DPSKHWDPLQHV 6KH ZDV WDFK\FDUGLDF RQ ,PSULQWLQJ:LWKLQD'H¿QHG'LPHQVLRQDO&KURPDWLQ6WUXFWXUH SUHVHQWDWLRQZLWKDKHDUWUDWHRIPLQXWHDQGDEORRGSUHVVXUH Abhik Banerjee of 110/66. Physical exam showed icteric sclera, jugular venous University of Southern California and California Institute of distention, right upper quadrant tenderness, and hepatomegaly Technology, South Pasadena, USA 2 cm below costal margin. Comprehensive metabolic panel *HQRPLF LPSULQWLQJ SURYLGHV DQ H[FHOOHQW PRGHO WR XQGHUVWDQG VKRZHG DQ DVSDUWDWH DPLQRWUDQVIHUDVH $67 8/ DODQLQH mechanisms responsible for cis gene regulation, including chromatin DPLQRWUDQVIHUDVH $/7 8/DQG,155LJKWXSSHUTXDGUDQW LQVXODWLRQHQKDQFHUORRSLQJLQWHUDFWLRQVDQGORQJQRQFRGLQJ51$ XOWUDVRXQG VKRZHG QRQKRPRJHQRXV KHSDWRPHJDO\ SXOVDWLOH OQF51$ IXQFWLRQ7KH.FQTRWOQF51$LVH[SUHVVHGLQDQWLVHQVH SRUWDOYHLQÀRZDQGULJKWSOHXUDOHႇXVLRQ%UHDWKLQJLPSURYHGZLWK orientation to Kcnq1 protein coding gene and is responsible for GLXUHVLVEXWOLYHUHQ]\PHVFRQWLQXHGWRULVHZLWK$678/DQG paternal imprinting of a conserved one megabase domain in $/78/$UWHULDOEORRGJDVHVUHYHDOHGK\SR[LDDQGPHWDEROLF PRXVH DQG KXPDQ 'LVUXSWLRQ RI LPSULQWLQJ LQ WKLV FOXVWHU UHVXOWV DFLGRVLVZLWKUHVSLUDWRU\FRPSHQVDWLRQ6XEVHTXHQWOLYHUIXQFWLRQ LQ DQ RYHUJURZWK GLVRUGHU FDOOHG %HFNZLWK:LHGHPDQQ 6\QGURPH WHVWV VKRZHG QR LPSURYHPHQW DQG ,15 LQFUHDVHG WR 3DWLHQW 'HVSLWHSUHYLRXVVWXGLHVLQYHVWLJDWLQJWKHUHJXODWLRQDQGIXQFWLRQRI was transferred to tertiary transplant facility for acute fulminant liver WKHOQF51$LWVHOIOLWWOHLVNQRZQUHJDUGLQJLWVPHFKDQLVPRIVLOHQFLQJ IDLOXUH 'LVFXVVLRQ %DVLF VFLHQFH UHVHDUFK LQ WKH DQLPDO PRGHO RUKRZWKHOQF51$LVDEOHWRGLVWLQJXLVKEHWZHHQWDUJHWDQGQRQ VKRZLQJ PHWKDPSKHWDPLQHLQGXFHG DFXWH OLYHU LQMXU\ KDV EHHQ target genes in cis. In order to answer these questions, we have ZHOO GRFXPHQWHG 1R FDVH UHSRUWV KDYH EHHQ SXEOLVKHG VKRZLQJ GHYHORSHG D .FQTRW GR[\F\FOLQHLQGXFLEOH PRXVH HPEU\RQLF this relationship. Hyperthermia is the predominant mechanism VWHPFHOOOLQH8VLQJWKLVV\VWHPZHGHPRQVWUDWHWKDWLQGXFWLRQRI causing liver injury. Researchers measured transaminase levels of .FQTRWOQF51$LVVXႈFLHQWWRVLOHQFHHQGRJHQRXVWDUJHWJHQHV rats receiving saline, methamphetamine, and methamphetamine DQGWKDWWKHOQF51$SULPDULO\ORFDOL]HVWRLWVLPSULQWLQJWDUJHWVZLWKLQ with environmental cooling. The most notable results showed a DGH¿QHGWRSRORJLFDODVVRFLDWHGGRPDLQ%DVHGRQWKHVHUHVXOWVZH VLJQL¿FDQWLQFUHDVHLQWKH$/7RIUDWVUHFHLYLQJPHWKDPSKHWDPLQH K\SRWKHVL]HWKDW.FQTRWOQF51$VFDႇROGVUHJXODWRU\IDFWRUVZLWKLQ YHUVXVVDOLQHFRQWURODQGQRVLJQL¿FDQWGLႇHUHQFHLQWKH$/7RIUDWV DGH¿QHGGLPHQVLRQDOFKURPDWLQVWUXFWXUHWRFRRUGLQDWHO\VLOHQFH receiving methamphetamine with environmental cooling versus target genes in cis. saline control. Conclusion: It is important for clinicians to be aware of the range of sequela from methamphetamine abuse and to provide 16 &RQWUROOHG 0DQLSXODWLRQ RI 3URWHLQ 3KRVSKRU\ODWLRQ DSSURSULDWHFRXQVHOLQJUHFRPPHQGDWLRQVDVZHOODVGHWR[L¿FDWLRQ DQG &HOO 5HJHQHUDWLRQ ZLWK /LJKW5HVSRQVLYH '1$ $SWDPHU programs for these patients. 5HDFWLRQV 14 Targeting heat shock protein 90 to alter evolution of Ameer S. Basta aggressive cancer phenotypes University of Florida, Gainesville, USA Nickolas Bacon Most cells in the human body respond to growth hormone, which Marshall University Joan C. Edwards School of Medicine, binds to cell surface receptors and induces growth and replication Huntington, USA for those cells. Our study is focusing on receptor tyrosine kinase (RTK), a cell receptor of growth hormone that phosphorylates The evolution of aggressive cancer phenotypes remains a downstream proteins inside the cells, leading changes in certain VLJQL¿FDQW FKDOOHQJH LQ FDQFHU PHGLFLQH DV WKH\ RIWHQWLPHV protein expression level that allows for cell growth and replication. become the source of chemotherapeutic resistance, relapse, and 8WLOL]LQJWKLVSDWKZD\KDVEHFRPHRQHRIWKHPRVWSRSXODU¿HOGVLQ PHWDVWDVLV LQ D SDWLHQW 7KHUHIRUH VLJQL¿FDQW FOLQLFDO EHQH¿W PD\ regenerative therapy, however, uncontrollable cell growth would be arise by refocusing cancer treatment on limiting the emergence of RQFRJHQLF ,Q RXU SURMHFW ZH GHVLJQ WKH '1$ UHDFWLRQV WR UHDOL]H WKHVHSKHQRW\SHV+HDWVKRFNSURWHLQ +63 LVDFKDSHURQH OLJKWUHVSRQVLYH VZLWFK EHWZHHQ WKH DFWLYDWLRQGHDFWLYDWLRQ RI WKH protein whose function is evolutionarily well conserved and plays 57.SDUWLFLSDWHGVLJQDOSDWKZD\

30 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

The activation of RTK pathway requires the close proximity of the 18 0HGLFDO 6WXGHQW DQG 3K\VLFLDQ .QRZOHGJH DQG two receptor subunits when bound with the growth factor, which Attitudes Towards the Patient Protection and Affordable ZRXOGEHDFKLHYHGE\XVLQJWKH'1$DSWDPHUVRIWKH57.SURWHLQ Care Act DQGWKHIRUPDWLRQRIWKHGRXEOHVWUDQGHGVWUXFWXUH7KHLQWURGXFWLRQ Evan Berger RI WKH 3&OLQNHU ZRXOG DOORZ WKH IHDVLEOH FOHDYDJH LQ WKH '1$ New York Institute of Technology College of Osteopathic structure, causing the disassembly of the receptor pair. The reaction Medicine, New York, USA ZDVPRQLWRUHGZLWK)5(7DQGJHOHOHFWURSKRUHVLVLQVROXWLRQDQG ÀRZ F\WRPHWU\ RQ WKH FHOO PHPEUDQH 7KH SKRVSKRU\ODWLRQ RI WKH 3KHQRPHQRQ,WLVLPSRUWDQWWRH[DPLQHWKH86KHDOWKFDUHZRUNIRUFH¶V SURWHLQVZRXOGEHDQDO\]HGZLWKZHVWHUQEORWWLQJDQGRWKHUFHOOXODU DWWLWXGHVDQGNQRZOHGJHDERXWWKH3DWLHQW3URWHFWLRQDQG$ႇRUGDEOH H[SHULPHQWV 7KLV GHVLJQ ZRXOG RႇHU D IHDVLEOH IDVW DQG VLPSOH Care Act (PPACA), as they communicate details about this act with platform for controllable cell regeneration. SDWLHQWV8QGHUVWDQGLQJWKHYLHZVRIPHGLFDOVWXGHQWVLVSDUWLFXODUO\ crucial as they are the future of the healthcare workforce. Additionally, 17 Interplay between the EWS-portion of EWS/FLI and it is important to assess whether these views change as individuals OHQJWK RI **$$PLFURVDWHOOLWH ELQGLQJ HOHPHQWV GH¿QHV go into clinical practice. This study sought to investigate the attitudes transcriptional activation function in Ewing sarcoma and knowledge that medical students and faculty possess about the Ariunaa Bayanjargal 8QLWHG6WDWHVKHDOWKFDUHV\VWHPDQGWKH33$&$DQGZKHWKHUWKHUH The Ohio State University, Columbus, USA DUHGLႇHUHQFHVEHWZHHQWKHWZRJURXSV S! (ZLQJ VDUFRPD LV DQ DJJUHVVLYH ERQHDVVRFLDWHG WXPRU ¿UVW $SSURDFK$ LWHP VXUYH\ ZDV GHYHORSHG DIWHU UHYLHZ RI KHDOWK GHVFULEHGE\-DPHV(ZLQJLQ0RVWFDVHVFRQWDLQDWUDQVORFDWLRQ policy literature and administered to medical students and faculty EHWZHHQ FKURPRVRPHV DQG WKDW IXVHV WZR JHQHV (:65 RI WKH 1HZ

www.jointmeeting.org 31 POSTER ABSTRACTS

20 7KH'<5.$SDWKZD\LOOXVWUDWHVDSDUDGR[LFDOSURJUDP molecules. Photosensitizers see broad use in the basic sciences in normal versus malignant lymphopoiesis WKURXJKWHFKQLTXHVVXFKDVWDUJHWHGFHOODEODWLRQDQGFKURPRSKRUH 5DKXO6%KDQVDOL DVVLVWHG OLJKW LQDFWLYDWLRQ RI VSHFL¿F SURWHLQV DV ZHOO DV LQ WKH Northwestern University, USA clinic through applications including photodynamic therapy for the treatment of cancers and inactivation of pathogenic microbes. This 'XDO VSHFL¿FLW\ W\URVLQHSKRVSKRU\ODWLRQUHJXODWHG NLQDVH $ study describes the characterization of photosensitizing agents '<5.$ LVDVHULQHWKUHRQLQH 67 NLQDVHWKDWUHJXODWHVGLYHUVH EDVHG XSRQ +DOR7DJ OLJDQG YDULDQWV RI WKH -DQHOLD )OXRU VFDႇROG SDWKZD\VVXFKDVVSOLFLQJFHOOF\FOHGLႇHUHQWLDWLRQDSRSWRVLVDQG using two approaches — halogenation and substitution of the central WUDQVFULSWLRQ'<5.$LVHQFRGHGZLWKLQWKH'RZQV\QGURPH '6 xanthene oxygen with a sulfur. The resulting candidate molecules are FULWLFDOUHJLRQRIFKURPRVRPHXQGHUO\LQJLWVLPSRUWDQFHLQ'6 compared for singlet oxygen generation potency, HaloTag binding UHODWHGSDWKRORJLHVVXFKDV$O]KHLPHU¶VGLVHDVH&KLOGUHQZLWK'6 NLQHWLFV DQG SKRWRVHQVLWL]DWLRQ DYDLODELOLW\ GXH WR WKH ODFWRQH have an increased risk of developing hematologic malignancies, zwitterion equilibrium typical of rhodamine dyes. Experiments in namely acute megakaryoblastic leukemia (AMKL) and acute their use for the manipulation of biological systems are currently O\PSKREODVWLFOHXNHPLD $// :HSUHYLRXVO\UHSRUWHGWKDW'<5.$ underway. This study provides the characterization of several new is necessary for normal lymphopoiesis through phosphorylation photosensitizing agents for use in the biomedical sciences and DQG GHVWDELOL]DWLRQ RI F\FOLQ ' '\UNDGH¿FLHQW O\PSKRF\WHV compares two canonical approaches to photosensitizer development, are unable to exit the cell cycle; however, these cells also lose highlighting potential pitfalls of each in the context of compatibility SUROLIHUDWLYHFDSDFLW\GXHWRDEORFNDWWKH*0WUDQVLWLRQ ZLWKVHOIODEHOLQJHQ]\PHWDJJLQJV\VWHPVVXFKDV+DOR7DJ *LYHQ WKH FULWLFDO UROH RI '<5.$ LQ O\PSKRSRLHVLV ZH DLPHG WR VHHN ZKHWKHU '<5.$ LV D VXLWDEOH WDUJHW LQ $// :H ¿UVW 22 A model for the analysis of schizophrenia as a disease of JHQHUDWHG PXULQH PRGHOV RI $// LQ SDQKHPDWRSRLHWLF '\UND brain connectivity FRQGLWLRQDO NQRFNRXW PLFH ([FLVLRQ RI '\UND LQ OHXNHPLF PLFH Daniel Biro LQFUHDVHGVXUYLYDODIWHUWUDQVSODQWQHDUO\WKUHHIROG1H[WLQRUGHU Albert Einstein College of Medicine, Bronx, USA WRGHWHUPLQHYLDELOLW\RIWDUJHWLQJ'<5.$ZHWUHDWHG$//FHOOOLQHV 6FKL]RSKUHQLD LV D UHPDUNDEO\ FRPSOH[ QHXURSV\FKLDWULF GLVHDVH ZLWK (+7 D SRWHQW DQG VHOHFWLYH '<5.VSHFL¿F LQKLELWRU with complex etiology that is one of the leading causes of disease EHT1610 sensitivity was observed in ALL cell lines harboring UHODWHGGLVDELOLW\LQWKH8QLWHG6WDWHVDQGZRUOGZLGH7KHPHFKDQLVWLF various oncogenic mutations, including those associated with both FDXVHVDQGHႇHFWVDFURVVPXOWLSOHOHYHOVRIELRORJLFDOKLHUDUFK\DUH QRQ'6DQG'6$//:HDOVRIRXQGWKDW RI RISULPDU\ poorly understood, although progress has been made in recent $//VDPSOHVZHUHVHQVLWLYHWR(+7WUHDWPHQWLQYLWURZLWK \HDUV 2QH OHYHO RI H[DPLQDWLRQ ZKLFK KROGV VLJQL¿FDQW SURPLVH RI RIWKH'6$//VDPSOHVGLVSOD\LQJVHQVLWLYLW\2IQRWHWKH is that of the brain network connectivity. Broadly speaking, brain observed induction of cycling also conferred increased sensitivity to connectivity approaches utilize tools such as functional magnetic traditional cytotoxic drugs, such as cytarabine. Furthermore, we saw resonance imaging and electroencephalography to measure the D PDUNHG GHFUHDVH LQ OHXNHPLF EXUGHQ LQ$//3'; PRGHOV DIWHU LQWHUDFWLRQV EHWZHHQ ODUJH DQG PHVRVFDOH EUDLQ UHJLRQV 7KHVH WUHDWPHQWZLWK(+7LQGLFDWLQJWKDW'<5.$LVDWDUJHWLQ$// approaches have been combined with computational models and Last, we performed global and directed phosphoproteomic studies graph theoretic concepts such as network structure in order to WRGHWHUPLQH'<5.$VXEVWUDWHVLQSUH%FHOOV/RVVRI'<5.$ examine how changes in both physical and functional connections DFWLYLW\ LQ SUH% FHOOV OHDGV WR FKDQJHV LQ SKRVSKRU\ODWLRQ RI can be correlated to the clinical changes seen in schizophrenic VXEVWUDWHVWKDWUHJXODWHFHOOF\FOHVSOLFLQJDQG51$PHWDEROLVP patients. We put forward a simple model of brain connectivity and 2QHRIWKHLGHQWL¿HGWDUJHWVLVVHULQHRI)2;2DSURDSRSWRWLF IXQFWLRQ ZKHUH D QHXUDO QHWZRUN LV WUDLQHG WR VROYH LQSXWRXWSXW transcription factor that is critical in B lymphopoiesis and negatively tasks, and then the network is “broken” in a manner consistent seen UHJXODWHGE\3,.$NWVLJQDOLQJ8VLQJDJUHHQÀXRUHVFHQWSURWHLQ with the connectivity changes in schizophrenia. We then analyze WDJJHG)2;2ZHIRXQGWKDWWUHDWPHQWRIODUJHSUH%FHOOVZLWK the patterns in which the neural network fails, and show parallels to EHT1610 shifted FOXO1 localization from the cytoplasm to the the failure of information processing seen in schizophrenic patients. nucleus, where it is active despite intact PI3K/Akt signaling. Moreover, Analogies can be drawn to the inability of schizophrenic individuals to WUHDWPHQWRISUH%FHOOVZLWK(+7DQG$6DQLQKLELWRU process pertinent information in the same was as healthy individuals. RI DFWLYDWHG )2;2 UHVFXHG WKH *0 EORFNDGH 3DUDGR[LFDOO\ 23 S$QGp53 tumor suppressor plays a fundamental are key to lymphocyte survival. role in triggering the mitochondrial permeability transition (mPT), leading to necrotic and apoptotic cell death in response to several 21 Characterization of novel photosensitizers based upon noxious stimuli. In particular, mPT is thought to result from the the Janelia Fluor rhodamine scaffold VXUJHRIUHDFWLYHR[\JHQVSHFLHV 526 WKDWDUHJHQHUDWHGGXULQJ Thomas C. Binns WKH LVFKDHPLDUHSHUIXVLRQ LQMXU\ RI P\RFDUGLDO LQIDUFWLRQ 0, Howard Hughes Medical Institute, Janelia Research Campus, USA DQG FHUHEURYDVFXODU DFFLGHQWV &9$ 7KH P37 SRUH FRPSOH[ Photosensitizing agents are excited by electromagnetic radiation, (mPTP) is famously mysterious in its composition, but it is known typically in the form of visible or ultraviolet light, and subsequently WREHUHJXODWHGE\F\FORSKLOLQ' &\S' DPLWRFKRQGULDOPDWUL[FLV generate free radicals via the transfer of energy to adjacent trans proline isomerase, and this has been proposed to be p53’s

32 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

intramitochondrial target. We have begun preliminary studies to 25 Associations between Lymphocyte Activation, FKDUDFWHUL]H WKH SURSRVHG LQWHUDFWLRQ EHWZHHQ S DQG &\S' Senescence, and Pulmonary Function in HIV-infected and HIV- :H KDYH PHDVXUHG GLUHFW ELQGLQJ EHWZHHQ S DQG &\S' ZLWK uninfected individuals PLFURPRODU DႈQLW\ XVLQJ ÀXRUHVFHQFH SRODUL]DWLRQ DQLVRWURS\ 0DULDP%UDPDK/DZDQL (FP), and investigated the impact of known cyclophilin inhibitor University of Pittsburgh School of Medicine, Pittsburgh, USA cyclosporine A. We have begun further structural and functional VWXGLHVXVLQJ105)3DQGDQDO\WLFDOXOWUDFHQWULIXJDWLRQWRLGHQWLI\ 5DWLRQDOH+,9LVDQLQGHSHQGHQWULVNIDFWRUIRUSXOPRQDU\G\VIXQFWLRQ the binding sites on both proteins, which we propose to be a new %RWK +,9 DQG &23' DUH LQGHSHQGHQWO\ DVVRFLDWHG ZLWK FKURQLF WDUJHWIRUSKDUPDFHXWLFDOWKHUDS\WRUHGXFHLQMXU\SRVW0,DQG&9$ LQÀDPPDWLRQVHQHVFHQFHDQGLPPXQHDFWLYDWLRQ/LPLWHGUHSRUWVLQ +,9&23'KDYHGHVFULEHGDVVRFLDWLRQVRIDFWLYDWHGVHQHVFHQW7FHOO 24 Characteristics of Patients Diagnosed with Catastrophic phenotypes and pulmonary function testing (PFT) abnormalities, Cutanenous Carcinomatosis but comparisons to uninfected persons have not been made. Nicole Bolick Additionally, abnormal lymphocyte memory subset redistribution The Brody School of Medicine at East Carolina University, LV DVVRFLDWHG ZLWK FKURQLF LQÀDPPDWLRQ PHPRU\ VXEVHWV KDYH Greenville, USA QRW EHHQ HYDOXDWHG LQ WKH FRQWH[W RI +,9DVVRFLDWHG SXOPRQDU\ Catastrophic Cutaneous Carcinomatosis (CCC) is a dermatologic dysfunction. We compared surface markers of lymphocyte activation FRQGLWLRQLQZKLFKDQRQRUJDQWUDQVSODQWSDWLHQWLVGLDJQRVHGZLWK and senescence and proportions of lymphocyte memory subsets to RUPRUHQRQPHODQRPDVNLQFDQFHUVLQDRQH\HDUSHULRG:H 3)7VLQ+,9LQIHFWHGDQGXQLQIHFWHGSHUVRQV0HWKRGV+,9LQIHFWHG LGHQWL¿HGSDWLHQWVIURPDODUJHVNLQFDQFHUGDWDEDVHZKRKDGEHHQ and uninfected persons were recruited from an outpatient cohort. diagnosed with at least 10 nonmelanoma skin cancers in one year. Clinical factors including demographics, smoking exposure, and We looked at characteristics of these patients and if they could be PHDVXUHVRI+,9YLUDOFRQWUROZHUHFROOHFWHG3DUWLFLSDQWVSHUIRUPHG diagnosed with CCC. $76VWDQGDUG3)7V3HULSKHUDOEORRGPRQRQXFOHDUFHOOO\PSKRF\WHV :H SHUIRUPHG D UHWURVSHFWLYH FKDUW UHYLHZ DW WKH %URG\ 6FKRRO ZHUHDQDO\]HGE\ÀRZF\WRPHWU\IRUH[SUHVVLRQRIDFWLYDWLRQ &' of Medicine of dermatology patients with 10 or more cases +/$'5 &' VHQHVFHQFH &'QXOO&' DQG PHPRU\ RI QRQPHODQRPD VNLQ FDQFHU LQ D RQH\HDU SHULRG WR LGHQWLI\ VXEVHWV QDwYH>7QDLYH &'5$&&5@ FHQWUDO PHPRU\ >7&0 characteristics of these patients. &'5$&&5@ HႇHFWRU PHPRU\ >7(0 &'5$&&5@ DQG WHUPLQDOO\GLႇHUHQWLDWHG>77(05$&'5$&&5@ 5HODWLRQVKLSV %URG\ 6FKRRO RI 0HGLFLQH¶V (+5 DQG SDSHU FKDUWV ZHUH XVHG WR EHWZHHQ 7FHOO PDUNHUV DQG 3)7V ZHUH WHVWHG E\ 6SHDUPDQ¶V review patients diagnosed with 10 or more cases of basal cell FRUUHODWLRQWWHVWRUUDQNVXP5HJUHVVLRQZDVXVHGWRDGMXVWIRU FDUFLQRPDVDQGRUVTXDPRXVFHOOFDUFLQRPDVLQDRQH\HDUSHULRG FOLQLFDOO\UHOHYDQWYDULDEOHV5HVXOWVSDUWLFLSDQWVZHUHHQUROOHG 7KH FKDUDFWHULVWLFV RI WKH SDWLHQWV HOLJLEOH IRU WKH VWXG\ ZHUH RIZKRP ZHUH+,9LQIHFWHG0HDQDJHRISDUWLFLSDQWVZDV compiled and analyzed to determine correlations. One patient’s \HDUV+,9LQIHFWHGLQGLYLGXDOVKDGDJUHDWHUVPRNLQJKLVWRU\ chart was unable to be located. WKDQ +,9XQLQIHFWHG PHGLDQ SDFN\HDUV YV S 2IWKHSDWLHQWVHOLJLEOHIRUWKHVWXG\DOOZHUH&DXFDVLDQZLWK RI +,9LQIHFWHG SHUVRQV XVHG$57 PHGLDQ &' FHOOV RIRXUSDWLHQWVEHLQJPDOHV$SSUR[LPDWHO\KDOI RIRXUSDWLHQWV PPUDQJH>@PHGLDQYLUDOORDGUDQJH>8'@ 3)7V ZHUHLPPXQRVXSSUHVVHG+\SHUWHQVLRQZDVFRPPRQZLWKRI ZHUHQRUPDORQDYHUDJHEXWKDGSRVWEURQFKRGLODWRU)(9 our patients having high blood pressure. Eight patients diagnosed )9& DQG KDG '/&2 7KHUH ZHUH QR VLJQL¿FDQW ZLWK GLDEHWHV KDG D FRPRUELGLW\ RI K\SHUWHQVLRQ DV ZHOO7ZHQW\ GLႇHUHQFHVLQ3)7VE\+,9VWDWXVLQWKLVFRKRUW&HUWDLQDFWLYDWHGDQG RQHRISDWLHQWV ZHUHGHFHDVHG2IWKHSDWLHQWVZKRZHUH VHQHVFHQW SKHQRW\SHV &'&' &' &'QXOO&' GHFHDVHG ¿YH GLHG GXH WR VNLQ FDQFHU 3DWLHQWV ZKR ZHUH &' &'QXOO&'&' &'&' &'&'QXOO LPPXQRVXSSUHVVHG ZHUH \RXQJHU DW WKH RQVHW RI WKHLU ¿UVW VNLQ &'&' &'&'QXOO&'&' ZHUH PRUH IUHTXHQW FDQFHU E\ \HDUV7KLV ZDV D VWDWLVWLFDOO\ VLJQL¿FDQW GLႇHUHQFH DPRQJ+,9LQIHFWHG QRWVKRZQ +LJKHUSURSRUWLRQVRIQDwYH&' 7KHUHZDVDOVRDVWDWLVWLFDOO\VLJQL¿FDQWGLႇHUHQFHLQWKHQXPEHURI 7FHOOVLQGHSHQGHQWO\FRUUHODWHGZLWKEHWWHU'/&2 EHWD S basal cell carcinomas; immunocompetent patients had more basal DQGKLJKHUSURSRUWLRQVRI&'77(05$ZHUHLQGHSHQGHQWO\ cell carcinomas than immunocompromised patients. Patients who DVVRFLDWHGZLWKJUHDWHURGGVRISRVWEURQFKRGLODWRU)(9 25 were immunosuppressed showed a greater number of squamous >&, S @ LQ +,9LQIHFWHG SHUVRQV RQO\ +LJKHU FHOOFDUFLQRPDVKRZHYHUWKLVGDWDZDVQRWVWDWLVWLFDOO\VLJQL¿FDQW &'&' H[SUHVVLRQ LQGHSHQGHQWO\ DVVRFLDWHG ZLWK SRVW The data shows that the majority of patients diagnosed with EURQFKRGLODWRU)(9)9& 25>&,S @ Catastrophic Cutaneous Carcinomatosis will be Caucasian and DQGKLJKHU&'QXOO&'&'H[SUHVVLRQDVVRFLDWHGZLWKORZHU male. Many CCC patients will have a comorbidity of hypertension. SRVWEURQFKRGLODWRU)(9SHUFHQWSUHGLFWHG EHWD S 'LႇHUHQFHVLQWKHUDWHVRIVTXDPRXVFHOOFDUFLQRPDVDQGEDVDOFHOO LQ +,9LQIHFWHG SHUVRQV &RQFOXVLRQV 5HVXOWV DUH FRQVLVWHQW ZLWK carcinomas exist between patients who are immunosuppressed SULRU¿QGLQJVWKDWXSUHJXODWLRQRIVHQHVFHQWDQGLPPXQHDFWLYDWLRQ DQGLPPXQRFRPSHWHQW3DWLHQWVZLWKPXOWLSOHVNLQFDQFHUVVXႇHU PDUNHUV DUH DVVRFLDWHG ZLWK OXQJ G\VIXQFWLRQ LQ +,9 /\PSKRF\WH VLJQL¿FDQWPRUELGLW\DQGPDQ\GLHIURPWKHLUGLVHDVH0DQDJHPHQW PHPRU\ FRPSDUWPHQWV PD\ EH QRYHO LPSRUWDQW PDUNHUV RI 7FHOO requires a coordinated multispecialty approach. LPPXQRSDWKRJHQHVLVLQ+,9DVVRFLDWHGOXQJG\VIXQFWLRQ

www.jointmeeting.org 33 POSTER ABSTRACTS

26 Exosomes secreted by mutant SOD1G93A motor cortex VWLFKRVRPHLQRULJLQHOLFLWVSURWHFWLYHLPPXQLW\LQ$.5PLFH8VLQJ reveal an insight into how cortical neurons communicate disease WKHSURWHFWLYHDQWLTm-(6VHUDZHLGHQWL¿HGDQWLJHQVE\ERWK in ALS immunoscreening the T. muris F'1$OLEUDU\DQGE\WZRGLPHQVLRQDO electrophoretic separation followed by western blotting. The leading Jonathan Brent three candidate antigens were ranked by their vaccine potential and Northwestern University Feinberg School of Medicine, ZHUHWHVWHGIRUHႈFDF\DJDLQVWT. muris in the AKR mouse model. Chicago, USA The most promising candidate recombinant Trichuris muris whey ([RVRPHVDUHH[WUDFHOOXODUYHVLFOHVWKDWFDUU\SURWHLQVDQG51$V DFLGLF SURWHLQ UTm-:$3 OHDG WR D VLJQL¿FDQW UHGXFWLRQ LQ which are secreted by cells into their surrounding milieu. In the ODUYDOZRUPEXUGHQ(QGSRLQW(/,6$WLWHUVUHYHDOHGDKLJKVHUXP nervous system exosomes are thought to function as a means of ,J*WR,J*DUDWLRUHÀHFWLYHRIDW\SHKXPRUDOLPPXQHUHVSRQVH FRPPXQLFDWLRQEHWZHHQQHXURQVJOLDDQGWKHLUWDUJHWV$/6LVD LQ SURWHFWHG JURXSV 6LPLODUO\ D SURIRXQG W\SH FHOOXODU LPPXQH devastating disease characterized by the dysfunction of both upper UHVSRQVH LQWHUOHXNLQ>,/@,/,/DQG,/ ZDVPHDVXUHG and lower motor neurons, and upper motor neuron degeneration is LQ WKH VSOHHQV PHVHQWHULF O\PSK QRGHV DQG YDFFLQHGUDLQLQJ DQHDUO\HYHQWLQWKHGLVHDVH&RUWLFRVSLQDOPRWRUQHXURQV &601 O\PSK QRGHV RI SURWHFWHG PLFH E\ SOH[ /XPLQH[ DQDO\VLV display cortical hyperexcitation prior to any clinical evidence of ,PPXQRÀXRUHVFHQW VWDLQLQJ ZLWK DQWLUTm:$3 FRQ¿UPHG KLJK GLVHDVHDQGWKH\GHJHQHUDWHDVHDUO\DV3SULRUWRDQ\HYLGHQFH production of the native protein in the stichosome of T. muris. We RI VSLQDO PRWRU QHXURQ DEQRUPDOLW\ LQ $/6 PRXVH PRGHOV 7KH also evaluated the translatability of rTm:$3 DV D SRWHQWLDO PROHFXODUPHFKDQLVPVWKDWXQGHUOLH&601GHJHQHUDWLRQDUHSRRUO\ vaccine candidate by testing its serological and cellular reactivity XQGHUVWRRGDQGWKHVLJQDOVWKDW&601DQGWKHLUQHLJKERUVXVHWR of biological samples collected from 236 individuals in Honduras, a communicate within the microenvironment of the diseased cortex region endemic for T. trichiura DIWHUFRQ¿UPLQJDFWLYHWUDQVPLVVLRQ have yet to be revealed. of T. trichiura WUDQVPLVVLRQE\UHDOWLPHSRO\PHUDVHFKDLQUHDFWLRQ We hypothesized that cortical neurons which become vulnerable 28 5ROH RI 2QFRPHWDEROLWH / +\GUR[\JOXWDUDWH LQ would utilize exosomes to communicate their cellular pathology 5HSURJUDPPLQJ5HQDO&HOO&DUFLQRPD0HWDEROLVP with the surrounding cells/neurons in the cerebral cortex and more Garrett Brinkley broadly in the central nervous system. Elucidating which signals act University of Alabama at Birmingham, Birmingham, USA to improve versus propagate disease is critical to our understanding RI$/6SDWKRJHQHVLV ,1752'8&7,215HQDOFHOOFDUFLQRPD 5&& LVDPRQJWKHWHQPRVW FRPPRQQHRSODVLDVLQWKH8QLWHG6WDWHVDQGLVZHOONQRZQWRXQGHUJR We collected conditioned medium from both healthy and diseased extensive metabolic reprogramming. Previous work by our lab has mixed cortical neuron cultures and isolated exosomes secreted to LGHQWL¿HG KLJK OHYHOV RI WKH RQFRPHWDEROLWH / +\GUR[\JOXWDUDWH the medium. Then, we performed proteomic assays to determine the /+* LQ5&&,WLVFXUUHQWO\XQNQRZQLIZHFDQXWLOL]HPHWDEROLF FRQWHQWRIH[RVRPHVVHFUHWHGZLWKUHVSHFWWRGLVHDVH2XU¿QGLQJV liabilities created by oncometabolites for personalized RCC therapy. UHYHDO WKDW GLVHDVHG FRUWLFDO QHXURQV VHFUHWH SURWHLQV ZLWKLQ 2%-(&7,9(67KHSULPDU\REMHFWLYHRIWKLVVWXG\LVWRXQGHUVWDQG exosomes. These proteins have diverse cellular functions, including the mechanism and impact of loss of GH QRYR serine and glycine transcription factors and kinases, suggesting that active signaling biosynthesis in RCC. In turn, we will assess how this liability can be takes place prior to disease symptom onset in the cortex. Our targeted therapeutically. XOWLPDWHJRDOLVWRGH¿QHWKHIXQFWLRQDOUHOHYDQFHRIWKHVHSURWHLQV and to reveal whether they promote disease progression or are sent 0(7+2'6 7KLV SURMHFW DQDO\]HG QRUPDO UHQDO FHOO OLQH +. DQG as a warning signal to the brain. UHQDO FDQFHU FHOO OLQHV 5;) 265& $ 2 3 &DNL6Q3PDQG$ XVLQJOHQWLYLUDOWUDQVJHQHRUNQRFNGRZQ 27 The preclinical development of a recombinant subunit H[SUHVVLRQ 3UROLIHUDWLRQ DVVD\V ZHUH FRXQWHG RYHU GD\ SHULRGV vaccine against whipworm: immunological characterization of DQGLQKLELWRUH[SHULPHQWVZHUHGRQHDWP0'DWDZDVDQDO\]HG SURWHFWLYHHI¿FDF\ YLDUHDOWLPH3&5DQGZHVWHUQEORW3DWLHQWVDPSOHVZHUHREWDLQHG Neima Briggs WKURXJKSURSHUSURFHGXUHVDW8$%$GGLWLRQDOO\7KH&DQFHU*HQRPH University of Texas - Houston / M.D. Anderson, Houston, USA Atlas was also analyzed. Trichuris trichiura, the common whipworm, is a leading cause 5(68/76 3KRVSKRJO\FHUDWH GHK\GURJHQDVH 3+*'+ WKH ¿UVW RI FKURQLF FROLWLV LQ WKH GHYHORSLQJ ZRUOG ZLWK DQ HVWLPDWHG DQGUDWHOLPLWLQJVWHSLQWKHVHULQHV\QWKHVLVSDWKZD\LVFRPPRQO\ million people living with whipworms in their colon. The disease reduced in both RCC patient samples and several RCC cell lines. GLVSURSRUWLRQDWHO\ DႇHFWV FKLOGUHQ UHVXOWLQJ LQ JURZWK VWXQWLQJ /HQWLYLUDOWUDQVJHQH/+*'+NQRFNGRZQRUUHH[SUHVVLRQZDVDEOH DQHPLDDQGFRJQLWLYHGH¿FLWV&XUUHQWDSSURDFKWRWKHFRQWUROVRLO WR HLWKHU GHFUHDVH RU LQFUHDVH 3+*'+ H[SUHVVLRQ UHVSHFWLYHO\ transmitted helminths, including trichuriasis, in endemic nations is 6HULQHDQGJO\FLQHVWDUYDWLRQVLJQL¿FDQWO\GHFUHDVHGSUROLIHUDWLRQLQ through annual mass drug administration. However, success has 5&&FHOOOLQHVZLWKUHGXFHG3+*'+ 265&3DQG2 EXW EHHQOLPLWHGGXHWRWKHFRPELQDWLRQRISRRUGUXJHႈFDF\KLJKUDWHV QRWLQ5&&FHOOOLQHVZLWKKLJKHUEDVDO3+*'+ 5;)6QSP RISRVWWUHDWPHQWUHLQIHFWLRQDQGIDLOXUHWRFRLPSOHPHQWDJJUHVVLYH 3KDUPDFRORJLFLQKLELWLRQRIVHULQHDQGJO\FLQHWUDQVSRUWHUV6/&$ VDQLWDWLRQ SURJUDPV 2XU ORQJWHUP JRDO LV WR GHYHORS D YDFFLQH DQG 6/&$ 61$7 DQG 61$7 ZLWK 0HO$% GHFUHDVHG against T. trichiura. Because there is no established laboratory animal SUROLIHUDWLRQ LQ 3 FHOOV ORZ 3+*'+ EXW QRW 5;) KLJK model for this human pathogen, we adapted the closely related 3+*'+ ZKHUHDVLQKLELWLRQRI6/&$DQG6/&$ $6&7DQG Trichuris muris parasite that infects rats and mice causing similar $6&7 GLGQRWDOWHUJURZWKRIHLWKHUFHOOOLQH pathophysiology. Both pathogens release macromolecules from a &21&/86,21/+*FRQWUROVGHQRYR serine and glycine synthesis unique anterior organ known as the stichosome, which facilitates LQ 5&& FHOO OLQHV 61$7 SDWKZD\ LQKLELWLRQ YLD 0H,$% UHGXFHV intracellular invasion into the colon. The majority of Trichuris genes SUROLIHUDWLRQ LQ ORZ 3+*'+ 5&& FHOO OLQHV 7DUJHWLQJ VHULQH DQG EHWZHHQ WKH WZR VSHFLHV DUH RUWKRORJV 9DFFLQDWLRQ ZLWK T. muris glycine transports looks to be a promising direction for novel, excretory/secretory (Tm-(6 SURWHLQV NQRZQ WR EH SUHGRPLQDQWO\ personalized RCC treatments.

34 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

29 Dynamics of dexmedetomidine-induced loss and return 30 6XUURXQGLQJ WKH HQHP\ LQYHVWLJDWLQJ WKH LQÀXHQFH of consciousness across primate neocortex of cervical microbiome and tumor microenvironment on the Jessica B. Briscoe prognosis of cervical cancer patients. Geisinger Commonwealth School of Medicine, USA Dewey Brooke Consciousness is the experience of perceiving the outside, as University of Alabama at Birmingham, Birmingham, USA well as our internal worlds, by synthesizing multiple sensory :KLOH QHDUO\ DOO FHUYLFDO WXPRUV DUH LQIHFWHG ZLWK +39 LQIHFWLRQ LQSXWVGHYHORSLQJHPRWLRQVRUIRUPLQJDQGUHÀHFWLQJRQRSLQLRQV DORQH LV QRW VXႈFLHQW IRU WXPRU GHYHORSPHQW $OWKRXJK PRVW However, we have yet to understand how the components of the FHUYLFDO +39 LQIHFWLRQV DUH FOHDUHG E\ FHOOPHGLDWHG LPPXQLW\ brain interact to mediate consciousness and arousal. Physicians progression to malignancy is linked to an immunosuppressive and scientists have manipulated arousal and consciousness for microenvironment comprising of a subset of protumorigenic decades, using anesthesia for purposes of surgery and procedures O\PSKRF\WHVDQGLPPXQRVXSSUHVVLYHVWURPDO¿EUREODVWV:KLOHWKH ZLWKRXWWKHNQRZOHGJHRIKRZLWDႇHFWVWKHLQWHUFKDQJHRIEUDLQ tumor microenvironment directs the biology of many cancers, recent networks. The body’s natural neural oscillations that create varying evidence has linked dysbiosis of the vaginal microbiome with the arousal and unconsciousness states during sleep have been shown extensive reprogramming and remodeling of the cervical stroma. to be physiologically distinct from the neural oscillation patterns 8VLQJ H[SUHVVLRQEDVHG FHOO GHFRQYROXWLRQ PHWKRGV RQ 51$VHT VHHQ GXULQJ DQHVWKHVLDLQGXFHGDURXVDODQGXQFRQVFLRXVQHVV IURPFHUYLFDOFDUFLQRPDVZHSHUIRUPHGKLHUDUFKLFDOFOXVWHULQJ This distinction may reveal more information about anesthesia’s on principle components to identify three patient clusters, which were HႇHFWVDVZHOODVWKHSKHQRPHQRQRIFKDQJHVLQDURXVDOVWDWHV LGHQWL¿HG DV HLWKHU LPPXQHULFK VWURPDOULFK RU DQ LQWHUPHGLDWH More importantly, electrophysiological studies conducted in immune/stromal type. Patients with immune enriched tumors URGHQWVQRQKXPDQSULPDWHVDQGKXPDQVDUHODUJHO\FRQGXFWHG exhibited a favorable prognosis. However, both the intermediate under anesthesia without a basic understanding of how anesthetic DQG VWURPDO HQULFKHG WXPRUV KDG VLJQL¿FDQWO\ ZRUVH RYHUDOO DQG agents interfere with baseline brain functional synchrony and GLVHDVHIUHHVXUYLYDO ')6 ZLWKWKHVWURPDOW\SHFDULQJWKHZRUVW QHXUDORVFLOODWLRQV:HK\SRWKHVL]HWKDWDQHVWKHWLFLQGXFHGDOWHUHG SURJQRVLV S DQG *HQH6HW(QULFKPHQW$QDO\VLV states of arousal are generated by highly structured and distinctive IRXQG WKDW JHQHV LPSOLFDWHG ZLWK WKH HSLWKHOLDOPHVHQFK\PDO oscillations, causing characteristic spatial and temporal neural transition were more strongly associated with the stromal subtype, patterns along the neocortex, thalamus, and brainstem. while the immune type was strongly associated with genes involved :HKDYHLQYHVWLJDWHGKRZWKHDQHVWKHWLFGH[PHGHWRPLGLQHHႇHFWV in p53 pathways and networks. Furthermore, we used microbial neural oscillations during loss of consciousness (LOC) and return transcriptomics to identify microbes that were both elevated in of consciousness (ROC) in the primate neocortex. We conducted SDWLHQWVZLWK')6 \HDUVDQGSDWLHQWVUHODSVHIUHHJUHDWHUWKDQ microelectrode array intracortical recordings in the somatosensory 5 years. 6 DQGIURQWDOYHQWUDOSUHPRWRU 30Y QHWZRUNVLQSULPDWHV 7KHVH UHVXOWV DUH VLJQL¿FDQW LQ WKDW WKH\ FRQ¿UP SUHYLRXV Following a behavioral task, to determine alertness and performance studies that tumors with higher stromal invasion and marked measures, dexmedetomidine infusion was administered through a immunosuppression exhibit the worst prognosis, while identifying YDVFXODUSRUW$OHUWQHVVDQGWULDOE\WULDOSHUIRUPDQFHZDVWKHQ IRUWKH¿UVWWLPHWRRXUNQRZOHGJHPLFUREHVDVVRFLDWHGZLWK used to analyze the primates’ behavior during LOC, ROC, and SURJQRVLV )XUWKHUPRUH ZH LGHQWL¿HG SRVVLEOH JHQHWLF PDUNHUV UHWXUQRISUHDQHVWKHWLFSHUIRUPDQFH 523$3 XVLQJWKHVWDWH WKDWZRXOGDLGERWKLQGLႇHUHQWLDWLQJWXPRUW\SHVDQGOLNHOLKRRGRI space model. recurrence. :H¿UVWDQDO\]HGWKHFKDQJHLQVSHFWURJUDPVLQ6DQG30Y'XULQJ ZDNHIXOQHVVEHWDRVFLOODWLRQVGRPLQDWHGLQ6DQG30YZKLOHWKH 31 Enteroendocrine cell activity modulates vagal response RQVHWRI/2&ZDVLGHQWL¿HGE\DEULHILQFUHDVHRIDOSKDSRZHU in vivo RVFLOODWLRQVPRUHREYLRXVLQ6WKDQ30Y7KURXJKRXWDQHVWKHVLD Kelly L. Buchanan VORZGHOWDRVFLOODWLRQVDSSHDUHGZKLOH52&ZDVDVVRFLDWHGZLWK Duke University, USA D UHWXUQ RI DOSKD RVFLOODWLRQ GRPLQDQFH DQG GHFUHDVH LQ VORZ Overeating is linked to an altered perception of the reward value delta waves. As the animal recovered, alpha waves appeared to of nutrients. But how this signal is transduced from the gut to the increase its frequency toward the beta range; however, ROPAP did brain remains unknown. Like taste receptor cells in the tongue, the QRW DFKLHYH SUHDQHVWKHWLF EHWD RVFLOODWLRQ IUHTXHQF\ DQG SRZHU gastrointestinal tract also has cells that sense nutrients. These are 6LQJOHQHXURQVSLNHUHVSRQVHVZHUHFOHDUO\GLႇHUHQWLQ6DQG called enteroendocrine cells (EECs). EECs are known to respond to 30Y7KH30YVSLNH¿ULQJUDWHLQFUHDVHGXSRQ/2&ZKLOH6 OXPLQDOVWLPXOLDQGUHOHDVHKRUPRQHVWKDWDFWRQYDJDOQHUYH¿EHUV neurons decreased — a response that continued through recovery. Recently, we discovered that EECs can also form synaptic links with 7KHVH¿QGLQJVVXJJHVWWKDWGH[PHGHWRPLGLQHLQGXFHG/2&DQG vagal nodose neurons. Here, we sought to establish whether EECs ROC are both associated with an increase in alpha oscillations GLUHFWO\ WUDQVGXFH VWLPXOL RQWR YDJDO QHUYH ¿EHUV :H FRPELQHG LQ6DQG307KHVORZGHOWDRVFLOODWLRQVDUHGRPLQDQWZKLOHWKH whole nerve electrophysiology of the cervical vagus nerve and EEC DQLPDOV DUH XQFRQVFLRXV 6SLNH ¿ULQJ UHVSRQVH DSSHDUV WR EH RSWRJHQHWLFVWRGLVVHFWWKHIXQFWLRQDOFRQQHFWLYLW\RIWKLVJXWEUDLQ UHJLRQVSHFL¿FEXWFOHDUO\DVVRFLDWHGZLWKFRQVFLRXVQHVVFKDQJHV neuroepithelial circuit. Our results show the following: Further investigation is underway to identify mechanisms of cortical, )LUVW VXJDUV GHOLYHUHG LQWUDOXPLQDOO\ VWLPXODWH YDJDO ¿ULQJ UDWH thalamic, and brainstem responses under dexmedetomidine 6XFURVH 'JOXFRVH WKH QRQQXWULWLYH VZHHWHQHU VXFUDORVH DQG anesthesia. WKH QRQPHWDEROL]HG VXJDU PHWK\O Į'JOXFRS\UDQRVLGH EXW QRW IUXFWRVHFDXVHDUDSLGDQGVLJQL¿FDQWLQFUHDVHLQYDJDO¿ULQJUDWH ZKHQGHOLYHUHGLQWUDOXPLQDOO\LQPLFH7KHUHVSRQVHLVQRWREVHUYHG when the stimulus is applied intraperitoneally or directly onto the

www.jointmeeting.org 35 POSTER ABSTRACTS

FHUYLFDOYDJXV7KHHႇHFWVRQFHUYLFDOYDJDO¿ULQJUDWHDUHDEROLVKHG genetic analysis reported AT/RT to have high expression of enhancer after a subdiaphragmatic vagotomy, indicating that an intact vagus is of zeste homolog 2 (EZH2), a methyltransferase known to have necessary for the response. oncogenic properties in many cancers. Our laboratory previously 6HFRQG ((&V WUDQVGXFH WKH VWLPXOL RI ERWK QXWULWLYH DQG QRQ GHPRQVWUDWHGWKDWWKHDQWLYLUDOGUXJULEDYLULQDSSURYHGE\WKH)'$ QXWULWLYH VXJDUV RQWR WKH YDJXV QHUYH 8VLQJ D PRXVH LQ ZKLFK for treatment of hepatitis C, inhibited glioma cell growth in vitro and EECs express the excitatory channelrhodopsin 2, we found that in vivo, potentially through modulation of EZH2. Based on these LQWUDOXPLQDOVWLPXODWLRQZLWKDQPODVHUUDSLGO\DQGVLJQL¿FDQWO\ ¿QGLQJV DQG WKH ODFN RI D SUHFOLQLFDO PRGHO RI ULEDYLULQ LQ $757 LQFUHDVHV YDJDO ¿ULQJ UDWH 7KLV LQFUHDVH LV FRPSDUDEOH WR WKH ZHLQYHVWLJDWHGWKHHႇHFWRIULEDYLULQRQ$757LQYLWURDQGLQYLYR sucrose response. Then, using a mouse in which EECs express the 7KUHH GLႇHUHQW KXPDQ $757 FHOO OLQHV %7 %7 DQG %7 inhibitory halorhodopsin, we found that both sucrose and sucralose were selected for investigation. Cell proliferation was assessed via vagal responses are attenuated when EECs are stimulated with a FHOO FRXQWLQJ &HOO F\FOH DQG FHOO GHDWK SURFHVVHV ZHUH TXDQWL¿HG QPODVHUOLJKW XVLQJ ÀRZ F\WRPHWU\ 7XPRU PLJUDWLRQ LQYDVLRQ DQG DGKHVLRQ capacities were assessed via scratch wound, Boyden chamber, and Third, EEC transduction of a sucrose stimulus is dependent upon the adhesion assays, respectively. Ribavirin’s mechanism of action in VRGLXPJOXFRVHWUDQVSRUWHU6*/7:HIRXQGWKDWWKHVXFURVHEXW AT/RT was studied using Western blots for several known ribavirin not sucralose stimulus is abolished when the solution contains the WDUJHWV)LQDOO\ZHWHVWHGULEDYLULQHႈFDF\LQYLYRXVLQJDQRUWKRWRSLF 6*/7UHFHSWRUEORFNHUSKORULG]LQ xenograft AT/RT model in athymic mice. These data suggest that EECs modulate vagal activity within seconds :HSURYLGHHYLGHQFHWKDWULEDYLULQVLJQL¿FDQWO\LPSDLUV$757 LQUHVSRQVHWR'JOXFRVHDQGWKDWWKHUHVSRQVHLVGHSHQGHQWXSRQ cell growth, increases cell cycle arrest, and induces cell death, WKHVRGLXPJOXFRVHWUDQVSRUWHU6*/77KLVQHXURHSLWKHOLDOFLUFXLW SRWHQWLDOO\WKURXJKPRGXODWLRQRIWKH(=+DQGRUH,)(SDWKZD\V represents a therapeutic target to alter the transduction of caloric :HDOVRGHPRQVWUDWHWKDWULEDYLULQVLJQL¿FDQWO\LPSDLUV$757FHOO reward from gut to brain and to modulate appetite. migration, invasion, and adhesion. Most importantly, we show that 32 Photoacoustic tomography of intact human prostates ULEDYLULQVLJQL¿FDQWO\LPSURYHVWKHVXUYLYDORIPLFHRUWKRWRSLFDOO\ and vascular texture analysis identify prostate cancer biopsy LPSODQWHG ZLWK %7 FHOOV 5LEDYLULQWUHDWHG DQLPDOV H[KLELWHG D targets VLJQL¿FDQWO\LQFUHDVHGPHGLDQVXUYLYDO GD\V FRPSDUHGZLWK FRQWUROV GD\V 3 Brittani Bungart Purdue University, Boston, USA 2XU ZRUN HVWDEOLVKHV WKDW ULEDYLULQ LV HႇHFWLYH DJDLQVW $757 LQ YLWUR DQG LQ YLYR *LYHQ WKH ODFN RI VWDQGDUG WKHUDS\ IRU $757 The current methods of the prostate biopsy either do not target WKHVH¿QGLQJV¿OODQDUHDRIXQPHWQHHGDQGFRXOGUHSUHVHQWDQHZ SRWHQWLDOWXPRUVRUUHTXLUHVHSDUDWHLPDJLQJIRUWDUJHWLGHQWL¿FDWLRQ therapeutic option for children with this deadly disease. of the biopsy procedure. Our objective is to determine the ability for the multimodal imaging technique of blood and lipid photoacoustic 34 Glucose transporter GLUT3: a novel molecular target in WRPRJUDSK\ 3$7 LPDJLQJ DQG XOWUDVRQRJUDSK\ 86 IROORZHG E\ bevacizumab-resistant glioblastoma WH[WXUHEDVHGLPDJHSURFHVVLQJWRLGHQWLI\WDUJHWVIRUWKHSXUSRVHRI Ankush Chandra JXLGLQJSURVWDWHELRSV\LQUHDOWLPH University of California, San Francisco, USA 1LQHH[YLYRKXPDQSURVWDWHVZHUHLPDJHGZLWKDQGQP In spite of optimal treatments and recent advances in our 3$7DQG0+]86GLUHFWO\IROORZLQJUDGLFDOSURVWDWHFWRP\7KH XQGHUVWDQGLQJRILWVELRORJ\JOLREODVWRPD *%0 UHPDLQVWKHPRVW 3$7DQG86LPDJHIUDPHVFRUUHVSRQGLQJWRZKROHPRXQWKLVWRORJ\ lethal primary adult brain tumor, with a poor median survival of less VOLGHVZHUHXVHGIRUHLWKHUWH[WXUHEDVHGNPHDQVFOXVWHULQJIHDWXUH than 15 months from diagnosis. While phase II clinical trials showed OHDUQLQJRUOHDUQHGIHDWXUHWHVWLQJ6L[SURVWDWHVZHUHDVVLJQHGWR encouraging results, randomized phase III clinical trials failed to the learning group and three to the testing group. Following cluster VKRZHႈFDF\RIWKH9(*)QHXWUDOL]LQJDQWLERG\EHYDFL]XPDEZKLFK center assignment of the testing group’s pixels, a regional density devascularizes the tumor, as most tumors progress during treatment ¿OWHURIWKHWXPRUFOXVWHUHGSL[HOVZDVDSSOLHG7KHFHQWHURIPDVV and develop a much more aggressive and invasive molecular IRUHDFKJURXSRIWXPRUDVVLJQHGSL[HOVZDVFRQVLGHUHGWKHELRSV\ SKHQRW\SHDVVRFLDWHGZLWKUHVLVWDQFH2XUODERUDWRU\KDVLGHQWL¿HG targets and compared to histopathology. DQGIRXQGRYHUH[SUHVVLRQRIWKHJOXFRVHWUDQVSRUWHU*/87WREH 8SRQ DVVHVVPHQW RI HDFK 3$7 FKDQQHO QP 3$7 GLG QRW DKDOOPDUNRIUHVLVWDQFHWRDQWLDQJLRJHQLFWKHUDS\LQ*%0FDXVLQJ provide a unique contribution to the clustering results, and thus only D PHWDEROLF UHFLUFXLWU\ ZLWKLQ WKH WXPRU ,Q RXU VWXGLHV ZH KDYH WKHQP3$7DQG86FKDQQHOVZHUHXWLOL]HGIRUIXUWKHUDQDO\VLV DOVRVKRZQ*/87RYHUH[SUHVVLRQWREHDVVRFLDWHGZLWKLQFUHDVHG %LRSV\WDUJHWVLGHQWL¿HG RIWKHSULPDU\WXPRUVDQG VXUYLYDODQGSUROLIHUDWLRQRIEHYDFL]XPDEUHVLVWDQW*%0FHOOVERWK (2/3) of the secondary tumors in the testing group. The total number LQYLWURDQGLQYLYR:HKDYHDOVRIRXQGWKDW*/87LQKLELWLRQXVLQJ RIWDUJHWVSHUFDVHDUHDQG,QFRQFOXVLRQQP3$7 DQ LQGLUHFW LQKLELWRU GHFUHDVHG VXUYLYDO RI EHYDFL]XPDEUHVLVWDQW DQG86WH[WXUHEDVHGIHDWXUHDQDO\VLVSURYLGHGVXFFHVVIXOSURVWDWH *%0 FHOOV LQ FXOWXUH VXJJHVWLQJ */87 DV D SRWHQWLDO WDUJHWDEOH biopsy targets with lower number of suggested cores compared to biomarker of resistance. We believe that direct molecular inhibition of current biopsy protocols. */87ZLOOUHYHUVHWKHDJJUHVVLYHELRORJ\RIEHYDFL]XPDEUHVLVWDQW *%0 DQG RYHUFRPH UHVLVWDQFH WR DQWLDQJLRJHQLF WKHUDSLHV 8VLQJ 33 5LEDYLULQDVDSRWHQWLDOWKHUDSHXWLFIRUDW\SLFDOWHUDWRLG VL[QRYHOGLUHFW*/87LQKLELWRUVV\QWKHVL]HGDQGSURYLGHGE\RXU rhabdoid rumors FROODERUDWRUVZHIRXQGWKDWDOOVL[LQKLELWRUVLQKLELWHGEHYDFL]XPDE Joshua Casaos UHVLVWDQW*%0SUROLIHUDWLRQZLWKWKUHHRIWKHVL[LQKLELWRUVLQKLELWLQJ Johns Hopkins University, USA SUROLIHUDWLRQE\:HDUHDQDO\]LQJWKHHႇHFWVRIWKHVHLQKLELWRUV Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive RQ EHYDFL]XPDEUHVLVWDQW *%0 FHOO ELRFKHPLVWU\ PRUSKRORJ\ pediatric brain tumors with no current standard of care. A recent LQYDVLYHQHVV DQG JURZWK LQ FXOWXUH DQG LQ YLYR WR IXOO\ GH¿QH WKH

36 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

HႇHFW RI GLUHFW */87 LQKLELWLRQ RQ EHYDFL]XPDEUHVLVWDQW *%0 ,Q WKH SUHVHQW VWXG\ ZHHNROG PDOH 7K\<)3 DQG 1*) :H EHOLHYH WKDW HOXFLGDWLQJ WKH ELRORJLFDO DFWLRQV RI GLUHFW */87 H*)3 UHSRUWHU PLFH XQGHUZHQW VWUHVV IUDFWXUH LQMXU\ XVLQJ D LQKLELWRUVZLOOGH¿QHWDUJHWLQJ*/87LQEHYDFL]XPDEUHVLVWDQW*%0 previously validated cyclic axial compression of the right forelimb. DVDQHႇHFWLYHVWUDWHJ\WRRYHUFRPH*%0UHVLVWDQFHWREHYDFL]XPDE Bone repair was assessed using routine histology as well as and unravel the full therapeutic potential of antiangiogenic agents. LPPXQRKLVWRORJLFDO DQDO\VLV WR DVVHVV IRU LQÀDPPDWRU\ UHVSRQVH &' DQG YDVFXODU SUROLIHUDWLRQ &' ,Q 7K\<)3 UHSRUWHU 35 7KH WDQGHP ]LQF ¿QJHU P51$ ELQGLQJ SURWHLQ samples, immunohistochemistry was performed for the sympathetic Tristetraprolin, is a novel regulator of cardiac fatty acid PDUNHU7+ W\URVLQHK\GUR[\ODVH DQGVHQVRU\QHUYHPDUNHU&*53 PHWDEROLVPWKURXJKLWVHIIHFWRQ33$5D FDOFLWRQLQJHQHUHODWHGSHSWLGH Hsiang-Chun Chang 6WUHVVIUDFWXUHLQGXFHVHDUO\DQGUREXVW1*)UHSRUWHUDFWLYLW\ZLWKLQ Northwestern University, Chicago, USA WKHLQMXUHGERQH$WDQGGD\VDIWHULQMXU\LQFUHDVHG1*)UHSRUWHU Introduction: Altered substrate utilization has been described in activity was observed among the resident periosteal stromal cells type II diabetes and heart failure (HF), but current therapies do not DV ZHOO DV LQÀDPPDWRU\ FHOOV DGMDFHQW WR WKH IUDFWXUH VLWH &' WDUJHWWKHPHWDEROLFGHUDQJHPHQWVLQWKHVHGLVRUGHUV,GHQWL¿FDWLRQ LPPXQRKLVWRFKHPLFDOVWDLQLQJKLJKOLJKWHGDGXDOVRXUFHRI1*)ZLWKLQ of novel pathways regulating cellular metabolism could facilitate the WKHHDUO\IUDFWXUHSHULRGDPRQJERWKVWURPDOFHOOVDQGLQÀDPPDWRU\ development of new therapies. Tristetraprolin (TTP) is a tandem FHOOV1H[WQHXURQDOVSURXWLQJDQGLQJURZWKZHUHH[DPLQHGZLWKLQ ]LQF¿QJHUSURWHLQWKDWELQGVWR$8ULFKHOHPHQWV $5(V LQWKH¶ WKHVDPHPRGHOXVLQJ7K\<)3UHSRUWHUDQLPDOV DSDQQHXURQDO XQWUDQVODWHG UHJLRQ 875 RI P51$ PROHFXOHV DQG FDXVHV WKHLU UHSRUWHU ,QWKHXQLQMXUHGSHULRVWHXP<)3QHUYH¿EHUVDUHRIWKLQ degradation. Its expression is reduced in patients with diabetes, caliber and indiscrete. Early time points after fracture demonstrated and its cellular level is regulated by mTOR, a key protein involved DQLQFUHDVHGGHQVLW\RI<)3QHUYH¿EHUVZDVREVHUYHGDGMDFHQW in cellular metabolism. Furthermore, the yeast homolog of TTP has WR WKH IUDFWXUH VLWH 7KH EXON RI <)3 QHUYHV VXUURXQGLQJ WKH been suggested to play a role in metabolism. Thus, we hypothesized IUDFWXUHVLWHZHUHIRXQGWREH&*53VHQVRU\QHUYHVZKLOHDVPDOO that TTP regulates cardiac metabolism and its deletion prevents the PLQRULW\ZHUHIRXQGWREH7+V\PSDWKHWLF¿EHUV$GGLWLRQDOO\DV GHYHORSPHQWRI+)WKURXJKLWVHႇHFWVRQVXEVWUDWHXWLOL]DWLRQLQWKH neural density increased, a trend toward increased vascularity of the KHDUW5HVXOWV:H¿UVWDVVHVVHGWKHHႇHFWVRI773PRGXODWLRQRQ fracture site was also observed. cellular substrate utilization, and found that TTP downregulation in 2XUGDWDGRFXPHQWVDWLPHOLQHRI1*)H[SUHVVLRQLQDQDSSHQGLFXODU cultured cardiomyocytes resulted in higher palmitate uptake and VWUHVVIUDFWXUHPRGHOZLWKLQWKHHDUO\VWURPDOLQÀDPPDWRU\PLOLHXRI R[LGDWLRQ ZKLOH LWV RYHUH[SUHVVLRQ KDG WKH RSSRVLWH HႇHFW 6LQFH WKH VRIW FDOOXV 7KLV UREXVW H[SDQVLRQ RI DQ 1*) GRPDLQ ZLWKLQ 773UHJXODWHVLWVWDUJHWVDWWKHP51$OHYHOZHVWXGLHGWKHP51$ early bone healing corresponds to later neural sprouting and OHYHOV RI $5(FRQWDLQLQJ JHQHV LQYROYHG LQ OLSLG PHWDEROLVP DQG LQJURZWK RI SUHGRPLQDQWO\ &*53 VHQVRU\ ¿EHUV LQWR DQG DURXQG IRXQG WKDW RQO\ 33$5 P51$ WR EH VLJQL¿FDQWO\ LQFUHDVHG ZLWK the bone repair site. Moreover, sensory nerve ingrowth seems to be TTP downregulation. Furthermore, we demonstrated that TTP FRRUGLQDWHGZLWKYDVFXODULQJURZWK7KHVHQHZ¿QGLQJVVXJJHVWD SK\VLFDOO\LQWHUDFWVZLWK33$5P51$DQGWKHDFWLYLW\RIDOXFLIHUDVH previously undescribed role for sensory nerves in the trophic support UHSRUWHU KDUERULQJ IXOOOHQJWK 33$5 ¶875 LV LQFUHDVHG ZLWK 773 for fracture repair. GRZQUHJXODWLRQ $GGLWLRQDOO\ 33$5 P51$ LV VWDELOL]HG ZLWK 773 knockdown. We then studied the role of TTP in cardiac metabolism 37 8VLQJ DUWL¿FLDO LQWHOOLJHQFH WR LGHQWLI\ QRQLQYDVLYH XVLQJ PLFH ZLWK FDUGLDFVSHFL¿F 773 NQRFNRXW $OWKRXJK FDUGLDF imaging biomarkers in lung cancer — a deep learning radiomic VSHFL¿F773NQRFNRXWPLFHKDGQRUPDOFDUGLDFIXQFWLRQDWEDVHOLQH approach they displayed higher fatty acid utilization compared to wild type Tafadzwa Chaunzwa OLWWHUPDWHFRQWURO:HDOVRGHPRQVWUDWHGDVLJQL¿FDQWO\KLJKHU773 Yale School of Medicine, USA levels in failing human and mouse cardiac samples, suggesting that TTP levels are altered in HF. Conclusion: Our results demonstrate Lung cancer is the leading cause of cancer death and morbidity. that TTP is a novel regulator of cardiac fatty acid metabolism through 7KHKLJKGHJUHHRILQWUDDQGLQWHUWXPRUKHWHURJHQHLW\SUHVHQWVD LWV HႇHFW RQ 33$5 DQG WKDW LWV OHYHOV DUH LQFUHDVHG LQ +)7KXV FKDOOHQJH LQ WUHDWPHQW +RZHYHU HDUO\VWDJH GLVHDVH VSHFL¿FDOO\ modulation of TTP may be a viable therapeutic approach for HF. VWDJH,QRQVPDOOFHOOOXQJFDQFHU 16&/& LVDPHQDEOHWRFXUDWLYH UHVHFWLRQ 3RRU VXUJLFDO FDQGLGDWHV PD\ EHQH¿W IURP VWHUHRWDFWLF 36 NGF signaling in stress fracture healing ERG\ UDGLDWLRQ WKHUDS\ 6%57 0DQ\ SURJQRVWLF PROHFXODU DQG Leslie L. Chang JHQRPLFELRPDUNHUVKDYHEHHQLGHQWL¿HGLQOXQJFDQFHUDQGWKHUHLV Johns Hopkins University, USA a growing body of evidence suggesting radiomic phenotypes (drawn from medical images) can augment prognostic power when used in In contrast to the large body of literature on the role of peripheral FRPELQDWLRQZLWKERWKFOLQLFDOIHDWXUHVDQGWXPRUJHQRPLFSUR¿OHV nerves in other tissues, few studies have investigated the function Recent advances in computation and convolutional neural networks RISHULSKHUDOQHUYHVLQWKHVNHOHWRQ'HYHORSLQJSHULSKHUDOWLVVXHV &11V KDYHDOVRRSHQHGQHZDYHQXHVWRWXPRUSDWFKDQDO\VLVDQG GLFWDWH LQQHUYDWLRQ E\ VHFUHWLRQ RI VSHFL¿F QHXURWURSKLQV ZKLFK IHDWXUHH[WUDFWLRQIURPGLႇHUHQWLPDJLQJPRGDOLWLHV promote neuronal survival by activation of tyrosine kinase receptors. 7KH SURWRW\SLF WDUJHW WLVVXHGHULYHG QHXURWURSKLQ LV QHUYH JURZWK In this study we set out to develop a deep learning model that can IDFWRU 1*) ,PSRUWDQWO\ WKH YDVW PDMRULW\ RI QHUYHV LQ PDWXUH act as a noninvasive prognostic biomarker in patients with stage I bone are thinly myelinated or unmyelinated sensory neurons, which 16&/&WUHDWHGZLWKVXUJHU\,QFRQWUDVWWR³FRQYHQWLRQDO´UDGLRPLFV H[SUHVVWKH1*)KLJKDႈQLW\UHFHSWRU7UN$$VVHQVRU\QHUYHVKDYH which relies on engineered quantitative imaging features (e.g., also been shown to be important mediators of early response to shape compactness, wavelet gray level nonuniformity HLH), deep mechanical loading, we sought to develop a better understanding of OHDUQLQJEDVHGLPDJHDQDO\VLVDOJRULWKPVDUHDEOHWRDXWRPDWLFDOO\ WKHH[SUHVVLRQRIWKHQHXURWURSKLQ1*)DQGVXEVHTXHQWLQQHUYDWLRQ ¿QGRSWLPDOUXOHVDQGSDUDPHWHUVIURPGDWD2XUPRGHOZRXOGEH of bone in a clinically relevant stress fracture model. DEOH WR DVVLJQ SDWLHQWV WR VKRUWWHUP RU ORQJWHUP VXUYLYDO JURXSV

www.jointmeeting.org 37 POSTER ABSTRACTS

based on computed tomography (CT) characteristics. for identifying potential synthetic lethal interactions by screening Initial data mining yielded a discovery cohort of 500 patients who for genes that are consistently retained in the context of a tumor XQGHUZHQW VXUJHU\ IRU VWDJH , 16&/& DW 0DVVDFKXVHWWV *HQHUDO VXSSUHVVRUGHOHWLRQRUDQRQFRJHQHDPSOL¿FDWLRQRQDSDQFDQFHU +RVSLWDO 0*+ EHWZHHQ DQG 3UHVXUJLFDO &7 VWXGLHV scale to analyze 11,025 cases encompassing 32 cancer types from ZLWKRUZLWKRXWFRQWUDVWZHUHUHWULHYHGIRUaSDWLHQWV,PDJHSUH WKH &DQFHU *HQRPH$WODV IRU JHQHV WKDW SRVVHVV ORVVRIIXQFWLRQ SURFHVVLQJLQFOXGHGPDQXDOWXPRULGHQWL¿FDWLRQDQGVHJPHQWDWLRQ PXWDWLRQV WKDW DUH PXWXDOO\ H[FOXVLYH RI ORVVRIIXQFWLRQ LQ 37(1 ZLWKVHHGSRLQWSODFHPHQWWRSUHGH¿QHDYR[HOFXELFDOUHJLRQRI JDLQRIIXQFWLRQ LQ (*)5 3,.&$ $.7 $.7 $.7 RU KLJK interest (ROI) that contains tumor, and creation of isotropic voxel SKRVSKR$NW 6HU E\ 533$ %DVHG RQ WKHVH FULWHULD dimensions in CT data with spatial interpolation. Further data curation FDVHV ZHUH FODVVL¿HG DV$NW SDWKZD\ JDLQRIIXQFWLRQ DQG \LHOGHGYROXPHWULFDQGGLPHQVLRQDOLPDJLQJVDPSOHVWRIHHG FDVHVZHUHFODVVL¿HGDVZLOGW\SH2XUVFUHHQLQJ\LHOGHGDOLQF51$ LQWR RXU QHXUDO QHWZRUNV$ GLPHQVLRQDO 9** &11 PRGHOHG /,1&WKDWKDG]HURORVVRIIXQFWLRQPXWDWLRQVLQWKH$NWJDLQ after the mammalian visual cortex was used to perform visual RIIXQFWLRQFRKRUWDQGORVVRIIXQFWLRQPXWDWLRQVLQWKHZLOGW\SH UHFRJQLWLRQDQGGDWDDQDO\VLV7KHPRGHOZDVWUDLQHGRQODEHOHG FRKRUW /,1& ZDV RYHUH[SUHVVHG LQ 37(1GH¿FLHQW 6) &7VFDQVPDWFKHGWRRQHRIWZRJURXSVEDVHGRQ\HDUVXUYLYDO JOLREODVWRPD DQG '8 SURVWDWH FDQFHU FHOO OLQHV VXJJHVWLQJ 'DWDFRQWDLQLQJYDULDWLRQVRIVFDQQHUVDQGLPDJLQJSURWRFROVZHUH LQFUHDVHG GHSHQGHQF\ RQ WKLV OLQF51$ GXULQJ WKH 37(1GH¿FLHQW used in training to create a model that is robust for the variations. VWDWH 7KXV ZH K\SRWKHVL]HG WKDW 37(1 GHOHWLRQ GLVLQKLELWV WKH $NWSDWKZD\WKHUHE\LQKLELWLQJ)R[2ZKLFKGLVLQKLELWV/,1& 2XUPRGHOOHDUQHGWRFODVVLI\SDWLHQWVZLWKORQJWHUPYHUVXVVKRUW expression. Three conserved FoxO binding sites were found using WHUPVXUYLYDOLQDWHVWVHWRISDWLHQWVZLWKDFFXUDF\7KHVH ),02WRVHDUFKIRUWKHFRQVHQVXVELQGLQJPRWLIEHWZHHQNEIURP SUHOLPLQDU\ ¿QGLQJV VXJJHVW WKDW DUWL¿FLDO LQWHOOLJHQFHHQKDQFHG WKHWUDQVFULSWLRQVWDUWVLWHWRNEIURPWKHWUDQVFULSWLRQHQGVLWHRI radiomic feature extraction and predictive modeling can improve /,1&LQDOLJQHGVHTXHQFHVRIKXPDQPRXVHDQGDWOHDVWRQH WKHFOLQLFLDQ¶VDELOLW\WRDVVHVVWKHEHQH¿WVRIWUHDWPHQWLQSDWLHQWV RIFRZUDEELWVKHHSSLJGRJFDWRUKRUVHZLWKSYDOXH ZLWKHDUO\VWDJH16&/&$QHYHQODUJHUGDWDVHWRIaSDWLHQWV %/$67 DJDLQVW +XPDQ 5HI6HT*HQH VHTXHQFHV GHWHUPLQHG ZLWKVWDJH,,DQGVWDJH,,,OXQJFDQFHUWUHDWHGDW0*+LVDOVREHLQJ putative ELQGLQJ HOHPHQWV LQ WZR VSOLFH YDULDQWV RI /,1& curated and added to separate analyses. In addition, pretrained 'HSOHWLRQRI/,1&E\&5,635PHGLDWHGGHOHWLRQRIWKHELQGLQJ GLPHQVLRQDOPRGHOVZLOODOVREHHPSOR\HG element for each splice variant yielded a reduction in cell proliferation 38 Targeting the vitamin B6 pathway as a novel therapeutic DQGVXUYLYDOLQ37(1GH¿FLHQW6)*%0FHOOV7KHVSOLFHYDULDQW strategy for cutaneous T cell lymphoma RI /,1& ZLWK WKH JUHDWHU GLႇHUHQFH LQ SKHQRW\SH EHWZHHQ 37(1.2DQG:7ZDVIXUWKHUDQDO\]HGE\FKURPDWLQLVRODWLRQE\ Cynthia Chen 51$SXUL¿FDWLRQLQRUGHUWRYDOLGDWHWKHSRWHQWLDOJHQHWDUJHWV Columbia University College of Physicians & Surgeons, USA LGHQWL¿HG E\ %/$677KH ELQGLQJ VLWHV YDULHG IURP DV VKRUW DV Cutaneous T cell lymphoma (CTCL) is a malignancy of predominantly ES LQ OHQJWK ZLWK VHTXHQFH LGHQWLW\ WR WKH OLQF51$ ELQGLQJ VNLQKRPLQJ&'O\PSKRF\WHV3DWLHQWVZLWKDGYDQFHGVWDJHVRI HOHPHQWWRDVORQJDVESZLWKLGHQWLW\7KH(UE%VLJQDOLQJ CTCL have a high mortality rate, and even those with more indolent SDWKZD\ ZDV IRXQG WR EH KLJKO\ UHSUHVHQWHG LQ WKLV OLVW E\ .(** disease experience severely diminished quality of life due to recurrent pathway enrichment analysis. Together, these data demonstrate VNLQLQIHFWLRQVSDLQDQGSUXULWXV&XUUHQWO\WKHUHDUHIHZVSHFL¿F the utility of synthetic essentiality as a powerful tool for identifying therapeutic targets known in CTCL, highlighting the need to identify SDQFDQFHU YXOQHUDELOLWLHV )XUWKHUPRUH ZH H[SORUH D QRYHO OLQN not only key mediators in disease pathogenesis, but also druggable EHWZHHQWKH$NWDQG(UE%SDWKZD\V/,1&ZKLFKKLJKOLJKWV ones. One aspect of CTCL cells that has not been well studied thus WKHLPSRUWDQFHRIOLQF51$VLQPHGLDWLQJWKHFURVVWDONEHWZHHQNH\ far is their dependence on unique metabolic pathways to support RQFRJHQLFVLJQDOLQJWRDႇHFWFDQFHUYLDELOLW\ dysregulated growth. Here, we identify the vitamin B6 pathway as a QRYHOSRWHQWLDOWDUJHWIRUWKHWUHDWPHQWRI&7&/8VLQJDQVJ51$ 40 Connecting the dots between pain modulation and pain mediated knockout platform, we found that loss of pyridoxal kinase transmission in acute and chronic pain 3';. DQ HQ]\PH WKDW FRQYHUWV YLWDPLQ % WR LWV DFWLYH IRUP QiLiang Chen pyridoxal phosphate (PLP), resulted in reduced proliferation of the Oregon Health & Science University, Portland, USA CTCL cell lines MyLa and PB2B. Consistently, administration of the Chronic pain is a prevalent condition with profound physical, )'$DSSURYHGGUXJLVRQLD]LGFRPPRQO\XVHGWRWUHDWWXEHUFXORVLV psychological, social and economic impacts. An important factor and known to block the vitamin B6 pathway, recapitulated this LQ ERWK QRUPDO DQG FOLQLFDOO\ VLJQL¿FDQW SDLQ LV WKH LQWULQVLF SDLQ proliferation defect in vitro. Furthermore, cells cultured with isoniazid modulating system, which regulates nociceptive processing via demonstrated higher levels of apoptosis and delayed cell cycle projections from the brainstem to the dorsal horn. The output of this progression. Future studies will assess the feasibility of repurposing PRGXODWLQJ V\VWHP WKH URVWUDO YHQWURPHGLDO PHGXOOD 590 FDQ LVRQLD]LGDVDQHZWUHDWPHQWIRU&7&/E\WHVWLQJWKHGUXJ¶VHႇHFWV facilitate or suppress nociceptive transmission at the dorsal horn on primary samples from patients with CTCL. E\ WKH UHVSHFWLYH DFWLRQ RI WZR GLVWLQFW FODVVHV RI QHXURQV ³21 39 Pan-cancer Akt pathway synthetic essential long FHOOV´ DQG ³2))FHOOV´ %RWK FODVVHV UHVSRQG WR QR[LRXV LQSXWV LQWHUJHQLFQRQFRGLQJ51$/,1& however, the pathway through which noxious inputs drive changes LQ 590 DFWLYLW\ LV RQO\ QRZ EHLQJ GH¿QHG$QDWRPLFDOO\ WKH 590 -DVSHU5&KHQ receives direct spinoreticular and trigeminal reticular inputs, as well The University of Texas MD Anderson Cancer Center, USA DVDႇHUHQWVIURPWKHSDUDEUDFKLDOFRPSOH[ 3% ZKLFKLVWKHPDMRU The Akt pathway is one of the most commonly activated in WDUJHWRIVXSUDVSLQDOSURMHFWLRQVIURPWKHVXSHU¿FLDOGRUVDOKRUQ7KH oncogenesis. To identify gene targets that could lead to the aim of this study was to test the hypothesis that noxious information is development of therapies across multiple cancer types, we applied UHOD\HGWRWKHSDLQPRGXODWLQJQHXURQVRIWKH590YLDWKH3%XQGHU the principle of synthetic essentiality, a recently described framework EDVDOFRQGLWLRQVDQGLQSHUVLVWHQWLQÀDPPDWLRQ21FHOOVDQG2))

38 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

FHOOVZHUHUHFRUGHGLQWKH590LQOLJKWO\DQHVWKHWL]HGUDWV7KH21 42 Chromosome bridge resolution requires mechanical DQG2))FHOODFWLYLW\ZHUHDWWHQXDWHGRUEORFNHGE\SKDUPDFRORJLFDO forces from actin-based contractility inactivation of the lateral PB FRQWUDODWHUDO, but not ipsilateral, to $QQD0&KHQJ the noxious stimulus. By contrast, in animals subjected to chronic University of South Florida Morsani College of Medicine, USA LQÀDPPDWLRQ &)$ LQ RQH KLQGSDZ EORFN RI 3% LSVLODWHUDO to the LQÀDPHGSDZLQWHUIHUHGZLWKWKH21DQG2))FHOODFWLYLW\HOLFLWHGE\ Chromosome bridges result from errors in cell division and form normally innocuous stimulation of that paw. This implies recruitment chromatin threads that connect daughter nuclei after division. These RIDQRUPDOO\LQDFWLYHSDWKZD\GXULQJLQÀDPPDWLRQ$GLUHFW3%LQSXW bridges eventually break (“resolve”), and the daughter cells inherit WR 590 ZDV GHPRQVWUDWHG XVLQJ RSWRJHQHWLF PHWKRGV$FWLYDWLRQ broken chromosome fragments. This is thought to initiate a major RIFKDQQHOUKRGRSVLQH[SUHVVLQJ3%WHUPLQDOVLQ590ZDVDEOHWR SDWKZD\ IRU RQFRJHQH DPSOL¿FDWLRQ DQG WXPRU JHQRPH HYROXWLRQ GULYH590QHXURQVLQYLYRDQGLQDQ590DGXOWVOLFHSUHSDUDWLRQ FDOOHGWKHEUHDNDJHIXVLRQEULGJH %)% F\FOH+RZHYHUZHVWLOOODFN evoked synaptic currents. These data show that a substantial a complete understanding of the mechanism(s) causing chromosome FRPSRQHQWRIWKHUHOHYDQWQRFLFHSWLYHGULYHWR590SDLQPRGXODWLQJ EULGJHVWREUHDNLQWKH¿UVWSODFH+HUHZHSUHVHQWQHZHYLGHQFH neurons is relayed through the parabrachial complex, and that WKDWEULGJHEUHDNDJHUHTXLUHVDFWLQGHSHQGHQWFRQWUDFWLOHIRUFHV$V 590QHXURQVUHFHLYHGLUHFWLQSXWIURP3%:KLOHWKHFRQWUDODWHUDO daughter cells connected by a bridge move away from each other, PB relays noxious input under basal conditions, the ipsilateral PB the bridge is typically stretched over long distances before breakage. LV UHFUXLWHG LQ SHUVLVWHQW LQÀDPPDWLRQ 7KXV WKH SDUDEUDFKLDO 8VLQJ¿EURQHFWLQPLFURSDWWHUQVWROLPLWGDXJKWHUFHOOVHSDUDWLRQZH complex, well known as an important relay for ascending nociceptive ZHUHDEOHWREORFNEULGJHUHVROXWLRQZLWKRYHURIEULGJHVVWLOO information, also accesses descending control systems through a intact as the daughter cells entered the next mitosis. In cells not FRQQHFWLRQZLWKWKH590 constrained by micropatterns, bridge resolution was similarly blocked by timed addition of inhibitors of actin contractility. We propose that 41 0DWXUH DGLSRF\WHV LPSDLU WKH DQWLPLFURELDO IXQFWLRQ PHFKDQLFDOIRUFHVIURPDFWLQEDVHGFRQWUDFWLOLW\SOD\DFHQWUDOUROHLQ of reactive dermal adipogenesis: an explanation for impaired bridge resolution. cutaneous defense in obesity We are also studying the genomic consequences of bridge breakage. Stella X. Chen BFB cycles have been observed in association with another form of University of California, San Diego, USA localized mutagenesis called chromothripsis. It has also been shown To defend against cutaneous infections, the skin must maintain that individual cells experiencing telomere dysfunction can grow into both a physical and immunological barrier. Recently, our laboratory FORQDO SRSXODWLRQV ZLWK FKURPRWKULSVLV 7KHVH ¿QGLQJV VXJJHVW D has shown that a layer of adipocytes in the dermis is necessary for mechanistic link between bridge breakage and chromothripsis, but antimicrobial defense by producing the cathelicidin antimicrobial the details of this relationship are unclear. To address this question, peptide (Camp) during a phenomenon known as reactive ZHDUHXVLQJRXU³/RRNVHT´DSSURDFKZKLFKFRPELQHVORQJWHUP adipogenesis. However, the increase in mature adipocytes in LPDJLQJZLWKVLQJOHFHOOVHTXHQFLQJ:HZLOOGLVFXVVZKHWKHUEULGJH obesity is paradoxically associated with greater rates of cutaneous breakage occurs directly via chromothripsis, or if the relationship is LQIHFWLRQ ,Q WKLV VWXG\ ZH LQYHVWLJDWHG ZKHWKHU WKH DQWLPLFURELDO indirect, with chromothripsis occurring as a downstream consequence, adipogenic response of reactive adipogenesis is impaired in obesity, perhaps through formation of micronuclei in subsequent cell cycles. DQG KRZ WKLV PD\ RFFXU 8VLQJ PRXVH PRGHOV RI GLHWLQGXFHG REHVLW\ ZH IRXQG WKDW REHVH PLFH IHG D KLJKIDW GLHW ORVW GHUPDO 43 Loss of function of the hepatic fatty acid translocase DGLSRJHQLFDQWLPLFURELDO DFWLYLW\ DQG KDG LQFUHDVHG VXVFHSWLELOLW\ UHFHSWRU&'LVLQVXI¿FLHQWWRSURWHFWIURPOLYHUVWHDWRVLVLQD WR 6WDSK\ORFRFFXV DXUHXV LQIHFWLRQ ,Q YLWUR VWXGLHV XVLQJ PRXVH murine model of parenteral nutrition-induced liver injury SULPDU\GHUPDODGLSRJHQLF¿EUREODVWVVKRZHGWKDW&DPSH[SUHVVLRQ Bennet S. Cho SHDNHG IROG 3 GXULQJ HDUO\ DGLSRJHQHVLV 7KLV ZDV Boston Children’s Hospital, USA FRQ¿UPHGXVLQJIXQFWLRQDODQWLPLFURELDODVVD\VZKLFKVKRZHGWKDW &KLOGUHQ ZLWK LQWHVWLQDO IDLOXUH ,) GXH WR LQVXႈFLHQW ERZHO OHQJWK PHWKLFLOOLQUHVLVWDQW6DXUHXVJURZWKGHFUHDVHGE\PRUHWKDQWKUHH RU ORVV RI IXQFWLRQ UHTXLUH LQWUDYHQRXV SDUHQWHUDO QXWULWLRQ 31 ORJV ZKHQ JURZQ LQ FXOWXUH VXSHUQDWDQW IURP QHZO\ GLႇHUHQWLDWLQJ +RZHYHU ORQJWHUP 31 DGPLQLVWUDWLRQ FDQ OHDG WR ,)DVVRFLDWHG immature adipocytes. However, as adipocytes continued to mature, OLYHU GLVHDVH ,)$/' FKDUDFWHUL]HG E\ FKROHVWDVLV DQG KHSDWLF 6DXUHXVLQKLELWLRQZDVORVWDQG&DPSP51$H[SUHVVLRQGHFUHDVHG LQÀDPPDWLRQ ,)$/' FDQ SURJUHVV WR HQGVWDJH OLYHU GLVHDVH QLQHIROG 3 Remarkably, we also found that coculturing requiring liver transplantation. Although there is no current Food GHUPDO DGLSRJHQLF ¿EUREODVWV ZLWK PDWXUH DGLSRF\WHV RU PDWXUH DQG 'UXJ $GPLQLVWUDWLRQ )'$ DSSURYHG WUHDWPHQW UHSODFLQJ adipocyte conditioned media led to a diminished ability of adipogenic WKH VWDQGDUG VR\EHDQ RLOEDVHG OLSLG HPXOVLRQ LQ 31 ZLWK D ¿EUREODVWVWRH[SUHVV&DPSP51$SURGXFHFDWKHOLFLGLQSURWHLQDQG ¿VK RLOEDVHG OLSLG HPXOVLRQ )2/( KDV EHHQ IRXQG WR UHYHUVH LQKLELW6DXUHXVJURZWK7KHVH¿QGLQJVVXJJHVWWKDWXQGLႇHUHQWLDWHG ,)$/' 2XU ODERUDWRU\ KDV GHPRQVWUDWHG WKDW )2/( SURWHFWV IURP DGLSRJHQLF¿EUREODVWVLQWKHGHUPLVDUHDQLPSRUWDQWDQWLPLFURELDO KHSDWRVWHDWRVLV LQ D PXULQH PRGHO RI 31LQGXFHG OLYHU LQMXU\ D reserve for cutaneous defense. However, mature adipocytes lose SURFHVV WKDW LV GHSHQGHQW RQ * SURWHLQFRXSOHG UHFHSWRU DQWLPLFURELDODFWLYLW\DQGPD\LPSDLUDGMDFHQWDGLSRJHQLF¿EUREODVWV *35 3HUR[LVRPH SUROLIHUDWRUDFWLYDWHG UHFHSWRU Ȗ 33$5Ȗ IURP¿JKWLQJLQIHFWLRQ7KHVHUHVXOWVSURYLGHDSRVVLEOHH[SODQDWLRQ expression, a transcription factor associated with hepatic lipogenesis for impaired cutaneous defense associated with obesity. and lipid droplet deposition, is normalized by FOLE treatment. Among WUDQVFULSWLRQDO WDUJHWV RI 33$5Ȗ&' H[SUHVVLRQ LV LQFUHDVHG LQ this model of liver injury and is normalized by FOLE treatment in a *35GHSHQGHQWIDVKLRQ)DWW\DFLGWUDQVORFDVHUHFHSWRU&' is a free fatty acid and lipoprotein transporter receptor associated with increased hepatic fatty acid uptake and triglyceride storage. The

www.jointmeeting.org 39 POSTER ABSTRACTS

JRDORIWKLVVWXG\ZDVWRGHWHUPLQHZKHWKHUORVVRIIXQFWLRQRI&' 45 8VLQJ 51$ VHTXHQFLQJ WR XQGHUVWDQG KRZ VWHURLGV LVVXႈFLHQWWRSURWHFWIURP31LQGXFHGOLYHULQMXU\ induce remission in Eosinophilic Esophagitis &GNQRFNRXW .2 &%/ PDOH PLFH DQG ZLOGW\SH :7 Yash Choksi OLWWHUPDWHVZHUHIHGDGOLELWXPFKRZRU31GLHWIRUGD\V/LYHUV Vanderbilt University, Nashville, USA spleens, and kidneys were weighed and stained for hematoxylin and Background: Current treatments of eosinophilic esophagitis (EoE) HRVLQ + ( KLVWRORJLFDQDO\VLV7RWDO51$ZDVH[WUDFWHGIURPOLYHU include proton pump inhibitors, topical steroids, and elimination DQG VXEMHFWHG WR TXDQWLWDWLYH UHDOWLPH SRO\PHUDVH FKDLQ UHDFWLRQ GLHWV:KLOHWKHVHWKHUDSLHVFDQEHVXFFHVVIXOQRQHDUHVSHFL¿F$ (qPCR) for measurement of hepatic regulators of lipid metabolism, previous study by Katzka et al CGH VKRZHGWKDWWRSLFDOVWHURLG LQFOXGLQJDFHW\O&R$FDUER[\ODVH $&& DQG33$5Į WUHDWPHQWLQSDWLHQWVZLWK(R(PRGL¿HGH[SUHVVLRQRIWLJKWMXQFWLRQ H&E staining revealed marked steatosis in livers from both WT SURWHLQV ,Q WKLV VWXG\ RXU DLP LV GH¿QH WUDQVFULSWLRQDO QHWZRUNV DQG.2PLFHIHG31ZKHUHDV:7DQG.2PLFHIHGUHJXODUFKRZ PRGL¿HGE\VWHURLGVLQ(R(VSHFL¿FDOO\ZLWKUHJDUGVWRFHOODGKHVLRQ revealed histologically normal livers. qPCR data demonstrated and epithelial to mesenchymal transition (EMT). LQFUHDVHGH[SUHVVLRQRI$&&DQG33$5ĮLQ31IHG&'.2PLFH 0HWKRGV0LG FPIURP*(MXQFWLRQ DQGGLVWDO FPIURP*( FRPSDUHGZLWKFKRZIHG:7DQG.2PLFH junction) esophageal mucosal biopsies from patients without EoE 7KHUHVXOWVRIWKLVVWXG\GHPRQVWUDWHWKDWORVVRIIXQFWLRQRI&' GH¿QHG DV XQGHUJRLQJ HQGRVFRS\ IRU *(5' QRQUHVSRQVLYH WR E\LWVHOILVQRWVXႈFLHQWWRSUHYHQWGHYHORSPHQWRIKHSDWRVWHDWRVLV WKHUDS\RUG\VSKDJLD Q IHPDOHPDOH SDWLHQWVZLWKDFWLYH LQDPXULQHPRGHORI31LQGXFHGOLYHULQMXU\,QFUHDVHG$&&DQG (R( Q IHPDOH PDOH DQG SDWLHQWV ZLWK VWHURLGLQGXFHG 33$5ĮH[SUHVVLRQLQ&'.2PLFHVXJJHVWVFRPSHQVDWRU\OLSLG KLVWRORJLF UHPLVVLRQ Q IHPDOH PDOH ZHUH VXEPLWWHG IRU DFFXPXODWLRQYLDSDUDOOHOSDWKZD\VLQWKHDEVHQFHRI&'IXQFWLRQ ZKROH WUDQVFULSWRPH DQDO\VLV XVLQJ 51$ VHTXHQFLQJ (VRSKDJHDO Further studies investigating these alternate pathways may elucidate WLVVXHZDVREWDLQHGIURPERWK9DQGHUELOWDQGWKH0D\R&OLQLF WKHSDWKRORJLFPHFKDQLVPVLQYROYHGLQWKHGHYHORSPHQWRI,)$/' 5HVXOWV&RQWUROSDWLHQWVKDGDQDYHUDJHDJHRI UDQJH 44 Oncogenic potential of noncanonical PIK3CA mutations SDWLHQWVZLWKDFWLYH(R(KDGDQDYHUDJHDJHRI UDQJH and implications for molecular targeting strategies in head and DQG SDWLHQWV LQ VWHURLGLQGXFHG UHPLVVLRQ KDG DQ DYHUDJH DJH RI neck cancer UDQJH JHQHV ZHUH VLJQL¿FDQWO\ GHFUHDVHG DIWHU VWHURLGWUHDWPHQWDQGJHQHVZHUHVLJQL¿FDQWO\LQFUHDVHGDIWHU Janice Cho VWHURLGWUHDWPHQW7KHOLVWRIJHQHVZKLFKZHUHGHFUHDVHGDIWHU University of California San Francisco, USA VWHURLGWUHDWPHQWZHUHFRPSDUHGZLWKERWKJHQHRQWRORJ\ *2 DQG 'HVSLWHWKHUHFHQW)'$DSSURYDORI3'LQKLELWRUVIRUKHDGDQGQHFN .\RWRHQF\FORSHGLDRIJHQHVDQGJHQRPHV .(** JHQHVHWV,Q VTXDPRXVFHOOFDUFLQRPD +16&& DERXWRISDWLHQWVVXFFXPE WKH*2VHWJHQHVDVVRFLDWHGZLWKFHOODGKHVLRQZHUHIRXQGWREH to their disease, and predictive biomarkers to guide therapy are VLJQL¿FDQWO\GHFUHDVHG )'5 ,QWKH.(**VHWJHQHV ODFNLQJ3,.&$WKHPRVWFRPPRQO\PXWDWHGRQFRJHQHLQ+16&& ZHUH DVVRFLDWHG ZLWK FHOO DGKHVLRQ ZHUH IRXQG WR EH VLJQL¿FDQWO\ HQFRGHV WKH SD FDWDO\WLF VXEXQLW RI SKRVSKRLQRVLWLGHNLQDVH GHFUHDVHG )'5 H :KHQFRPSDULQJWKHOLVWRIJHQHV (PI3K), which triggers downstream pathways involved in cell growth WRKDOOPDUNJHQHVHWVJHQHVUHODWHGWR(07ZHUHVLJQL¿FDQWO\ DQG VXUYLYDO $FFRUGLQJ WR 7KH &DQFHU *HQRPH $WODV 1HWZRUN GRZQUHJXODWHG )'5 JHQHVUHODWHGWRWKHDSLFDOMXQFWLRQ 7&*$ DSSUR[LPDWHO\ RI 3,.&$ PXWDWLRQV LQ +16&& ZHUHDOVRVLJQL¿FDQWO\GRZQUHJXODWHG )'5 T3&5ZDV FOXVWHUDWWKUHHFDQRQLFDO³KRWVSRW´PXWDWLRQVLWHV (.(. SHUIRUPHG WR FRQ¿UP FKDQJHV LQ H[SUHVVLRQ RI UHPRGHOLQJ JHQHV +5 ZKLOH RI +16&&DVVRFLDWHG 3,.&$ PXWDWLRQV ZLWK VWHURLG WUHDWPHQW $&7* &2/$ 32671 &$31 $V occur at noncanonical sites. Although there is considerable H[SHFWHG WKHUH ZHUH DOVR JHQHV WKDW ZHUH GHFUHDVHG UHODWHG evidence illustrating the oncogenic properties of canonical, “hotspot” WRLQÀDPPDWRU\UHVSRQVH )'5 3+(:$6VWXGLHVZHUH 3,.&$ PXWDWLRQV WKH UROH RI QRQFDQRQLFDO PXWDWLRQV LQ +16&& SHUIRUPHG RQ FDQGLGDWH JHQH &$31 DV LW LV QRW NQRZQ WR EH tumorigenesis is unclear. Preliminary data from our lab demonstrate associated with diseases other than EoE. When comparing known that PIK3CA mutations may lead to tumorigenesis via hyperactivation &$31YDULDQWVWRSKHQRW\SHVDVVRFLDWHGZLWKLQIHFWLRXVGLVHDVHV RI WKH 3,.&2;3*( VLJQDOLQJ SDWKZD\ DQG WKDW FRPELQHG an association with H.pyloriZDVLGHQWL¿HG therapeutic targeting of PI3K and COX2 may be a viable therapeutic &RQFOXVLRQ 6WHURLGV FDXVH FKDQJHV LQ H[SUHVVLRQ RI JHQHV VWUDWHJ\ IRU 3,.&$DOWHUHG WXPRUV 7KURXJK D JHQRPLFVEDVHG associated with cell adhesion and EMT. approach to treatment selection, this project aims to uncover the role of PIK3CA noncanonical mutations in conferring oncogenic driver 46 0\RFDUGLDO ,QIDUFW =RQH ,PDJLQJ ZLWK $FRXVWLFDOO\ function, with the goal of identifying viable therapeutic strategies for Activated Nanodroplets patient subsets based on PIK3CA mutational status. To accomplish Songita Choudhury WKLV DLP ZH DUH HQJLQHHULQJ DQ +16&& FHOO OLQH WKDW LV VHQVLWLYH University of Nebraska Medical Center, Omaha, USA to serum deprivation to express a panel of noncanonical PIK3CA mutations. The oncogenic properties of the noncanonical mutants ,QWURGXFWLRQ &RPPHUFLDOO\ DYDLODEOH 'H¿QLW\ /DQWKHXV 0HGLFDO will then be assessed by examining the engineered cell lines for PLFUREXEEOHV 0% FDQEHFRPSUHVVHGWRQDQRGURSOHWV 1' DWWKH proliferation in the absence of serum. In addition, activation of PI3K/ EHGVLGH7KHVH1'DUHVXEPLFURQLQVL]HDQGH[KLELWVLJQL¿FDQWO\ &2;3*( VLJQDOLQJ ZLOO EH H[DPLQHG YLD LPPXQREORW DQDO\VLV GLႇHUHQW DFRXVWLF EHKDYLRU WKDQ WKH 0% 1' PD\ FURVV GHIHFWLYH 6XEVHTXHQWO\ ZH ZLOO GHWHUPLQH ZKHWKHU 3,.&$ QRQFDQRQLFDO HQGRWKHOLDO EDUULHUV DQG DFFXPXODWH LQ QRQYLDEOH WLVVXH :H mutations exhibiting “driver” tumor growth confer sensitivity to K\SRWKHVL]HG WKDW 1' LQ FRPELQDWLRQ ZLWK GLDJQRVWLF XOWUDVRXQG conventional or molecular targeting strategies used in the treatment could be utilized to highlight areas of infarcted myocardial tissue. RI+16&&,IVXFFHVVIXOWKLVSURMHFWZLOOJXLGHWKHUDS\IRUSDWLHQWV 0HWKRGV5DWV Q XQGHUZHQWDFXWHP\RFDUGLDOLQIDUFWLRQYLDOHIW SRVVHVVLQJ3,.&$PXWDWHGWXPRUV FRURQDU\DUWHU\OLJDWLRQ$WKRXUVSRVWSURFHGXUHWUDQVWKRUDFLF XOWUDVRXQGLPDJLQJZLWKFRQWUDVWVSHFL¿FVHTXHQFHV 6LHPHQV/

40 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

0.5 and 1.5 MI) was performed. Myocardial contrast enhancement in YLHZV 9LVLWFRXQWSHDNHGDWYLHZVSHUKRXUULJKWDIWHUWKHOLQN the infarct and normal zones were analyzed and compared after 200 ZDV GLVWULEXWHG E\ HPDLO RI DOO KRXU LQWHUYDOV VDZ QR SDJH X/EROXVLQMHFWLRQVRI'H¿QLW\RU'H¿QLW\1'7ULJJHUHGLPDJLQJ YLHZVH[FOXGLQJWKHVHWKHUHZHUHRQDYHUDJHYLHZVSHUKRXU was performed at 1 frame/3 cardiac cycles immediately following the ,Q VXPPDU\ ZH GHYHORSHG D ZHEEDVHG UHSRUW WKDW SUHVHQWV EROXVLQMHFWLRQVDQGDJDLQPLQXWHVSRVWLQMHFWLRQ$WWKHPLQXWH relevant statistics regarding respiratory pathogen testing in our time point, the MI was transiently increased to 1.5 to activate, and, laboratory. The report is updated daily to provide critical data to all subsequently, destroy droplets within the infarct zone. The transient stakeholders, including the general public. We developed the site enhanced zone (TEZ) was planimetered and compared to post with mobile devices in mind, which allows the charts and fonts to be mortem measurements of infarct size with TTC staining and confocal readable on any platform. The charts are interactive, allowing the PLFURVFRS\ )OXRUHVFHQWO\ ODEHOOHG 1' ZHUH DGPLQLVWHUHG WR user to switch between daily and weekly reports using radio buttons. determine accumulation of particles in the normal and infarct zones 'DWDFDQEH¿OWHUHGE\FOLFNLQJWKHGDWDODEHOVLQWKHFKDUWOHJHQG PLQXWHVSRVWLQMHFWLRQ5HVXOWV,QIDUFWVL]HUDQJHGIURPRI These features are possible because of our decision to develop WKHVKRUWD[LVSODQH WUDQVPXUDOQRQWUDQVPXUDO 'H¿QLW\0% DZHEEDVHGUHSRUWDVRSSRVHGWRD3RUWDEOH'RFXPHQW)RUPDW injections provided excellent contrast delineation of the infarct zone 3') VSUHDGVKHHW RU ZRUG SURFHVVLQJ GRFXPHQW $QHFGRWDO with clearance of the contrast by 2 min. Transient enhancement of feedback collected at the time of rollout was universally positive. WKHLQIDUFW]RQHXVLQJWKH1'ZDVREVHUYHGDWPLQSRVWLQMHFWLRQ The report continues to be viewed daily. 7KH DUHD RI 7(= FRUUHODWHG FORVHO\ ZLWK LQIDUFW VL]H U S 1' DFFXPXODWLRQ ZLWKLQ WKH LQIDUFW ]RQH ZDV FRQ¿UPHG 48 ,PPXQHSUR¿OLQJRIUHMHFWLRQELRPDUNHUVLQ+,9SRVLWLYH by confocal microscopy. Recent studies looking at myocardial infarct transplant recipients detection in a porcine model of acute myocardial infarction appear to Simon N. Chu FRQ¿UPWKDW'H¿QLW\1'FDQEHXVHGWRGH¿QHWKHLQIDUFW]RQHZLWK University of California, San Francisco, USA GHOD\HG HQKDQFHPHQW LPDJLQJ &RQFOXVLRQV 1' IRUPXODWHG IURP +,9 VROLGRUJDQ WUDQVSODQW UHFLSLHQWV DUH SUHGLVSRVHG WR D commercially available MB appear to accumulate in infarct zones three times higher rate of rejection episodes when compared to following injection. Their detection with delayed echo activation +,9 UHFLSLHQWV EXW LPPXQRORJLFDO FRUUHODWHV RI UHMHFWLRQ LQ WKLV SUHVHQWVDSRWHQWLDOPHWKRGRILQIDUFWGHWHFWLRQDQGTXDQWL¿FDWLRQ SRSXODWLRQKDYHQRWSUHYLRXVO\EHHQLGHQWL¿HG+HUHZHGHVFULEH as well as targeted drug delivery. our investigation of immunologic phenotype and gene expression 47 $ :HE%DVHG 5HVSLUDWRU\ 3DWKRJHQ /DERUDWRU\ 5HSRUW SUR¿OLQJ WR LGHQWLI\ IXQFWLRQDO GLႇHUHQFHV EHWZHHQ 5HMHFWRUV 5HM IRU6XPPDUL]LQJ.H\0HWULFVWR6WDNHKROGHUV DQG1RQ5HMHFWRUV 15 Paul Christensen 'RQRU DQG UHFLSLHQW SHULSKHUDO EORRG PRQRQXFOHDU FHOOV 3%0&V Texas A&M Health Science Center / Houston Methodist ZHUHFROOHFWHGSULRUWRWUDQVSODQW5HMZHUHVHOHFWHGEDVHGRQELRSV\ Hospital, Houston, USA proven acute cellular rejection. Kidney transplant recipients were 7KH&HQWHUIRU'LVHDVH&RQWURODQG3UHYHQWLRQ &'& SURYLGHVGDWD VWUDWL¿HGE\5HM Q YHUVXV15 Q DVFRPSDUHGWRPDWFKHG UHJDUGLQJ ,QÀXHQ]D DFWLYLW\ +RZHYHU GDLO\ DQG ZHHNO\ VWDWLVWLFV +,9 NLGQH\ WUDQVSODQW UHFLSLHQWV +,9 QRQWUDQVSODQW FRQWUROV summarizing regional hospital system observations are possibly DQG+,9(65'KHDOWK\FRQWUROVXEMHFWV Q SHUJURXS 7KHVH most relevant for local decision making. Our microbiology laboratory SDWLHQWVZHUHSUR¿OHGXVLQJÀRZF\WRPHWULFSDQHOVWRFKDUDFWHUL]H LPSOHPHQWHG D GDLO\ ZHEEDVHG UHSRUW WR GLVWULEXWH UHVSLUDWRU\ FHOOXODUVXEVHWVDFWLYDWLRQVWDWXVDQG7UHJSKHQRW\SH*URXSVZHUH SDWKRJHQ GDWD IRU RXU HLJKWKRVSLWDO V\VWHP WR FOLQLFLDQV KRVSLWDO FRPSDUHGIRUYDULDQFHXVLQJWKH.UXVNDO:DOOLVWHVWZLWKSDLUZLVH epidemiologists, infection control committees, system leadership, FRPSDULVRQ SHUIRUPHG EHWZHHQ JURXSV E\ 'XQQ¶V SRVWWHVW )RU and the general public. JHQHH[SUHVVLRQDQDO\VLVSUHWUDQVSODQW+,9OLYHUUHFLSLHQW3%0&V IURP5HM Q DQG15 Q ZHUHFRFXOWXUHGLQPL[HGO\PSKRF\WH Molecular and antigen laboratory result data from respiratory UHDFWLRQ 0/5 LQ YLWUR ZLWK HLWKHU &'/VWLPXODWHG GRQRU RU UG pathogen tests are extracted from our lab information system SDUW\%FHOOV'RQRU%FHOOVZHUHUHPRYHGE\LPPXQRGHSOHWLRQDQG DQG VXEVHTXHQWO\ LQVHUWHG LQWR D 0\64/ GDWDEDVH 8VLQJ µ3+3 UHFLSLHQW FHOOV ZHUH DQDO\]HG XVLQJ D FXVWRP 1DQR6WULQJ SDQHO Hypertext Preprocessor’, we analyzed the laboratory result data to 5DZFRXQWVZHUHQRUPDOL]HGDQGSYDOXHVZHUHDGMXVWHGXVLQJWKH SURGXFHDZHEEDVHGUHSRUWXVLQJWKH&KDUWMVIUDPHZRUN7KHIRXU %HQMDPLQL+RFKEHUJSURFHGXUH charts summarize the number of positive tests over time, the number of positive tests by patient location in our hospital system, the percent +,9 5HM ZHUH IRXQG WR KDYH PDUNHUV RI LQFUHDVHG SUHWUDQVSODQW SRVLWLYH WHVWV DQG WKH QXPEHU RI HDFK SDWKRJHQ LGHQWL¿HG E\ RXU LPPXQHDFWLYDWLRQDVFRPSDUHGWR15ZLWKDELDVWRZDUGDFWLYDWLRQ molecular test during a set time interval. RIWKHLQQDWHLPPXQHV\VWHP7KH\H[KLELWHGDVLJQL¿FDQWO\DOWHUHG PRQRF\WH SKHQRW\SH LQFOXGLQJ GHFUHDVHG +/$'5 H[SUHVVLRQ RQ We advertised the report at three separate committee meetings, &'&' LQWHUPHGLDWH PRQRF\WHV S 0RUHRYHU 5HM where we requested informal feedback. A link to the report was KDYHLQFUHDVHG%FHOODFWLYDWLRQE\+/$'5H[SUHVVLRQ S included in an email from the executive vice president of the hospital DQGOHVVDFWLYDWHG7UHJVE\GHFUHDVHGSHUFHQWDJHRI&'7UHJV system. We monitored the visitor statistics, including Internet Protocol S 7KHIUHTXHQF\RI7UHJVGLGQRWGLႇHUEHWZHHQWKHWZR (IP) addresses. groups. After alloantigen stimulation, Rej showed increased gene We deployed the report to the cloud (bit.ly/HMFlu). Over 1 week, the H[SUHVVLRQRI7FHOODFWLYDWLRQPDUNHUV&'DQG,&26 S UHSRUWZDVDFFHVVHGWLPHVRIWKHRULJLQDWLQJ,3DGGUHVVHV ,QWHUHVWLQJO\ 15 GLVSOD\HG XSUHJXODWLRQ RI UHJXODWRU\ ZHUHIURPRXUKRVSLWDOV\VWHPZHUHIURPRWKHUORFDWLRQVZLWKLQ OLJDQGVLQWKHOHXNRF\WHLPPXQRJOREXOLQOLNHUHFHSWRUIDPLO\ /,/5 WKH8QLWHG6WDWHVZHUHIURPORFDWLRQVRXWVLGHWKH8QLWHG6WDWHV LQFOXGLQJ/,/5%/,/5%DQG/,/5$ S DQG ZHUH IURP DGGUHVVHV WKDW FRXOG QRW EH PDSSHG 'LႇHUHQWLDO JHQH H[SUHVVLRQ EHWZHHQ 5HM DQG 15 ZDV SUHVHUYHG of the views were on mobile devices. The most common browser irrespective of stimulus by either donor or 3rd party. IRUGHVNWRSFRPSXWHUVZDV0LFURVRIW,QWHUQHW([SORUHU RIDOO

www.jointmeeting.org 41 POSTER ABSTRACTS

2YHUDOORXUUHVXOWVVXJJHVWWKDWLQFUHDVHGUDWHVRIUHMHFWLRQLQ+,9 WRWKULYH$IWHUDERXWPRQWKVRIQRUPDOGHYHORSPHQWWKH3:6 NLGQH\DQGOLYHUWUDQVSODQWVFRUUHODWHZLWKSUHWUDQVSODQWUHFLSLHQW patients develop obesity and hyperphagia along with short stature VSHFL¿F LPPXQH G\VIXQFWLRQ &RQFRUGDQFH LQ JHQH H[SUHVVLRQ DQGEHKDYLRUDOSUREOHPV3:6LVFDXVHGE\WKHORVVRIWKHSDWHUQDO SUR¿OH IROORZLQJ VWLPXODWLRQ ZLWK GRQRU RU UG SDUW\ VXJJHVWV WKDW FRQWULEXWLRQ RI WKH FKURPRVRPH TT ORFXV 7KLV ORFXV LV GLႇHUHQWLDOJHQHH[SUHVVLRQLVDQLQWULQVLFUHFLSLHQWGULYHQSURSHQVLW\ governed by genomic imprinting and thus the genes are expressed WRLPPXQHDFWLYDWLRQLQ5HMDQGLPPXQHUHJXODWLRQLQ15 IURP RQH SDUHQWDO DOOHOH$OWKRXJK 3:6 SDWLHQWV ODFN WKH SDWHUQDO contribution of this region, they possess an intact but transcriptionally 49 Oral microbiome of braces patients silent set of genes on the maternal chromosome. Thus the activation Jennifer Chung of the silent maternal genes may be an attractive potential therapy University of Connecticut School of Medicine, New Britain, IRU 3:6 7KH ZRUN SUHYLRXVO\ GRQH LQ RXU ODE LQGLFDWHG WKH USA LPSRUWDQFHRI=LQF)LQJHU3URWHLQ =1) LQWKHUHSUHVVLRQRI 7KHUH KDV EHHQ D VLJQL¿FDQW LQFUHDVH LQ WKH QXPEHU RI SDWLHQWV WKHPDWHUQDOJHQHVRQWKHFKURPRVRPHTTORFXV=1) being treated for orthodontic care over the past decade. Orthodontic recruits epigenetic silencing factors that mediate the deposition of treatments, particularly braces, are known for increasing the risk of UHSUHVVLYH+.PHKLVWRQHPDUNV&KURPDWLQLPPXQRSUHFLSLWDWLRQ periodontal disease, but not all patients with orthodontic interventions &K,3 FRQ¿UPHG WKDW ERWK =1) DQG +.PH PDUNV DUH UHVXOWLQSHULRGRQWLWLV&HUWDLQEDFWHULDSUHGRPLQDWHO\JUDPQHJDWLYH VSHFL¿FDOO\HQULFKHGLQWKHPDWHUQDODOOHOHEXWQRWWKHSDWHUQDODOOHOH anaerobic bacteria, have been found to be responsible for periodontal In the subsequent studies, a knockout of ZNF274 was generated in GLVHDVHV7KHKXPDQPRXWKKDUERUVPDQ\GLႇHUHQWPLFURRUJDQLVPV 3:6LQGXFHGSOXULSRWHQWVWHPFHOOV L36&V $OWKRXJKWKHDFWLYDWLRQ collectively they are known as the oral microbiota. RIWKHPDWHUQDOTTJHQHVZDVPRGHVWLQWKHVHFHOOVDIXOO activation of the maternal genes was observed in neural precursors We hypothesize that a distinct oral microbiome increases the 13&V DQGQHXURQVWKDWZHUHGHULYHGIURPWKHP,QDGGLWLRQWKH likelihood for periodontal disease among braces patients. We UHSUHVVLYH+.PHPDUNVZHUHDOVRVKRZQWREHUHGXFHGLQ&K,3 KDYH SUR¿OHG WKH VXEJLQJLYDO EDFWHULD DW IRXU VLWHV ¿UVW PRODU H[SHULPHQWV7KXVZHK\SRWKHVL]HWKDW=1)LVDQDWWUDFWLYHDQG FHQWUDO LQFLVRU EXFFDO ¿UVW ELFXVSLG DQG OLQJXDO ¿UVW ELFXVSLG LQ YLDEOHWKHUDSHXWLFWDUJHWIRU3:6,QRUGHUWRWHVWWKLVK\SRWKHVLV SDWLHQWV UHFHLYLQJ EUDFNHWV Q FOHDU DOLJQHUV Q DQG KHDOWK\ we have generated several tools to deplete ZNF274LQ3:6 FRQWUROV Q DWWKUHHWLPHSRLQWV ZHHNV XVLQJVU51$ cell models. With these reagents, we aim to answer whether the gene sequencing and assessed bleeding on probing, plaque, and depletion of ZNF274 in neurons will recapitulate the results found periodontal status. in our earlier studies. Furthermore, we will determine whether a :H REWDLQHG D PHDQ RI VHTXHQFHV SHU VDPSOH DQG sustained depletion of ZNF274 is required to activate the normally DJJUHJDWHGWRDWRWDORIRSHUDWLRQDOWD[RQRPLFXQLWV 278V ,Q VLOHQW PDWHUQDO JHQHV /DVWO\ ZH ZLOO GHWHUPLQH WKH JHQRPHZLGH RXUEUDFNHWFRKRUWZHREVHUYHGWKDWWKHUHZDVDVLJQL¿FDQWLQFUHDVH consequences of ZNF274 depletion. The results of these studies in microbial richness between samples obtained before braces PD\VHUYHDVDSURRIRISULQFLSOHIRUQRYHO=1)EDVHGWKHUDSLHV intervention and six weeks after intervention among three of the four IRUWKHWUHDWPHQWRI3:6 sites. Richness stayed at a similarly high microbial richness by 12 weeks. This increase in richness was accompanied by the decrease 51 4XDQWLWDWLYH DQDO\VLV RI 53( PRUSKRORJ\ DIWHU JHQH in 6WUHSWRFRFFXV, the most abundant genera found across all therapy rescue in a mouse model of retinitis pigmentosa VDPSOHV6LPLODUWUHQGVZHUHVHHQZKHQORRNLQJDWGLYHUVLW\DPRQJ 0LFKHOOH-&KXQJ VDPSOHV E\ %UD\ &XUWLV 6DPSOHV WDNHQ EHIRUH EUDFNHW WUHDWPHQW Harvard Medical School, USA FOXVWHUHGPRUHWLJKWO\DQGGLႇHUHQWO\FRPSDUHGWRWKHWZRWLPHSRLQWV 5HWLQLWLVSLJPHQWRVD 53 LVDGLVHDVHLQZKLFKDPXWDWLRQLQ! after, which clustered similarly among each other. GLႇHUHQWORFLOHDGVWRDFRQVHUYHGSDWWHUQRIFOLQLFDOV\PSWRPVDQG ,QDGGLWLRQRYHURIRXUEUDFNHWFRKRUWGHYHORSHGSHULRGRQWLWLV cell death in the eye. Photoreceptors, the cell types that capture FRPSDUHGWRRIRXUFRQWUROVE\VL[ZHHNVRILQWHUYHQWLRQ2YHUDOO DQG SURFHVV OLJKW DUH WKH FHOOV SULPDULO\ DႇHFWHG E\ WKH JHQHWLF samples that were associated with periodontitis had a lower relative lesion. Rod photoreceptors, which we use for dim light vision, die abundance of 6WUHSWRFRFFXV. ¿UVW IROORZHG E\ FRQHV WKH W\SH WKDW ZH XVH IRU RXU GD\OLJKW DQG :H DOVR REVHUYHG WKDW WKHUH ZHUH IHZHU 278V VKDUHG DPRQJ color vision. Retinal pigmented epithelial cells (RPE) provide support the four sites in time point one than in time point two and three, IRUURGVDQGFRQHVDQGWKH\DUHDOVRDႇHFWHGLQ53:HUHFHQWO\ suggesting that the whole oral microbiome becomes more uniformed VKRZHGWKDWDQDGHQRDVVRFLDWHGYLUDO $$9 YHFWRURYHUH[SUHVVLQJ ZLWKEUDFNHWWUHDWPHQW,QWHUHVWLQJO\WKHXQLTXH278VWRHDFKVLWH 1UI D WUDQVFULSWLRQ IDFWRU WKDW ¿JKWV R[LGDWLRQ DQG LQÀDPPDWLRQ over time did not remain the same, suggesting that the uniqueness rescues cones and vision in an RP mouse model (rd1). We have RIHDFKWRRWK¶VEDFWHULDOSUR¿OHPD\EHYHU\WUDQVLHQW more recently found that it also rescues the RPE. My project concerns quantifying the degree of RPE rescue so that we can better score ,QFRQFOXVLRQZHREVHUYHGVLJQL¿FDQWPLFURELDOFKDQJHVLQWKH WKLVSKHQRW\SHDQGWHVW1UIUHODWLYHWRRWKHU53WUHDWPHQWVWKDWZH oral microbiome of patients with bracket intervention and the are developing. composition of these communities may contribute to periodontitis. (\HV IURP UG PLFH UHFHLYHG D VXEUHWLQDO LQMHFWLRQ RI DQ $$9 50 (YDOXDWLQJ =1) DV D WKHUDSHXWLF WDUJHW IRU 3UDGHU HQFRGLQJIRU1UIGULYHQE\DQ53(VSHFL¿FSURPRWHU %(67 RU Willi Syndrome DQ$$9HQFRGLQJ*)3GULYHQE\WKHVDPHSURPRWHU7KHH\HVZHUH 0LFKDHO6&KXQJ WKHQÀDWPRXQWHGDQGWKH53(F\WRVNHOHWRQVLPDJHGZLWKSKDOORLGLQ UConn Health, Farmington, USA The uniform hexagonal monolayer of the RPE became increasingly G\VPRUSKLFLQXQWUHDWHGRUFRQWUROPLFHEXWUHPDLQHGUHJXODULQ1UI 3UDGHU:LOOL 6\QGURPH 3:6 LV D QHXURGHYHORSPHQWDO GLVRUGHU WUHDWHGPLFH0DQXDOVHJPHQWDWLRQRI53(FHOOVDQGTXDQWL¿FDWLRQ DႇHFWLQJaOLYHELUWKVDQGKDVQRNQRZQFXUH,QGLYLGXDOV with Fiji found that the RPE of untreated rd1 mice had mean areas ZLWK3:6SUHVHQWZLWKK\SRWRQLDK\SRJRQDGLVPDQGLQLWLDOIDLOXUH

42 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

ODUJHUWKDQLQWUHDWHGPLFH&RQWURO $$9*)3 UG53(DOVR 53 0RQLWRULQJUHDOWLPH+,9YLULRQIXVLRQDQGGRZQVWUHDP KDG D PHDQ DVSHFW UDWLR ORZHU WKDQ WKDW IRXQG LQ UG 53( PHWDEROLFFRQVHTXHQFHVZLWKÀXRUHVFHQFHOLIHWLPHLPDJLQJ IURPH\HVWUHDWHGZLWK1UI%HFDXVHRIWKHWLPHFRQVXPLQJQDWXUH Charles Coomer RIWKLVDQDO\VLVZHGHYHORSHGDFXVWRPL]HGHLJKWVWHS&HOO3UR¿OHU University of Kentucky and University of Oxford (NIH Oxford- SLSHOLQH WR DXWRPDWH VHJPHQWDWLRQ &HOO3UR¿OHU ZDV OHVV HႇHFWLYH Cambridge Scholars Program), Louisville, USA WKDQPDQXDOVHJPHQWDWLRQIRUERWKPHDQFHOODUHD 52&$8& IRUPDQXDOYVIRU&HOO3UR¿OHU DQGDVSHFWUDWLRPHDQ 52&$8& 4XDQWLWDWLYHO\ PRQLWRULQJ +,9 IXVLRQ HQDEOHV PHFKDQLVWLF IRUPDQXDOYVIRU&HOO3UR¿OHU investigations of viral entry, its downstream consequences, and LWV SKDUPDFRORJLFDO LQKLELWLRQ 6HYHUDO DVVD\V KDYH EHHQ XVHG :H ZHUH DEOH WR GHPRQVWUDWH D TXDQWLWDWLYH GLႇHUHQFH EHWZHHQ previously to evaluate viral fusion. However, these approaches (i.e. UHVFXHG DQG QRQUHVFXHG 53( XWLOL]LQJ SDUDPHWHUV RI FHOO DUHD ȕJDODFWRVLGDVH HOHFWURQ PLFURVFRS\ S DQG YLUXV SDUWLFOH and cell aspect ratio. Aspect ratio mean was a better parameter for FRORFDOL]DWLRQEDVHG PHWKRGV QRW RQO\ ODFN WKH FDSDELOLW\ WR WUDFN discriminating between treated and untreated RPE than mean cell YLUDO IXVLRQ LQ UHDOWLPH EXW DOVR IDLO WR GLVWLQJXLVK ZKLFK YLUDO DUHD$OWKRXJKPDQXDOVHJPHQWDWLRQRI53(RႇHUVPRUHVHQVLWLYLW\ IXVLRQ HYHQWV UHVXOWHG LQ SURGXFWLYH RU QRQSURGXFWLYH LQIHFWLRQ &HOO3UR¿OHULVDEOHWRGHWHFWGLႇHUHQFHVLQUHVFXHGYVQRQUHVFXHG Furthermore, no attempt has been made to multiplex a viral fusion H\HV)XUWKHULPSURYHPHQWVWRWKH&HOO3UR¿OHUSLSHOLQHPD\EULQJLWV DVVD\ ZLWK PHWKRGV DLPHG WR PRQLWRU VHSDUDWH YLUDOLQGXFHG performance closer to that of human segmentation. FHOOXODU HYHQWV LQ UHDOWLPH :H GHYHORSHG D YLUDO IXVLRQ DVVD\ 52 The role of renalase and its potential serum binding taking advantage of Forster Resonance Energy Transfer (FRET) partner in pancreatitis multiplexed with FRET biosensors of host cell metabolism and YDULRXV VHFRQG PHVVHQJHUV :H XWLOL]HG ELPROHFXODU ÀXRUHVFHQW Shang-Lin Chung FRPSOHPHQWDWLRQ %L)& WRGHWHFWIXVLRQSRVLWLYHFHOOVZKHUH*DJ Yale School of Medicine, USA P&KHUU\ODEHOOHG -5)/ YLULRQV FRQWDLQLQJ QXFOHDUORFDOL]HG 935 5HQDODVH 51/6 LVDSODVPDSURWHLQVHFUHWHGE\WKHNLGQH\DQGRWKHU WDJJHG&WHUPLQDOKDOIP9HQXVZHUHXVHGWRLQIHFWFHOOVH[SUHVVLQJ tissues that has been found to be protective in acute injury including DFWLYDWLRQLQGXFHGF\WLGLQHGHDPLQDVH $,' WDJJHGZLWK1WHUPLQDO models of ischemic injury to the kidney and heart. In addition, it has KDOIP9HQXV &HOOV WKDW ZHUH SURGXFWLYHO\ LQIHFWHG ZHUH GHWHFWHG been shown that renalase appears to disappear from serum during ZLWK*DJP&KHUU\ZKLOHIXVLRQSRVLWLYHFHOOVZHUHGHWHFWHGE\%L)& DFXWH NLGQH\ LQMXU\ *LYHQ LWV DSSDUHQW F\WRSURWHFWLYH SURSHUWLHV ORFDWHGLQWKHQXFOHXV7KLVIXVLRQDVVD\ZDVPXOWLSOH[HGZLWK)5(7 and connection to other organ systems and disease, we investigate EDVHGVHQVRUVRIWKH>$73@>$'3@UDWLRF$031$'+ODFWDWHS+ WKHUHODWLRQVKLSRIUHQDODVHZLWKSDQFUHDWLWLV8VLQJLVRODWHGPXULQH Ca , and H2O2 concentration, which were characterized, optimized, pancreatic lobules, pretreatment with recombinant human renalase DQG H[SUHVVHG LQ 7=0EO FHOOV &RQVHTXHQWO\ ZH GHWHFWHG DQG U51/6 EORFNHG ]\PRJHQ DFWLYLW\ FDXVHG E\ ERWK FHUXOHLQ DQG PRQLWRUHG +,9LQGXFHG FKDQJHV RI FHOOXODU PHWDEROLVP GXULQJ FDUEDFKROWZRDJHQWVWKDWFDQFDXVHSDQFUHDWLWLVLQYLYR&HUXOHLQ IXVLRQ DQG LQIHFWLRQ FRPSDUHG WR EDVHOLQH DW WKH VLQJOHFHOOXODU induced histological changes commonly seen in pancreatitis was level. Fluorescence lifetimes and average intensities per cell were DOVRSUHYHQWHGZLWKU51/6SUHWUHDWPHQWDQGFHUXOHLQDGPLQLVWUDWLRQ calculated to elucidate the changes in concentration of metabolites to mice with a genetic deletion of renalase resulted in more severe and second messengers during fusion and infection. We therefore pancreatitis. Furthermore, serum endogenous renalase was found WUDFNHG YLUDOLQGXFHG FKDQJHV LQ JOREDO KRVW FHOO PHWDEROLVP DQG to be undetectable within an hour after the onset of experimental VLJQDOWUDQVGXFWLRQGXULQJIXVLRQDQGSURGXFWLYHLQIHFWLRQLQUHDOWLPH FHUXOHLQLQGXFHGPXULQHSDQFUHDWLWLV51/6UHWXUQHGWROHYHOVKLJKHU DWWKHVLQJOHFHOOOHYHO2XUUHVXOWVZLOODGGWRH[LVWLQJNQRZOHGJHRI WKDQ EDVDO YDOXHV RQFH FHUXOHLQ DGPLQLVWUDWLRQ FHDVHG 6LPLODUO\ several key metabolic changes and signal transduction processes in preliminary studies in human plasma from individuals with acute UHTXLUHG IRU +,9 WR VXFFHVVIXOO\ HQWHU DQG SURGXFWLYHO\ LQIHFW LWV SDQFUHDWLWLVZHREVHUYHGVLJQL¿FDQWGHFUHDVHVLQSODVPDOHYHOVZKHQ host. This data is key for the development of alternative therapeutic compared to healthy controls. We found that renalase is transported VWUDWHJLHVWRFRQWURO+,9UHSOLFDWLRQLQLQIHFWHGSDWLHQWV in serum in a high molecular weight complex, and this complex may have a role in its apparent disappearance from serum during the 54 Astrocytes mediate brain reward signaling in the nucleus onset of disease. Through mass spectrometry, we determined that accumbens SXWDWLYHPXULQH51/6ELQGLQJSURWHLQFDQGLGDWHVLQPXULQHPRGHOV 0LFKHOOH&RUNUXP include murinoglobulin, pregnancy zone protein, C3, and C5, which University of Minnesota, minneapolis, USA DUHPHPEHUVRIWKHDOSKDPDFURJOREXOLQGRPDLQFRQWDLQLQJJHQH Objective: The present study aims to determine the role of astrocytes family. Together, these results suggest that renalase and its serum in drug addiction, to reveal potential novel cellular targets for the binding protein may play an important role in the regulation of injury treatment of this brain disorder. Background: Over 200 million people and recovery in pancreatitis. To better understand how, I am using ZRUOGZLGH VXႇHU IURP WKH GHELOLWDWLQJ FRQVHTXHQFHV RI GUXJ XVH LPPXQRSUHFLSLWDWLRQ DVVD\V WR FRQ¿UP WKH LGHQWLW\ RI WKH ELQGLQJ and abuse; and, unfortunately, even with treatment, the relapse rate protein and investigate its interactions with renalase during periods IRUGUXJDEXVHLVEHWZHHQ7KHFXUUHQWSURMHFWVSHFL¿FDOO\ of pancreatic injury and recovery. I am also working with human H[DPLQHV DPSKHWDPLQH D SV\FKRVWLPXODQW WKDW DGYHUVHO\ DႇHFWV VDPSOHVWRFRQ¿UPWKDWWKHVDPH51/6ELQGLQJSURWHLQ V IRXQGLQ multiple organ systems including the brain. Amphetamine works murine plasma is the same in humans. in the brain by blocking and reversing dopamine transporters and increasing the amount of synaptic dopamine. In addition to the disruption of dopaminergic signaling, a major neural circuit disrupted by amphetamine is excitatory transmission in the nucleus accumbens 1$F D SULPDU\ EUDLQ UHJLRQ LPSOLFDWHG LQ UHZDUG DQG DGGLFWLRQ behavior). Most studies on reward and addiction have focused on neurons. Little is known about astrocytes, which are emerging

www.jointmeeting.org 43 POSTER ABSTRACTS

as important cellular elements of synaptic function regulation. vitro in combination with the standard of care neuraminidase inhibitor Traditionally, astrocytes have been viewed as passive players in RVHOWDPLYLU DQG LV DFWLYH DJDLQVW DW OHDVW RQH RVHOWDPLYLUUHVLVWDQW nervous system function. However, although astrocytes are not VWUDLQ,QDPRXVHPRGHORIOHWKDOLQÀXHQ]DYLUXVLQIHFWLRQ+7LV electrically excitable, astrocytes respond to chemical transmitters QRQPLWRJHQLFDQGERWKHDUO\DQGGHOD\HGWKHUDSHXWLFDGPLQLVWUDWLRQ with cytoplasmic calcium elevations, which, in turn, can trigger the RI +7 LQWUDSHULWRQHDOO\ DUH KLJKO\ SURWHFWLYH )XUWKHUPRUH +7 release of additional chemical transmitters leading to the modulation DGPLQLVWHUHGYLDDHURVROZLWKWKH7ROOOLNHDQGUHFHSWRUDJRQLVWV of synaptic transmission and animal behavior. The present study 3DP&6.DQG2'1UHVSHFWLYHO\LVDOVRKLJKO\HႈFDFLRXV LQYHVWLJDWHVWKHHႇHFWVRIGRSDPLQHDQGDPSKHWDPLQHRQDVWURF\WH ,Q HႇRUWV WR XQGHUVWDQG WKH PHFKDQLVP RI DFWLRQ RI +7 DJDLQVW QHXURQVLJQDOLQJLQWKH1$FDQGWHVWVWKHK\SRWKHVLVWKDWDVWURF\WHV LQÀXHQ]DYLUXVZHKDYHIRXQGE\LPPXQRÀXRUHVFHQFHWKDWLQÀXHQ]D are activated by dopaminergic signaling and mediate excitatory virus replication is inhibited at or before the step of protein translation. V\QDSWLF WUDQVPLVVLRQ LQ WKH 1$F DQG EHKDYLRUDO VHQVLWLYLW\ WR $WWDFKPHQWLVQRWLQKLELWHGE\+7LQTXDQWLWDWLYHSRO\PHUDVHFKDLQ amphetamine. 0HWKRGV We combined confocal calcium imaging UHDFWLRQEDVHGDQGKHPDJJOXWLQDWLRQDVVD\V,QVWHDG+7DSSHDUV with selective optogenetic stimulation of dopaminergic axons to WRLQKLELWLQÀXHQ]DYLUXVIXVLRQDWVXEPLFURPRODUFRQFHQWUDWLRQVXVLQJ investigate astrocytic responsiveness to dopamine. To investigate the TXDQWLWDWLYH ÀXRUHVFHQFH GHTXHQFKLQJ DQG LPPXQRÀXRUHVFHQFH consequences of astrocyte activation on synaptic transmission we EDVHG DSSURDFKHV ZLWK VHYHUDO GLႇHUHQW VWUDLQV 7DNHQ WRJHWKHU performed electrophysiological recordings of excitatory transmission WKHVHVWXGLHVUHYHDOWKDW+7LVHႈFDFLRXVDJDLQVWLQÀXHQ]DYLUXV and activated astrocytes with selective optogenetic stimulation ERWKLQYLWURDQGLQYLYRE\WZRGLႇHUHQWURXWHVRIDGPLQLVWUDWLRQDQG RI GRSDPLQHUJLF D[RQV DQG E\ DFWLYDWLQJ 'HVLJQHU 5HFHSWRUV WKDWLWLQKLELWVLQÀXHQ]DYLUXVIXVLRQXQGHUVFRULQJLWVSRWHQWLDOXWLOLW\ ([FOXVLYHO\ $FWLYDWHG E\ 'HVLJQHU 'UXJV '5($''V VSHFL¿FDOO\ DVDQHZEURDGVSHFWUXPDQWLLQÀXHQ]DWKHUDSHXWLF expressed in astrocytes. Behaviorally, we investigated locomotor DFWLYLW\LQUHVSRQVHWRDPSKHWDPLQHLQZLOGW\SHDQGWUDQVJHQLFPLFH 56 )UDWD[LQ GH¿FLHQF\ LQGXFHV HQGRWKHOLDO PHWDEROLF with decrease astrocyte activity. 5HVXOWVWe found that astrocytes dysregulation to promote pulmonary hypertension responded to dopamine and amphetamine with intracellular calcium 0LUDQGD&XOOH\ HOHYDWLRQV7KHVHGRSDPLQHLQGXFHGFDOFLXPHOHYDWLRQVLQDVWURF\WHV University of Pittsburgh, Pittsburgh, USA were associated with a depression of excitatory synaptic transmission Pulmonary hypertension (PH) is a progressive vascular disease through activation of adenosine A1UHFHSWRUV)XUWKHUPRUHVSHFL¿F that causes increased pulmonary arterial pressure, right heart DFWLYDWLRQRIDVWURF\WHVZLWK'5($''VUHVXOWHGLQDGHSUHVVLRQRI IDLOXUH DQG GHDWK :H KDYH SUHYLRXVO\ VKRZQ LURQVXOIXU )H6 V\QDSWLFWUDQVPLVVLRQWKDWPLPLFNHGWKHGRSDPLQHPHGLDWHGV\QDSWLF FOXVWHUGH¿FLHQF\GXHWRUHSUHVVLRQRILURQVXOIXUFOXVWHUDVVHPEO\ depression. Transgenic mice with decreased astrocyte calcium SURWHLQDQG ,6&8 SURPRWHVPLWRFKRQGULDOG\VIXQFWLRQDQG signaling exhibited attenuated locomotor responses to amphetamine. 3+)UDWD[LQ );1 DELQGLQJSDUWQHURI,6&8LVFUXFLDOWR)H6 3UHVHQWUHVXOWVLQGLFDWHWKDWDVWURF\WHVLQWKH1$FFRUHDUHLQYROYHGLQ FOXVWHUDVVHPEO\*HQHWLF);1GH¿FLHQF\FDXVHV)ULHGUHLFK¶VDWD[LD reward signaling by responding to dopamine and amphetamine and a disease of neurologic and cardiovascular dysfunction. The latter PHGLDWLQJ GRSDPLQHLQGXFHG V\QDSWLF GHSUHVVLRQ DQG EHKDYLRUDO is often accompanied by PH, but the molecular etiology is unclear. responses to amphetamine. Conclusions: The present results aid 7KXVWKHUHPD\EHDGLUHFWUROHIRU);1LQ3+:HK\SRWKHVL]HG in elucidating the cellular mechanisms involved in the neural plasticity WKDW );1 GH¿FLHQF\ GXH WR JHQHWLF RU DFTXLUHG WULJJHUV GLVUXSWV associated with drugs of abuse and provides insight into novel endothelial metabolic function to promote PH. therapeutic cellular targets. );1 H[SUHVVLRQ ZDV PRGXODWHG LQ KXPDQ SXOPRQDU\ DUWHULDO 55 Broad-spectrum antiviral banana lectin is highly endothelial cells (PAECs) by gene transfection and exposure to HI¿FDFLRXVDJDLQVWOHWKDOLQÀXHQ]DYLUXVLQIHFWLRQLQYLYRDQG EURPRGRPDLQLQKLELWRU,%(7K\SR[LDDQG,/ȕ6LPXOWDQHRXVO\ LQKLELWVLQÀXHQ]DYLUXVIXVLRQ DQDO\VHVZHUHSHUIRUPHGLQLQGXFHGSOXULSRWHQWVWHP L36 FHOOGHULYHG Evelyn Coves-Datson HQGRWKHOLDO FHOOV IURP SDWLHQWV ZLWK )ULHGUHLFK¶V DWD[LD )H6 FOXVWHUV University of Michigan, Ann Arbor, USA ZHUHTXDQWL¿HGE\ÀXRUHVFHQWVHQVRUJO\FRO\WLFÀX[ZDVPHDVXUHGE\ 6HDKRUVHDVVD\3KHQRW\SLFFKDQJHVVXFKDVDSRSWRVLVPLJUDWLRQ ,QÀXHQ]D YLUXVHV FDXVH ERWK VHDVRQDO HSLGHPLFV UHVXOWLQJ LQ WKH vasomotor gene expression, and angiogenesis, were measured. In death of up to 500,000 people each year, and pandemics, which are YLYRFHOOVSHFL¿FFRQGLWLRQDOFXNNQRFNRXWPLFHDQGPLFHZLWK);1 XQSUHGLFWDEOHDQGKDYHWKHSRWHQWLDOWRNLOOPLOOLRQV9DFFLQDWLRQDV VL51$GHOLYHUHGWRWKHYDVFXODUHQGRWKHOLXPZHUHVWXGLHG a preventive measure and neuraminidase inhibitors as treatment IRU VHYHUH LQÀXHQ]D LQIHFWLRQV DUH RQO\ PRGHUDWHO\ HႇHFWLYH DQG ,Q 3$(&V FKURQLF K\SR[LD IROG FKDQJH 3 resistance to extant therapies is increasing among circulating strains. DQG ,/ȕ IROG FKDQJH 3 GRZQUHJXODWHG );1 Thus, there is a strong unmet need for a new antiviral therapeutic H[SUHVVLRQ,%(7LQKLELWLRQRIEURPRGRPDLQFRQWDLQLQJSURWHLQ IRU WKH SUHYHQWLRQ DQG WUHDWPHQW RI LQÀXHQ]D LQIHFWLRQ SDUWLFXODUO\ %5' DVZHOODVVL51$NQRFNGRZQRI%5'UHVWRUHG);1OHYHOV RQHWKDWLVEURDGVSHFWUXP:HKDYHGHYHORSHGDQRYHOJHQHWLFDOO\ IROORZLQJK\SR[LD IROGFKDQJH3 DQG,/ȕ RSWLPL]HG OHFWLQ VXJDUELQGLQJ SURWHLQ RULJLQDOO\ LVRODWHG IURP IROGFKDQJH3 );1GH¿FLHQF\GHFUHDVHG)H6FOXVWHU EDQDQDVFDOOHG+7EDQDQDOHFWLQ +7%DQ/HF+7 WKDWKDV DVVHPEO\ IROGFKDQJH3 DQGLQFUHDVHGJO\FRO\VLV EURDGVSHFWUXPDQWLYLUDODFWLYLW\DJDLQVWPXOWLSOHLQFOXGLQJSDQGHPLF IROG FKDQJH 3 DQG 526 SURGXFWLRQ OHDGLQJ WR DQGDYLDQVWUDLQVRILQÀXHQ]DDVZHOODVYLUXVHVIURPRWKHUIDPLOLHV LQFUHDVHG DSRSWRVLV GHFUHDVHG PLJUDWLRQ DOWHUHG HႇHFWRUV RI VXFKDVKXPDQLPPXQRGH¿FLHQF\YLUXV +,9 DQGKHSDWLWLV&YLUXV YDVRPRWRU WRQH DQG GHFUHDVHG DQJLRJHQHVLV LQ YLWUR 6LPLODU +&9 :H SUHYLRXVO\ GHPRQVWUDWHG LQ YLWUR WKDW WKH VLQJOH DPLQR phenotypic changes were also observed in endothelial cells derived DFLGPXWDWLRQDWSRVLWLRQIURPDKLVWLGLQHWRDWKUHRQLQHPLQLPL]HV IURP L36 FHOOV IURP SDWLHQWV ZLWK )ULHGUHLFK¶V DWD[LD (QGRWKHOLDO WKH PLWRJHQLFLW\ RI WKH ZLOGW\SH OHFWLQ ZKLOH PDLQWDLQLQJ DQWLYLUDO VSHFL¿F );1 NQRFNGRZQ LQ FKURQLFDOO\ K\SR[LF PLFH SURPRWHG DFWLYLW\DJDLQVWLQÀXHQ]D+,9DQG+&9:HQRZUHSRUWWKDW+7 KHPRG\QDPLF 5963PP+JY3 V\QHUJLVWLFDOO\LQKLELWVWKHUHSOLFDWLRQRIVHYHUDOVWUDLQVRILQÀXHQ]DLQ and histologic indices of PH in vivo.

44 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

);1GH¿FLHQF\LQGXFHGE\K\SR[LDDQG,/ȕSURPRWHVHQGRWKHOLDO 58 5HFLSURFDO WUDQVSODQWDWLRQ DQG $7$&VHT SUR¿OLQJ RI VSHFL¿F PHWDEROLF FKDQJHV OHDGLQJ WR 3+ GHYHORSPHQW LQ YLYR ¿EUREODVWVUHYHDOVFDUIRUPLQJEHKDYLRULVFHOOLQWULQVLF Our results may provide a target for diagnostic and therapeutic Heather E. desJardins-Park LQWHUYHQWLRQIRU3+DQGPD\JXLGHJHQHWLFLGHQWL¿FDWLRQRIDQRYHO Stanford University School of Medicine, USA cohort of patients at risk for PH. 6FDUV FDQ EH SK\VLFDOO\ DQG SV\FKRORJLFDOO\ GHYDVWDWLQJ DQG 57 0LFH ODFNLQJ W\SH LQWHUIHURQ UHFHSWRU JHQHUDWH$'&. UHSUHVHQW D PDMRU ¿QDQFLDO EXUGHQ RQ WKH 86 KHDOWKFDUH V\VWHP DQWLERGLHVLQUHVSRQVHWRǻJ'YDFFLQDWLRQEXWKDYHGHIHFWV Interestingly, mammalian fetuses heal scarlessly by regenerating in ADCK mobilization native tissue. In mice, the transition from regenerative healing -RVHSK0'DUGLFN WR VFDUULQJ RFFXUV EHWZHHQ HPEU\RQLF GD\ H DQG H $ Albert Einstein College of Medicine, USA OLQHDJH RI ¿EUREODVWV WKH FHOOV NQRZQ WR SURGXFH VFDUV GH¿QHG by embryonic expression of Engrailed 1 deposits all scar tissue in ǻJ' LV D OLYHDWWHQXDWHG +HUSHV 6LPSOH[ 9LUXV W\SH +692) DGXOWPLFH+RZHYHUWKHVH(QJUDLOHGSRVLWLYH¿EUREODVWV (3)V VWUDLQ JHQHWLFDOO\ GHOHWHG IRU JO\FRSURWHLQ ' J' RQH RI WKH contribute to scarless healing before e16.5, then transition into a LPPXQRGRPLQDQW DQWLJHQV J' LV UHTXLUHG IRU FHOO HQWU\ OLPLWLQJ scarring phenotype as development progresses. Therefore, we ǻJ'WRDVLQJOHURXQGRIUHSOLFDWLRQLQQRQFRPSOHPHQWLQJFHOOV hypothesized that EPFs accumulate epigenetic changes over time ǻJ'LVDQRYHOLPPXQRJHQLQWKDWLWHOLFLWVFRPSOHWHO\SURWHFWLYH that result in the shift from scarless to scarring phenotype, and that LPPXQLW\ DJDLQVW +69 DQG +69 WKURXJK DQWLERG\GHSHQGHQW EPF healing phenotype is thus cell intrinsic rather than dependent on FHOOPHGLDWHG F\WRWR[LFLW\ DQG SKDJRF\WRVLV FROOHFWLYHO\ UHIHUUHG cell microenvironment. WR KHUH DV DQWLERG\GHSHQGHQW FHOOPHGLDWHG NLOOLQJ $'&. 7KH PHFKDQLVPVE\ZKLFKLPPXQRJHQVHOLFLW$'&.DFWLYDWLQJDQWLERGLHV )LEUREODVWV ZHUH LVRODWHG IURP (Q&UH5P7P* PLFH XVLQJ DUHQRWZHOOXQGHUVWRRGEXWW\SHLQWHUIHURQV ,)1Įȕ KDYHEHHQ ÀXRUHVFHQFHDFWLYDWHG FHOO VRUWLQJ )$&6 DW JHVWDWLRQDO DJHV VKRZQWRSOD\DUROHDFWLYDWLQJKXPRUDOLPPXQLW\DQG)FȖ5PHGLDWHG H H H DQG SRVWQDWDO GD\ S DQG S 5HFLSURFDO immune modulation. transplantation experiments were performed to analyze EPF behavior LQYLYRE\LQMHFWLQJ(3)VIURPHRUS(Q&UH5P7P*PLFH 7RLQYHVWLJDWH WKH UROH RI ,)1Įȕ LQ JHQHUDWLQJ DQ HႇHFWLYH$'&. LQWR WKH GRUVXP RI &%/- PLFH DW S RU H UHVSHFWLYHO\ DQWLERG\ UHVSRQVH ZH SULPHERRVW YDFFLQDWHG ,)1Įȕ UHFHSWRU Epigenetic analysis was performed using the Assay for Transposase NQRFNRXW PLFH ,)1$5 ZLWK D ÀXRUHVFHQW ǻJ' YDULDQW DQG $FFHVVLEOH&KURPDWLQZLWKKLJKWKURXJKSXWVHTXHQFLQJ $7$&VHT compared the resulting immunity to that of WT mice. Both strains RIPLFHYDFFLQDWHGZLWKǻJ'JHQHUDWHGVLPLODUSURSRUWLRQVRIWRWDO EPFs at e16.5 transplanted into a scarring microenvironment (p1) DFWLYDWHGDQGJ%VSHFL¿F&'7FHOOV$GGLWLRQDOO\ǻJ'YDFFLQDWHG H[KLELWQRQVFDUULQJPRUSKRORJ\DQGFRORFDOL]HZLWKW\SH,FROODJHQ ,)1$5 PLFH GHYHORSHG VLPLODU RYHUDOO DQG LVRW\SH VSHFL¿F DQWL LQ RQO\ RI FHOOV ZKHUHDV (3)V DW S WUDQVSODQWHG LQWR D +69,J*WLWHUVDVFRPSDUHGWR:7PLFH$'&.DVVD\VXVLQJERQH scarless microenvironment (e16.5) exhibit scarring morphology and PDUURZGHULYHGPDFURSKDJHV %0'0V IURP:7PLFHVKRZHGWKDW FRORFDOL]HZLWKW\SH,FROODJHQLQRIFHOOV$7$&VHTSUR¿OLQJ VHUXP IURP YDFFLQDWHG ,)1$5 PLFH LQGXFHV VLJQL¿FDQWO\ PRUH UHYHDOV H ¿EUREODVWV DUH RI D VLQJOH OLQHDJH WKH\ ZHUH WKXV $'&. NLOOLQJ WKDQ VHUXP IURP YDFFLQDWHG :7 PLFH S 7R H[FOXGHG IURP DQDO\VLV 7LPH FRXUVH DQDO\VLV RI HS (3)V GHWHUPLQHZKHWKHUWKHKXPRUDOLPPXQLW\LQ,)1$5PLFHLQLWLDWHG DQG (QJUDLOHG QHJDWLYH ¿EUREODVWV (1)V GHPRQVWUDWHV UHOLDEOH $'&.LQYLYRVHUXPIURPYDFFLQDWHG,)1$5PLFHZDVSDVVLYHO\ biological reproducibility. Principal component analysis indicates that WUDQVIHUUHG LQWR QDLYH :7 DQG )FȖ5,9 NQRFNRXW PLFH :7 PLFH ZKLOH(3)VDQG(1)VDUHVLPLODUDWHWKH\HYHQWXDOO\GLYHUJHDV that received the vaccinated serum were partially protected from 10x GLVWLQFWSRSXODWLRQVZLWKWKHJUHDWHVWGLႇHUHQFHVREVHUYHGDWS /'FKDOOHQJHZLWK+69EXW)FȖ5,9PLFHZHUHQRW S ([DPLQLQJWKH(3)OLQHDJHVSHFL¿FDOO\WKHPRVWHSLJHQHWLFFKDQJHV However, in a simultaneous experiment, serum from vaccinated WT RFFXU EHWZHHQ H DQG H ZLWK IHZHU HSLJHQHWLF FKDQJHV PLFHGLGQRWFRQIHUDQ\SURWHFWLRQWRQDLYH,)1$5PLFHLQGLFDWLQJ RFFXUULQJ SRVWQDWDOO\ EHWZHHQ S DQG S VLJQL¿FDQW SHDNV GLႈFXOW\ LQ PRELOL]LQJ DQ $'&. UHVSRQVH S 6XUSULVLQJO\ YV 8SRQDQDO\]LQJWKHJHQHVIRUDVPRRWKPXVFOHDFWLQ ,)1$5 PLFH WKDW ZHUH SULPHERRVW YDFFLQDWHG ZLWKǻJ' ZHUH DQG YLPHQWLQ WZR JHQHV LPSOLFDWHG LQ ¿EURVLV ZKRVH H[SUHVVLRQ still completely protected from morbidity and mortality following a 10x LVWKRXJKWWREHFKDUDFWHULVWLFRIDOO¿EUREODVWVZHIRXQGWKDWWKHLU /'FKDOOHQJHZLWK+69 S 6XEVHTXHQWTXDQWL¿FDWLRQ JHQHWLFDFFHVVLELOLW\VLJQL¿FDQWO\GLႇHUVEHWZHHQ(3)VDQG(1)V of viral copies in the dorsal root ganglia of the challenged mice 2XU GDWD VWURQJO\ VXJJHVW WKDW ¿EUREODVW SKHQRW\SH LV OLQNHG WR IRXQGQRGLႇHUHQFHLQVWHULOL]DWLRQRILQIHFWLRQEHWZHHQYDFFLQDWHG WUDQVFULSWRPLFUHJXODWLRQ$GGLWLRQDOO\¿EUREODVWVZKLOHWKH\PD\EH :7 DQG ,)1$5 PLFH 7R GHWHUPLQH ZKHWKHU WKH GLVUXSWLRQ LQ capable of activation, behave in a stereotyped manner not dependent $'&.GXULQJWKHSDVVLYHWUDQVIHUH[SHULPHQWVZDVGXHWRGHIHFWV RQFHOOPLFURHQYLURQPHQW'LUHFWHGLQWHUYHQWLRQVRQ(3)VPD\WKXV LQPDFURSKDJHUHVSRQVHDVVD\VZHUHSHUIRUPHGXVLQJ:7%0'0V enable scarless healing in adult animals. In future experiments, we LQ WKH SUHVHQFH RI ,)1$5 EORFNLQJ$EV +RZHYHU WKH DGGLWLRQ RI KRSHWRLGHQWLI\WDUJHWVIRUJHQHWLFSHUWXUEDWLRQXVLQJ&5,635&DV DQWL,)1$5 DQWLERGLHV GLG QRW DႇHFW$'&. DFWLYLW\ LQGLFDWLQJ WKDW %\FRUURERUDWLQJRXU$7$&VHTGDWDZLWKIXQFWLRQDODVVD\VVXFKDV ,)1$5VLJQDOLQJLVQRWUHTXLUHGIRUPDFURSKDJHVWRFDUU\RXW$'&. :HVWHUQEORWVDQG51$DQDO\VLVZHZLOOSLQSRLQWJHQHVUHJXODWLQJ 7RJHWKHURXUGDWDVKRZVWKDWWKHSURGXFWLRQRI$'&.DQWLERGLHVLQ ¿EUREODVWEHKDYLRUWRXOWLPDWHO\LGHQWLI\QRYHOWKHUDSHXWLFRSWLRQVIRU UHVSRQVHWRǻJ'LVLQGHSHQGHQWRI,)1ĮȕEXW,)1$5VLJQDOLQJLV human patients. UHTXLUHGIRUSURWHFWLRQE\SDVVLYHWUDQVIHU7KHVH¿QGLQJVLOOXVWUDWH DQRYHOGUDZEDFNRIWKH,)1$5PRGHOZKLOHKLJKOLJKWLQJWKHXWLOLW\ RIǻJ' DV D YDFFLQH YHFWRU IRU SDWKRJHQV ZKLFK DUH FRPPRQO\ VWXGLHGLQ,)1$5PLFH

www.jointmeeting.org 45 POSTER ABSTRACTS

59 Interactions of calcium, 25-OH vitamin D, and kidney the general population and 3.53 in the PEA students. The prevalence function with parathyroid hormone levels LQWKHWRSULVNIDFWRUVEHWZHHQERWKJURXSVZDVDOVRJUHDWHULQWKH Sangeet Dhillon-Jhattu PEA adolescents compared to the general population. PEA had six University of Chicago, IL, Chicago, USA VWDWLVWLFDOO\VLJQL¿FDQWO\ODUJHUULVN\EHKDYLRUFDWHJRULHVGHSUHVVLRQ SYDOXH YLFWLP RI EXOO\LQJ SYDOXH DQ[LHW\ Parathyroid hormone (PTH) is a crucial factor in regulating calcium SYDOXH GLVWUDFWHG GULYLQJ SYDOXH QR DGXOW KRPHRVWDVLV DQG ERQH PLQHUDO GHSRVLWLRQ 2+ 9LWDPLQ ' DQG VXSSRUW SYDOXH DQG HDWLQJ GLVRUGHU SYDOXH HVWLPDWHG JORPHUXODU ¿OWUDWLRQ UDWH H*)5 DOVR LQWHUDFW ZLWK 37+ Conclusions: PEA students are more prone to risky behavior than and we aimed to better characterize the interplay between these a general population of adolescents. High academic performance is factors. QRWDQLQGLFDWRURIUHGXFHGULVN\EHKDYLRUDQGZHGLGQRW¿QGDQ\ Laboratory results performed at Laboratory Corporation of America correlation at all between the two. +ROGLQJV /DE&RUS EHWZHHQ$SULO DQG )HEUXDU\ ZHUH DVVHVVHGLIVLPXOWDQHRXV37+FDOFLXPYLWDPLQ'DQGH*)5ZHUH 61 The role of spinal meningeal lymphatic vessels in DYDLODEOH &DOFLXP DQG YLWDPLQ ' ZHUH FDWHJRUL]HG DQG DQDO\VHV recovery from spinal cord injury ZHUH VWUDWL¿HG IRU 1DWLRQDO .LGQH\ )RXQGDWLRQ VWDJH RI FKURQLF 0LFKDHO'RQJ NLGQH\ GLVHDVH &.' 3HUFHQWDJHV RI WHVWV LQ ZKLFK D 37+! University of Virginia, USA was observed were calculated and plotted for each combination of 6SLQDO FRUG LQMXU\ LV D GHELOLWDWLQJ GLVHDVH LQYROYLQJ GDPDJH IURP FDOFLXPYLWDPLQ'DQGH*)5 initial injury and secondary degeneration with recruitment of immune $PRQJSDWLHQWVZHUHPDOHDQGPHDQDJHZDV FHOOV WR IDFLOLWDWH UHSDLU +RZHYHU WKH WUDႈFNLQJ RI LPPXQH FHOOV \HDUV &RPSDUHG WR WKRVH ZLWK H*)5! 37+ OHYHOV ZHUH PRUH between the peripheral immune system and the spinal cord is poorly OLNHO\ WR EH DEQRUPDO LQ &.' VWDJHV DQG $ +LJKHU YLWDPLQ ' XQGHUVWRRG,QDGGLWLRQWKHFRQWURYHUV\RYHUWKHEHQH¿FLDORUKDUPIXO levels were associated with lower PTH in all patients, and this DVSHFWVRIWKHLQÀDPPDWRU\UHVSRQVHLQVSLQDOFRUGLQMXU\KDVOHGWR HႇHFWEHFDPHPRUHSURPLQHQWZLWKGHFUHDVLQJH*)57KHQRUPDO greater discussion over immunotherapy strategies. 8VKDSHGUHODWLRQVKLSVEHWZHHQFDOFLXPDQG37+ZHUHGLVWRUWHGLQ The spinal meningeal lymphatic network has recently been &.'VWDJHVDQG characterized and provides an unexplored avenue for communication PTH levels become detectably abnormal even in very early between the nervous system and immune system. The role of spinal &.'5HSOHWLRQRIYLWDPLQ'WROHYHOVRIQJP/RUJUHDWHUZDV meningeal lymphatics has never been studied in the context of spinal DVVRFLDWHGZLWKVLJQL¿FDQWO\ORZHU37+OHYHOVLQSDWLHQWVZLWKH*)5 cord injury. We demonstrate marked alterations in lymphatic vessels )XUWKHUZRUNLVQHHGHGWRGHWHUPLQHLILQWHUYHQWLRQVWRUHSOHWH in the spinal cord dural meningeal compartment as a result of spinal YLWDPLQ ' !QJPO PLJKW UHGXFH K\SHUSDUDWK\URLGLVP DQG LWV cord injury. We have assessed their morphological and functional YDVFXODUFRPSOLFDWLRQVLQHDUO\&.' FKDQJHVDQGWKHUROHRIPDMRUO\PSKDQJLRJHQHVLVSURPRWLQJIDFWRUV in meningeal lymphatic vessel changes associated with spinal cord 60 5LVN$VVHVVPHQWLQ+LJK$FKLHYLQJ$GROHVFHQWV injury. We hypothesize that spinal meningeal lymphatic vessels Anshul Dhingra respond to injury and communicate with the peripheral immune Case Western Reserve University, Menomonee Falls, USA system to activate the adaptive immune response. Further work is Background: Adolescence is a period of social, physical, and required to establish the causal link between meningeal lymphatic psychological development. While it has its stages of exploration WUDႈFNLQJRILPPXQHFHOOVDQGUHFRYHU\LQVSLQDOFRUGLQMXU\:HDLP and experimentation, it is accompanied by a fair share of risky WRVHWWKHIRXQGDWLRQIRUVSLQDOPHQLQJHDOO\PSKDWLFPRGL¿FDWLRQDV behaviors. Most health problems among adolescents are due to risky a therapeutic option in spinal cord injury. behaviors as opposed to biological dysfunction (genetic diseases, 62 Activation of DAF-16/FOXO by reactive oxygen species SK\VLRORJLFDO DLOPHQWV HWF $OPRVW RI WKH FDXVHV RI GHDWK LQ promotes longevity in long-lived mitochondrial mutants. the adolescent population are preventable, and therefore addressing Dylan Dues these risky behaviors in health care visits is essential to reducing Michigan State University College of Human Medicine / Van morbidity and mortality. The Rapid Assessment for Adolescent Andel Research Institute, Grand Rapids, USA 3UHYHQWLYH6HUYLFHV 5$$36 LVDLWHPTXHVWLRQQDLUHGHVLJQHG to identify risk factors in adolescents based on generally accepted 0LOGGH¿FLWVLQPLWRFKRQGULDOIXQFWLRQKDYHEHHQVKRZQWRLQFUHDVH risk categories. Objectives: Our goal was to evaluate and analyze OLIHVSDQ LQ PXOWLSOH VSHFLHV LQFOXGLQJ ZRUPV ÀLHV DQG PLFH +HUH the most prevalent risk factors in a general adolescent population ZH VWXG\ WKUHH & HOHJDQV PLWRFKRQGULDO PXWDQWV FON LVS DQG DW0LFKLJDQ0HGLFLQH+HDOWK&OLQLFVDQGFRPSDUHWKLVWRULVNIDFWRUV QXR WRLGHQWLI\RYHUODSSLQJJHQHWLFSDWKZD\VWKDWFRQWULEXWHWRWKHLU RI KLJKDFKLHYLQJ DGROHVFHQWV LQ WKH 0+63($ SURJUDP 7KH JRDO ORQJHYLW\ :H ¿QG WKDW JHQHV UHJXODWHG E\ WKH )2;2 WUDQVFULSWLRQ ZDVWRGHWHUPLQHZKHWKHURUQRWKLJKDFKLHYLQJVWXGHQWVDUHPRUH IDFWRU '$) DUH XSUHJXODWHG LQ DOO WKUHH VWUDLQV DQG WKDW WKH RU OHVV SURQH WR ULVN\ EHKDYLRU 0HWKRGV 5$$36 TXHVWLRQQDLUH WUDQVFULSWLRQDOFKDQJHVSUHVHQWLQWKHVHZRUPVRYHUODSVLJQL¿FDQWO\ ZDVDGPLQLVWHUHGWRDGROHVFHQWVDJHVFRPLQJWRRXWSDWLHQW ZLWKWKHORQJOLYHGLQVXOLQ,*)VLJQDOLQJSDWKZD\PXWDQWGDI:H clinics at Michigan Medicine Health Clinics for annual health VKRZWKDW'$)DQGPXOWLSOH'$)LQWHUDFWLQJSURWHLQV 0$7+ PDLQWHQDQFH H[DPV 'HPRJUDSKLF FKDUDFWHULVWLFV ZHUH REWDLQHG ,0% &67 %$5 DUH UHTXLUHG IRU WKH ORQJHYLW\ RI DOO WKUHH IURP D UHWURVSHFWLYH FKDUW UHYLHZ 7KH 5$$36 TXHVWLRQQDLUH ZDV mitochondrial mutants. Our results suggest that the activation of FRQVWUXFWHG LQ WKH IRUP RI D 4XDOWULFV VXUYH\ DQG HPDLOHG WR WKH '$) LQ WKHVH PXWDQWV UHVXOWV IURP HOHYDWHG OHYHOV RI UHDFWLYH FXUUHQW DQG SUHYLRXV FRKRUWV LQ WKH 0+63($ SURJUDP 7KH UDWHV oxygen species. Overall, this work reveals an overlapping genetic RIKLJKULVNEHKDYLRULQERWKSRSXODWLRQVZHUHGHWHUPLQHGDQGWKHQ pathway required for longevity in three mitochondrial mutants, FRPSDUHG XVLQJ WKH &KLVTXDUHG WHVW IRU FDWHJRULFDO YDULDEOHV DQG FRPELQHG ZLWK SUHYLRXV ZRUN GHPRQVWUDWHV WKDW '$) LV D 5HVXOWV7KHDYHUDJHULVN\EHKDYLRUVFRUHSHUDGROHVFHQWZDVLQ downstream mediator of lifespan extension in multiple pathways of longevity.

46 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

63 The Scaffolding Protein IQ motif-containing GTPase SDWLHQWV3QFNLVDOVRVLJQL¿FDQWO\XSUHJXODWHGLQEUHDVWFDUFLQRPD Activating Protein 1 (IQGAP1) Promotes Hepatic Proliferation lung squamous carcinoma and renal papillary carcinoma patients. and Protects the Liver from Injury ,Q5&&SDWLHQWV3QFNLVRYHUH[SUHVVHGE\IROGLQWXPRUWLVVXH Hanna L. Erickson compared to adjacent normal tissue. Pnck overexpression correlates University of Illinois at Urbana-Champaign, Champaign, USA with various pathological and clinical outcomes such as Fuhrman JUDGH7VWDJLQJDQGRYHUDOOVXUYLYDO 26 ,Q$NLGQH\FDQFHUFHOO /LYHU FDQFHU LV WKH VHFRQG OHDGLQJ FDXVH RI FDQFHUUHODWHG GHDWK OLQHVZHKDYHGHWHUPLQHGRYHUH[SUHVVLRQRI31&.WREHDGULYHURI ZRUOGZLGH ZLWK GHDWKV DQQXDOO\DQG WKH PRUWDOLW\ UDWHLV FDQFHUSURJUHVVLRQ*HQRPLFHGLWLQJZLWK&5,635&DVVLJQL¿FDQWO\ LQFUHDVLQJUDSLGO\LQWKH8QLWHG6WDWHV/LYHUGLVHDVHDPDMRUULVN reduced cellular proliferation and cell viability. Collectively, this factor for liver cancer is becoming increasingly prevalent due to its HYLGHQFHYDOLGDWHV31&.DVDNLQDVHGUXJWDUJHWRILQWHUHVW$VDQ association with the growing obesity epidemic. Bile acids (BA) are XQGHUVWXGLHGSURWHLQ31&.KDVQRNQRZQFU\VWDOVWUXFWXUHDQGQR known liver tumor promoters but the mechanisms by which BAs NQRZQ H[RJHQRXV OLJDQGV 8VLQJ UHODWHG SURWHLQ FU\VWDO VWUXFWXUHV SURPRWHWXPRULJHQHVLVDUHXQNQRZQ7KHVFDႇROGLQJSURWHLQ,4PRWLI as templates, we have developed a structural homology model of FRQWDLQLQJ*73DVH$FWLYDWLQJ3URWHLQ ,4*$3 LVRYHUH[SUHVVHG 31&.WRXVHLQVWUXFWXUHEDVHGGRFNLQJVFUHHQVWRLGHQWLI\SRWHQWLDO in numerous cancers, which is associated with a more aggressive KLW FRPSRXQGV DJDLQVW 31&. NLQDVH DFWLYLW\ :H KDYH GHYHORSHG phenotype. We show that elevated BAs induced expression of OLJDQGEDVHG/DSODFLHQPRGL¿HG1DwYH%D\HVLDQFODVVL¿HUVIRUWKH ,4*$3DQGWKLVLQGXFWLRQFRUUHODWHGZHOOZLWK%$OHYHOVLQDGRVH use of machine learning kinase predictive models that leverages dependent manner both LQYLWUR and LQYLYR7UHDWLQJ:7DQG,4*$3 -/- data from across the kinome and computed the probability of activity null (Iqgap1 PLFHZLWKDFKROLFDFLG &$ GLHWWRLQFUHDVH%$ DJDLQVW31&.RIRYHUPLOOLRQFRPPHUFLDOO\DYDLODEOHFRPSRXQGV OHYHOVUHYHDOHGWKDWORVVRI,4*$3GRHVQRWDOWHU%$KRPHRVWDVLV obtained from eMolecules. In a large scale virtual screen, we have Iqgap1-/- mice fed CA diet showed reduced hepatic proliferation, -/- LGHQWL¿HGDVHULHVRILQVLOLFRKLWFRPSRXQGVZLWKGLYHUVHFKHPLFDO ZKHUHDV HFWRSLF DGHQRYLUDO H[SUHVVLRQ RI ,4*$3 LQ Iqgap1 VFDႇROGV WKDW ZH KDYH WHVWHG LQ YLWUR LQ 5&& FHOO OLQHV ZKLFK ZH OLYHUV UHVWRUHG %$LQGXFHG SUROLIHUDWLRQ LQGLFDWLQJ WKDW ,4*$3LV KDYH FRQ¿UPHG VLJQL¿FDQW 31&. RYHUH[SUHVVLRQ 7KLV UHSUHVHQWV required for hepatocyte proliferation in response to elevated BAs. the early stages in a drug discovery pipeline. We will determine To determine whether the proliferative defect in Iqgap1-/- mice could -/- ELQGLQJ DႈQLW\ RI WRS FRPSRXQGV LQ ELRFKHPLFDO DVVD\V DQG ZLOO DႇHFWWKHUHVSRQVHWRPRUHVHYHUHOLYHULQMXU\:7DQGIqgap1 mice XVH FRPSXWDWLRQDO VWUXFWXUHDFWLYLW\UHODWLRQVKLS PHWKRGRORJLHVWR ZHUH IHG D GLHWKR[\EDURQ\OGLK\GURFROOLGLQH ''& improve our hits with medicinal chemistry. GLHWIRUZHHNV7KH''&GLHWUHVXOWHGLQHOHYDWHGVHUXP%$VDQG total bilirubin, which are both higher in Iqgap1-/- mice. Consistently, 65 7,5$FRQVHUYHGLQQDWHLPPXQLW\VLJQDOLQJGRPDLQWKDW histological analysis revealed more severe liver damage including GH¿QHVDQHZIDPLO\RI1$'DVHHQ]\PH LQFUHDVHG LQÀDPPDWRU\ FHOOV DQG ¿EURVLV DORQJ ZLWK LQFUHDVHG Kow Essuman BA accumulation in the livers of Iqgap1-/- PLFH *HQH H[SUHVVLRQ Washington University School of Medicine, Saint Louis, USA analysis further revealed reduced expression of proliferation markers 7KH 7ROO,QWHUOHXNLQ 5HFHSWRU 7,5 GRPDLQ LV DQ HYROXWLRQDU\ DQGLQFUHDVHGH[SUHVVLRQRILQÀDPPDWRU\PDUNHUVLQWKHDEVHQFH conserved protein domain, present in numerous receptors and RI,4*$37KHVHUHVXOWVLQGLFDWHWKDW,4*$3FRXOGEHSURWHFWLYH DGDSWRUSURWHLQVDQGLVWKHVLJQDWXUHVLJQDOLQJGRPDLQRI7ROO/LNH against liver injury by promoting proliferation of hepatocytes and Receptors (TLRs). In eukaryotes, these TIR domains generally UHGXFLQJLQÀDPPDWLRQ7RGHWHUPLQHZKHWKHUWKLVFRXOGLPSDFWOLYHU VHUYH DV VFDႇROGV WKDW SURPRWH WKH DVVHPEO\ RI VLJQDOLQJ WXPRULJHQHVLVZHDGPLQLVWHUHGPJNJGLHWK\OQLWURVDPLQH '(1 FRPSOH[HV WR WULJJHU DFWLYDWLRQ RI SURLQÀDPPDWRU\ F\WRNLQHV DQG WRGD\ROGPLFHDQGDVVHVVHGWXPRUEXUGHQDWZHHNVSRVW RWKHU GHIHQVHUHODWHG SURGXFWV ,Q SODQWV 7,5 GRPDLQ SURWHLQV LQMHFWLRQ 3UHOLPLQDU\ DQDO\VLV UHYHDOHG QR RYHUW HႇHFW RI ,4*$3 are known to mediate disease resistance, and in bacteria, they RQ WKH FKHPLFDOO\LQGXFHG OLYHU WXPRU GHYHORSPHQW +RZHYHU ZH have been associated with virulence. In pursuing our work on expect that histological and biochemical analysis of the tumors will axon degeneration, we made the surprising discovery that the TIR reveal more aggressive tumors in WT mice compared to Iqgap1-/- GRPDLQ RI 6$50 D7/5 DGDSWRU SURWHLQ KDV HQ]\PDWLF DFWLYLW\ PLFH7DNHQWRJHWKHUWKHVHGDWDLQGLFDWHWKDWWKHVKRUWWHUPUROHIRU 8SRQ D[RQ LQMXU\ WKH 6$50 7,5 GRPDLQ FOHDYHV 1LFRWLQDPLGH ,4*$3 GRZQVWUHDP RI %$ VLJQDOLQJ LQFOXGHV FRQWUROOLQJ KHSDWLF $GHQLQH 'LQXFOHRWLGH 1$'), destroying this essential metabolic proliferation, maintaining biliary homeostasis, and protecting against FRIDFWRU WR WULJJHU D[RQ GHVWUXFWLRQ 7KLV ¿QGLQJ LGHQWL¿HG D injury. druggable target for axonopathies such as peripheral neuropathy 64 Data-Driven Computational Drug Discovery for Novel DQGRWKHUQHXURGHJHQHUDWLYHGLVHDVHVDQGDOVRLGHQWL¿HGWKH¿UVW understudied kinase, PNCK HQ]\PDWLFDFWLYLW\LQWULQVLFWRD7,5GRPDLQWKHUHE\UHGH¿QLQJ7,5 Derek Essegian IXQFWLRQ )XUWKHUPRUH 1$' ELRORJ\ SURIRXQGO\ LQÀXHQFHV P\ULDG University of Miami Miller School of Medicine, Miami, USA aspects of biology, from metabolism, to aging, to cancer biology, to neurodegeneration, and until our discovery, it was thought that the 7KH GUXJJDEOH JHQRPH FRQVLVWV RI DERXW SURWHLQHQFRGLQJ SDWKZD\VUHJXODWLQJ1$' biosynthesis and degradation were mostly genes that may be amenable to small molecule therapy. Currently, NQRZQ+RZHYHURXUVWXGLHVVKRZLQJWKDWWKH6$507,5GRPDLQLV OHVVWKDQRIGUXJJDEOHSURWHLQVDUHEHLQJWDUJHWHGE\DSSURYHG DSRWHQW1$'DVHQHFHVVLWDWHVDUHHYDOXDWLRQRIWKHIXQFWLRQRIWKLV drugs. Thus, it is important that this space be explored to identify ZHOOVWXGLHGVFDႇROGLQJGRPDLQDQGLWVLPSDFWRQ1$' metabolism novel, clinically relevant targets for the treatment of cancer and other and disease. Here, we dramatically extend our understanding of GLVHDVHV7KURXJKLQWHJUDWLYHDQDO\VHVRIWKH&DQFHU*HQRPH$WODV this protein domain, by demonstrating that the ancestral prokaryotic 7&*$ WUDQVFULSWRPLFDQGFOLQLFDOGDWDZHKDYHLGHQWL¿HG31&. 7,5 GRPDLQV FRQVWLWXWH D QHZ IDPLO\ RI 1$'DVH HQ]\PHV 8VLQJ as one such understudied target that may be clinically relevant for SXUL¿HG SURWHLQV IURP D FHOOIUHH WUDQVODWLRQ V\VWHP ZH VKRZ WKDW WKH WUHDWPHQW RI YDULRXV FDQFHUV 3QFN LV WKH PRVW VLJQL¿FDQWO\ 7,5GRPDLQSURWHLQVIURPERWKEDFWHULDDQGDUFKDHDFOHDYH1$' GLႇHUHQWLDOO\ RYHUH[SUHVVHG NLQDVH LQ UHQDO FHOO FDUFLQRPD 5&& LQWR1LFRWLQDPLGHDQG$'35LERVH $'35 ZLWKFDWDO\WLFFOHDYDJH

www.jointmeeting.org 47 POSTER ABSTRACTS

H[HFXWHGE\DFRQVHUYHGJOXWDPLFDFLGUHVLGXH:H¿QGWKDWDVXEVHW 67 &RQVWLWXWLYHO\ DFWLYH 67$7 LQ DQWLJHQVSHFL¿F &' 7 RI EDFWHULDO DQG DUFKDHDO7,5 GRPDLQV JHQHUDWHV D QRQFDQRQLFDO cells enhances the antitumor effect of adoptive cell transfer YDULDQW F\FOLF$'35 PROHFXOH DQG WKDW WKH IXOOOHQJWK7,5 GRPDLQ with peptide vaccination protein from pathogenic 6WDSK\ORFRFFXV DXUHXV LQGXFHV 1$' Aaron Fan ORVVLQPDPPDOLDQFHOOV7KHVH¿QGLQJVVXJJHVWWKDWWKHSULPRUGLDO Augusta University, Augusta, USA IXQFWLRQ RI WKH 7,5 GRPDLQ LV WKH HQ]\PDWLF FOHDYDJH RI 1$', and establishes TIR domain proteins as a new class of metabolic $GRSWLYH FHOO WKHUDS\ $&7 RI UHWURYLUDOO\ WUDQVGXFHG 59 &' regulatory enzymes. T cells is a powerful technique that has shown promise in tumor eradication in cancer patients. However, some major barriers to :DVKLQJWRQ 8QLYHUVLW\ -0 $' .( ':6 <6 ;0 KDYH current methods are that ACT is expensive, time consuming, and SDWHQW V UHODWHG WR WKLV ZRUN DQG LQFRPH PD\ EH GHULYHG IURP requires harmful and toxic adjunct procedures. Our laboratory OLFHQVLQJRIWHFKQRORJ\WR'LVDUP7KHUDSHXWLFVDQG&KURPDGH[-0 KDV GHPRQVWUDWHG WKH XVH RI7UL9D[ D SRWHQW SHSWLGH YDFFLQDWLRQ DQG$'DUHFRIRXQGHUVRI'LVDUP7KHUDSHXWLFVDQGPHPEHUVRI strategy that dramatically expands ACT cell populations and LWVVFLHQWL¿FDGYLVRU\ERDUG bypasses the necessity for adjunct procedures. Our purpose was 66 0\ULVWR\ODWHG DODQLQHULFK &NLQDVH VXEVWUDWH SHSWLGH WRHQKDQFHFXUUHQWPHWKRGVRI$&77UL9D[E\WHVWLQJDQDQWLJHQ mimetic triggers apoptosis in glioblastoma cells VSHFL¿F DQWLWXPRU UHVSRQVH RI 59 &' 7 FHOOV DQG LI LW FRXOG EH HQKDQFHGZLWKFRQVWLWXWLYHO\DFWLYH67$7 &$67$7 H[SUHVVLRQ Nicholas Eustace a protein activated downstream several cytokine pathways that have University of Alabama at Birmingham, Birmingham, USA EHHQVKRZQWRSOD\DUROHLQLQFUHDVHG&'7FHOOSHUVLVWHQFHDQG ,1752'8&7,21*OLREODVWRPD¶V *%0 PHGLDQVXUYLYDOLVMXVW resistance to apoptosis. Here, we aimed to test the hypothesis that months despite the best standard of care of maximally safe resection, &$67$7LQ&'7FHOOVHQKDQFHVDQDQWLWXPRUHႇHFWE\LQFUHDVLQJ FKHPRWKHUDS\DQGUDGLDWLRQWUHDWPHQW1RYHOWKHUDSHXWLFVDUHQHHGHG 7FHOOSHUVLVWHQFHDQGHႈFDF\ WRWDUJHWGUXJDQGUDGLDWLRQUHVLVWDQWJOLREODVWRPDFHOOV *%0 WKDW 2XUUHVXOWVVKRZWKDW7UL9D[DGPLQLVWUDWLRQVHOHFWLYHO\H[SDQGHGWKH UHPDLQ5HFHSWRUW\URVLQHNLQDVH 57. DPSOL¿FDWLRQV3KRVSKDWDVH $&7FHOOSRSXODWLRQH[SUHVVLQJJS7&5LQERWKEORRGDQGVSOHHQ DQG WHQVLQ KRPRORJ 37(1 ORVV DQG 3KRVSKDWLG\OLQRVLWRO :KHQFRWUDQVGXFHGZLWK&$67$7DQHYHQKLJKHUIROGH[SDQVLRQ ELVSKRVSKDWHNLQDVHPXWDWLRQVDUHDOOFRPPRQPXWDWLRQLQ*%0 RIDQWLJHQVSHFL¿FFHOOVZDVREVHUYHG&$67$7FHOOVZHUHDEOHWR ZKLFKOHDGVWRG\VUHJXODWLRQRISKRVSKDWLG\OLQRVLWROELVSKRVSKDWH H[SDQGPRUHUREXVWO\WKDQ&$67$7FHOOVXSRQUHSHDWHGDQWLJHQ (PIP2) enhancing cell proliferation, invasion, chemotherapy and VWLPXODWLRQ YDFFLQH ERRVW GHPRQVWUDWLQJ IROG LQFUHDVHV LQ UDGLDWLRQ UHVLVWDQFH 0\ULVWR\ODWHG DODQLQHULFK &.LQDVH VXEVWUDWH WHWUDPHU &' 7 FHOOV &$67$7 FHOOV DOVR VHHPHG WR SHUVLVW 0$5&.6 HႇHFWRU GRPDLQ ELQGV DQG VHTXHVWHUV 3,3 UHJXODWLQJ longer LQYLYRRYHUWLPHDQGWKH\H[SUHVVHGORZHUOHYHOVRI3' LWVDYDLODELOLW\DQGSRWHQWLDOO\FRXQWHULQJWKHHႇHFWVRIPXWDWLRQVLQ 8VLQJ %) PHODQRPD $&77UL9D[ RI WKHVH FHOO SRSXODWLRQV *%0 LQWRWXPRUEHDULQJPLFHGHPRQVWUDWHGDSRZHUIXODQWLWXPRUHႇHFW 2%-(&7,9(67KLVVWXG\WHVWVWKHHႈFDF\RID0$5&.6HႇHFWRU OHDGLQJ WR WXPRU UHJUHVVLRQ LQ WUHDWHG JURXSV &$67$7VHHPHG domain peptide mimetic in suppressing the growth of glioblastoma WRUHFDSLWXODWHVLPLODUDQWLWXPRUHႇHFWVZHREVHUYHGSUHYLRXVO\ZLWK *%0 SDWLHQW GHULYHG [HQRJUDIWV 3'; PRGHOV DQG WR EHWWHU FRPELQDWRULDOD3'/WUHDWPHQWRU,/D,/P$EFRPSOH[HV ,/&[ understand its of action. VXJJHVWLQJ D SRWHQWLDO UROH IRU 67$7 LQ UHVLVWLQJ WKH 3'3'/ 0(7+2'6 0$5&.6 SHSWLGH VHTXHQFH FRQWDLQLQJ WKH 3,3 LQKLELWRU\SDWKZD\$OWRJHWKHUWKHVHUHVXOWVGHPRQVWUDWHWKDW597 binding domain and a control peptide sequence of similar length FHOOVH[SUHVVLQJJS7&5DQG&$67$7DUHFDSDEOHRIDQWLJHQ and MW was screened against a panel of molecularly characterized GHSHQGHQWH[SDQVLRQLQUHVSRQVHWR7UL9D[&$67$7SOD\VDUROH 3';OLQHVIRUF\WRWR[LFLW\XVLQJWKHOXPLQHVFHQWFHOOYLDELOLW\DVVD\ in increasing T cell proliferation and persistence, as well as increasing &HOO7LWHU*OR7LPLQJRIFHOOXODUXSWDNHDQGYLVXDOL]DWLRQRI0$5&.6 HႈFDF\WKURXJKUHVLVWDQFHWR3'3'/LQKLELWLRQ SHSWLGHZLWKLQ*%0ZDVGHWHUPLQHGXVLQJD&\DQLQHÀXRUHVFHQW Skeletal muscle Krüppel-like factor 15 is a major regulator SHSWLGHDQGFRQIRFDOPLFURVFRS\$Q;F\WRTXDQWLWDWLYHÀXRUHVFHQW 68 of systemic lipid metabolism microscope was used to quantify apoptosis, the impact on cell cycle as well determine concentrations of the peptide in the cytoplasm and Liyan Fan nucleus. Kinase signaling was assessed through western blot and Cardiovascular Research Institute, Case Western Reserve gene expression was analyzed using the pan cancer gene set on University, Cleveland Heights, USA nanostring. 6NHOHWDOPXVFOHVHUYHVDVDPDMRUVLWHIRULQVXOLQPHGLDWHGJOXFRVH 5(68/76 7KH SURQHXUDO OLQH ' ZDV KLJKO\ VHQVLWLYH WR uptake and use, glycogen storage, lipid metabolism, and fatty acid 0$5&.6SHSWLGH !NLOO DWX0FRPSDUHGWRDFRQWUROSHSWLGH R[LGDWLRQ'LVWXUEDQFHVLQVNHOHWDOPXVFOHPHWDEROLVPOHDGWRZKROH ZLWKFODVVLFDOOLQHV;DQGEHLQJPRGHUDWHO\VHQVLWLYH body metabolic dysregulation, resulting in disease such as obesity (p<0.001) and normal human astrocytes being least sensitive. There and insulin resistance. Previous work from our group and others ZDVDVLJQL¿FDQWLQFUHDVHLQDSRSWRVLVIROORZLQJGRVLQJRI0$5&.6 KDYHLGHQWL¿HG.USSHOOLNHIDFWRU ./) DVDPDMRUUHJXODWRU peptide compared to control. Peptide accumulated throughout the of nutrient homeostasis:for example, V\VWHPLF./)GH¿FLHQF\LV F\WRSODVPDQGQXFOHXVRI'LQDSXQFWDWHSDWWHUQE\KUVNLQDVH associated with reduced exercise capacity, severe hypoglycemia VLJQDOLQJDQGJHQHH[SUHVVLRQZDVVLJQL¿FDQWO\DOWHUHGDWDQG during fasting, and impaired amino acid metabolism. Here we show hours after peptide respectively. that VNHOHWDOPXVFOHVSHFL¿F KLF15 is a critical regulator of systemic lipid metabolism. Additionally, we show that KLF15 expression &21&/86,21 0$5&.6 SHSWLGH DFFXPXODWHV LQVLGH *%0 FHOOV is downregulated in response to insulin, the major hormonal DQGKDVVLJQL¿FDQWF\WRWR[LFLW\WRVXEW\SHVRI*%0 coordinator of whole body nutrient homeostasis. We utilized mice ZLWKVNHOHWDOPXVFOHVSHFL¿F.OINQRFNRXW .6.2 RUVNHOHWDO PXVFOHVSHFL¿F.OIRYHUH[SUHVVLRQ .6NP7J SODFHGRQHLWKHU

48 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

DKLJKIDWGLHW +)' RUQRUPDOFKRZ 1& IRUZHHNV.6.2 :HKRSHWRH[SDQGRXUPHWKRGVLQIXWXUHVWXGLHVWRPHDVXUH PLFHIHG1&GLVSOD\HGLQFUHDVHGERG\ZHLJKWLQFUHDVHGFLUFXODWLQJ elderly subjects (cognitively normal, mild cognitive impairment IUHHIDWW\ DFLGV DQG WULJO\FHULGH OHYHOV JOXFRVH LQWROHUDQFH DQG DQG$' DVZHOODVSRWHQWLDOFROODERUDWLYHHႇRUWVLQRWKHUDUHDVRI LQFUHDVHGZKLWHDGLSRVHFHOOVL]HFRPSDUHGWRFRQWUROV:LWK+)' neuroscience. FKDOOHQJH.6.2DQLPDOVJDLQHGVLJQL¿FDQWO\PRUHERG\ZHLJKW DQGDUHVHYHUHO\JOXFRVHLQWROHUDQW.6NP7JPLFHZHUHUHVLVWDQW 70 Protein tyrosine kinase 2 beta is required for cultured WR +)'LQGXFHG ZHLJKW JDLQ DQG DUH PRUH JOXFRVH VHQVLWLYH WKDQ beige adipocyte differentiation controls. Importantly, compared to control animals, expression of lipid Jared S. Farrar ÀX[ JHQHV HJ )DWS &SWȕ 6OFD ZHUH GHFUHDVHG LQ . Virginia Commonwealth University School of Medicine, 6.2DQGLQFUHDVHGLQ.6NP7JPLFH7RHOXFLGDWHLQVXOLQ¶VHႇHFW Richmond, USA RQ./)H[SUHVVLRQ&&FHOOVZHUHFXOWXUHGDQGGLႇHUHQWLDWHG Brown adipose tissue (BAT) is a unique adipose tissue which IRU GD\V DQG WKHQ WUHDWHG ZLWK LQVXOLQ DQG SKDUPDFRORJLFDO can increase energy expenditure through the thermogenic action LQKLELWRUVRIWKHLQVXOLQVLJQDOLQJSDWKZD\57T3&5DQGFKURPDWLQ RI XQFRXSOLQJ SURWHLQ 8&3 LQ PLWRFKRQGULD 7KHUPRJHQLF immunoprecipitation assays revealed that KLF15 is negatively DGLSRF\WHVDUHWKHUHIRUHDQDSSHDOLQJWDUJHWWRSURPRWHDVLJQL¿FDQW UHJXODWHGE\LQVXOLQWKURXJKDQ$NW)R[2VLJQDOLQJSDWKZD\7KHVH shift in energy expenditure and increase glucose utilization. White data indicate skeletal muscle KLF15’s critical role in regulating whole adipose tissue (WAT), in contrast to BAT, has an energy storing, ERG\OLSLGKRPHRVWDVLV*LYHQWKHFHQWUDOUROHWKDWVNHOHWDOPXVFOH rather than consuming function. However, WAT can be “browned” dysfunction plays in the pathogenesis of diseases such as metabolic OHDGLQJWRWKHJHQHUDWLRQRIIXQFWLRQDOWKHUPRJHQLFEURZQLQZKLWH V\QGURPH DQG REHVLW\ RXU ¿QGLQJV LPSRUWDQWO\ VKHG OLJKW RQ WKH EULWH RU EHLJH DGLSRF\WHV 3UHYLRXVO\ VHYHUDO UHFHSWRU DQG QRQ mechanisms that govern metabolic plasticity in skeletal muscle. UHFHSWRUNLQDVHVKDYHEHHQLGHQWL¿HGDVLPSRUWDQWPROHFXODUWDUJHWV LQ WKHUPRJHQLF DGLSRF\WH GLႇHUHQWLDWLRQ DQG IXQFWLRQ +RZHYHU APOE0HWDEROLVPDQG&RJQLWLYH)XQFWLRQ$Q 69 NQRZOHGJH RI VSHFL¿F SURWHLQ NLQDVH DFWLRQV LQ WKHUPRJHQLF Assessment via Indirect Calorimetry DGLSRF\WHGLႇHUHQWLDWLRQDQGIXQFWLRQUHPDLQVOLPLWHG,QWKLVVWXG\ Brandon Farmer ZHGHPRQVWUDWHWKDWWKHQRQUHFHSWRUSURWHLQW\URVLQHNLQDVHEHWD University of Kentucky, Lexington, USA (PTK2B, also known as PYK2 or FAK2) plays a critical role in beige Both genetic factors and metabolic disturbances are associated with DGLSRF\WHGLႇHUHQWLDWLRQ,QRUGHUWRVWXG\WKHUROHRI37.%LQ8&3 declines in cognitive performance and increased risk of dementia. mediated thermogenesis, an immortalized murine inguinal WAT The gene Apolipoprotein E (APOE) encodes for three isoforms in SUHDGLSRF\WHFHOOOLQHZDVJHQHUDWHGZKLFKFRXOGEHGLႇHUHQWLDWHG WKHKXPDQSRSXODWLRQ ((DQG( DQGWKH(LVRIRUP±FDUULHG to either beige or white adipocytes. We observed that PTK2B protein E\ DSSUR[LPDWHO\ RI WKH SRSXODWLRQ ± LV WKH VWURQJHVW JHQHWLF H[SUHVVLRQ ZDV HOHYDWHG GXULQJ EHLJH DGLSRF\WH GLႇHUHQWLDWLRQ ULVN IDFWRU IRU ODWH RQVHW $O]KHLPHU¶V 'LVHDVH $' %RWK $' DQG LQ WKLV FHOOXODU PRGHO 8VLQJ WKH JHQHUDWHG FHOO OLQH 3WNE was (KDYHEHHQDVVRFLDWHGZLWKLQHႈFLHQWEUDLQJOXFRVHXSWDNHDQG NQRFNHGRXWXVLQJ&5,635&DVJHQRPHHGLWLQJ:KHQ3WNE KO impaired metabolism. Interestingly, our preliminary data show that 3.2 SUHDGLSRF\WHV ZHUH GLႇHUHQWLDWHG WR EHLJH DGLSRF\WHV WKH\ DJHG PLFH H[SUHVVLQJ KXPDQ ( GHPRQVWUDWH D PHWDEROLF ³VKLIW´ had altered expression of thermogenic adipocyte signature genes FRPSDUHG WR WKRVH H[SUHVVLQJ KXPDQ ( 7KLV LV UHÀHFWHG DV D DQG SURWHLQV )XUWKHUPRUH EHLJH DGLSRF\WH GLႇHUHQWLDWLRQ ZDV SUHIHUHQFHRI(PLFHIRUOLSLGVYVFDUERK\GUDWHVDVDIXHOVRXUFH delayed in PKO preadipocytes and mature PKO beige adipocytes As the brain relies primarily on glucose as an energy source, these had increased lipid droplet accumulation. We also deleted 37.% GDWDVXJJHVWWKDW(PD\QHJDWLYHO\LQÀXHQFHPHWDEROLFSDWKZD\V LQ KXPDQ VXEFXWDQHRXV IDW SUHDGLSRF\WHV WR H[WHQG WKH ¿QGLQJV which are critical for cognitive function. We hypothesize that similar of our mouse model. Together, our data establish a unique role DSR(GLႇHUHQFHVDUHSUHVHQWLQFRJQLWLYHO\QRUPDOLQGLYLGXDOVDQG IRU37.%LQWKHGLႇHUHQWLDWLRQRIIXQFWLRQDOEHLJHDGLSRF\WHVDQG WKHUHIRUHDLPWRWUDQVODWHWKHVHH[FLWLQJ¿QGLQJVWRKXPDQVXEMHFWV suggest PTK2B may be a potential therapeutic target to increase :HEHOLHYHDQ(GLUHFWHGVKLIWDZD\IURPJOXFRVHXWLOL]DWLRQPD\ thermogenic adipocyte capacity and improve treatment of obesity represent a critical step in the progression of cognitive decline, and DQGW\SHGLDEHWHV WKXVDSRWHQWLDOQRYHOELRPDUNHUIRU$'ULVN7RWHVWRXUK\SRWKHVHV ZH DLP WR PHDVXUH PHWDEROLF UDWH DQG UHVSLUDWRU\TXRWLHQW 54 ± 71 $5HWURVSHFWLYH$QDO\VLV6OHHS'LVRUGHUHG%UHDWKLQJ,Q D UHÀHFWLRQ RI VXEVWUDWH SUHIHUHQFH ± XVLQJ LQGLUHFW FDORULPHWU\ Patients With Cystic Fibrosis (IC). Metabolic analyses employing IC are commonly used in Noor Fatima clinical settings and exercise studies. However, while technically Xavier University of Louisiana, Metairie, USA feasible, to our knowledge, IC has never been applied to investigate Objective: Cystic Fibrosis (CF) is an autosomal recessive disease biomarkers of cognitive impairment. Thus, repurposing IC to study that causes exocrine gland dysfunction; this leads to thick mucus WKH PHWDEROLF HႇHFWV RI DQ$' ULVN IDFWRU VXFK DV ( UHSUHVHQWV WKDW UHVXOWV LQ REVWUXFWLRQ RI DLUZD\V LQ WKH OXQJV DQG DOVR DႇHFWV D VLPSOH DQG FRVWHႇHFWLYH QHZ DSSURDFK ,Q WKH FXUUHQW VWXG\ WKH*,WUDFWDQGRWKHURUJDQV3UHYLRXVUHVHDUFKLQ&)DQGVOHHS UHDOWLPH PHWDEROLF PHDVXUHV ZLOO EH DVVHVVHG LQ LQGLYLGXDOV ZLWK has shown daytime sleepiness and impaired neurocognitive function YDULRXV$32(JHQRW\SHV±ERWKDWUHVWDQGGXULQJDFRJQLWLYHDQG DV DQ HႇHFW RI SRRU VOHHS TXDOLW\1,2 The goal of this study is to GLHWDU\FKDOOHQJH$FFXUDF\DQGLQWHUSUHWDWLRQRI54ZLOOEHDLGHGE\ DVVHVVVOHHSGLVRUGHUHGEUHDWKLQJ 6'% DQGGLႇHUHQFHVLQVOHHS measuring adiposity, blood glucose, and urinary urea nitrogen (for DUFKLWHFWXUHLQSDWLHQWVZLWK&)DVFRPSDUHGWRDJHPDWFKHGQRQ estimation of protein oxidation). Our initial feasibility studies show CF controls. PHDVXUDEOHLQFUHDVHVLQ54GXULQJDFRJQLWLYHFKDOOHQJHDVZHOO 0HWKRGV7KLVLVDUHWURVSHFWLYHVWXG\RQ&)SDWLHQWVZLWKDJH as a trend toward increased resting energy expenditure (REE). PDWFKHGFRQWUROV \HDUVRIDJH ZLWKQRVOHHSSDWKRORJ\ZKR Additionally, an acute dietary challenge (sugar water drink) resulted KDGDVOHHSVWXG\DW8QLYHUVLW\RI0LFKLJDQVOHHSODERUDWRU\EHWZHHQ LQDVWHDG\LQFUHDVHLQ54IROORZLQJLQJHVWLRQ5HFUXLWPHQWRIa WKH\HDUVDQG3DWLHQWGDWDVXFKDVGHPRJUDSKLFVDQG young, cognitively normal subjects is scheduled to begin in January

www.jointmeeting.org 49 POSTER ABSTRACTS

polysomnogram values were taken from Epic and analyzed via $NUGE\DW5$ZDVDVVRFLDWHGZLWKDGHFUHDVHLQXULQH0%*LQ+2 6366VRIWZDUH YVSPROKUEDVHOLQHYVDW5$S EXWQRW 5HVXOWV 767 &$, 2, R[\JHQ GHVDWXUDWLRQ DQG 26$ DUH DOO LQ:7 YVSPROKUEDVHOLQHYVDW5$S! VWDWLVWLFDOO\VLJQL¿FDQWIRUWKHWRWDOSRSXODWLRQVDVZHOODVIRUVRPHDJH &RQFOXVLRQV 7KH XSUHJXODWLRQ RI KHSDWLF $NUG HQ]\PH LQ JURXSV7KHGLႇHUHQFHEHWZHHQVOHHSHႈFLHQF\PHDQSHUFHQWDJHIRU &\SD PLFH PD\ FRPSHQVDWH IRU D ODFN RI &\SD DQG WKHWZRSRSXODWLRQVLVWUHQGLQJWRZDUGVVLJQL¿FDQFHLWLVVLJQL¿FDQW SURPRWH SURGXFWLRQ RI 0%* ,QKLELWLRQ RI $NUG UHVXOWHG LQ D IRUWKHDJHJURXS7KHUHLVQRVWDWLVWLFDOO\VLJQL¿FDQWGLႇHUHQFH GHFUHDVH RI 0%* SURGXFWLRQ LQ &\SD PLFH RQO\ LQGLFDWLQJ in sleep stages between the two total populations, but some trends WKDW &\SD LV D SUHGRPLQDQW HQ]\PH LQ 0%* ELRV\QWKHVLV DQG VLJQL¿FDQW GLႇHUHQFHV H[LVW LQ WKH DJH JURXSV DQG 7KXV PDPPDOLDQ VWHURLG 0%* LV V\QWKHVL]HG IURP WKH SURGXFWV IRU11DQG5,QWHUHVWLQJO\WKH&)SRSXODWLRQVSHQWPRUH and intermediates in the acidic and classical BA pathways. Further WLPHLQ1VOHHSWKDQWKHDJHPDWFKHGFRQWUROVZLWKDSURORQJHG LQYHVWLJDWLRQRI0%*ELRV\QWKHVLVZLOOKHOSWRFRXQWHUDFW0%*OHYHO transition period between being awake and going to sleep. There elevation observed in devastating human diseases. LV QR VWDWLVWLFDOO\ VLJQL¿FDQW GLႇHUHQFH LQ DQ\ YDULDEOHV LQ WKH $FNQRZOHGJHPHQW7KLVZRUNZDVVXSSRUWHGE\1,+1,$,QWUDPXUDO DJHUDQJHRQO\DWUHQGLQR[\JHQGHVDWXUDWLRQ+\SRWKHVLVLV Research Program correct as sleep of CF population is disturbed with apnea, oxygen GHVDWXUDWLRQLQHႈFLHQWVOHHSDQGUHGXFHGVOHHSWLPH+\SRWKHVLV 73 Translocation of a pathobiont induces lymphocyte is rejected as the younger age group did not show increased rates of migration to internal organs and systemic autoimmunity 2,QRUGLGWKHROGHUSRSXODWLRQVKRZDVWDWLVWLFDOGLႇHUHQFHLQ&$, 5HEHFFD/)LQH 6PDOOVDPSOHVL]HFRXOGOHDGWRVNHZHGUHVXOWV Yale School of Medicine, USA &RQFOXVLRQV 7KHUH DUH VWDWLVWLFDOO\ VLJQL¿FDQW GLႇHUHQFHV LQ WKH 7KH PHFKDQLVPV DQG VLWHV RI KRVWPLFURELRWD LQWHUDFWLRQV LQ VOHHSSDWWHUQVRIWKH&)FRPSDUHGWRQRQ&)SDWLHQWSRSXODWLRQV autoimmunity are largely unknown. We hypothesized that certain This warrants regular sleep studies (polysomnographies) for CF FRPPHQVDOVWUDYHUVHWKHJXWEDUULHULQDXWRLPPXQHSURQHKRVWVDQG SDWLHQWVWRHYDOXDWHIRU6'%DQGSURYLGHLQWHUYHQWLRQDVQHHGHG LQWHUDFW ZLWK LPPXQH FHOOV LQ QRQJXW RUJDQV WR SURPRWH V\VWHPLF DXWRLPPXQLW\ 'XULQJ WKLV SURFHVV JXWLPSULQWHG O\PSKRF\WHV DUH A mammalian steroidal Na-pump ligand marinobufagenin 72 expected to migrate to sites of pathobiont colonization. To test these is synthesized from the intermediates in the acidic and classical K\SRWKHVHV ZH XVHG WKH OXSXVSURQH 1=:[%;6% ) PRXVH bile acid pathways PRGHOZKLFKFDUULHVDGXSOLFDWLRQRIWROOOLNHUHFHSWRU 7/5 RQ Olga V. Fedorova the Y chromosome. National Institute on Aging, NIH, Baltimore, USA :H¿UVWGHWHUPLQHGWKHLPSRUWDQFHRIWKHPLFURELRWDE\PRGXODWLQJ 2EMHFWLYHV 7KH ELRDFWLYH VWHURLGDO 1D.$73DVH LQKLELWRU the commensal community with single antibiotics. Treatment with oral PDULQREXIDJHQLQ 0%* D SURK\SHUWHQVLYH DQG D SUR¿EURWLF YDQFRP\FLQUHGXFHGDFWLYDWHG&'7FHOOV7KFHOOV7IROOLFXODU IDFWRULVLQYROYHGLQWKHSDWKRJHQHVLVRISUHHFODPSVLDVDOWVHQVLWLYH KHOSHU FHOOV DQWLȕ*3, 51$ ,J* GV'1$ DXWRDQWLERGLHV DQG K\SHUWHQVLRQDQGFKURQLFUHQDOIDLOXUH0%*V\QWKHVLVLQPDPPDOV protected mice from autoimmune deaths. Culture of small intestinal LV FRQWUROOHG E\ WKH &\SD HQ]\PH F\WRFKURPH 3 IDPLO\ VHJPHQWV PHVHQWHULF O\PSK QRGHV 0/1 OLYHUV DQG VSOHHQV VXEIDPLO\DSRO\SHSWLGH ZKLFKLQLWLDWHVWKHDFLGLFELOHDFLG UHYHDOHGSURJUHVVLYHWUDQVORFDWLRQRIWKHJUDPSRVLWLYHFRPPHQVDO %$ SDWKZD\LQH[WUDKHSDWLFWLVVXHVLHLQUDWDGUHQDOFRUWH[DQG Enterococcus gallinarum that was suppressed by vancomycin. KXPDQSODFHQWD1HYHUWKHOHVVWKHNQRFNRXWRI&\SDLQDPRXVH ,QWUDPXVFXODU YDFFLQDWLRQ RI 1=:[%;6% ) PDOHV ZLWK ( PRGHOGLGQRWUHGXFH0%*SURGXFWLRQ0RUHRYHUGRZQUHJXODWLRQ gallinarum, but not other commensals, prevented translocation, RI&\SDZDVDFFRPSDQLHGE\DQXSUHJXODWLRQRI$NUGHQ]\PH DXWRDQWLERG\SURGXFWLRQDQGDXWRLPPXQHUHODWHGGHDWKV DOGRNHWRUHGXFWDVHIDPLO\PHPEHU' ZKLFKSDUWLFLSDWHVLQWKH ¿QDOVWHSVRIERWKDFLGLFDQGFODVVLFDO%$SDWKZD\V:HK\SRWKHVL]HG 7RHOXFLGDWHWKHFRQWULEXWLRQRIKRVWJHQHWLFVWR(JDOOLQDUXPGULYHQ L WKDW0%*LVV\QWKHVL]HGIURPWKHLQWHUPHGLDWHVLQWKHDFLGLFDQG OXSXVZHWHVWHGZKHWKHULQWHUQDORUJDQVRIIHPDOH 1=:[%;6% ) FODVVLFDO %$ SDWKZD\ XQGHU &\SD DQG$NUG FRQWURO DQG LL PLFHZKLFKGRQRWFDUU\WKH7/5GXSOLFDWLRQDQGGHYHORSPLOGHU WKDWLQKLELWLRQRI$NUGZLOOGHFUHDVH0%*SURGXFWLRQLQ&\SD disease than males, are colonized by translocated E. gallinarum. E. NQRFNRXW &\SD KRPR]\JRXVPLFH JDOOLQDUXPWUDQVORFDWHGWR0/1LQIHPDOHVRQO\DIWHU¿UVWGHSOHWLQJ the niche with broad spectrum antibiotics. To determine the role of 0HWKRGV $OOWUDQV UHWLQRLF DFLG DW5$ VXSSUHVVHV $NUG )RXU E. gallinarum in the development of lupus in the absence of genetic PRQWKROGKRPR]\JRXV&\S$ +2 PDOHPLFHDQGZLOGW\SH predisposition, we next studied whether dense monocolonization of male mice (WT) were fed atRA diet (150 mg/kg of diet) or control QRQDXWRLPPXQHSURQH&%/JHUPIUHHPLFHZLWK(JDOOLQDUXP GLHW &75/ IRUGD\V Q JURXS +HSDWLF&\SDDQG$NUG could induce signs of systemic autoimmunity. In this gnotobiotic P51$DQGSURWHLQDEXQGDQFHDQG0%*H[FUHWLRQZHUHDVVHVVHG VHWWLQJ ( JDOOLQDUXP ZDV DEOH WR WUDQVORFDWH DQG LQGXFH 7K EHIRUH EDVHOLQH DQG DIWHU DW5$ GLHW 'DWD ZHUH DQDO\]HG XVLQJ FHOOV DQG VHUXP DXWRDQWLERGLHV $JHG PRQRFRORQL]HG &%/ ZD\$129$DQGDUHSUHVHQWHGDVPHDQVWDQGDUGHUURU PLFHKDGDOVRJUHDWHUOHYHOVRI3H\HU¶VSDWFKDQGVSOHQLF&'7 Results: Hepatic Cyp27a1P51$OHYHOZDVGRZQUHJXODWHGE\ FHOOVWKDQJHUPIUHHFRQWUROV*XWKRPLQJĮȕ&'7FHOOVZHUH in HO vs. WT (p<0.01), hepatic $NUG P51$ OHYHO ZDV WZRIROG VLJQL¿FDQWO\ LQFUHDVHG LQ VSOHHQV VXJJHVWLQJ WKDW O\PSKRF\WHV overexpressed in HO vs. WT (p<0.01). AtRA decreased expression previously imprinted in the gut follow E. gallinarum to internal organs. of hepatic $NUGP51$LQERWKVWUDLQV +2E\YV&75/ )XUWKHUPRUHLQ 1=:[%;6% )PDOHVFLUFXODWLQJ&'&'FHOOV S :7 E\ YV &75/ S +HSDWLF$NUG SURWHLQ H[SUHVVLQJĮȕRU&&5LQFUHDVHGZLWKDJHDQGZHUHUHGXFHG level was decreased in both genotypes by atRA (HO: fourfold vs. with oral antibiotics. Lastly, E. gallinarum was detected in human CTRL, p<0.05; WT: threefold vs. CTRL, p<0.01). Baseline urine livers of patients with autoimmune hepatitis and systemic lupus 0%*OHYHOZDVWZRIROGKLJKHULQ+2YV:7 S ,QKLELWLRQRI HU\WKHPDWRVXVEXWQRWQRQDXWRLPPXQHFLUUKRWLFOLYHUV

50 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

Together, these data support that a gut commensal translocates 76 Pro-efferocytic nanotherapy in atherosclerosis spontaneously to initiate autoimmunity in genetically prone hosts $O\VVD0)ORUHV E\ LQGXFLQJ 7K UHVSRQVHV DXWRDQWLERGLHV DQG KRPLQJ RI JXW Stanford University School of Medicine, USA imprinted lymphocytes to internal organs colonized by the pathobiont. 9DFFLQDWLRQ DJDLQVW WKLV SDWKRELRQW SUHYHQWHG WUDQVORFDWLRQ DQG Atherosclerotic cardiovascular disease continues to be the leading autoimmune deaths. Because the same species was detected in cause of death worldwide. It is now known that defective clearance human livers from autoimmune patients, similar processes may occur RIDSRSWRWLFWLVVXH HႇHURF\WRVLV LVDNH\GULYHURIDWKHURVFOHURWLF in humans. Overall, these discoveries represent a new paradigm plaque progression. We previously demonstrated that blocking the RIKRVWPLFURELRWDLQWHUDFWLRQVLQDXWRLPPXQLW\DQGUHYHDODQRYHO ³GRQ¶W HDW PH´ VLJQDO &' FDQ UHYHUVH WKLV GHIHFW DQG SUHYHQW treatment target aimed at the microbiota. SODTXHH[SDQVLRQKRZHYHUWKLVDQWLERG\EDVHGWKHUDS\DOVRFDXVHG RႇWDUJHWFOHDUDQFHRIUHGEORRGFHOOV7RDYRLGWKLVWR[LFLW\ZHDUH 75 Bdnf rs6265 variant confers a differential response to HYDOXDWLQJ VLQJOHZDOOHG FDUERQ QDQRWXEHV 6:17V DV D QRYHO pharmacotherapies in early-stage Parkinson’s disease SODWIRUPWKDWPD\EHDEOHWRGHOLYHU&'LQKLELWRUVVSHFL¿FDOO\WR D. Luke. Fischer WKHDWKHURVFOHURWLFSODTXHZLWKRXWDQ\RႇWDUJHWWR[LFLW\ Michigan State University, Grand Rapids, USA 6PDOOPROHFXOH LQKLELWRUV RI &' VLJQDOLQJ ZHUH HYDOXDWHG LQ Background: Patient response to antiparkinsonian therapies is YLWUR LQ 5$: PDFURSKDJHV WR YHULI\ GLVUXSWLRQ RI W\URVLQH heterogeneous, so the use of patient genotype to inform optimal SKRVSKDWDVH 6+3 WKH FRPPRQ GRZQVWUHDP VLJQDOLQJ SDWKZD\ WUHDWPHQW VWUDWHJLHV ZRXOG EH D SRZHUIXO WRRO %UDLQGHULYHG RI&'6:17VZHUHSUHSDUHGE\ORDGLQJFDUERQQDQRWXEHVZLWK QHXURWURSKLFIDFWRU %'1) LVDFULWLFDOPRGXODWRURIQHXURWUDQVPLVVLRQ SRO\HWK\OHQH JO\FRO 3(* IRU VROXELOL]DWLRQ &\ ÀXRURSKRUH IRU and synaptic plasticity within the basal ganglia. Preclinical work GHWHFWLRQ E\ ÀXRUHVFHQFHDFWLYDWHG FHOO VRUWLQJ )$&6 DQG SUR KDV LPSOLFDWHG %'1) VLJQDOLQJ LQ WKH DQWLSDUNLQVRQLDQ HႈFDF\ RI HႇHURF\WLF WKHUDSLHV VPDOOPROHFXOH LQKLELWRUV RI &'6+3 ERWK OHYRGRSD DQG GHHS EUDLQ VWLPXODWLRQ '%6 6HYHUDO VLQJOH VLJQDOLQJ 6:17VZHUHWKHQHYDOXDWHGIRUWKHLUDELOLW\WREHWDNHQ nucleotide variants exist in the gene %GQI with one in particular XSE\PRQRF\WHVPDFURSKDJHVDQGSURPRWHHႇHURF\WRVLVLQYLWURE\ UV UHVXOWLQJLQUHGXFHGDFWLYLW\GHSHQGHQW%'1)UHOHDVH:H )$&67RVWXG\6:17DFFXPXODWLRQLQWKHDUWHULDOSODTXHDQGRWKHU KDYH SUHYLRXVO\ VKRZQ LQ D SLORW VWXG\ WKDW HDUO\VWDJH 3DUNLQVRQ systemic tissues, samples of atherosclerotic aortae, blood, spleen, GLVHDVH 3' VXEMHFWVFDUU\LQJWKHUVPLQRUDOOHOHH[KLELWDOHVV OLYHUOXQJDQGKHDUWZHUHGLVVRFLDWHGDQGDQDO\]HGKKDQG robust response to levodopa therapy. VHYHQGD\VDIWHUWDLOYHLQLQMHFWLRQRI6:17VLQWRDWKHURSURQHPLFH DSROLSRSURWHLQ(GH¿FLHQWDSR(PLFH Objective: We validated the impact of the rs6265 variant and explored WKHHႇHFWRIDGGLWLRQDO%GQI variants in two additional, larger subject ,PPXQRÀXRUHVFHQFHVWDLQLQJFRQ¿UPHGWKDWVPDOOPROHFXOH6+3 FRKRUWV HDUO\VWDJH3'VXEMHFWVIURPWKH1,+1,1'6([SORUDWRU\ LQKLELWRUVVXSSUHVVSKRVSKRU\ODWLRQRI6+3LQPDFURSKDJHV'\H 7ULDOV LQ 3DUNLQVRQ¶V 'LVHDVH /RQJWHUP 6WXG\ 1(73' /6 FRQMXJDWHG QDNHG 6:17VUDSLGO\DQGSUHIHUHQWLDOO\DFFXPXODWHG WUHDWHG RYHU WZR \HDUV ZLWK HLWKHU OHYRGRSD DORQH Q RU DQ\ LQ PRXVH 5$: DQG KXPDQ 7+3 PDFURSKDJHV LQ YLWUR FRPELQDWLRQ RI GRSDPLQHUJLF PHGLFDWLRQV Q DQG HDUO\ ! FRPSDUHG WR RWKHU LPPXQH FHOOV DQG YDVFXODU VPRRWK VWDJH3'VXEMHFWVIURPWKH3DUNLQVRQ3URJUHVVLRQ0DUNHUV,QLWLDWLYH muscle cells. In vivo pharmacokinetic studies showed enhanced 330, WUHDWHGZLWKGRSDPLQHUJLFSKDUPDFRWKHUDS\ Q XSWDNH RI 6:17V LQWR LQWUDSODTXH PDFURSKDJHV RI DSR( PLFH RYHUWLPH)ROORZLQJVHYHQGD\VLQFLUFXODWLRQWRWDO6:17GHWHFWLRQ Methods: All subjects were genotyped for %GQI variant rs6265, decreased in mouse blood, liver, lung, spleen, and heart, indicating DQG 1(73' /6 VXEMHFWV ZHUH DOVR JHQRW\SHG IRU UV PLQLPDO V\VWHPLF DFFXPXODWLRQ 6WDQGDUG LQ YLWUR HႇHURF\WRVLV UVUVUVDQGUV5HVSRQVHWR DVVD\VGHPRQVWUDWHGWKDW6+3ORDGHG6:17VHႇHFWLYHO\SURPRWH WKHUDS\ZDVDVVHVVHGE\8QL¿HG3DUNLQVRQ'LVHDVH5DWLQJ6FDOH FOHDUDQFHRIDSRSWRWLFFHOOV IROG FRPSDUHGWRQDNHG6:17V 83'56 VFRUHVDWYDULRXVYLVLWVRYHUPRQWKV0HDQ83'56 DQG6+3LQKLELWRUVDORQH7KLVHႇHFWZDVVLPLODUWRHႇHURF\WRVLV VFRUHVZHUHVWUDWL¿HGE\YDULDQWDOOHOHVWDWXVDQGDGMXVWHGIRUVLWH UDWHVLQGXFHGE\DQWL&'DQWLERGLHVLQYLWUR DJHUDFH3'GXUDWLRQWKHUDS\GRVHDQGWUHDWPHQWJURXS )XWXUHVWXGLHVZLOOHYDOXDWHSURHႇHURF\WLF6:17VIRUWKHLUDELOLW\WR )LQGLQJV ,Q 1(73' /6 VXEMHFWV RQO\ WUHDWHG ZLWK OHYRGRSD stably deliver to macrophages and enhance lesional phagocytosis UV PLQRU DOOHOH FDUULHUV DQG UV PDMRU DOOHOH in mouse models of atherosclerosis, without causing anemia. If FDUULHUV H[KLELWHG KLJKHU PHDQ 83'56 VFRUHV WKDQ WKRVH HႇHFWLYH6:17VPD\IRUPWKHEDVLVRIDQHZ³7URMDQKRUVH´SODWIRUP ZLWKRXWWKHULVNDOOHOHDWPRQWKV YVS IRUUV IRUGHOLYHU\RISURHႇHURF\WLFWKHUDSLHVWRSUHYHQWDWKHURVFOHURVLV YVS IRUUV 1HLWKHUDOOHOHZDVDVVRFLDWHG with an altered response to other dopaminergic medications. Analysis 77 EWS-FLI1 driven transcription suppressed by a of PPMI subjects is ongoing. combination therapy of mithramycin and cyclin-dependent Interpretation: Presence of risk alleles for %GQI variants was kinase 9 inhibition associated with a worsened therapeutic response to levodopa. Guillermo Flores *HQRW\SLQJ IRU VSHFL¿F %GQI YDULDQWV PD\ EH D XVHIXO µSUHFLVLRQ Michigan State College of Human Medicine/Van Andel Institute PHGLFLQH¶DSSURDFKWRFRXQVHO3'SDWLHQWVUHJDUGLQJWKHHႈFDF\RI Graduate School, Grand Rapids, USA levodopa or other dopaminergic medications. %DFNJURXQG (ZLQJ VDUFRPD (6 LV D SHGLDWULF VRIW WLVVXH WXPRU 7KLVUHVHDUFKZDVVXSSRUWHGE\JUDQWVIURPWKH1DWLRQDO,QVWLWXWH ZLWKDSRRUSURJQRVLV(6LVGHSHQGHQWRQWKHSUHVHQFHDQGDFWLYLW\ RI1HXURORJLFDO'LVRUGHUVDQG6WURNH 1,1'616 DQGWKH RI WKH RQFRJHQLF WUDQVFULSWLRQ IDFWRU (:6)/, WKDW G\VUHJXODWHV 6DLQW0DU\¶V)RXQGDWLRQ gene expression at hundreds of targets. We have previously LGHQWL¿HG PLWKUDP\FLQ 00$ DV D SRWHQW LQKLELWRU RI (:6)/, GULYHQ WUDQVFULSWLRQ +RZHYHU RQO\ VXEWKHUDSHXWLF FRQFHQWUDWLRQV have been achieved in pediatric patients. To maximize inhibition, we

www.jointmeeting.org 51 POSTER ABSTRACTS

FRQGXFWHGDQVL51$VFUHHQWRLGHQWLI\JHQHWDUJHWVWKDWSRWHQWLDWHG FRPSRVLWLRQDQGPHWK\ODWLRQSUR¿OHVDUHVROYHGZLWKDQDOWHUQDWLQJ WKH HႇHFWV RI 00$ LQ (6 .QRFNGRZQ RI VHYHUDO WUDQVFULSWLRQDOO\ RSWLPL]DWLRQ VFKHPH LQFOXGLQJ D PRGL¿HG +LGGHQ 0DUNRY 0RGHO UHODWHGJHQHVVLJQL¿FDQWO\VHQVLWL]HG(6FHOOVWRWKHHႇHFWVRI00$ $IWHUZDUGVWKHDOOHOLFPHWK\ODWLRQSUR¿OHVIRUDOOJHQHVDUHDVVLJQHG We next developed a drug matrix screening platform to identify WR WKHLU FRUUHVSRQGLQJ VXESRSXODWLRQV E\ VROYLQJ D PL[HGLQWHJHU commercially available transcriptional inhibitors that also potentiated quadratic program. WKH HႇHFWV RI 00$ RQ (:6)/, GULYHQ WUDQVFULSWLRQ DQG (6 FHOO 7UDLQLQJ IRU ';0 ZDV FRQGXFWHG ZLWK ELVXO¿WH VHTXHQFLQJ GDWD YLDELOLW\3+$DF\FOLQGHSHQGHQWNLQDVHLQKLELWRU &'.L of somatic tissues available from the Roadmap Epigenomics UHYHUVHV WKH HႇHFW RQ (:6)/, RQ VHYHUDO WDUJHWV DW ERWK WKH 3URMHFW7RWHVW ';0 DQG EHQFKPDUN LWV SHUIRUPDQFH UHDGV IURP P51$DQGSURWHLQOHYHODFURVVPXOWLSOH(6FHOOOLQHVZKHQFRPELQHG ELVXO¿WHVHTXHQFLQJH[SHULPHQWVRIYDULRXVO\PSKRF\WHV %OXHSULQW with MMA. (SLJHQRPH3URMHFW DQGFHOOOLQHV (1&2'( ZHUHVXEVDPSOHGDQG 0HWKRGV :H XWLOL]H PDWUL[ GUXJ VFUHHQLQJ WR LGHQWLI\ WKDW 3+$ combined to form synthetic “mixtures,” where the read counts from V\QHUJL]HVZLWK00$LQWHUPVRIDUHGXFWLRQLQFHOOYLDELOLW\ HDFKXQGHUO\LQJFHOOW\SHUHÀHFWHGLWVH[SHFWHGSHUFHQWFRPSRVLWLRQ DVPHDVXUHGE\076DQGFHOOJURZWKDVPHDVXUHGE\WLPHODSVH LQ WKH PL[WXUH ';0 DFFXUDWHO\ GHFRQYROYHG WKHVH PL[WXUHV LQWR PLFURVFRS\ :H XVH 57T3&5 WR PHDVXUH FKDQJHV LQ JHQH the number of major subpopulations, their prevalence, and their H[SUHVVLRQ DFURVV PXOWLSOH ZHOO FKDUDFWHUL]HG WDUJHWV RI (:6 UHVSHFWLYH PHWK\ODWLRQ SUR¿OHV 2Q WKHVH PL[WXUHV ';0 DOVR FLI1 driven transcription. We use western blot analysis to measure RXWSHUIRUPHGH[LVWLQJPHWK\ODWLRQGHFRQYROXWLRQDOJRULWKPVVXFKDV changes at the protein level for these targets as well. We then use PHWK\O3XULI\DQGPHWK\O)ORZ7RYDOLGDWH';0PHWK\O6HT $JLOHQW an orthotopic xenograft mouse model to measure changes in tumor SURPRWHUFDSWXUH ZDVFRQGXFWHGRQSULPDU\'/%&/VDPSOHV';0 VL]HDIWHUDGPLQLVWUDWLRQRIRXU00$&'.LFRPELQDWLRQWKHUDS\ accurately deconvolved these samples, as compared to reference 5HVXOWV2XUFRPELQDWLRQRI00$DQG3+$GLVSOD\VVWURQJ PHWK\ODWLRQSUR¿OHVDQGWRFOLQLFDOÀRZGDWDIRUWKHVHVDPSOHV:H V\QHUJ\DVPHDVXUHGE\%OLVV,QGHSHQGHQFH0XOWLSOH(6FHOOOLQHV are currently planning analyses to identify epigenetic subclones of EHFRPH XQYLDEOH ZLWK PLQLPDO HႇHFW RQ QRQ(6 FHOOV DQG WKLV '/%&/DQGDFXWHP\HORLGOHXNHPLD $0/ ZKHUHJHQHWLFVXEFORQDO HႇHFW LV VWDEOH DIWHU UHPRYDO RI WKH FRPSRXQGV 7KLV V\QHUJ\ LV DUFKLWHFWXUHLVZHOOFKDUDFWHUL]HG,QWKHIXWXUHZHKRSHWKDW';0 UHFDSLWXODWHGDVDUHYHUVDORI(:6)/,GULYHQWUDQVFULSWLRQDFURVV can be broadly applied to understand epigenetic clonality of multiple PXOWLSOH WDUJHWV DW ERWK WKH P51$ DQG SURWHLQ OHYHOV :H VHH D cancer types and improve patient prognostics and therapy. VLPLODUHႇHFWLQRXUDQLPDOPRGHOZLWKDVLJQL¿FDQWGHFUHDVHLQWXPRU 79 *UDQG9DOOH\6WDWH8QLYHUVLW\3UH0'3K'&OXE volume with our combination therapy when compared to control or Alexia Frantzeskakis HLWKHUDJHQWDORQH,PSRUWDQWO\RXU00$&'.LFRPELQDWLRQXVHV Grand Valley State University, Canton, USA drug concentrations that are clinically achievable. 7KH 3UH0'3K' &OXE DW *UDQG 9DOOH\ 6WDWH 8QLYHUVLW\ IRFXVHV Conclusions :H GHVFULEH DQ 00$&'.L FRPELQDWLRQ WKDW RQ SURPRWLQJ DZDUHQHVV RI 0'3K' SURJUDPV DQG GHYHORSLQJ GLVSOD\V H[FHOOHQW DFWLYLW\ DJDLQVW (:6)/, GULYHQ WUDQVFULSWLRQ LQGLYLGXDOV WR EULGJH WKH JDS EHWZHHQ VFLHQWL¿F UHVHDUFK DQG :HFRQ¿UPHGWKLVXVLQJPXOWLSOHLQGHSHQGHQWDVVD\VLQERWKLQYLWUR clinical medicine. The club advocates professional and personal and LQYLYR models. We complete this work with the hope that it can development, emphasis on research, and networking skills. Career eventually be translated to patients. H[SORUDWLRQRQSK\VLFLDQVFLHQWLVWVDQGFOLQLFDOSK\VLFLDQVLVSURYLGHG 78 ';0 D QRYHO DOJRULWKP WR GHFRQYROYH JHQRPLF '1$ E\JXHVWVSHDNHUVXQLYHUVLW\&DUHHU6HUYLFHVYLGHRVVXFKDV7(' methylation data to understand epigenetic clonality. 7DONVDQG FRQIHUHQFHV 6WXGHQWV DUH SURYLGHG ZLWK WKH UHVRXUFHV Jerry Fong WR GLVVHFW PHGLFDO MRXUQDOV DQG XQGHUVWDQG WKH VFLHQWL¿F OLWHUDF\ MD-PhD Program, Washington University in St. Louis, St. RI DUWLFOHV7KH 3UH0'3K' FOXE DLGV LWV PHPEHUV LQ GLVFRYHULQJ Louis, USA research interests, how to build strong applications for medical/ graduate school, and balance school life. '1$ PHWK\ODWLRQ UHIHUV WR WKH SUHVHQFH RI PHWK\OF\WRVLQH LQ D &*GLQXFOHRWLGHFRQWH[W&DQFHUH[KLELWVJOREDOO\DOWHUHGSDWWHUQV 80 7KH ,QÀXHQFH RI 3KRVSKRPLPHWLF 1DWR RQ 'RSDPLQH RI'1$PHWK\ODWLRQDQGLQVRPHLQVWDQFHVSURPRWHUPHWK\ODWLRQ Neuron Gene Expression can silence expression of tumor suppressor genes. One study in 0HOLQD)UDQW]HVNDNLV GLႇXVHODUJH%FHOOO\PSKRPD '/%&/ GHPRQVWUDWHGWKDWSDWLHQWV Grand Valley State University, Canton, USA ZLWKLQFUHDVHGKHWHURJHQHLW\LQ'1$PHWK\ODWLRQDWSUHVHQWDWLRQKDG 0LGEUDLQ'RSDPLQHQHXURQV P'$ FDQDULVHIURPWKHÀRRUSODWHRI worse prognosis. However, this study did not analyze the subclonal the midbrain and are responsible for the symptoms of Parkinson’s architecture that underlies epigenetic heterogeneity, and individual GLVHDVH ZKHQ WKH\ FHDVH WR IXQFWLRQ P'$ QHXURJHQHVLV DQG tumor subclones have been implicated in cancer progression, PDWXUDWLRQDUHUHJXODWHGE\PXOWLSOHJHQHVVXFKDV6KK)R[DDQG WUHDWPHQW UHVLVWDQFH DQG PHWDVWDVLV *LYHQ WKDW H[SHULPHQWDO /P[DEDPRQJRWKHUV*HQHVWKDWSURPRWHIRUPDWLRQRIP'$KDYH techniques to identify epigenetic subclones have some limitations potential to be used for clinical therapy development in Parkinson’s DQG WKDW WKHUH LV D SOHWKRUD RI ELVXO¿WH VHTXHQFLQJ GDWD EHLQJ disease. One gene involved in dopamine neurogenesis is the basic generated from heterogeneous tumor samples, there is a need to KHOL[ORRSKHOL[WUDQVFULSWLRQIDFWRU1DWR+RZHYHULWVPHFKDQLVP develop computational methods to analyze this methylation data at RIDFWLRQLVQRWZHOONQRZQ1DWRLVH[SUHVVHGWKURXJKRXWWKHHQWLUH the subclonal level. ÀRRUSODWHKRZHYHULWRQO\SURGXFHVGRSDPLQHQHXURQVLQWKHFDXGDO :H KDYH GHYHORSHG D QRYHO DOJRULWKP ';0 WR GHFRQYROYH UHJLRQRIWKHPLGEUDLQ7REHWWHUXQGHUVWDQGWKHPHFKDQLVPRI1DWR methylation sequencing data of a heterogeneous clinical sample VSHFL¿F DPLQR DFLGV ZHUH DOWHUHG WR PLPLF WKH FKDUJH DW SXWDWLYH into the number of major subpopulations, their prevalence, and their phosphorylation sites, creating multiple variants of phosphomimetic UHVSHFWLYHPHWK\ODWLRQSUR¿OHV%ULHÀ\IRUHDFKJHQH';0VROYHV 1DWR 301DWR :HK\SRWKHVL]HGWKDW301DWRKDGWKHDELOLW\ for the number of subpopulations (alleles) iteratively. The percent to upregulate the dopamine neuron marker expression in vivo and

52 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

LQ YLWUR PRUH HႇHFWLYHO\ WKDQ ZLOGW\SH 1DWR 7KHVH FXUUHQW GDWD sustained fasting also alters the dynamics of insulin regulation, show greater upregulation of genes important for the formation of resulting in diminished insulin output, glucose intolerance, and GRSDPLQH QHXURQV E\ VRPH YDULDQWV RI 30 1DWR WKDQ ZLOG W\SH “starvation diabetes.” While the role of incretins in promoting insulin 1DWR LQ YLYR DQG WKH LPPRUWDOL]HG PRXVH PLGEUDLQ FHOO OLQH 30 VHFUHWLRQ GXULQJ IHHGLQJ LV ZHOOGRFXPHQWHG D FRXQWHUUHJXODWRU\ 1DWRXSUHJXODWLRQRIWKHVHJHQHVVXJJHVWWKDWWKHSKRVSKRU\ODWLRQ hormone that decreases insulin output (a “decretin”) during fasting VWDWXVRI1DWRFDQLQÀXHQFHWKHH[SUHVVLRQRIJHQHVNQRZQWRGULYH KDV QRW \HW EHHQ LGHQWL¿HG LQ PDPPDOV 5HFHQWO\ RXU JURXS dopamine neurogenesis, raising it as a potential target for therapeutic FKDUDFWHUL]HGDQLQGH[GHFUHWLQKRUPRQHLQ'URVRSKLODDQGLGHQWL¿HG development. 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These studies address essential were used to identify important gene sets in the transformed state, TXHVWLRQV DERXW OLQNV FRQQHFWLQJ SHULSKHUDO 108 IXQFWLRQ DQG DQG DVVHVV WKH FKURPDWLQ ODQGVFDSH LQ QHDUE\ JHQHUHJXODWRU\ insulin biology, and a better understanding of the role of decretins in regions, respectively. Conclusions: Here we demonstrate the insulin regulation may transform current therapeutic approaches to LPSRUWDQFHRI$5,'$LQSDQFUHDWLFWLVVXHKRPHRVWDVLVDQGFDQFHU treating metabolic diseases. 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K\SRWKHVL]HGWKDWWKHDSSDUHQWVSRUDGLFRFFXUUHQFHRI92*0PD\ Previous research has focused on understanding hormones that frequently be attributable to damaging de novo mutation events or regulate insulin secretion in the fed state, but it is apparent that LQFRPSOHWHSHQHWUDQFHRIUDUHWUDQVPLWWHGYDULDQWV8QELDVHGZKROH

www.jointmeeting.org 53 POSTER ABSTRACTS

H[RPH VHTXHQFLQJ :(6 FDQ RYHUFRPH WKHVH EDUULHUV IRU JHQH FKDUDFWHULVWLF FOHDYDJH VSHFL¿FLW\ IRU WKH KLQJH UHJLRQ RI KXPDQ discovery. IgA1. We hypothesize that expression of IgA protease changes 8VLQJ D G\QDPLF DQG LQQRYDWLYH +,&,5%DSSURYHG VRFLDO PHGLD GXULQJSHUVLVWHQWLQIHFWLRQRIORZHUDLUZD\VLQ&23' campaign and teaming with multiple domestic and international IgA protease expression was determined by immunoblot assay after FROODERUDWRUV ZH UHFUXLWHG WKH ODUJHVW 92*0 FRKRUW WR GDWH LQ LQFXEDWLRQ RI EURWK FXOWXUH VXSHUQDWDQWV ZLWK SXUL¿HG KXPDQ ,J$ OHVVWKDQ\HDUV*HUPOLQH'1$ZDVLVRODWHGIURPXQUHODWHG antibody. We analyzed IgA protease gene sequences from genome SUREDQGV KDUERULQJ UDGLRJUDSKLFDOO\FRQ¿UPHG 92*0V %RWK sequences in strains that demonstrated changes in enzymatic SDUHQWVZHUHDYDLODEOHIRUSUREDQGV:(6ZDVSHUIRUPHGRQDOO activity during persistence. SDUWLFLSDWLQJLQGLYLGXDOV Q 9DULDQWVLQERWKFRKRUWVZHUHFDOOHG $V SDUW RI D \HDU ORQJLWXGLQDO VWXG\ RI DGXOWV ZLWK &23' DW XVLQJ WKH *HQRPH $QDO\VLV 7RRONLW *$7. +DSORW\SH &DOOHU DQG WKH %XႇDOR 9$ 0HGLFDO &HQWHU VWUDLQV RI 17+L WKDW SHUVLVWHG annotated for allele frequencies in Exome Aggregation Consortium LQ DGXOWV ZLWK &23' IURP WR PRQWKV ZHUH DVVHVVHG IRU ,J$ ([$& *HQRPHV.DYLDUDQG([RPH9DULDQW6HUYHU (96 protease activity. Two of the 50 strains that expressed IgA protease 'HQRYRPXWDWLRQVZHUHLGHQWL¿HGXVLQJ7ULR'H1RYRDQGWKHLPSDFW A1 upon acquisition by the patient showed absent expression after RIPLVVHQVHPXWDWLRQVZDVLQIHUUHGXVLQJ0HWD690DQGDFXVWRP SHUVLVWHQFHLQ&23'DLUZD\V7ZRRIWKHLQLWLDOVWUDLQVH[SUHVVLQJ ELRLQIRUPDWLFVSLSHOLQH7UDQVIHFWLRQVRIFRQVWUXFWVKDUERULQJ92*0 IgA protease A2 upon acquisition stopped expressing and two of the PXWDWLRQV LQ +(. FHOOV IROORZHG E\ LPPXQRSUHFLSLWDWLRQ DQG initial 23 strains expressing IgA protease B1 stopped expressing immunoblotting, were performed to determine impact on biochemical DIWHU SHUVLVWHQFH 6HTXHQFH DQDO\VLV UHYHDOHG WKDW LQVHUWLRQV RU function. Further functional validation in vivo was performed in GHOHWLRQVUDQJLQJLQVL]HIURPWREDVHSDLUVFDXVLQJWKHJHQHVWR ;HQRSXVWURSLFDOLVXVLQJ&5,635&DVJHQHHGLWLQJ be out of frame conferred these phenotypic changes in each of the *HQHEXUGHQDQDO\VLVUHYHDOHGH[RPHZLGHVLJQL¿FDQWHQULFKPHQW VWUDLQVWKDWVKXWRႇH[SUHVVLRQRI,J$SURWHDVH$$DQG%GXULQJ RIUDUHWUDQVPLWWHGGDPDJLQJPXWDWLRQVLQHSKULQW\SH%UHFHSWRU persistence. (3+%Q S [IROGHQULFKPHQW DNH\UHJXODWRU The change in IgA protease B2 expression was not explained by RIDUWHULRYHQRXVGLႇHUHQWLDWLRQ$GGLWLRQDOGDPDJLQJUDUHLQKHULWHG examining the open reading frames, but instead we discovered an PXWDWLRQVZHUHLGHQWL¿HGLQWKHXSVWUHDP(3+%OLJDQGHSKULQ% upstream “TCAAAAT” simple sequence repeat that varied in number ()1% WKHGRZQVWUHDP(3+%HႇHFWRU5DV*73DVHDFWLYDWLQJ among strains with the IgA protease B2 gene. Analysis of 10 strains SURWHLQ 5$6$ PXWDWHGLQ&0$90W\SHDQGWKHDVVRFLDWHG UHYHDOHGWKDWZKHQWKHQXPEHURIWKLVQXFOHRWLGHUHSHDWFDXVHG (SKULQ%(SK%UHJXODWRUDFWLYLQ$UHFHSWRUOLNHW\SH $&95/ the gene to be out of frame, it was not expressed, whereas when the mutated in Hereditary Haemorrhagic Telangiectasia. Two novel number of repeats caused the gene to be in frame, it was expressed. GDPDJLQJPXWDWLRQVZHUHLGHQWL¿HGLQWKH$&95/SDUDORJDFWLYLQ$ Thus, IgA protease B2 expression varies during persistence, and its UHFHSWRUW\SH $&95 QRWSUHYLRXVO\LPSOLFDWHGLQKXPDQGLVHDVH expression is regulated by slipped strand mispairing. 7RJHWKHUPXWDWLRQVLQ(3+%VLJQDOLQJFRPSRQHQWVDFFRXQWHGIRU RI FDVHV 92*0DVVRFLDWHG (3+% PXWDQWV UHODWLYH In summary, IgA proteases A1, A2, and B1 undergo genetic changes WR ZLOG W\SH DUH DVVRFLDWHG ZLWK VLJQL¿FDQW LPSDLUPHQW RI 5$6 that result in altered expression during persistence. Expression of IgA MAPK/ERK1/2 and PI3K/AKT/mTOR signaling in mammalian cells. SURWHDVH%LVUHJXODWHGE\VOLSSHGVWUDQGPLVSDLULQJRIDQXSVWUHDP ;WURSLFDOLVHPEU\RVLQMHFWHGZLWK&5,635&DVWDUJHWHGDJDLQVW QXFOHRWLGH UHSHDW GXULQJ SHUVLVWHQFH LQ DGXOWV ZLWK &23' :H 5$6$RU(3+%KDUERUHGVHYHUHQHXUDOWXEHGHIHFWVFRPSDUHGWR FRQFOXGH WKDW 17+L UHJXODWHV H[SUHVVLRQ RI ,J$ SURWHDVHV GXULQJ controls, and decreased and irregular expression of msr and prox1, persistence in the human respiratory tract. demonstrating widespread impairment of vascular and lymphatic 85 Fibrotic scar formation in the retina following laser injury development. 5\DQ$*DOOR This work demonstrates the power of social media to recruit University of Miami Miller School of Medicine, Miami, USA actionable genetic cohorts for rare diseases in unprecedented time, ,QMXU\WRWKHFHQWUDOQHUYRXVV\VWHP &16 OHDGVWRVFDUIRUPDWLRQWKDW and has uncovered the critical genetic determinants and molecular KDVERWKJOLDODQG¿EURWLFFRPSRQHQWV6FDUIRUPDWLRQLVLPSRUWDQWIRU PHFKDQLVPV RI 92*0 7KHVH UHVXOWV KDYH SRWHQWLDO GLDJQRVWLF repairing the lesion, but also results in inhibition of nerve regeneration. VFUHHQLQJ LPSOLFDWLRQV IRU IDPLO\ PHPEHUV DQG LGHQWLI\ VSHFL¿F 8QOLNHWKHJOLDOVFDUPXFKOHVVLVNQRZQDERXWWKH¿EURWLFVFDU:H genes and pathways for the development of targeted therapeutics. FKDUDFWHUL]H¿EURWLFVFDUIRUPDWLRQLQWKH&16XVLQJLQYLYRUHWLQDO 84 5HJXODWLRQ RI ,J$ SURWHDVH H[SUHVVLRQ LQ QRQW\SHDEOH ODVHUWUDXPDDQGLPDJLQJ7UDQVJHQLFPLFHLQZKLFK*)3LVH[SUHVVHG Haemophilus LQÀXHQ]DH during persistence in chronic XQGHUWKHFRQWURORIWKHFROODJHQSURPRWHU &ROĮ*)3PLFH ZHUH obstructive pulmonary disease VXEMHFWHGWRUHWLQDOLQMXU\E\DSKRWRGLVUXSWLYH1G<$*ODVHU,QHDFK 0DU\*DOOR animal, the retina of one eye was lasered while the contralateral eye 8QLYHUVLW\DW%X௺DOR-DFREV6FKRRORI0HGLFLQHDQG ZDVXVHGDVDQRQODVHUHGFRQWURO6SHFWUDOGRPDLQRSWLFDOFRKHUHQFH %LRPHGLFDO6FLHQFHV%X௺DOR86$ WRPRJUDSK\ 6'2&7 FRQIRFDO VFDQQLQJ ODVHU RSKWKDOPRVFRS\ F6/2 DQG ÀXRURVFHLQ DQJLRJUDSK\ )$ ZHUH SHUIRUPHG DW 1RQW\SHDEOH +DHPRSKLOXV LQÀXHQ]DH 17+L LV WKH PRVW FRPPRQ EDVHOLQHDQGDWYDULRXVWLPHSRLQWVIROORZLQJLQMXU\$QWLJHQLFSUR¿OLQJ cause of acute exacerbations of chronic obstructive pulmonary ZDVFDUULHGRXWWZRZHHNVDIWHULQMXU\WRGH¿QHWKHFHOOXODULGHQWLW\RI GLVHDVH &23' 17+L DOVR SHUVLVWHQWO\ LQIHFWV WKH ORZHU DLUZD\V UHFUXLWHG&ROĮ*)3FHOOVWKDWFRQWULEXWHWR¿EURWLFVFDUIRUPDWLRQ RI DGXOWV ZLWK &23' FDXVLQJ ZRUVHQLQJ RI LQÀDPPDWLRQ DQG %DVHOLQH F6/2 DQG )$ LPDJLQJ UHYHDOHG &ROĮ ¿EUREODVW FHOOV V\PSWRPV 2QH YLUXOHQFH IDFWRU RI 17+L LV ,J$ SURWHDVHV WKDW promptly localized within the major retinal blood vessels. A weaker cleave human mucosal IgA1 antibody at the hinge region and *)3VLJQDOZDVREVHUYHGZLWKLQWKHFKRURLGDOYDVFXODUEHG&ROĮ mediate intracellular survival in respiratory epithelial cells. There cells were observed around the site of injury as early as three days DUHWZRGLVWLQFW,J$SURWHDVHJHQHVDWGLႇHUHQWORFLLJD$ and LJD%, after laser injury, and recruitment peaked at approximately two weeks HDFKZLWKWZRYDULDQWV(DFKRIWKH,J$SURWHDVHYDULDQWVKDVD

54 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

ODWHU 6'2&7 DQG F6/2 LPDJLQJ GHPRQVWUDWHG WKDW GLVUXSWLRQ RI could be achieved with heparin alone indicating related pathways %UXFK¶VPHPEUDQHZDVQHFHVVDU\IRU&ROĮUHFUXLWPHQW&ROĮ ZKLFK VXSSRUWV SUHYLRXV GDWD GHPRQVWUDWLQJ D VLPLODU 1WHUPLQDO *)3VLJQDOZDVFRQ¿QHGRQO\WRWKHFKRURLGDQGQRWUHWLQDLQERWK 3&6. ELQGLQJ UHJLRQ IRU ERWK PHGLDWRUV 2XU VWXGLHV SURYLGH control eyes and areas of damage that lacked Bruch’s membrane IXUWKHULQVLJKWLQWR3&6.ELRFKHPLFDOSURFHVVLQJDQGPRGXODWRUV disruption. In areas of injury with Bruch’s membrane damage, RI 3&6. PHWDEROLVP ZLWK LPSOLFDWLRQV IRU ¿QGLQJ QHZ WDUJHWV WR &ROĮ*)3VLJQDOZDVREVHUYHGEHWZHHQWKHFKRURLGDQGWKHUHWLQD ORZHU/'/FKROHVWHURODQGSUHYHQWDWKHURVFOHURVLV &HOOXODUSUR¿OLQJRIWKH¿EURWLFVFDUWZRZHHNVDIWHULQMXU\UHYHDOHG SRVLWLYH DQWLJHQLFLW\ IRU 3'*)5ȕ &' DQG YLPHQWLQ 'DPDJH 87 A tale of two viruses: cognitive recovery in the post- to the retina in mammals results in scarring and irreversible loss of infectious CNS UHWLQDO QHXURQDO SKHQRW\SHV 8VLQJ WUDQVJHQLF PLFH ZH VKRZ WKDW Charise Garber &ROĮ FHOOV FRQWULEXWH WR WKH ¿EURWLF VFDU LQ WKH UHWLQD IROORZLQJ Washington University in St Louis, School of Medicine, Saint LQMXU\ ,Q YLYR LPDJLQJ VWURQJO\ VXJJHVWV WKDW SHULYDVFXODU &ROĮ Louis, USA cells migrate to the injury site from the arteries or choroidal vascular Cognitive dysfunction following viral encephalitis is associated bed of the eye after disruption to Bruch’s membrane. At two weeks ZLWKSHUVLVWHQWUHDFWLYHFKDQJHVLQPLFURJOLDDQGDVWURF\WHV7FHOO DIWHU LQMXU\&ROĮ FHOOV LQ WKH ¿EURWLF VFDU H[SUHVV FKDUDFWHULVWLFV LQ¿OWUDWLRQ LQWR WKH &16 LV QHFHVVDU\ IRU YLUDO FOHDUDQFH KRZHYHU RI SHULYDVFXODU FHOOV ZLWK WKHLU 3'*)5ȕ immunoreactivity. Other VXEVHTXHQW SHUVLVWHQFH RI PHPRU\ 7FHOOV DIWHU WKH DFXWH LQVXOW FHOOW\SHVFRQWULEXWHWRVFDUIRUPDWLRQWKDWDUH&ROĮ and express may lead to altered neuroimmune communication and contribute to &'RUYLPHQWLQZKLFKDUH¿EURF\WHOHXNRF\WHDQGPHVHQFK\PDO GHOD\HGUHFRYHU\RIFRJQLWLYHIXQFWLRQ8VLQJDQHVWDEOLVKHGPRGHO cell markers, respectively. A better understanding of the underlying RI :HVW 1LOH 9LUXV :19 QHXURLQYDVLYH GLVHDVH ZH VKRZ WKDW PHFKDQLVPVRI¿EURWLFVFDUIRUPDWLRQLQWKHUHWLQDRႇHUVSURPLVHIRU SHUVLVWHQW&'7FHOOVLQWKH&16H[SUHVVF\WRNLQHVWKDWLQÀXHQFH promoting retinal regeneration. 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These assays allowed us to Harvard Medical School Department of Genetics, Boston, USA analyze key residues for both events using saturation mutagenesis Hypertrophic cardiomyopathy (HCM) is a dominant myocardial OLEUDULHVGHWHUPLQLQJUHVLGXHV3DQG3WKURXJK3¶RIWKHFOHDYDJH disease caused by missense mutations in sarcomere proteins. VHTXHQFHWREHKLJKO\VSHFL¿FIRUPDLQWHQDQFHRIIXQFWLRQ:HDOVR The pathophysiology of HCM has been long described as one of HYDOXDWHG VLQJOH QXFOHRWLGH SRO\PRUSKLVP 613 HႇHFWV RQ HDFK cellular hypercontractility with poor relaxation (a hallmark of diastolic PHFKDQLVP RI 3&6. SURFHVVLQJ DQG IRXQG D KLJK SHUFHQWDJH RI LQVXႈFLHQF\ DQG HQHUJHWLFDOO\ H[SHQVLYH FDUGLDF VDUFRPHUHV WKH 613V DQDO\]HG WR DOWHU SURWHRO\VLV %DVHG RQ RXU UHVXOWV ZH but the link between pathogenic genotypes and this characteristic H[DPLQHG SRWHQWLDO VWUXFWXUDO LPSOLFDWLRQV RI WKH 613V GH¿QHG SKHQRW\SH UHPDLQV LQFRPSOHWHO\ HOXFLGDWHG 8QFHUWDLQW\ SHUVLVWV SURWHRO\VLV WR EH WKH UDWH OLPLWLQJ VWHS RI 3&6. SURFHVVLQJ DQG regarding how sarcomere mutations increase sarcomere power, as LGHQWL¿HG D UHJLRQ RI WKH SURWHLQ LQYROYHG LQ DOORVWHULF UHJXODWLRQ RI mutated amino acids more commonly reduce the function of proteins, 3&6.SURWHRO\VLV and how amino acid substitutions perturb sarcomere relaxation. :KLOH 3&6. SURFHVVLQJ LQYROYHV WKHVH WZR VWHSV IRU SURGXFWLRQ &U\RHOHFWURQ PLFURVFRS\ RI WDUDQWXOD VWULDWHG PXVFOH SUHGLFWV DQ OLWWOH LV NQRZQ DERXW PHGLDWRUV RI 3&6. DQG /'/5 ELQGLQJ LQWHUDFWLQJKHDGVPRWLI ,+0 WKDWSOD\VDQLPSRUWDQWUROHLQKHDOWK\ &HOOEDVHG VWXGLHV KDYH VKRZQ /'/& LQKLELWV 3&6.PHGLDWHG sarcomere function. In this dynamic interaction, one or both heads GHJUDGDWLRQWKRXJKWKHPHFKDQLVPRILWVHႇHFWLVXQFOHDU5HFHQWO\ RI D P\RVLQ KHDG SDLU ELQG WKH WKLFN ¿ODPHQW EDFNERQH LQKLELWLQJ KHSDUDQ VXOIDWH SURWHRJO\FDQV +63* ZHUH VXJJHVWHG WR DFW myosin ATPase and limiting its ability to bind actin. IHM stability is DV FRUHFHSWRUV RQ WKH KHSDWRF\WH IDFLOLWDWLQJ WKH /'/53&6. important to maintain appropriate sarcomere relaxation, and IHM LQWHUDFWLRQ%\DGDSWLQJRXUKLJKWKURXJKSXWDVVD\ZHLQYHVWLJDWHG destabilization may promote sarcomeric hypercontractility and WKHUHODWLRQVKLSRIWKHVHWZRHႇHFWRUVRQ3&6.XSWDNHWRHOXFLGDWH energy expenditure by enabling extra myosin heads to hydrolyze WKH PHFKDQLVP RI /'/&¶V LQKLELWRU HႇHFW RQ 3&6. :H DOVR ATP. We believe IHM disruption represents an important part of FRPSDUHGWKHLQKLELWRU\HႇHFWVRI/'/&YDULDQWVVXFKDVR[LGL]HG disease pathogenesis in certain HCM variants. /'/& DQG OLSRSURWHLQ D RQ 3&6.PHGLDWHG GHJUDGDWLRQ 8VLQJKXPDQLQGXFHGSOXULSRWHQWVWHPFHOOGHULYHGFDUGLRP\RF\WHV :H IRXQG WKH LQKLELWLRQ RI 3&6. XSWDNH WR EH DGGLWLYH ZLWK WKH KL36&&0V WRJHWKHU ZLWK &5,635&DV ZH LQWURGXFH +&0 LQWURGXFWLRQRIH[RJHQRXVKHSDULQFRPSHWLQJIRU+63*FKDSHURQH OLQNHG VDUFRPHUH PXWDWLRQV LQWR LVRJHQLF KL36& OLQHV JHQHUDWLQJ ELQGLQJDQG/'/&+RZHYHUPD[LPDOLQKLELWLRQRI3&6.XSWDNH heterozygous and homozygous variants in genes that may impact

www.jointmeeting.org 55 POSTER ABSTRACTS

the IHM, including 0<%3& truncations and missense mutations 90 0ROHFXODU HYROXWLRQ RI DGHQRDVVRFLDWHG YLUXV IRU in 0<+ TNNT2, and 711, 7R DQDO\]H KL36&&0 FRQWUDFWLOLW\ targeting of microglia in Parkinson`s disease WR PRGHO GLVHDVH ZH LQWURGXFH RXU SDWLHQWVSHFL¿F PXWDWLRQV LQWR Aysegul Gezer DOLQHZLWKD*)3IXVLRQUHSRUWHUWDJJHGWRWKH1WHUPLQXVRIWLWLQ Michigan State University, Grand Rapids, USA WKLVÀXRUHVFHQWWDJLOOXPLQDWHVWKH=GLVFERXQGDULHVRIVDUFRPHUHV without disrupting sarcomere assembly or function. 3DUNLQVRQ¶V 'LVHDVH 3' LV D QHXURGHJHQHUDWLYH GLVRUGHU ZLWK PXOWLV\VWHP IDLOXUH 7KH SDWKRORJLFDO KDOOPDUN RI 3' LV SURWHLQ ,VRJHQLF HGLWHG DQG ZLOG W\SH KL36&&0V DUH FKDUDFWHUL]HG WR aggregates, termed Lewy bodies, found inside neurons and assess contractile parameters including resting sarcomere length, implicated in the disease process. Ongoing research demonstrates relaxation time, and shortening fraction, using pacing (1 Hz) to WKDWQHXURLQÀDPPDWLRQSOD\VDQLPSRUWDQWUROHLQWKHSDWKRSK\VLRORJ\ approximate the adult human heart rate. Imaging is acquired with D .H\HQFH %=; PLFURVFRSH XVLQJ D *)3 ¿OWHU FXEH DQG D 1LNRQ RI3'$FFXPXODWLQJHYLGHQFHIURPVWXGLHVLQFOXGLQJSRVWPRUWHP [REMHFWLYHDQGDQDO\]HGXVLQJDFXVWRPEXLOW0$7/$%SURJUDP LQYHVWLJDWLRQVRIKXPDQ3'EUDLQVDWWHVWVWKHFRQWULEXWLRQRIFKURQLF WKDW HQDEOHV WUDFNLQJ RI ÀXRUHVFHQW VDUFRPHUHV 7R LQYHVWLJDWH LI LQÀDPPDWLRQWRWKHGHDWKRIGRSDPLQHUJLFQHXURQVRIWKHVXEVWDQWLD mutations alter IHM properties, permeabilized cells are studied using QLJUDLQ3'0LFURJOLDWKHGRPLQDQWDQWLJHQSUHVHQWLQJFHOOVRIFHQWUDO 0DQW$73 ZKLFK LV D ÀXRUHVFHQW QRQK\GURO\VDEOH DQDORJXH RI QHUYRXVV\VWHP &16 SOD\DFUXFLDOUROHLQQHXURLQÀDPPDWLRQ\HW ATP. From biochemical analyses, the relative proportions of myosin WKHH[DFWUROHRIWKHVHFHOOVLQ3'GLVHDVHHWLRORJ\LVQ¶WZHOOGH¿QHG heads in the bound versus unbound states of the IHM are deduced, One of the challenges to study microglial biology is the lack of an yielding insight into sarcomere pathophysiology in human HCM H[SHULPHQWDOWRROWRVSHFL¿FDOO\PDQLSXODWHPLFURJOLD7KHDLPRIWKLV cardiomyocytes. Each of these assays are repeated after treatment project is 1) to generate a novel tool to study microglial biology and 2) with a small molecular myosin ATPase inhibitor to determine if this LQYHVWLJDWHUROH V RIPLFURJOLDLQQHXURGHJHQHUDWLRQLQ3' therapy corrects functional aberrations. $GHQRDVVRFLDWHGYLUXV $$9 LVWKHPRVWFRPPRQO\XVHGWRROIRU gene therapy because of sustained gene expression and safety 5HFRUGLQJIURPODUJHHQVHPEOHVRIQHXURQVLQSULPDWH 89 SUR¿OH ,Q WKH FHQWUDO QHUYRXV V\VWHP $$9 WUDQVGXFHV QHXURQV primary visual cortex however microglia remain remarkably refractory to transduction. Anupam Garg 9LUDOFDSVLGHQFRGHGE\WKH&$3JHQHGHWHUPLQHV$$9WURSLVP$ Salk Institute for Biological Studies, San Diego, USA SOHWKRUDRIQDWXUDODQGUHFRPELQDQW$$9VHURW\SHVDUHGLVFRYHUHGVR 'HFDGHV RI SUHYLRXV ZRUN KDYH UHYHDOHG WKH IXQFWLRQDO DQG IDUGLႇHULQJLQFDSVLGVWUXFWXUH7KLVVWXG\XWLOL]HVWZRWHFKQLTXHVWR DQDWRPLFDORUJDQL]DWLRQRISULPDWHSULPDU\YLVXDOFRUWH[ 9 DWWKH HQJLQHHU$$9FDSVLGVWRVHOHFWLYHO\DQGVSHFL¿FDOO\WDUJHWPLFURJOLD level of cortical layers and columns. However, recent technological )LUVW LV UDQGRP '1$ IDPLO\ VKXႉLQJ RI QDWXUDO DQG UHFRPELQDQW DGYDQFHVLQH[WUDFHOOXODUHOHFWURSK\VLRORJ\DQGWZRSKRWRQFDOFLXP FDSVLGV7KLVLQYROYHVGLJHVWLRQRIYDULRXVFDSJHQHVIURPGLႇHUHQW imaging have allowed for investigation of more detailed cortical $$9 VHURW\SHV DQG UDQGRPO\ UHDVVHPEOLQJ WKHP LQWR IXOO OHQJWK organization at the cellular level. We aim to develop and further chimeric capsids. The second method is using a peptide display UH¿QHDSSURDFKHVWROLQNODUJHHQVHPEOHVRIQHXURQVLQ9WRWKHLU OLEUDU\ZKHUHVKRUWSHSWLGHVDDORQJSLHFHVRINQRZQPLFURJOLDO laminar identity, cell types, functions, and connectivity. In this study, VXUIDFHUHFHSWRUOLJDQGVDUHLQWURGXFHGLQWRWKH$$9FDSVLGV&DSVLG ZH GHPRQVWUDWH WKH DELOLW\ RI KLJKGHQVLW\ 1HXURSL[HOV HOHFWURGH libraries are then selected for microglia in vivo. DUUD\VDQGWZRSKRWRQFDOFLXPLPDJLQJXVLQJ*&D03IWRLQFUHDVH our understanding of the principles and mechanisms by which :H DLP WR XWLOL]H WKH PLFURJOLDOVSHFL¿F$$9V WR VWXG\ WKH UROHRI large populations of neurons transform sensory input to give rise DOSKDV\QXFOHLQ ĮV\Q LQ 3' ĮV\Q LV WKH FKLHI FRPSRQHQW RI WRSDWWHUQVRIQHXURQDODFWLYLW\LQPDFDTXH9,QWHJUDWLQJPXOWLSOH /HZ\ERGLHVDQGĮV\QPHGLDWHGQHXURWR[LFLW\LVWKRXJKWWRLQYROYH imaging and recording technologies enables us to perform detailed QHXURLQÀDPPDWLRQ +HUH ZH K\SRWKHVL]H WKDW RYHUH[SUHVVLRQ RI studies revealing computational and organizational principles of ĮV\QLQPLFURJOLDZLOOH[DFHUEDWHQHXURGHJHQHUDWLRQ functional cortical connectivity. )LQDOO\ LW LV FUXFLDO WR QRWH WKDW PLFURJOLDVSHFL¿F$$9 YHFWRUV DUH 8VLQJQH[WJHQHUDWLRQ1HXURSL[HOVHOHFWURGHDUUD\VZHGHPRQVWUDWH SURPLVLQJWRROVWRVWXG\QRWRQO\3'EXWDOVRRWKHUQHXURLQÀDPPDWRU\ WKHDELOLW\WRVLPXOWDQHRXVO\UHFRUGIURP9QHXURQVDFURVV diseases of which the role of microglia is being increasingly all cortical layers. In these experiments, we present a series of recognized. chromatic and achromatic visual stimuli consisting of stationary and 91 Investigation of changes in extracellular vesicles from moving gratings, which allows us to characterize cellular receptive glioblastoma cells treated with gene-mediated cytotoxic ¿HOGVRIDZLGHDUUD\RIFHOOW\SHV6LPXOWDQHRXVO\UHFRUGLQJIURP immunotherapy large ensembles of neurons enables us to use reverse correlation DQGFURVVFRUUHODWLRQDQDO\VHVWRUHYHDOFLUFXLWPHFKDQLVPVEHWZHHQ $OH[DQGUD0*LDQWLQL/DUVHQ functionally connected pairs or groups of neurons. Combining these Brigham and Women’s Hospital UHVXOWVZLWKFXUUHQWVRXUFHGHQVLW\ &6' DQDO\VLVLQZKLFKZHDVVLJQ *OLREODVWRPD *%0 LV D GHYDVWDWLQJ PDOLJQDQW EUDLQ FDQFHU a laminar identity to each recorded neuron, enables us to reveal the ZKRVH SURJUHVVLRQ LV GULYHQ E\ D VXEVHW RI *%0 VWHPOLNH FHOOV ODPLQDURUJDQL]DWLRQRIFRORUUHVSRQVLYHQHXURQVLQPDFDTXH9 *6&V ,Q RUGHU WR LPSURYH VXUYLYDO QRYHO WKHUDSHXWLFV XVLQJ In combination with our work using extracellular electrophysiology, JHQHPHGLDWHGF\WRWR[LFLPPXQRWKHUDS\ *0&, DUHEHLQJVWXGLHG ZH UREXVWO\ H[SUHVV *&D03I LQ 9 XVLQJ WKH 7(72ႇ LQGXFLEOH *0&, LQVHUWV WKH JHQH IRU D WKHUDSHXWLF HQ]\PH RU SURWHLQ LQWR gene expression system, allowing simultaneous imaging of calcium FHOOV XVLQJ DQ HQJLQHHUHG YLUXV 2QH XVH RI *0&, WR WDUJHW *%0 UHVSRQVHVIURPKXQGUHGVRIQHXURQV8VLQJWKHVHUHVXOWVZHFDQ LQYROYHVLQWUDWXPRUDOLQMHFWLRQRIDQRQUHSOLFDWLQJDGHQRYLUXV $G9 align the calcium imaging responses with postmortem cytochrome WKDWH[SUHVVHVWKHKHUSHVVLPSOH[YLUXVWK\PLGLQHNLQDVH +69WN R[LGDVHVWDLQLQJWRLGHQWLI\WKHORFDWLRQVRIEOREVDQGLQWHUEOREVDQG JHQH$QDQWLKHUSHWLFSURGUXJWKDWUHTXLUHVDFWLYDWLRQE\+69WNLV FRPSDUHWKHGLႇHUHQFHVEHWZHHQQHXURQDODFWLYLW\LQHDFKRIWKHVH administered and the activated toxic nucleotide causes cell death locations in response to a variety of visual stimuli. WKDW SURPRWHV DQ LPPXQH UHVSRQVH *0&, LV QRZ LQ FOLQLFDO WULDOV

56 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

IRU SDWLHQWV ZLWK *%0 +RZHYHU WKH LGHQWL¿FDWLRQ RI ELRPDUNHUV 6$00,ZDVWHVWHGWRVHOHFW06$VIRUIXQFWLRQDOUHVLGXHSUHGLFWLRQ that measure tumor responsiveness to the treatment is still needed. E\DQDO\VLVRIFRQVHUYDWLRQSDWWHUQVRQDGLYHUVHFURVVVHFWLRQRIWKH ([WUDFHOOXODUYHVLFOHV (9V DUHLPSRUWDQWPHGLDWRUVRILQWHUFHOOXODU SURWHRPHFRQVLVWLQJRIDVHWRISURWHLQVREWDLQHGIURPSURWHLQ FRPPXQLFDWLRQ DQG FDQ WUDQVPLW ELRORJLFDO LQIRUPDWLRQ 7XPRU OLJDQG SHSWLGHVQXFOHLFDFLGVDQGVPDOOPROHFXOHVXEVWUDWHV DQG GHULYHG(9VDUHIRXQGLQVHYHUDOELRORJLFDOÀXLGVLQFOXGLQJ&6)DQG SURWHLQSURWHLQLQWHUDFWLRQGDWDEDVHV2XUUHVXOWVGHPRQVWUDWHWKDWLQ blood, and represent an excellent source of biomarkers. The goal the majority of proteins, the conservation pattern of an appropriately RIWKLVVWXG\ZDVWRLGHQWLI\FKDQJHVLQ(9VVHFUHWHGE\*%0FHOOV VHOHFWHG06$FDQFDSWXUHRQDYHUDJHRIIXQFWLRQDOO\LPSRUWDQW WUHDWHGZLWK*0&,FRPSDUHGWRFRQWUROFHOOV UHVLGXHVFRPSDUHGWRLQFRQWUROV S WKHVHUHVXOWVdouble 7RGHWHUPLQHWKHWLPHRIPD[LPXPH[SUHVVLRQRIWKH+69WNJHQH WKHFXUUHQWVWDWHRIWKHDUW. Furthermore, a detailed analysis of the and optimal time for exosome collection, the expression of green minority of proteins whose functionally important residues were ÀXRUHVFHQW SURWHLQ *)3 ZDV PRQLWRUHG DIWHU FHOOV ZHUH LQIHFWHG ³PLVVHG´LQGLFDWHVWKDWWKHFRQVHUYDWLRQSDWWHUQVRI06$VVHOHFWHG ZLWKDQ$G9H[SUHVVLQJWKH*)3JHQH0D[LPDOH[SUHVVLRQRFFXUUHG E\6$00,DUHOLNHO\WRUHSUHVHQWXQDQQRWDWHGIXQFWLRQDOUHVLGXHV DWKRXUV9LUDOLQIHFWLRQRIFHOOVZLWKDQ$G9H[SUHVVLQJWKH+69 This suggests that “failed” cases are simply “unannotated” and WNJHQH $G9WN ZDVFRQ¿UPHGE\WUHDWPHQWRIFHOOVZLWKLQFUHDVLQJ UHSUHVHQWQRVSHFL¿FIDLOLQJRIRXUDOJRULWKP FRQFHQWUDWLRQVRIWKHDQWLKHUSHWLFSURGUXJJDQFLFORYLU *&9 *&9 Addressing the genome functional annotation problem will only VKRZHGVWURQJF\WRWR[LFLW\DJDLQVWWKH*6&VZLWKDQ,&RIX0 increase in importance as the number of available protein sequences DWKRXUV'LႇHUHQFHVLQ(9VL]HZHUHGHWHFWHGEHWZHHQFRQWURO exponentially grows. Finding ways to extract useful knowledge from FHOOVDQGYLUDOO\LQIHFWHGFHOOVXVLQJWKH1DQRVLJKWDWDQGKRXUV WKLV PDVV RI LQIRUPDWLRQ LV FULWLFDO WR ELRPHGLFDO SURJUHVV 6$00, DIWHULQIHFWLRQ7KHFRQFHQWUDWLRQRI(9VLQYLUDOO\LQIHFWHGFHOOVZDV represents an important contribution to solving this problem by IROGOHVVWKDQFRQWUROFHOOVDWDQGKRXUV+RZHYHUFRQWURO SURYLGLQJDQREMHFWLYHGDWDGULYHQZD\RIVHOHFWLQJRSWLPDO06$V (9VVKRZHGDPDLQSRSXODWLRQRI(9VDURXQGQPZKLOHYLUDOO\ which are a central tool for genome analysis in bioinformatics. LQIHFWHGFHOOVVHFUHWHGWZRGLႇHUHQWSRSXODWLRQVRI(9VDURXQGRI DQGQP$WKDIWHULQIHFWLRQWKHVL]HRIWKHPDLQSRSXODWLRQRI 93 $,5( LQ SUHJQDQF\ DXWRLPPXQH UHJXODWRU JHQH PD\ (9VUHPDLQHGFRQVLVWHQWZKLOHWKHYLUDOO\LQIHFWHGFHOOVVHFUHWHG(9V support maternal-fetal tolerance via deletion of reactive maternal shifted more to the larger population. T cells (YD0*LOOLV%XFN 2XUUHVXOWVVXJJHVWWKDW$G9WNWUHDWPHQWRIJOLREODVWRPDFHOOVPD\ University of California San Francisco, USA DOWHU(9TXDQWLW\DQGVL]H2QJRLQJVWXGLHVDUHEHLQJSHUIRUPHGWR IXUWKHUFKDUDFWHUL]HWKHVH(9V Complications of pregnancy, such as recurrent miscarriage, PD\ UHSUHVHQW D IDLOXUH RI PDWHUQDOIHWDO LPPXQH WROHUDQFH 7KH 92 Identifying functionally informative multiple sequence autoimmune regulator gene (AIRE) is a crucial component of tolerance alignments WRVHOIDQWLJHQVEXWLWVUHOHYDQFHIRUPDWHUQDOIHWDOWROHUDQFHKDVQRW Nelson H. Gil yet been explored. AIRE contributes to both central and peripheral Albert Einstein College of Medicine, Bronx, USA WROHUDQFH YLD WKH SUHVHQWDWLRQ RI WLVVXH VSHFL¿F DQWLJHQV 76$V $OWKRXJK KLJKWKURXJKSXW JHQRPH VHTXHQFLQJ WHFKQRORJLHV KDYH OHDGLQJ WR WKH FORQDO GHOHWLRQ RI VHOIUHDFWLYH7 FHOOV7KHVH 76$V made on the order of 100,000,000 unique protein sequences include placental antigens, which we call “distant self” antigens, available in current public databases, there are only approximately since they are encoded in the maternal genome, but have not been 1,000 detailed annotations of protein function. In other words, expressed since the mother was herself an embryo with a placenta. roughly only a single protein function is known for every 100,000 :HK\SRWKHVL]HWKDW$,5(GULYHQPDWHUQDOWROHUDQFHRI³GLVWDQWVHOI´ available sequences. A central goal of bioinformatics is to close this SODFHQWDO76$VDUHFULWLFDOIRUVXFFHVVIXOHPEU\RLPSODQWDWLRQDQG monumental gap through functional annotation of genomes. The GHYHORSPHQW7RWHVWWKLVZH¿UVWLQYHVWLJDWHG$,5(H[SUHVVLRQLQ principal motivation for this is that detailed functional annotations SUHJQDQW DQG QRQSUHJQDQW IHPDOH PRXVH WLVVXHV 8VLQJ T3&5 are necessary for progress in biomedicine, particularly in the area of 51$VFRSHDQGLPPXQRKLVWRFKHPLVWU\ZHIRXQG$,5(H[SUHVVLQJ rational drug design. A common approach to functional annotation is cells in the uterine draining lymph nodes. To test the functional role the analysis of conservation patterns in multiple sequence alignments RI$,5( GXULQJ SUHJQDQF\ZH QH[W XVHG DQ$,5(GLSKWKHULD WR[LQ 06$V WKH LGHD EHLQJ WKDW HYROXWLRQDULO\ FRQVHUYHG DPLQR DFLG UHFHSWRU '75 WUDQVJHQLFPRXVHPRGHOWRDEODWH$,5(H[SUHVVLQJ SRVLWLRQV LQ SURWHLQV 06$ FROXPQV DUH IXQFWLRQDOO\ LPSRUWDQW FHOOVGXULQJWKH¿UVWQLQHGD\VRIDQDOORJHQHLFSUHJQDQF\:HIRXQG However, the optimal selection of sequences to obtain biologically VLJQL¿FDQWO\ VPDOOHU OLWWHU VL]HV S DQG VPDOOHU HPEU\RV LQIRUPDWLYH 06$V LV SRRUO\H[SORUHG DQG KDV WUDGLWLRQDOO\ EHHQ S LQ D VXEVHW RI $,5('75 SUHJQDQFLHV RI 1 performed manually, which is tedious and subjective. FRPSDUHG WR ZLOGW\SH :7 SUHJQDQFLHV JLYHQ '7 1 )ORZ F\WRPHWU\RIPDWHUQDOWLVVXHVVKRZHG$,5('75SUHJQDQFLHVKDG :H SUHVHQW 6HOHFWLRQ RI$OLJQPHQW E\ 0D[LPDO 0XWXDO ,QIRUPDWLRQ PRUH &' 7 FHOOV S DQG IHZHU )R[3 7UHJV S 6$00, DQ DXWRPDWHG VHTXHQFHEDVHG DSSURDFK WR REMHFWLYHO\ LQWKHXWHUXVDQGPRUH&'&'7FHOOV S LQSHULSKHUDO VHOHFWDQRSWLPDO06$IURPDODUJHVHWRIDOWHUQDWLYHVVDPSOHGIURP O\PSKQRGHV$,5('75PLFHZHUHOHVVOLNHO\WREHSUHJQDQWDIWHU a general sequence database search. The hypothesis driving this D FRQ¿UPHG SOXJ UDWH RI SUHJQDQF\ RQ HPEU\RQLF GD\ approach is that the mutual information (a mathematical quantity $,5('75 YV :7 VXJJHVWLQJ GHFUHDVHG IHUWLOLW\ RU HDUO\ LQGLFDWLQJ VWUHQJWK RI FRUUHODWLRQ DPRQJ 06$ FROXPQV ZLOO EH pregnancy loss. Thus, although AIRE expression may decrease PD[LPDOIRUWKRVH06$VWKDWFRQWDLQWKHPRVWGLYHUVHVHWSRVVLEOH GXULQJSUHJQDQF\$,5(H[SUHVVLQJFHOOVPD\VWLOOSOD\DQLPSRUWDQW of the most structurally and functionally homogeneous protein UROHLQPDWHUQDOIHWDOWROHUDQFHE\GHOHWLQJUHDFWLYHPDWHUQDO7FHOOV sequences. This is based on the idea that correlation patterns among DQG SURPRWLQJ PDWHUQDO 7UHJ GLႇHUHQWLDWLRQ )XWXUH ZRUN ZLOO XVH amino acid positions in protein sequences encode a structural and 51$VHTXHQFLQJ WR FRPSDUH WUDQVFULSWLRQ SUR¿OHV RI WK\PLF DQG IXQFWLRQDO ¿QJHUSULQW WKDW XQLTXHO\ GH¿QHV D VHW RI HYROXWLRQDULO\ SHULSKHUDO $,5(H[SUHVVLQJ FHOOV LQ SUHJQDQW YHUVXV QRQSUHJQDQW related proteins.

www.jointmeeting.org 57 POSTER ABSTRACTS

IHPDOHPLFHZLWKWKHJRDORILGHQWLI\LQJFDQGLGDWHSODFHQWDO76$V RI VXFFHVV RI SK\VLFLDQVFLHQWLVWV DUH WDQJLEOH 4XDOLWLHV RI that may be responsible for maternal T cell reactivity towards the VXFFHVVRISK\VLFLDQVFLHQWLVWVFDQEHPHDVXUHGDQG ([HPSODU placenta and developing embryo. SK\VLFLDQVFLHQWLVWVNQRZKRZWRUHÀHFWRQWKHLUVXFFHVVXQGHUVWDQG and clearly articulate what has led to their success. 95 (VWDEOLVKPHQWRID0XULQH%HKDYLRUDO0RGHOWR,QYHVWLJDWH WKH5ROHRIWKH0LFURELRPHLQ0DMRU'HSUHVVLYH'LVRUGHUDQG 7KLVZDVDQDWLRQDOVWXG\ZLWKWKHPRVWH[HPSODUSK\VLFLDQVFLHQWLVWV Crohn’s Disease of our generation. Two earlier phases of the study provided a national GH¿QLWLRQRIVXFFHVVZKLFKZDVXVHGWRLGHQWLI\H[HPSODUSK\VLFLDQ Adrian S. Gomez-Nguyen VFLHQWLVWV7KHSULPDU\VRXUFHVRIGDWDZHUHLQGHSWKLQWHUYLHZVRI Case Western Reserve University, Cleveland, USA QLQHWHHQH[HPSODUSK\VLFLDQVFLHQWLVWVDIRFXVJURXSZLWKSK\VLFLDQ The microbiome plays an intimate and multifaceted role in Crohn’s scientists, and document analysis. 'LVHDVH &' ,QFUHDVLQJHYLGHQFHKDVGHPRQVWUDWHGWKDW&'SDWLHQWV .H\¿QGLQJVRIWKHVWXG\UHYHDOHG ([HPSODUSK\VLFLDQVFLHQWLVWV exhibit an inappropriate immune response to the microbiome. In are overwhelmingly intrinsically motivated by both the need to addition, recent evidence has cemented the connection between the understand the science and the desire to help their patients; (2) PLFURELRPHWKHJXWDQGWKHEUDLQ7KLVLVVLJQL¿FDQWEHFDXVHSDWLHQWV ([HPSODU SK\VLFLDQVFLHQWLVWV DUH DFWLYHO\ HQJDJHG LQ RYHUVHHLQJ ZLWK&'KDYHGLVSURSRUWLRQDWHO\KLJKUDWHVRIGHSUHVVLRQDQGDQ[LHW\ the design and execution of experiments, bringing in the unique Alternations in the microbiome leads to major changes in behavior perspective of both the physician and scientist; (3) Perseverance which reinforces the microbiome as a previously unrecognized, but ZDVLGHQWL¿HGDVWKHPRVWFULWLFDOIDFWRURIVXFFHVVDQG ,QIRUPDO VLJQL¿FDQWWKHUDSHXWLFWDUJHWZKLFKZLOOUHYROXWLRQL]HWKHWKHUDSHXWLF PHDQVSOD\HGDQLQWHJUDOUROHLQWKHOHDUQLQJRISK\VLFLDQVFLHQWLVWV ODQGVFDSHRIWUHDWLQJSDWLHQWVZLWK&'DQGGHSUHVVLRQ7KHDLPRIWKLV most notably through dialogue and formal mentoring programs. study is to establish a mechanistic link between the microbiome and GHSUHVVLRQLQ&'2XUXOWLPDWHJRDOLVWRLPSURYHSDWLHQW¶VEHKDYLRUDO ,QIRUPDOOHDUQLQJZDVGHVFULEHGE\&RRPEV DVVHOIGLUHFWHG diagnoses through manipulation of the microbiome. incidental, and socialization or tacit learning was used to understand WKHPDQQHULQZKLFKSK\VLFLDQVFLHQWLVWVOHDUQDQGXQGHUVFRUHGWKH To establish a behavioral baseline for our model, we performed synthesis and analysis of the study. EHKDYLRUDOVWXGLHVXVLQJPDOH6$03PLFH Q DWYDULRXVDJHV ZLWK$.5- $.5 &%/6$03DQG6$05PLFHDVFRQWUROV 1XPHURXVUHFRPPHQGDWLRQVZHUHSURYLGHGIRUFXUUHQWDQGIXWXUH %HKDYLRUDO VWXGLHV LQFOXGHG WDLO VXVSHQVLRQ 76 RSHQ ¿HOG 2) SK\VLFLDQVFLHQWLVWV DV ZHOO DV WR WKH QXPHURXV VWDNHKROGHUV² HOHYDWHGSOXVPD]H (30 URWDURGJULSVWUHQJWK%DUQHVPD]HDQG those who hire, train, and fund them. These recommendations <PD]H)ORZF\WRPHWU\VRUWHGPLFURJOLDOLPPXQRKLVWRFKHPLVWU\DQG include suggestions for admissions practices that more accurately 7EUDLQ05,ZHUHXVHGWRDQDO\]HEUDLQV,OHDOP\HORSHUR[LGDVH VKRZFDVHWKHTXDOLWLHVRIH[HPSODUSK\VLFLDQVFLHQWLVWVUHWKLQNLQJ activity, histological severity, and cytokine transcription and secretion the architecture of our spaces to allow for more collaborative were used to measure disease severity. Fecal microbiome was dialogue, suggestions for how to make the most of informal learning DQDO\]HGXVLQJVU51$JHQHVHTXHQFLQJ RSSRUWXQLWLHVDQGDQHPSKDVLVRQPHQWRULQJVSHFL¿FDOO\PHQWRULQJ the mentors. $V H[SHFWHG RXU 6$03 PLFH H[KLELWHG PDUNHG LOHDO LQÀDPPDWLRQ ZKHQ FRPSDUHG WR $.5 PLFH *URVV FREEOHVWRQLQJ LQFUHDVHG 97 Analysis of the role of Glutamatergic and GABAergic MPO activity, and worse histology score all indicated severe ileitis. periaqueductal gray neuronal subpopulations in a mouse model 6XUSULVLQJO\WKH6$03PLFHGLGQRWGHYHORSGHSUHVVLYHRUDQ[LHW\ RISHUVLVWHQWLQÀDPPDWRU\SDLQ OLNH EHKDYLRU ZLWK LQFUHDVLQJ LQÀDPPDWLRQ GHSUHVVLYH EHKDYLRU -RVH**UDMDOHV5H\HV PHDVXUHGZLWK76DQGDQ[LHW\OLNHEHKDYLRUPHDVXUHGZLWK(30DQG Washington University School of Medicine, Saint Louis, USA 2) &RQYHUVHO\GHVSLWHDEHQLJQLQÀDPPDWRU\SKHQRW\SHWKH$.5 mice demonstrated marked depressive behavior when compared ,W KDV EHHQ HVWLPDWHG WKDW PLOOLRQ DGXOWV VXႇHU IURP WR6$03 S 7KHVHFKDQJHVZHUHQRWGXHWRFKDQJHVLQ FKURQLF SDLQ LQ WKH 8QLWHG 6WDWHV ZLWK DQ DQQXDO VRFLHWDO FRVW PRWRUIXQFWLRQDVGHPRQVWUDWHGE\QRQVLJQL¿FDQWGLႇHUHQFHVLQWKH of approximately 600 billion dollars. Endogenous analgesic URWDURGJULSVWUHQJWKDQGRSHQ¿HOGDFWLYLW\ S!S!DQG pathways represent an alternative route for the development of S! UHVSHFWLYHO\ 0LFURELRPH UHVXOWV DUH SHQGLQJ EXW ZLOO EH new therapies. Pharmacological and electrical stimulation studies available at the time of the conference. RI WKH YHQWURODWHUDO SHULDTXHGXFWDO JUD\ YO3$* KDYH LPSOLFDWHG LWV UROH LQ GHVFHQGLQJ SDLQ PRGXODWLRQ 7KH *$%$ GLVLQKLELWLRQ 7KH DELOLW\ RI WKH 6$03 PLFH WR PDLQWDLQ D FRQVWDQW EHKDYLRUDO hypothesis put forward by Basbaum and Fields proposes that tonic phenotype despite worsening disease is a welcomed surprise. With *$%$HUJLF QHXURWUDQVPLVVLRQ DW WKH OHYHO RI WKH YO3$* VHUYHV WKHVHUHVXOWVZHQRZKDYHDPRGHORIVSRQWDQHRXV&'WKDWGRHV to inhibit output excitatory projections that mediate descending not naturally develop depressive behavior. In addition, we also have DQDOJHVLDDQGGLVLQKLELWLRQRIYO3$*H[FLWDWRU\QHXURQVWKDWSURMHFW D PRGHO WKDW GRHV QRW GHYHORS LQWHVWLQDO LQÀDPPDWLRQ EXW GRHV WR WKH URVWUDO YHQWURPHGLDO PHGXOOD 590 LV WKRXJKW WR DOORZ develop spontaneous depressive behavior. These powerful models VXEVHTXHQWDFWLYDWLRQRI590FHOOVWKDWSURMHFWWRWKHGRUVDOKRUQRI will allow us to manipulate behavior and microbiome to further WKHVSLQDOFRUGDQGLQKLELWQRFLFHSWLYHWUDQVPLVVLRQ1XPHURXVOLQHV HOXFLGDWHWKHFRQQHFWLRQEHWZHHQ&'DQGGHSUHVVLRQ of evidence are consistent with this hypothesis, but experimental 96 Optimizing Success of Physician-Scientists PDQLSXODWLRQV XVHG LQ SULRU VWXGLHV ODFN FHOOW\SH VSHFL¿FLW\ SUHYHQWLQJXQDPELJXRXVGHWHUPLQDWLRQRIWKHUROHRIVSHFL¿FVXEVHWV 5XWK*RWLDQ RI YO3$* QHXURQV LQ DQDOJHVLD 7HFKQLTXHV VXFK DV FKHPR DQG Weill Cornell Medicine, New York, USA RSWRJHQHWLFVQRZDႇRUGXVWKHRSSRUWXQLW\WRVHOHFWLYHO\PDQLSXODWH This qualitative case study was designed to explore with a group LGHQWL¿HGVXEFODVVHVRIYO3$*QHXURQV:LWKWKH*$%$GLVLQKLELWLRQ RI H[HPSODU SK\VLFLDQVFLHQWLVWV ZKDW IDFWRUV FRQWULEXWHG WR WKHLU hypothesis as our model, we hypothesized that stimulation of success. 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58 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

WRQH ZRXOG UHVXOW LQ DQDOJHVLD :H ¿QG FKHPRJHQHWLF VWLPXODWLRQ 3ULRUZRUNLQRXUODEKDVHVWDEOLVKHGD]HEUD¿VK0\FLQGXFHG7FHOO RIJOXWDPDWHUJLFQHXURQVRULQKLELWLRQRI*$%$HUJLFYO3$*QHXURQV DFXWHO\PSKREODVWLFOHXNHPLD 7$// PRGHOWKDWPLPLFVWKHPRVW results in an elevation of withdrawal thresholds to noxious stimuli in DJJUHVVLYHDQGWUHDWPHQWUHVLVWDQWIRUPRIKXPDQ7$//8VLQJWKLV QDwYHDQLPDOV,QWKHFRWH[WRISHUVLVWHQWLQÀDPPDWRU\SDLQZH¿QG V\VWHP ZH LVRODWHG VLQJOH /6&V WKURXJK D QRYHO WUDQVSODQWDWLRQ WKDWRSWRJHQHWLFVWLPXODWLRQRI9JOXWRUFKHPRJHQHWLFLQKLELWLRQRI VWUDWHJ\ /LPLWLQJ GLOXWLRQ DQDO\VLV VKRZHG VLJQL¿FDQW GLႇHUHQFHV 9JDWYO3$*QHXURQVUHVXOWVLQDWWHQXDWLRQRILQÀDPPDWLRQLQGXFHG LQ WKH UDWH RI VHOIUHQHZDO EHWZHHQ GLႇHUHQW /6&V VXJJHVWLQJ K\SHUDOJHVLD8VLQJDQLQWHUVHFWLRQDOJHQHWLFDSSURDFKZHSURYLGH KHWHURJHQHLW\ LQ /6& UHODSVH SRWHQWLDO :H JHQHUDWHG D OLEUDU\ RI direct experimental evidence for the proposed analgesic role for ]HEUD¿VK7$//ZLWKKLJKVHOIUHQHZDOUDWHV DERXWLQOHXNHPLD JOXWDPDWHUJLF SURMHFWLRQV IURP WKH 3$* WR WKH 590 ,Q EULHI RXU FHOOVLVD/6& IRUXVHLQEXON51$VHTDVZHOODVVLQJOHFHOOT3&5 ¿QGLQJVVXSSRUWWKH*$%$GLVLQKLELWLRQK\SRWKHVLVKLJKOLJKWLQJWKH DQGVLQJOHFHOO51$VHTWRLGHQWLI\DVHOIUHQHZDOVLJQDWXUHXQLTXH UROH RI ORFDO WRQLF *$%$HUJLF QHXURWUDQVPLVVLRQ DV DQ DQDOJHVLF WR /6&V 6LQJOH FHOO DQDO\VHV VKRZHG D SRSXODWLRQ RI FHOOV WKDW JDWHNHHSHUDWWKHOHYHORIWKHYO3$* H[SUHVVHGNQRZQVHOIUHQHZDOJHQHVDQGFOXVWHUHGVHSDUDWHO\IURP the rest of the leukemia cells in the population. Ongoing work in 98 Vesicular Ca2+ sensor Synaptotagmin 1 mediates our laboratory is focused on functionally testing whether this gene neurotransmission from mammalian rod photoreceptors H[SUHVVLRQSUR¿OHLVOLQNHGZLWKVHOIUHQHZDO$GGLWLRQDOO\IURPWKLV Justin Grassmeyer DQDO\VLVWKH:QWSDWKZD\PRUHVSHFL¿FDOO\FDWHQLQZDVHQULFKHG University of Nebraska Medical Center, Omaha, USA LQWKHSXWDWLYH/6&SRSXODWLRQ7KHVHGDWDVXSSRUWSUHYLRXV¿QGLQJ Rod photoreceptors initiate vision by converting light into neuronal in mammalian models of ALL. signals that are passed to downstream neurons in the retina and :HK\SRWKHVL]HWKDWLQKLELWRUVRIWKH:QWSDWKZD\ZLOOLQKLELWVHOI EH\RQG '\VIXQFWLRQ RI PROHFXOHV WKDW PHGLDWH SKRWRUHFHSWRU UHQHZDORI/6&VDQGIRUFHWKHPWRWHUPLQDOO\GLႇHUHQWLDWH+RZHYHU neurotransmission can lead to visual dystrophies and blindness. WKHUHDUHQR:17LQKLELWRUVFOLQLFDOO\DYDLODEOHGXHWRXQGHVLUDEOH 5RGVDUHGHSRODUL]HGLQGDUNQHVVDOORZLQJ&DLRQVWRHQWHUWKH VLGHHႇHFWV:HDUHFXUUHQWO\XVLQJD[7&)/()*)3]HEUD¿VK:QW FHOODQGVWLPXODWHWKHUHOHDVHRIJOXWDPDWHODGHQYHVLFOHV([RF\WRWLF reporter model for high throughput screens to identify new, less toxic &DVHQVRUSURWHLQVELQGLQWUDFHOOXODU&DDQGWULJJHUWKHYHVLFXODU Wnt pathway inhibitors. Thus far, several compounds have showed UHOHDVHSURFHVVPRVWQHXURQVXWLOL]HRQHRUPRUH6\QDSWRWDJPLQ VLJQL¿FDQWO\GHFUHDVHG7&)/()DFWLYLW\DIWHUGUXJWUHDWPHQWZLWK LVRIRUPV DV D &D VHQVRU 7KH LGHQWLW\ RI WKH &D VHQVRU WKDW QRHႇHFWVRQDQLPDOKHDOWK)XWXUHVWXGLHVZLOOWHVWWKHVHLQKLELWRUV operates in mammalian rods, which appear to exhibit an atypical LQ RXU ]HEUD¿VK KLJK /6& OHXNHPLD VDPSOHV DQG SDWLHQW GHULYHG UHODWLRQVKLS EHWZHHQ &D LQÀX[ DQG QHXURWUDQVPLWWHU UHOHDVH [HQRJUDIW PRGHOV 8OWLPDWHO\ WKHVH LQKLELWRUV PD\ UHSUHVHQW D UHPDLQV XQNQRZQ :H K\SRWKHVL]HG WKDW 6\QDSWRWDJPLQ 6\W SRWHQWLDOWKHUDSHXWLFVWUDWHJ\IRUWDUJHWLQJWUHDWPHQWUHVLVWDQW/6&V VHUYHVDVWKHH[RF\WRWLF&DVHQVRUDWPDPPDOLDQURGV\QDSVHV and preventing ALL relapse. 7RLQYHVWLJDWHWKHUROHRI6\WLQYLVLRQZHJHQHUDWHGQRYHOPRXVH OLQHVLQZKLFK6\WH[SUHVVLRQZDVVSHFL¿FDOO\DEROLVKHGLQURGVDQG 100 Dietary sodium restriction following high salt intake compared these conditional knockouts to littermate controls. Rod and reduces arterial stiffness, vascular wall transforming growth FRQHIXQFWLRQZDVHYDOXDWHGXVLQJH[YLYRHOHFWURUHWLQRJUDP (5* IDFWRUEHWD 7*)ȕ GHSHQGHQW ¿EURVLV DQG PDULQREXIDJHQLQ recordings of responses to light stimuli. Immunohistochemistry was level in young normotensive rats XVHGWRHYDOXDWHWKHHႈFDF\RIFRQGLWLRQDO6\WUHPRYDODQGH[DPLQH Yulia N. Grigorova UHWLQDODQDWRP\2XUUHVXOWVFRQ¿UPWKHSUHVHQFHRI6\WLQPRXVH National Institute on Aging / NIH, Baltimore, USA URG WHUPLQDOV DQG GHPRQVWUDWH WKDW 6\W VHUYHV DV WKH SULQFLSDO +LJKVDOWLQWDNH +6 LVDFFRPSDQLHGE\EORRGSUHVVXUH %3 LQFUHDVHV &DVHQVRUUHJXODWLQJQHXURWUDQVPLWWHUUHOHDVHIURPURGV6\WLV LQVDOWVHQVLWLYHK\SHUWHQVLRQ+6VWLPXODWHVPDULQREXIDJHQLQ 0%* WKHUHIRUHDQHVVHQWLDOSURWHLQIRUURGPHGLDWHGYLVLRQLQPDPPDOV DQ HQGRJHQRXV 1D.$73DVH OLJDQG ZKLFK DFWLYDWHV SUR¿EURWLF $OWKRXJKGHOHWLRQRI6\WIURPURGVGLVUXSWHGQHXURWUDQVPLVVLRQLWV signaling in the cardiovascular system. In normotensive animals, absence did not appear to alter outer retinal anatomy, suggesting that +6GLGQRWFDXVH%3HOHYDWLRQ1HYHUWKHOHVVLWZDVDVVRFLDWHGZLWK normal synaptic release from rods is not required for development of 0%*LQFUHDVHDQGDRUWLF¿EURVLV+HUHZHLQYHVWLJDWHGZKHWKHU+6 SURSHUFRQQHFWLRQVEHWZHHQURGVDQGVHFRQGRUGHUUHWLQDOQHXURQV DFWLYDWHVDQDRUWLF7*)ȕSUR¿EURWLFVLJQDOLQJDQG0%*SURGXFWLRQ ,Q FRQWUDVW WR UHOHDVH IURP RWKHU 6\WPHGLDWHG QHXURQV UHOHDVH LQ QRUPRWHQVLYH \RXQJ 6SUDJXH'DZOH\ UDWV 6' DQG ZKHWKHU from mammalian rods appears to exhibit a nearly linear relationship WKHVHFKDQJHVDUHUHYHUVDEOHE\QRUPDOVDOWGLHW 16 EHWZHHQ&DDQGH[RF\WRVLVVXJJHVWLQJWKDWDFFHVVRU\SURWHLQV DOVRVKDSH&DVHQVLWLYLW\DWWKLVV\QDSVH 6' PRQWK ROG PDOHV UHFHLYHG 16 IRU DQG ZHHNV 1D&O16DQG16 RU+6IRUDQGZHHNV 1D&O+6DQG 99 Identifying Novel Therapeutics to Inhibit the Wnt Self- +6 RU+6IRUZHHNVIROORZLQJE\16IRUZHHNV +616 5HQHZDO3DWKZD\LQ/HXNHPLD6WHP&HOOV Q SHUJURXS6\VWROLF%3 6%3 SXOVHZDYHYHORFLW\ 3:9 0%* 0HJKDQ*UHHQ+DQH\ H[FUHWLRQDRUWLFFROODJHQĮDQG7*)ȕP51$DQGWRWDOFROODJHQ University of Kentucky, Lexington, USA DEXQGDQFHZHUHPHDVXUHGDWEDVHOLQH %/ DQGRQZHHNVDQG 6WDWLVWLFDODQDO\VLVZDVSHUIRUPHGXVLQJDRQHZD\$129$ The relapse rate of pediatric Acute Lymphoblastic Leukemia (ALL) LV DQG WKHVH SDWLHQWV KDYH OLPLWHG WUHDWPHQW RSWLRQV DQG +6LQFUHDVHG0%* YVSPROKUNJ+6YV a poor prognosis. Relapse rate is likely due to a small population of %/S DQG3:9 YVPV+6YV16 FHOOVNQRZQDVOHXNHPLDVWHPFHOOV /6&V ZKLFKKDYHWKHDELOLW\WR 3 ZKLOH6%3ZDVQRWDႇHFWHG YVPP+J VHOIUHQHZDQGFDQUHIRUPDOHXNHPLDIURPDVLQJOHFHOO$GGLWLRQDOO\ +6YV%/S! +6ZDVDVVRFLDWHGZLWKIXUWKHULQFUHDVHLQ DPDMRUFOLQLFDOFRQFHUQLVZKHWKHUWKHVH/6&VDUHHႇHFWLYHO\NLOOHG 0%*DQG3:9ZLWKDQLQFUHDVHLQDRUWLFCol1a2 (twofold), 7JIE E\FRQYHQWLRQDOF\WRWR[LFFKHPRWKHUDSLHV&XUUHQWHႇRUWVWRVWXG\ DQG6PDG P51$VDQGDRUWLFZDOOFROODJHQ /6&V KDYH IDFHG VHULRXV OLPLWDWLRQV ZKLFK KDYH LPSHGHG RXU YV16 DOOS 16IROORZLQJ+6GRZQUHJXODWHG+6LQGXFHG understanding of this important population of cells. IDFWRUVLQ+6160%*OHYHOZDVSPROKUNJ WZRIROG

www.jointmeeting.org 59 POSTER ABSTRACTS

ORZHUYV+6S 3:9ZDVYVPV +6 ULVNJHQRW\SHVZHUHQRWHGLQRI$IULFDQ$PHULFDQDQGRI 16YV+6S DRUWLFZDOO7JIE, &ROD 6PDGP51$V Hispanic patients. and collagen abundance were reversed by salt reduction to the BL 2XU ¿QGLQJV KLJKOLJKW WKH JHQHWLF DQG SKHQRW\SLF KHWHURJHQHLW\ levels (p < 0.05). RI KHUHGLWDU\ QHSKURSDWKLHV VXSSRUWLQJ WKH YDOXH RI :(6 IRU WKH +6 LQ \RXQJ QRUPRWHQVLYH UDWV ZDV DVVRFLDWHG ZLWK DQ DFWLYDWLRQ GHWHFWLRQRIJHQHWLFIRUPVRI&.'7KHKLJKGLDJQRVWLF\LHOGREVHUYHG RI7*)ȕVLJQDOLQJDRUWLF¿EURVLVDQGDRUWLFVWLႇQHVVDFFRPSDQLHG DPRQJSDWLHQWVZLWK&.'³RIXQNQRZQHWLRORJ\´VXJJHVWVWKDW:(6 E\0%*LQFUHDVHLQDSUHVVXUHLQGHSHQGHQWPDQQHU5HGXFWLRQRI may have substantial diagnostic utility for patients with undiagnosed GLHWDU\VDOWIROORZLQJ+6GHFUHDVHG0%*3:9DRUWLFZDOOFROODJHQ &.'DVZHOODVIRUWKRVHFOLQLFDOO\VXVSHFWHGWRKDYHDKHUHGLWDU\ DQG 7*)ȕ 7KXV +6LQGXFHG DRUWLF VWLႇQHVV LQ QRUPRWHQVLYH form of disease. DQLPDOVRFFXUUHGLQWKHFRQWH[WRIHOHYDWHG0%*ZKLFKPD\DFWLYDWH SUHVVXUHLQGHSHQGHQW 7*)ȕGHSHQGHQW SUR¿EURWLF VLJQDOLQJ 7KLV 102 0<&IDPLO\PHPEHUVGULYHFKHPRUHVLVWDQFHLQVPDOOFHOO data suggests that decreases in salt consumption could help to restore lung cancer aortic elasticity and to reduce the risk of cardiovascular disease. Eli Grunblatt University of Washington-Fred Hutchinson Cancer Research 6XSSRUWHGE\WKH1,+1,$,QWUDPXUDO5HVHDUFK3URJUDP Center, Seattle, USA 101 Diagnostic utility of whole-exome sequencing for kidney 6PDOO FHOO OXQJ FDQFHU 6&/& LV D KLJKO\ DJJUHVVLYH IUHTXHQWO\ disease metastatic cancer that accounts for approximately 35,000 new Emily E. Groopman FDVHV DQQXDOO\ LQ WKH 8QLWHG 6WDWHV DORQH :KLOH PDQ\ SDWLHQWV Columbia University, New York, USA LQLWLDOO\UHVSRQGZHOOWRFLVSODWLQEDVHGFKHPRWKHUDS\UHODSVHZLWKLQ +HUHGLWDU\HWLRORJLHVDFFRXQWIRUaRIDGXOWDQG!RISHGLDWULF months is nearly universal. Relapsed disease is frequently resistant NLGQH\GLVHDVHDQGRIWHQGLႇHUPDUNHGO\IURPDFTXLUHGIRUPVLQWKHLU to chemotherapy, contributing substantially to the poor overall prognosis, course, and clinical management. However, due to high SURJQRVLVRI6&/&SDWLHQWV'HFDGHVRIVWXG\KDYH\HWWRSURGXFH genetic and phenotypic heterogeneity, diagnosis can remain elusive DQ )'$DSSURYHG WDUJHWHG WKHUDS\ RU D GHWDLOHG XQGHUVWDQGLQJ RI using traditional modalities alone, and in more than 1 in 10 patients chemoresistance, severely limiting treatment options for patients with ZLWK HQGVWDJH UHQDO GLVHDVH WKH SULPDU\ FDXVH LV ³XQNQRZQ´ relapsed disease. However, recent studies indirectly suggest that :KROHH[RPHVHTXHQFLQJ :(6 KDVLOOXPLQDWHGWKHJHQHWLFEDVLV overexpression of MYC family members, such as 0<&/ and 0<&1, of a variety of disorders, and is becoming increasingly deployed as PD\ SOD\ D UROH LQ 6&/& FKHPRUHVLVWDQFH 7KHUHIRUH GHWDLOHG D ¿UVWOLQH GLDJQRVWLF DFURVV FOLQLFDO PHGLFLQH +RZHYHU LWV EURDG LQYHVWLJDWLRQ RI 0<& IDPLO\ PHPEHU RYHUH[SUHVVLRQ LQ 6&/& clinical value for patients with nephropathy, particularly among could lead to meaningful clinical advances. We used genetically DGXOWVKDV\HWWREHH[DPLQHG7RWKLVDLPZHSHUIRUPHG:(6LQD HQJLQHHUHGPRXVH *(0 PRGHOVRI6&/&WRVWXG\WKHHႇHFWVRI ODUJHFRKRUWRISDWLHQWVZLWKDOOFDXVHFKURQLFNLGQH\GLVHDVH &.' 0<&1 and 0<&/RYHUH[SUHVVLRQRQ6&/&FKHPRUHVLVWDQFH8SRQ and assessed the diagnostic yield and prevalence of other medically WUHDWLQJ FRKRUWV RI *(0V ZLWK FLVSODWLQHWRSRVLGH ZH IRXQG WKDW UHOHYDQW VHFRQGDU\ ¿QGLQJV ZKLOH6&/&WXPRUVLQFRQWUROPLFHH[KLELWHGDF\WRVWDWLFUHVSRQVH to chemotherapy, tumors in mice that overexpressed either 0<&/ &.' SDWLHQWV XQGHUZHQW :(6 DW WKH &ROXPELD ,QVWLWXWH IRU or 0<&1 did not respond to treatment and continued to grow. In *HQRPLF 0HGLFLQH 5RFKH RU ,'7 FDSWXUH NLWV ZHUH DGXOWV parallel, we used lentiviral vectors to overexpress 0<&1 in patient DQG ZHUH QRQ&DXFDVLDQ 6HTXHQFH GDWD ZDV SURFHVVHG GHULYHG[HQRJUDIW 3'; PRGHOVRI6&/&WKDWKDGSUHYLRXVO\EHHQ XVLQJ *$7. 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We found that while control tumors regressed when pathogenic variants. treated with cisplatin/etoposide, tumors that overexpressed 0<&1 'LDJQRVWLF YDULDQWV ZHUH GHWHFWHG LQ RI SDWLHQWV did not respond to treatment and continued to grow through multiple HQFRPSDVVLQJGLႇHUHQWJHQHWLFGLVHDVHV,QRIFDVHVWKH F\FOHVRIFKHPRWKHUDS\7DNHQWRJHWKHURXU¿QGLQJVVKRZWKDW0<& genetic diagnosis gave novel clinical insight, informing subsequent family members can drive the development of chemoresistance in clinical workup and management, disease prognosis, and/or family 6&/&7RHOXFLGDWHDSRWHQWLDOPHFKDQLVPIRU0<&IDPLO\PHPEHU FRXQVHOLQJRISRVLWLYHFDVHVKDGDXWRVRPDOGRPLQDQWGLVRUGHUV GULYHQFKHPRUHVLVWDQFHZHSHUIRUPHG51$VHTDQDO\VLVRI6&/& DXWRVRPDOUHFHVVLYHDQG;OLQNHGRISRVLWLYHFDVHV tumors derived from control, 0<&/ overexpressing, and 0<&1 KDG GXDO PROHFXODU GLDJQRVHV RI GLDJQRVWLF YDULDQWV KDG overexpressing mice. Our preliminary results show that multiple ABC EHHQSUHYLRXVO\UHSRUWHGDQGZHUHQRYHO7KHPRVWUHFXUUHQW WUDQVSRUWHUV DQWLDSRSWRWLF IDFWRUV DQG F\FOLQ GHSHQGHQW NLQDVH phenotypes were &2/$DVVRFLDWHG QHSKURSDWKLHV 802' inhibitors are upregulated in MYC family member overexpressing associated tubulointerstitial disease, and 753&DVVRFLDWHG samples. These pathways have previously been implicated in IRFDO VHJPHQWDO JORPHUXORVFOHURVLV +RZHYHU RI PROHFXODU the development of chemoresistance in other cancers, and we GLDJQRVHV ZHUH GHWHFWHG LQ D VLQJOH FDVH 'LDJQRVWLF \LHOG ZDV hypothesize that 0<&1 and 0<&/ GULYHQ 6&/& FKHPRUHLVWDQFH highest among patients with a clinical diagnosis of a Mendelian occurs through one or more of these avenues. Further work in this IRUPRI&.'ZLWKSRVLWLYH¿QGLQJVLQKRZHYHURISRVLWLYH ongoing study will follow up on these hits to determine potentially cases did not have a clinical diagnosis of a hereditary nephropathy. druggable targets in pathways downstream of MYC members. These 6WULNLQJO\WKHVHFRQGKLJKHVWGLDJQRVWLF\LHOGZDVIRXQGLQSDWLHQWV results can ultimately inform development of novel therapies to ZLWK &.' RI ³XQNQRZQ HWLRORJ\´ ZLWK GLDJQRVWLF JHQHWLF ¿QGLQJV VXFFHVVIXOO\WDUJHWFKHPRUHVLVWDQFHLQ6&/&DQGDOOHYLDWHVXႇHULQJ LGHQWL¿HG LQ RI SDWLHQWV KDG D VHFRQGDU\ ¿QGLQJ LQ for patients with this disease. RQHRIWKH$&0*PHGLFDOO\DFWLRQDEOHJHQHVDQGWKH $32/

60 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

103 Examining the postmitotic roles of STAG2 mutations in HႇHFWRI57RQWKHWHPSRUDODQGFHOOVSHFL¿FH[SUHVVLRQSDWWHUQVRI solid tumors 7*)ȕLVRIRUPVLQPRXVHWXPRUPRGHOV7KLVZLOOLQIRUPWUHDWPHQW 0DU\/*XDQ UHJLPHQVFRPELQLQJLVRIRUPVSHFL¿FDQWL7*)ȕWKHUDS\ZLWK57 University of Michigan Medical School, USA )OXRUHVFHQFHDFWLYDWHG FHOO VRUWLQJ )$&6 &%/ PLFH ZHUH Mutations in the cohesin complex are associated with cancer, namely LPSODQWHGRQWKHKLQGOLPEZLWK%)PHODQRPDFHOOV2QGD\ (ZLQJ¶V 6DUFRPD (:6 DQG EODGGHU FDQFHU %& 7KH 67$* WXPRUVZHUHLUUDGLDWHGORFDOO\ZLWK*$[SUHVVLRQRI7*)ȕ subunit of cohesin is essential for its loading onto chromatin and LVRIRUPVZDVPHDVXUHGDWDQGGD\VSRVW57E$$&6 SURSHUIXQFWLRQRIWKHFRPSOH[(:6DQG%&SDWLHQWVZKRFDUU\D ,QYLYR &%/ PLFH ZHUH LPSODQWHG ZLWK WXPRUV DQG LUUDGLDWHG 67$*PXWDWLRQVKRZGHFUHDVHGVXUYLYDO+RZ67$*IXQFWLRQVDV DVGHVFULEHG0LFHZHUHWUHDWHG JURXS ZLWKDQWL7*)ȕDQWL DWXPRUVXSSUHVVRULVQRWIXOO\XQGHUVWRRG6RPHVWXGLHVVKRZWKDW 7*)ȕ RU D SDQ7*)ȕ DQWLERG\ EHJLQQLQJ GD\ DIWHU 57 JLYHQ 67$* PXWDWLRQV FDXVHV DQHXSORLG\ LQ FDQFHUV ZKLOH RWKHU GDWD LQWUDSHULWRQHDOO\ XJPRXVH HYHU\RWKHUGD\IRUGRVHV7XPRU VXJJHVW WKDW 67$* PXWDWLRQV UHVXOW LQ DOWHUHG JHQH H[SUHVVLRQ growth and overall survival were monitored. A similar experiment :H K\SRWKHVL]H WKDW LQ (:6 ZKHUH WKH (:65)/, IXVLRQ LV ZDVFRQGXFWHGLQWKH7EUHDVWFDQFHUPRGHOLQZKLFKPLFHZHUH SDWKRJQRPRQLFWKHJHQHWLFHSLVWDVLVRI(:65)/,DQG67$*LV treated 1 day prior to radiation. GXHWRWKHVXSSUHVVLYHUROHRI67$*RQ(:65)/, )$&6GDWDLQGLFDWHGWKDW7*)ȕDQG7*)ȕH[SUHVVLRQLQFUHDVHV ,QWKLVVWXG\ZHXVHGFRLPPXQRSUHFLSLWDWLRQ FR,3 WRH[DPLQHD on most immune cells in the tumor 1 day after RT, decreases WHUQDU\LQWHUDFWLRQEHWZHHQ(:65)/,DQG67$*:HH[SORUHG 3 days after RT and reaches a peak 5 days after RT. Preliminary WKHSKHQRW\SLFHႇHFWRI67$*NQRFNGRZQLQYLWURLQ+7%&FHOOV LQYLYR VWXGLHV GHPRQVWUDWH WKDW ERWK Į7*)ȕ DQG Į7*)ȕ DV DQG$(:6FHOOVYLDVL51$NQRFNGRZQDQGSUROLIHUDWLRQFXUYHV monotherapies have activity against B16 melanoma. In combination )LQDOO\ZHGHWHUPLQHGWKHHႇHFWRI67$*NQRFNGRZQRQH[SUHVVLRQ ZLWK 57 Į7*)ȕ VKRZV JUHDWHU DQWLWXPRU DFWLYLW\ FRPSDUHG WR RI(:65)/,DQGLWVGRZQVWUHDPWDUJHWVXVLQJ573&5 Į7*)ȕLQPHODQRPD6LPLODUREVHUYDWLRQVZHUHREWDLQHGLQD7 :H GLG QRW GHWHFW DQ\ SK\VLFDO LQWHUDFWLRQ EHWZHHQ 67$* DQG EUHDVWPRGHOKRZHYHUĮ7*)ȕDORQHDQGLQFRPELQDWLRQZLWK57 (:65)/, LQ$ (:6 FHOOV YLD FR,3 ZLWK 67$* RU (:6 DVZHOODVĮ7*)ȕ57VKRZHGDVLJQL¿FDQWGHOD\DJDLQVWWXPRU )/, 3KHQRW\SLFDOO\ LQ YLWUR SUROLIHUDWLRQ ZDV QRW DႇHFWHG XSRQ JURZWK 1R VLJQL¿FDQW GLႇHUHQFHV LQ VXUYLYDO ZHUH VHHQ LQ HLWKHU 67$*NQRFNGRZQLQ+7%&FHOOV:HDOVRFRXQWHG+7 tumor model. Analysis of tumor, lymph node and spleen from animals FHOODWGD\VSRVWVL67$*WUDQVIHFWLRQ&RQVLVWHQWO\QRVLJQL¿FDQW WUHDWHG ZLWK LVRIRUPVSHFL¿F DQWL7*)ȕ WKHUDS\ ZLWK DQG ZLWKRXW GLႇHUHQFH ZDV REVHUYHG IURP FHOO FRXQW EHWZHHQ VL67$* DQG 57LVXQGHUZD\WRXQGHUVWDQGWKHFRQWULEXWLRQRIĮ7*)ȕYHUVXV QHJDWLYH FRQWURO VL1& 8WLOL]LQJ &HOO7LWHU*OR /XPLQHVFHQW &HOO Į7*)ȕWRDQWLWXPRUHႈFDF\ 9LDELOLW\ $VVD\ ZH IXUWKHU FRQ¿UPHG WKDW WKH JURZWK FXUYH RI 7*)ȕ DQG 7*)ȕ DUH H[SUHVVHG RQ QXPHURXV O\PSKRLG DQG VL67$* +7 FHOOV ZDV QRW VLJQL¿FDQWO\ GLႇHUHQW IURP WKDW RI P\HORLGFHOOVLQ%WXPRUVDQGVSOHHQV7*)ȕLVRIRUPH[SUHVVLRQ VL1&+7FHOOV573&5RIVL67$*(:6$FHOOVVKRZHG SHDNV GD\V SRVW57$QWL7*)ȕ WKHUDS\ LV HႇHFWLYH LQ GHOD\LQJ LQFUHDVHGH[SUHVVLRQRIWKHIXVLRQSURWHLQ(:65)/,([SUHVVLRQ tumor growth and may synergize with RT in certain cancers. This OHYHOV RI (:65)/, WDUJHWHG JHQHV ZHUH DOVR LQFUHDVHG DIWHU GHPRQVWUDWHVUDWLRQDOHIRUWKHXVHRIDQWL7*)ȕWKHUDS\WRHQKDQFH 67$*NQRFNGRZQLQ$FHOOV WKHHႇHFWLYHQHVVRI57LQFDQFHU ,Q VXPPDU\ RXU UHVXOWV VXJJHVW 67$* PHGLDWHV H[SUHVVLRQ RI 106 To analyze the aliphatic amyloid forming oligo (:65)/,DQGLWVWDUJHWHGJHQHVKRZHYHUQRWWKURXJKSK\VLFDO peptides,their catalytic activities and nano-structure evolution LQWHUDFWLRQ ,QVWHDG 67$* FRXOG DFW RQ FKURPDWLQ WR UHJXODWH of the resulting self-assembly. 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In order to analyze the enzyme mimic catalysis, the ester Aditi Gupta K\GURO\VLV RI V\QWKHWLF WHWUDSHSWLGHV ZLWK SQLWURSKHQ\O DFHWDWH Memorial Sloan-Kettering Cancer Center, USA S13$ ZDV SHUIRUPHG +\GURODVH LV WKH PRVW DEXQGDQW VWXGLHG 7*)ȕLVDSOHRWURSLFF\WRNLQHZKLFKKDVHPHUJHGDVDSRWHQWLDO reaction to understand the peptide that mimics the natural enzyme target in cancer treatment due to its dual role in tumorigenesis and SURSHUWLHV7KHVHWHWUDSHSWLGHVHTXHQFHVFRQWDLQ/\VDQG+LVDV KRPHRVWDVLV7KHUHDUHWKUHHLVRIRUPVRI7*)ȕ 7*)ȕ7*)ȕ nucleophilic units, Leu as hydrophobic enforcer for aggregation and DQG 7*)ȕ ZKLFK DUH VHFUHWHG E\ LPPXQH DQG QRQLPPXQH Met, Thr as polar residues that could assist potentially in hydrolytic FHOOV DV D ODWHQW FRPSOH[ 'HSHQGLQJ RQ WKH ORFDO FRQWH[W7*)ȕ DFWLYLW\7KHHQ]\PHVXEVWUDWHDႈQLW\DQGWKHVDWXUDWLRQNLQHWLFVIRU adopts opposing roles in carcinogenesis and in modulating the HDFKSHSWLGHZDVDQDO\]HGE\WKH896SHFWURVFRS\ZKLFKKHOSHG LPPXQHV\VWHP7KHVHGXHOLQJUROHVRI7*)ȕDUHGHSHQGHQWRQLWV LQDQDO\]LQJWKHHQ]\PHVXEVWUDWHFRPSOH[IRUPDWLRQLQWRHQ]\PH secretion and activation. Local radiation therapy (RT) can activate and product. Moreover, the protein aggregation study was performed 7*)ȕ YLD UHDFWLYH R[\JHQ VSHFLHV 6XFK 7*)ȕ H[SUHVVLRQ LV E\XVLQJ7KLRÀDYLQ7G\HDVDQLQGLFDWRUZKLFKFDQKHOSLGHQWLI\LQJ OLQNHG WR UDGLRUHVLVWDQFH DQG GRVHOLPLWLQJ WR[LFLWLHV UHGXFLQJ WKH the high molecular weight catalytic aggregates. Also, the structural HႇHFWLYHQHVV RI 57 ,Q WKHVH VWXGLHV ZH DLP WR FKDUDFWHUL]H WKH components of these peptides were visualized at a nanoscale by

www.jointmeeting.org 61 POSTER ABSTRACTS

using the atomic force microscopy which helped in determining the WUDYHOHGYVP'66YV6'S PRUSKRORJ\RISHSWLGHV&RPELQDWLRQRIVHOIDVVHPEO\ZLWKSHSWLGH &RQFOXVLRQ'HYHORSPHQWRIK\SHUWHQVLRQLQDJHG'66LVDVVRFLDWHG FDWDO\VLV LV D UDWLRQDO PRYH WRZDUGV DUWL¿FLDO HQ]\PHV WR SURGXFH ZLWK LPSDLUPHQWV LQ VHYHUDO FRPSRQHQWV RI FRJQLWLRQ 9DULDWLRQV biologically inspired catalysts. LQ FDUGLRYDVFXODU IXQFWLRQ DQG REVHUYDEOH EHKDYLRU PD\ UHÀHFW 107 Noninvasive Imaging of Fluorescent Probe Delivery in GLႇHUHQFHV LQ V\PSDWKHWLF DFWLYDWLRQ DQ[LHW\ K\SHUDFWLYLW\ RU ,QWUDFUDQLDO 7XPRU ;HQRJUDIWV 8VLQJ )OXRUHVFHQFH 0ROHFXODU PHPRU\LPSDLUPHQWV:KLOHDJHLQGXFHGGHFOLQHLQFRJQLWLRQVXFK Tomography DVPHPRU\PD\EHDFFHOHUDWHGLQ'66FRPSDUHGWR6'WKHFKDQJH in motor function is delayed. Investigation of the brain and cerebral /H0R\QH+DELPDQD*ULI¿Q vascular structural changes associated with memory decline and Washington University in Saint Louis, Saint Louis, USA corresponding behavioral changes in a rat model of hypertension 7KHEORRGEUDLQEDUULHU %%% LVDVLJQL¿FDQWREVWDFOHWRGHWHFWLQJDQG may merit future studies. WUHDWLQJEUDLQWXPRUV'HYHORSPHQWRIPHWKRGVWRPRQLWRUGHOLYHU\ $FNQRZOHGJHPHQW6XSSRUWHGE\WKH1,+1,$,QWUDPXUDO5HVHDUFK of diagnostic and therapeutic agents to the brain is imperative to Program. overcome this challenge. In this work, we developed optical imaging methods to provide a highly sensitive, noninvasive, low cost platform 111 Proper centromere mechanical maturation is required to to monitor delivery of diagnostic and therapeutic agents utilizing PDLQWDLQWKH¿GHOLW\RIFKURPRVRPHVHJUHJDWLRQGXULQJPLWRVLV QRQLRQL]LQJ UDGLDWLRQ IRU SUHFOLQLFDO EUDLQ WXPRU PRGHOV 8WLOL]LQJ Lauren A. Harasymiw ÀXRUHVFHQFHPROHFXODUWRPRJUDSK\ )07 ZHTXDQWL¿HGWKHXSWDNH University of Minnesota, Minneapolis, USA RIQHDULQIUDUHGÀXRUHVFHQWSUREHVLQDQLQWUDFUDQLDOWXPRU[HQRJUDIW model. We used FMT to longitudinally monitor BBB breakdown in this 'XULQJ PLWRVLV WHQVLRQ GHYHORSV DFURVV WKH FKURPRVRPH¶V model. Furthermore, we demonstrated earlier detection of tumors FHQWURPHUHDVDUHVXOWRIVSLQGOHEDVHGIRUFHV,QPHWDSKDVHWHQVLRQ XVLQJ IRFXVHG XOWUDVRXQG )86 WR SHUPHDELOL]H WKH %%% 7KHVH at the centromere may play a critical role in preventing chromosome methods provide a framework for future studies in brain tumors as segregation errors. In human cells, disrupting the centromere’s well as other neurological diseases. normal structure and function has been shown to increase the rate of chromosome missegregation, a cellular phenotype which is strongly 108 Age-dependent hypertension development is associated implicated in cancer progression. However, the role of centromere with cognitive function decline and behavioral activity changes PHFKDQLFV LQ LQÀXHQFLQJ WKH PDJQLWXGH DQG FHOOF\FOH VSHFL¿FLW\ in Dahl Salt-Sensitive rats RI WHQVLRQ DW WKH FHQWURPHUH DQG WKHLU HႇHFW RQ FKURPRVRPH 0DGHOHLQH+DJRRG segregation outcomes, remains unknown. We combined quantitative, National Institute on Aging / NIH, Baltimore, USA biophysical microscopy with computational analysis in order to elucidate the mechanics of the centromere in unperturbed, mitotic Background: Blood pressure (BP) increases may be accompanied mammalian cells. Our approach revealed that the mechanics of by a cognitive decline, however, it remains unclear what cognitive the mammalian centromere mature with a signature pattern during impairments emerge due to the development of hypertension with PLWRWLFSURJUHVVLRQ7KLVPDWXUDWLRQOHDGVWRDPSOL¿HGFHQWURPHUH an advancing age. Hippocampal memory changes were described WHQVLRQVSHFL¿FDOO\DWPHWDSKDVH)XUWKHUZHIRXQGWKDWDGLVUXSWLRQ LQ 'DKO 6DOW6HQVLWLYH UDWV '66 ZKLFK GHYHORS DJHDVVRFLDWHG in centromere mechanical maturation led to diminished tension at hypertension and cardiovascular changes even in the absence of metaphase in human cancer cells, and that this disruption increased high salt intake. Here we study what cognitive functions will decline LQVHYHULW\ZLWKLQFUHDVLQJFKURPRVRPHQXPEHU6WULNLQJO\WKHUDWHRI DQG ZKDW EHKDYLRUDO DEQRUPDOLWLHV ZLOO EH DVVRFLDWHG ZLWK DJH ODJJLQJFKURPRVRPHVDWDQDSKDVHZKLFKUHVXOWIURPWHQVLRQEDVHG GHSHQGHQWK\SHUWHQVLRQLQ'66 NLQHWRFKRUHPLFURWXEXOH DWWDFKPHQW HUURUV ZDV HOHYDWHG LQ FHOOV 0HWKRGV )LIW\WKUHH PDOHV '66 DQG 6SUDJXH'DZOH\ UDWV 6' with disrupted centromere mechanical maturation. Further, these ZHUHNHSWRQDQRUPDO1D&OGLHWIRUWKHGXUDWLRQRIWKHFURVV errors persisted into chromosome segregation defects at telophase. VHFWLRQDO VWXG\ %3 SOHWK\VPRJUDSK\ WDLO FXႇ PHWKRG DQG D Thus, we reveal a novel role for the centromere in regulating tension EDWWHU\RIEHKDYLRUDOWHVWVZHUHSHUIRUPHGDWPRDQGPRROG during mitosis, and demonstrate a direct link between aneuploidy, DQLPDOV Q JURXS %HKDYLRUDO WHVWV ZHUH DLPHG WR DVVHVV centromere mechanics, and chromosome missegregation. WKH GLႇHUHQFHV LQ PHPRU\ H[SORUDWRU\ EHKDYLRU DQG DQ[LHW\ DQG LQFOXGHRSHQ¿HOGWHVW 2)7 WRDVVHVVYHUWLFDODFWLYLW\DQGGLVWDQFH 112 3$; LQFUHDVHV PLJUDWLRQ DQG PHWDVWDVLV RI RYDULDQ traveled; Rotarod test to examine balance and motor coordination FDQFHUWKURXJKXSUHJXODWLRQRI3.&DDQG5KR*73DVHV learning; novel object recognition test to examine memory and Laura Hardy object exploration; a version of Morris Water Maze (MWM) test to University of Illinois - Chicago, Chicago, USA H[DPLQHKLSSRFDPSDOGHSHQGHQWPHPRU\6WDWLVWLFDODQDO\VHVZHUH High grade serous ovarian cancer, the most lethal subtype of ovarian SHUIRUPHGXVLQJ7WHVWVDQG$129$ cancer, can originate in either the fallopian tube epithelium (FTE) 5HVXOWVPR6'DQG'66GLGQRWGLႇHULQ%3FRJQLWLYHIXQFWLRQ RU RYDULDQ VXUIDFH HSLWKHOLXP 26( 3$; LV D OLQHDJH VSHFL¿F DQGPRWRUOHDUQLQJWDVNVPR'66VKRZHGKLJKHU%3YVPR WUDQVFULSWLRQ IDFWRU WKDW LV XELTXLWRXVO\ H[SUHVVHG LQ +*62& :H '66 YV PP+J S XQOLNH 6' PR 6' KDYHVKRZQWKDWNQRFNGRZQRI3$;XVLQJVK51$LQPXOWLSOHRYDULDQ DQG'66GLႇHUHGIURPPRFRXQWHUSDUWVRQ2)7LQWRWDOGLVWDQFH WXPRUFHOOVOLQHVOHDGVWRDSRSWRVLVVXJJHVWLQJWKDW3$;SOD\VDQ traveled (p<0.0001) and vertical activity (p<0.0001), on the latency HVVHQWLDO UROH LQ FDQFHU VXUYLYDO ,Q WKLV VWXG\ ZH XVHG &5,635 GXULQJURWDURGWHVWZLWKDPDLQHႇHFWRIVWUDLQ S RQWLPH JHQRPLFHGLWLQJWRGHOHWH3$;IURPWKH29&$5FHOOOLQH3$; exploring objects in the test phase of the novel object recognition deletion led to a decrease in migration and invasion in vitro and an WDVNZLWKDPDLQHႇHFWRIDJH S DQGDQLQWHUDFWLRQRIDJH increase in survival and a reduction in tumor volume in vivo. Previous DQG VWUDLQ S PR '66 GHPRQVWUDWHG LPSDLUPHQW LQ ZRUN XVLQJ 51$ VHTXHQFLQJ DQG &K,3VHTXHQFLQJ LGHQWL¿HG FHOO identifying the location of the invisible platform in a MWM (distance DGKHVLRQDVDWRSGLႇHUHQWLDOO\H[SUHVVHGJHQHEHWZHHQPDOLJQDQW

62 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

ovarian cancer and benign fallopian tube cell lines. We performed RI<$37$=DQGWKHPL5FOXVWHUDUHDOVRXSUHJXODWHGVXFK TXDQWLWDWLYH SURWHRPLF DQDO\VLV RI WKH 29&$53$; FHOO OLQH DVWKHFROODJHQLVRIRUPDQGLWVFURVVOLQNLQJHQ]\PHO\V\OR[LGDVH WR GH¿QH 3$; DOWHUHG SURWHLQV :H DOVR SHUIRUPHG TXDQWLWDWLYH DQGWKHDQDSOHURWLFHQ]\PHV*/6DQGS\UXYDWHFDUER[\ODVH proteomics and transcriptomic analyses on a previously generated Conclusions: Taken together, the upregulation of the matrix PXULQH26(FHOOOLQHZLWKIRUFHG3$;H[SUHVVLRQ 026(3$; UHPRGHOLQJFRPSRQHQWVDQGDQDSOHURWLFHQ]\PHVLPSOLHVWKDW+,9 7KHVH DQDO\VHV LGHQWL¿HG VHYHUDO JHQHV WKDW FRQWULEXWH WR DQ infection may be acting, in part, through our previously established LQFUHDVHLQPLJUDWLRQDQG(076SHFL¿FDOO\RXUGDWDLQGLFDWHV3$; <$37$=PL5*/6D[LVLQWKHGHYHORSPHQWRI3$+DQG upregulates key drivers involved in altering cell morphology including that upregulation of this axis may be under regulatory control of PKCჴ DQG WKH *73DVHV 5KR$ &GF DQG 5DV 8SUHJXODWLRQ RI PL57KHLPSOLFDWLRQVRIRXUGDWDVXJJHVWWKDW*/6PD\KDYHD PKCჴ LQFUHDVHG WKH PLJUDWRU\ DELOLW\ RI 29&$5 ZKLOH LQKLELWLQJ FULWLFDOUROHLQ+,93$+SDWKRJHQHVLVDQGWKDWWKH*/6LQKLELWRU&% PKCჴ decreased this ability. Inhibition of RhoA led to a greater ²FXUUHQWO\LQFOLQLFDOWULDOIRUFDQFHU²PD\EHUDSLGO\UHSXUSRVHG GHFUHDVHLQPLJUDWLRQIRUERWK29&$53$;DQG026(3$; for this devastating vascular disorder. ZKHQ FRPSDUHG WR FRQWURO ,QKLELWLRQ RI 5DV KDG D JUHDWHU HႇHFW LQ29&$53$;ZKLOHLQKLELWLRQRI&GFKDGDJUHDWHUHႇHFW 114 Amino acid metabolism as a drug target to treat persistent LQ026(3$;7KHVHGDWDSURYLGHDPHFKDQLVWLFH[SODQDWLRQIRU 0\FREDFWHULXPWXEHUFXORVLV WKHUROHRI3$;RQLQFUHDVLQJPLJUDWLRQDQGPHWDVWDVLVLQRYDULDQ Erik Hasenoehrl cancer. Albert Einstein College of Medicine, New York, USA 113 HIV-infected macrophages induce endothelial cell Most chemotherapeutics currently used in the treatment of dysfunction and metabolic reprogramming to promote HIV- 0\FREDFWHULXPWXEHUFXORVLV 0WE WDUJHWKDOOPDUNV\VWHPVRIDQWL associated pulmonary arterial hypertension PLFURELDOWKHUDS\OLNHFHOOZDOODQG'1$ELRV\QWKHVLV:KLOHWDUJHWLQJ Lloyd Harvey SDWKZD\VHVVHQWLDOIRUSUROLIHUDWLRQLVVXႈFLHQWWRFXUHPRVWEDFWHULDO University of Pittsburgh School of Medicine, Pittsburgh, USA infections, these approaches require at least six months to treat tuberculosis (TB) in order to clear persistent cell populations that are Background & Hypothesis: Pulmonary arterial hypertension phenotypically tolerant to antibiotics. The severity of the TB epidemic (PAH) is an enigmatic vascular disease characterized by complex mandates the development of drugs that target pathways essential pulmonary vascular remodeling, an increase in pulmonary vascular during persistence. The “aspartate pathway” is responsible for the resistance, subsequent right ventricular hypertrophy, and right biosynthesis of essential amino acids (lysine, threonine, isoleucine, KHDUW IDLOXUH 7KHUH LV DQ LQFUHDVHG SUHGLVSRVLWLRQ WR 3$+ LQ +,9 methionine), the peptidoglycan precursor diaminopimelate and the infected populations, and as a historically neglected vascular FRIDFWRUVDGHQRV\OPHWKLRQLQH:HKDYHSUHYLRXVO\GHPRQVWUDWHG GLVHDVHWKHSDWKRJHQHVLVRI+,9LQGXFHG3$+ +,93$+ UHPDLQV that a methionine auxotroph induced rapid killing and was avirulent largely unknown. Recently, our laboratory has demonstrated a novel in immunocompromised mice. Here, we investigate the requirement SDUDGLJPRIPHWDEROLFUHSURJUDPPLQJVHFRQGDU\WRYHVVHOVWLႇHQLQJ RI WKUHH EUDQFKSRLQW HQ]\PHV LQ WKH DVSDUWDWH SDWKZD\ GXULQJ DVDSDWKRJHQLFGULYHURI3$+0RUHVSHFL¿FDOO\H[WUDFHOOXODUPDWUL[ persistence and characterize the cellular response to pathway VWLႇHQLQJLQGXFHVWKHPHFKDQRVHQVLWLYHWUDQVFULSWLRQDOFRDFWLYDWRUV LQKLELWLRQ 8VLQJ D JHQHWLF LQGXFLEOH NQRFNGRZQ V\VWHP ZH IRXQG <$3DQG7$=UHVXOWLQJLQWKHXSUHJXODWLRQRIWKHPLFUR51$ PL5 that that all three enzymes were required for both acute and chronic FOXVWHUPL5DQGJOXWDPLQDVH */6 LQKXPDQSXOPRQDU\ infection in a mouse model. Transcriptomic and metabolomic arterial endothelial cells (HPAECs). The implications of this discovery characterization of inactivation of the aspartate pathway revealed DUH WZRIROG LQFUHDVHG PL5 IXUWKHU SURPRWHV PDWUL[ a novel killing mechanism by which threonine auxotrophy causes UHPRGHOLQJ ZKLOHXSUHJXODWHG*/6LQFUHDVHVJOXWDPLQRO\VLV² a toxic accumulation of cytosolic lysine. We demonstrate that this an anaplerotic reaction that sustains energetic demands in RFFXUVWKURXJKDORVVRIWKUHRQLQHPHGLDWHGIHHGEDFNUHJXODWLRQRI SUROLIHUDWLQJQHRSODVWLFOLNH+3$(&V,QDGGLWLRQRXUODERUDWRU\KDV the pathway, and that the cell tries to compensate for this toxicity by GHPRQVWUDWHGWKDWPL5LVXSUHJXODWHGLQWKHSODVPDRI+,93$+ upregulating novel pathways for lysine degradation and export. In SDWLHQWVDQGWKDWPL5LVOLQNHGWRWKHPL5FOXVWHUWRH[HUW summary, our results strongly indicate that the aspartate pathway is EURDGLQÀXHQFHRYHU3$+7DNHQWRJHWKHUZHK\SRWKHVL]HWKDW+,9 a valuable and target rich space for development of drugs that can LQIHFWHG PDFURSKDJHV DFWLYHO\ VHFUHWH PL5 WR SURPRWH YHVVHO clear persistent TB infection. VWLႇHQLQJJOXWDPLQRO\VLVDQGWKHSDWKRJHQHVLVRI+,93$+ Methods: Peripheral blood mononuclear cells are isolated from 115 1R[ 0RGXODWHV /XQJ 0DFURSKDJH 3RODUL]DWLRQ LQ KXPDQEORRGE\SXOOGRZQRI&'PRQRF\WHV&'PRQRF\WHV 3XOPRQDU\)LEURVLV9LD5HJXODWLRQ2I0LWRFKRQGULDO%LRJHQHVLV DUHWKHQVWLPXODWHGZLWKJUDQXORF\WHPDFURSKDJHFRORQ\VWLPXODWLQJ Chao He IDFWRU QJP/ IRU¿YHWRVHYHQGD\VWRSURGXFHPRQRF\WHGHULYHG University of Alabama at Birmingham, Birmingham, USA

PDFURSKDJHV 0'0V 0'0VDUHLQIHFWHGZLWKWKH+,9BaL strain 7KH SKHQRW\SH RI PDFURSKDJHV FDQ FRQWULEXWH WR ¿EURWLF for two days using a multiplicity of infection of one or left uninfected. development. We have previously shown that lung macrophages 0'0V DUH VXEVHTXHQWO\ FRFXOWXUHG ZLWK +3$(&V IRU WZR GD\V IURP VXEMHFWV ZLWK SXOPRQDU\ ¿EURVLV KDYH HOHYDWHG SUR¿EURWLF before experiment termination. gene expression and increased mitochondrial dynamics compared 5HVXOWV2XUGDWDDUHFRQVLVWHQWZLWKDSUHYLRXVO\GH¿QHGPRGHORI with lung macrophages from normal subjects. Here, we found that WKH<$37$=PL5*/6D[LVDVDQRYHOSDUDGLJPLQ3$+ OXQJ PDFURSKDJHV LVRODWHG IURP VXEMHFWV ZLWK SXOPRQDU\ ¿EURVLV 8VLQJ D FRFXOWXUH V\VWHP PL5 H[SUHVVLRQ LV XSUHJXODWHG LQ KDYH D VLJQL¿FDQW LQFUHDVH LQ QR[ JHQH H[SUHVVLRQ VXJJHVWLQJ +3$(&V0'0VDQGWKHFRQGLWLRQHGPHGLDLQZKLFKWKHFHOOVZHUH D SLYRWDO UROH RI 12; LQ UHJXODWLQJ PDFURSKDJH SKHQRW\SH DQG UDLVH²VXJJHVWLYHRISRVVLEOHFHOOWRFHOOWUDQVPLVVLRQ$GGLWLRQDOO\ SURPRWLQJ ¿EURVLV GHYHORSPHQW :H K\SRWKHVL]H WKDW 12; LV LQGXFHUVRIYHVVHOVWLႇHQLQJDQGJOXWDPLQRO\VLV²<$37$=DQGWKH UHTXLUHG SUR¿EURWLF SRODUL]DWLRQ RI OXQJ PDFURSKDJHV :H IRXQG PL5FOXVWHU²DUHLQFUHDVHGLQ+3$(&V'RZQVWUHDPWDUJHWV WKDW 12; RYHUH[SUHVVLRQ LQFUHDVHV 7*)ȕ SURPRWHU DFWLYLW\ DV

www.jointmeeting.org 63 POSTER ABSTRACTS

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64 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

present with more mild elevations in calcium and/or parathyroid 120 ,QÀXHQFHRIQHXURJHQHVLVWLPLQJRQFHUHEHOODUFLUFXLWU\ KRUPRQH 37+ 0(7+2'6:HUHYLHZHGDSURVSHFWLYHGDWDEDVH Kelly K. Hill RISDWLHQWVZLWKSULPDU\K\SHUSDUDWK\URLGLVPZKRXQGHUZHQW Washington University in St. Louis, St. Louis, USA parathyroidectomy by one endocrine surgeon. Of these patients, KDG NLGQH\ VWRQHV :H FRPSDUHG SDWLHQWV ZLWK DQG ZLWKRXW 1HXURQV DUH FRQQHFWHG LQ HODERUDWH FLUFXLWV XQGHUO\LQJ VSHFL¿F NLGQH\VWRQHVXVLQJHLWKHUWKH3HDUVRQ&KL6TXDUH)LVKHU¶V([DFW functions, yet little is known about how these circuits are established 7HVWRU6WXGHQW¶V77HVWZKHUHDSSURSULDWH5(68/767KHPHDQ during development or how they go awry in the context of DJHRIRXUFRKRUWZDV\HDUVZLWKIHPDOHV3DWLHQWV neurodevelopmental disorders. This study tests the hypothesis that ZLWK NLGQH\ VWRQHV ZHUH \RXQJHU YV \HDUV S DQG the timing of neurogenesis is a key regulator of cerebellar cortical PRUHPDOHVKDGNLGQH\VWRQHVWKDQIHPDOHV YVS GHYHORSPHQW 6SHFL¿FDOO\ ZH HYDOXDWH ZKHWKHU WKH ELUWKGDWH RI 1RUPRFDOFHPLF K\SHUSDUDWK\URLGLVP ZDV PRUH FRPPRQ LQ WKRVH D FHUHEHOODU JUDQXOH QHXURQ LQÀXHQFHV LWV IXQFWLRQ LQ WKH PDWXUH ZLWK NLGQH\ VWRQHV YV S 3DWLHQWV ZLWK NLGQH\ FLUFXLW6HYHUDOOLQHVRIHYLGHQFHVXSSRUWWKLVK\SRWKHVLVLQFOXGLQJ VWRQHV DOVR KDG D ORZHU PHDQ SUHRSHUDWLYH 37+ YV SJ DQDWRPLFDO DQG LQ YLWUR GLႇHUHQFHV EHWZHHQ HDUO\ DQG ODWHERUQ PO S &21&/86,216 3DWLHQWV ZLWK NLGQH\ VWRQHV GXH WR JUDQXOH QHXURQV 7R WHVW RXU K\SRWKHVLV ZH ¿UVW GHPRQVWUDWH D hyperparathyroidism are more likely to present with mild parathyroid PHWKRGRORJ\WRÀXRUHVFHQWO\WDJLQYLYRFRKRUWVRIJUDQXOHQHXURQV disease characterized by normal calcium and lower PTH levels. LQDELUWKGDWHGHSHQGHQWPDQQHU:HQH[WHYDOXDWHWKHIXQFWLRQDO Primary care providers, endocrinologists, and urologists must responses of hundreds of mature granule neurons by performing in be aware of this to avoid missing or delaying the diagnosis of YLYRFDOFLXPLPDJLQJRIWUDQVJHQLFPLFHWKDWH[SUHVVWKH*&D03I hyperparathyroidism. Therefore, we recommend that patients with calcium indicator in cerebellar granule neurons. Finally, by kidney stones be evaluated with a serum calcium and PTH level. intersecting our birthdating technique with our transgenic approach, ZH FRPSDUH WKH IXQFWLRQV RI HDUO\ DQG ODWHERUQ JUDQXOH QHXURQ 119 Discrete dopamine systems for learning and motivation cohorts in the mature cerebellar circuit. converge to maximize reward behavior gabriel Heymann 121 7KHUROHRIPL5LQ%FHOOGHYHORSPHQWDQGIXQFWLRQ University of Washington, Seattle, USA 0DUFXV+LQHV NYU School of Medicine, New York, USA The capacities to assign value, associate environmental cues with SRVLWLYHRUQHJDWLYHRXWFRPHVDQGPRWLYDWHJRDOGLUHFWHGDFWLRQV :HSUHYLRXVO\SXEOLVKHGDSDSHUVKRZLQJWKDWPL51$VDUHLPSRUWDQW are fundamental aspects of adaptive behavior. These coordinated LQUHJXODWLQJ37(1DQG3,.LQDVHVLJQDOLQJSDWKZD\GRZQVWUHDPRI elements of reward processing are regulated by Ventral WKH%FHOOUHFHSWRU:HK\SRWKHVL]HPL5VSHFL¿FDOO\UHJXODWHV Tegmental Area (VTA) dopamine neurons and their diverse WKH37(13,.LQDVHD[LVLQ%FHOOVDQGFDQFRQWURO%FHOOVXUYLYDO projections to forebrain structures. While it is appreciated that distinct DQGVLJQDOLQJ7KHPL5IDPLO\RIPL51$VLVWUDQVFULEHGIURPWZR GLႇHUHQWORFLWKHPL5DEORFXVJHQHUDWHVPL5DDQGPL5E 97$GRSDPLQHSRSXODWLRQVDQGSDWKZD\VPHGLDWHGLVFUHWHDVSHFWV ZKLOHWKHPL5EFORFXVJHQHUDWHVPL5EDQGPL5F0DWXUH RI JRDOGLUHFWHG EHKDYLRU DWWULEXWLQJ VSHFL¿F IXQFWLRQV WR VHOHFW VHTXHQFHVRIPL5EIURPERWKWKHPL5DEDQGPL5EFORFL FHOO SRSXODWLRQV DQG FLUFXLWV KDV SURYHQ GLႈFXOW +HUH ZH XWLOL]H DUHLGHQWLFDO7KHVHHGUHJLRQXVHGWRUHFRJQL]HWKH¶875RIP51$ QRYHO&UHGULYHUOLQHVWRLVRODWHJHQHWLFDOO\GLVWLQFW97$GRSDPLQH WDUJHWVDUHLGHQWLFDOIRUPL5DPL5EDQGPL5F3UHYLRXVO\ subpopulations with dissociable roles in reward association and WKHPHPEHUVRIWKHPL5IDPLO\KDYHEHHQLPSOLFDWHGLQLPPXQH PRWLYDWLRQ DV ZHOO DV FRPSOHPHQWDU\ LQQHUYDWLRQ SUR¿OHV ZLWKLQ UHODWHGGLVHDVHVVXFKDVDFXWHP\HORLGOHXNHPLD $0/ DQG7FHOO WKH1XFOHXV$FFXPEHQV 1$F Crhr1±1$F ; &FN±1$F . CORE 6+(// DFXWHO\PSKREODVWLFOHXNHPLD 7$// EXWWKHUROHWKDWPL5SOD\V Channel rhodopsin (ChR2) mediated activation of Crhr197$ LQ%O\PSKRF\WHSK\VLRORJ\KDVQRWEHHQIXOO\H[DPLQHG8VLQJPLFH GRSDPLQH QHXURQV ZLWK UHVWULFWHG LQQHUYDWLRQ RI WKH 1$F CORE GH¿FLHQWIRUWKHPL5DEORFXVWKHPL5EFORFXVRUERWKPL5 VXEGLYLVLRQLVVXႈFLHQWWRIDFLOLWDWHWKHDFTXLVLWLRQRILQVWUXPHQWDO ORFL GRXEOH.2 ZHKDYHEHJXQWRLQYHVWLJDWHKRZPL5DႇHFWV UHVSRQGLQJ IRU RSWLFDO LQWUDFUDQLDO VHOIVWLPXODWLRQ R,&66 ,Q B lymphocyte development and function. Our observations suggest contrast, activating the &FN97$SRSXODWLRQZLWKD1$F 6+(//VSHFL¿F WKDWDEODWLRQRIERWKPL5ORFLGLGQRWKDYHDSSUHFLDEOHLPSDFWRQ projection cannot promote initial learning, but will sustain and early B cell hematopoiesis but had a profound impact on the survival augment an already learned operant reward behavior. Interestingly, RIVSOHQLF%O\PSKRF\WHV8VLQJLQWUDFHOOXODU)$&6ZHH[DPLQHGWKH concerted activity of both subpopulations and dual activation of FRQWULEXWLRQRIHDFKRIWKHWZRPL51$FOXVWHUVRQWKHUHJXODWLRQRI 1$F CORE DQG 1$F6+(// 97$ GRSDPLQH SDWKZD\V LV UHTXLUHG IRU PI3K signaling and also assessed the direct impact on B cell survival. PD[LPDO R,&66 :KLOH WKHVH UHVXOWV VXJJHVW GLVFUHWH DVVRFLDWLYH :HKDYHDOVRSHUIRUPHGDVHULHVRILQYLWURGLႇHUHQWLDWLRQDVVD\VWR and motivational processes that work in a coordinated fashion to H[DPLQHWKHUROHRIPL5IDPLO\PL51$VRQSUROLIHUDWLRQVXUYLYDO drive behavior, future experiments will combine optical inhibition FODVVVZLWFKUHFRPELQDWLRQDQGSODVPDFHOOGLႇHUHQWLDWLRQ2XUGDWD and excitation during Pavlovian and extinction learning to further VXJJHVWVDFULWLFDOUROHIRUWKHPL53,.LQDVHUHJXODWRU\D[LVLQ probe the dissociable functions of Crhr1 and &FN subpopulations. PDWXUH%FHOOVXUYLYDODQGWHUPLQDOGLႇHUHQWLDWLRQ Furthermore, we employ combinatorial genetic strategies to VHOHFWLYHO\ DEROLVK GRSDPLQH VLJQDOLQJ DQG FRQ¿UP WKH GRSDPLQH 122 )XQFWLRQDO FKDUDFWHUL]DWLRQ RI OQF51$V LQ PHODQRPD GHSHQGHQFHRILQGHSHQGHQWUHZDUGEHKDYLRUV2XU¿QGLQJVEHJLQWR maintenance consolidate the operational roles of discrete dopamine populations Kate Hockemeyer and signals, a crucial step in identifying more precise therapeutic New York University School of Medicine at NYU Langone targets for drug addiction and depression, disorders associated with Health, New York, USA aberrations in mesolimbic dopamine signaling. Accumulating data suggest that mutations in coding genes are not VXႈFLHQW WR H[SODLQ PHODQRPD PDLQWHQDQFH DQG SURJUHVVLRQ WR PHWDVWDVLV1HDUO\QRQFRGLQJ51$VDUHH[SUHVVHGDWYDULRXV

www.jointmeeting.org 65 POSTER ABSTRACTS

VWDJHVRIGHYHORSPHQWDQGGLVHDVHRIZKLFKOQF51$VFRPSULVHD SUR¿OLQJ ZDV IHDVLEOH IRU &7& '1$ PXWDWLRQV DQG &19V DQG PDMRUDQGKHWHURJHQHRXVFODVV/QF51$VKDYHGLYHUVHUROHVZLWKLQ PDWFKHG SODVPD FI'1$ PXWDWLRQV DQG FI51$ JHQH H[SUHVVLRQ WKH FHOO DQG UHFHQW ¿QGLQJV LPSOLFDWH QXPHURXV OQF51$V LQ WKH 7KHVH GLVHDVHVSHFL¿F PROHFXODU SUR¿OHV ZHUH RIWHQ FRQFRUGDQW RQVHW SURJUHVVLRQ DQGRU PHWDVWDVLV RI FDQFHU :KLOH OQF51$V with tumor tissues but also contained new, potentially actionable have been shown to play roles in apoptosis, proliferation, and DOWHUDWLRQV XQLTXH WR &7& '1$ RU FI'1$ ([SDQGHG VWXGLHV ZLOO LQYDVLRQLQPHODQRPDDFRPSUHKHQVLYHXQELDVHGVWXG\RIOQF51$ build upon this approach to optimally leverage liquid biopsies for expression and involvement in melanoma progression has not been molecularly directed patient management. SHUIRUPHG DQG WKH UROH RI OQF51$V LQ PHODQRPD IRUPDWLRQ DQG &2,'HFODUDWLRQV(+'=*0$&<;-&3'7''4DQG$* PHWDVWDVLVUHPDLQVSRRUO\XQGHUVWRRG$SSOLFDWLRQRIRXULQKRXVH 1RQH3'-8.')%$.3&006*DUHHPSOR\HHVRIFRPSDQLHV OQF51$SLSHOLQHLGHQWL¿HGQRYHODQGDQQRWDWHGOQF51$VGLႇHUHQWLDOO\ VHHDႈOLDWLRQV WKDWGHYHORSHGSODWIRUPVXWLOL]HGLQWKLVZRUN expressed in melanoma relative to melanocytes and in metastatic UHODWLYHWRSULPDU\VLWHV7RLGHQWLI\FULWLFDOGHSHQGHQFLHVRQOQF51$V )XQGLQJ3&$3DUWLDOVXSSRUWSURYLGHGE\&\QYHQLR LQ PHODQRPD ZH FDUULHG RXW D IRFXVHG &5,635L ORVV RI IXQFWLRQ /LTXLG*HQRPLFV0HQDULQL6LOLFRQ%LRV\VWHPVDQG5HVHDUFK'; VFUHHQLQDPHODQRPDFHOOOLQHH[SUHVVLQJLQGXFLEOHG&DV.5$% for assays conducted using their respective platforms. in vitro and in vivo. We designed a library targeting the transcription 124 1RYHO&U\VWDO)RUPVRIWKH$QWLELRWLF&H¿[LPH VWDUWVLWH 766 RIOQF51$VVLJQL¿FDQWO\XSUHJXODWHGLQPHODQRPD Win Hon SDWLHQW VDPSOHV UHODWLYH WR PHODQRF\WHV 8VLQJ VWULQJHQW FULWHULD Grand Valley State University, Allendale, USA WKLV VFUHHQ LGHQWL¿HG H[SHFWHG OQF51$V VXFK DV 0$/$7 DQG 6$00621 DV ZHOO DV OQF5*6 *0'6$6 DQG QRYHO ;/2& ,QWKHSKDUPDFHXWLFDO¿HOGVROLGIRUPVHOHFWLRQLVRIWHQSODJXHGE\ *0'6$6 ZDV KLJKO\ H[SUHVVHG DFURVV DOO VWDJHV RI low bioavailability, a property determined by intestinal permeability melanoma, and knockdown resulted in modest proliferation defects. and water solubility of a drug. The poor performance of these Intriguingly, the expression correlates strongly with nearby genes. pharmaceuticals, however, can be improved through the use of novel :H ZLOO HOXFLGDWH WKH PHFKDQLVP E\ ZKLFK *0'6$6 VXSSRUWV crystal forms. Methods used to approach and adjust the solubility melanoma survival. This work will elucidate the complex epigenetic include the use of various crystallization techniques as well as crystal and transcriptional programs underlying melanoma pathogenesis engineering of multicomponent forms, such as solvates or cocrystals. and provide basis for novel therapeutic strategies leveraging this &U\VWDOV DUH DQDO\]HG XVLQJ GLႇHUHQW WHFKQLTXHV LQFOXGLQJ RSWLFDO information to improve patient outcomes. PLFURVFRS\ 5DPDQ VSHFWURVFRS\ DQG SRZGHU ;UD\ GLႇUDFWLRQ Herein, we describe the novel crystalline forms discovered for the 123 0XOWLSDUDPHWULF OLTXLG ELRSV\ DQDO\VLV RI FLUFXODWLQJ DQWLELRWLF FH¿[LPH &U\VWDOOL]DWLRQ FRQGLWLRQV XVHG LQ RXU UHVHDUFK WXPRU FHOOV &7&V FHOOIUHH '1$ FI'1$ DQG FHOOIUHH 51$ include evaporation at room temperature, heated evaporation, FI51$ LQPHWDVWDWLFFDVWUDWHUHVLVWDQWSURVWDWHFDQFHU P&53& FRROLQJ DGGLWLRQ RI DQ DQWLVROYHQW YDSRU GLႇXVLRQ JULQGLQJ DQG Emmanuelle Hodara slurrying. Our results show that molecules containing carboxylic Keck School of Medicine of USC, Beverly Hills, USA DFLGVLQWHUDFWEHVWWRIRUPFU\VWDOVZLWKFH¿[LPH6FDOHXSLVQHHGHG Background: MROHFXODU SUR¿OLQJ RI SURVWDWH FDQFHU XVLQJ OLTXLG in order to perform further characterization on these novel crystal ELRSVLHVVXFKDV&7&FDSWXUHDQGFHOOIUHHQXFOHLFDFLGDQDO\VLV\LHOG forms. informative yet distinct datasets. Additional insights may be gained 125 0DVW FHOOV SURPRWH -DSDQHVH HQFHSKDOLWLV YLUXV by simultaneously interrogating multiple liquid biopsy components penetration of the blood-brain barrier WR FRQVWUXFW D PRUH FRPSUHKHQVLYH PROHFXODU GLVHDVH SUR¿OH :H have conducted an initial proof of principle study aimed at piloting Justin Hsieh WKLVPXOWLSDUDPHWULFDSSURDFK Duke-NUS Medical School, Singapore, Singapore 0HWKRGV %ORRG ZDV GUDZQ XQGHU DQ ,5%DSSURYHG SURWRFRO IURP -DSDQHVH HQFHSKDOLWLV YLUXV -(9 LV WKH OHDGLQJ FDXVH RI YLUDO P&53& SDWLHQWV 6DPSOHV ZHUH DQDO\]HG VLPXOWDQHRXVO\ IRU HQFHSKDOLWLVLQ$VLD+RZHYHUWKHPHFKDQLVPVRI-(9SHQHWUDWLRQ the following: CTC enumeration and single CTC and matched white RI WKH EORRGEUDLQEDUULHU %%% UHPDLQ SRRUO\ XQGHUVWRRG +HUH EORRGFHOOFDSWXUHIRUZKROHJHQRPHDPSOL¿FDWLRQDQGORZSDVVFRS\ we identify that mast cells (MCs), which are key immune sentinel QXPEHUYDULDWLRQ&7&'1$DQGPDWFKHGFI'1$IRUVRPDWLFVLQJOH cells located throughout peripheral connective tissues and in the QXFOHRWLGHYDULDQWDQDO\VLVSODVPDFI51$H[WUDFWLRQDQGT573&5 FHQWUDO QHUYRXV V\VWHP &16 FRQWULEXWH WR %%% OHDNDJH GXULQJ IRU $5 $59 DQG 3&$ :KHQ DYDLODEOH OLTXLG ELRSVLHV ZHUH -(9LQIHFWLRQ-(9LQIHFWLRQLQGXFHVDFWLYDWLRQDQGGHJUDQXODWLRQRI FRPSDUHGZLWKPDWFKHGWXPRUSUR¿OHV MCs both LQYLWUR and LQYLYR. Consistent to the role of MCs during LQIHFWLRQE\UHODWHGÀDYLYLUXVHVZHREVHUYHGWKDWWKH\SOD\DUROHLQ 5HVXOWV )LIWHHQ RI SDWLHQWV KDG GHWHFWDEOH &7&V E\ SHULSKHUDOFOHDUDQFHRI-(9+RZHYHU0&VDOVRLQGXFHGVLJQL¿FDQW &HOO6HDUFK UDQJH P/ PHGLDQ P/ 7KLUWHHQ %%% OHDNDJH LQ -(9LQIHFWHG DQLPDOV ,Q 0&GH¿FLHQW PLFH ERWK RI SDWLHQWV KDG GHWHFWDEOH 6619V LQ &7& '1$ DQGRU %%%OHDNDJHDQG-(9LQIHFWLRQRIWKH&16ZHUHUHGXFHG:KLOHZLOG PDWFKHGFI'1$LQFOXGLQJPXWDWLRQVLQ73, 3,.&$, +5$6, and W\SHPLFHGHYHORSHGQHXURORJLFDOGH¿FLWVGXULQJ-(9LQIHFWLRQWKHVH (*)50DWFKHG&7&'1$DQGFI'1$GHPRQVWUDWHGERWKVKDUHGDQG HႇHFWV ZHUH DEVHQW LQ WKH 0&GH¿FLHQW PLFH 2XU UHVXOWV VXSSRUW GLVWLQFW6619V&RS\QXPEHUDQDO\VLVRIVLQJOH&7&VZDVSHUIRUPHG D UROH IRU 0&V LQ SHULSKHUDO LPPXQRVXUYHLOODQFH DJDLQVW -(9EXW LQSDWLHQWVDQGERWKKDG&19VLQPXOWLSOHFDQFHUUHOHYDQWJHQHV LQGLFDWHWKDW0&VDOVRIDFLOLWDWH%%%SHQHWUDWLRQE\-(97KXV0&V $PDMRULW\RI&19VZHUHSUHVHQWLQPDWFKHGVROLGWXPRUSUR¿OHVEXW play a previously unrecognized role in worsening viral encephalitis. some were exclusive to the liquid biopsies. Plasma PCA3 and AR WUDQVFULSWVZHUHGHWHFWHGLQ DQG$59LQ FI51$VDPSOHV8QLTXH6619VZHUHGHWHFWHGDWVHFRQGWLPHSRLQWV at disease progression (more are being collected). &RQFOXVLRQV ,Q WKLV SLORW FRKRUW VLPXOWDQHRXV PXOWLSDUDPHWULF

66 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

126 A complement protein mediates neuroprotection in a LQMXU\ $7, DQG LQÀDPPDWLRQ RQ ELRSVLHV %LRPDUNHU VWXGLHV model of Parkinson’s disease via a gut-neuron axis published to date have used endpoints such as renal function decline Paishiun Hsieh and mortality rather than histopathology. We reasoned that kidney Case Western Reserve University, Cleveland, USA biopsy histopathology would serve as a novel approach to biomarker LGHQWL¿FDWLRQDQGYDOLGDWLRQ Aging is accompanied by an increased risk of chronic disease, notably neurodegenerative diseases such as Parkinson’s disease. :HHQUROOHGSDWLHQWVXQGHUJRLQJQDWLYHNLGQH\ELRSV\DWWKUHH%RVWRQ Therefore, a central challenge of aging research is the extension of DUHDKRVSLWDOVLQWRWKH%RVWRQ.LGQH\%LRSV\&RKRUW %.%& 8ULQH WLPHVSHQWIUHHRIDJHUHODWHGGHELOLW\RUKHDOWKVSDQ2YHUWKHODVW SODVPDDQG'1$ZHUHFROOHFWHGDWWKHWLPHRIELRSV\IURPSDWLHQWV several decades, studies in model organisms like the roundworm who provided written informed consent. Kidney histopathological &DHQRUKDEGLWLVHOHJDQVKDYHLGHQWL¿HGWUDQVFULSWLRQDOUHJXODWRUV HJ lesions were independently adjudicated by two study pathologists, FOXO) which modify the fundamental biology of aging, modulating who scored each biopsy on a semiquantitative scale. We used OLIHVSDQDVZHOODVGHOD\LQJWKHRQVHWRIDJLQJDVVRFLDWHGSDWKRORJ\ 6SHDUPDQ FRUUHODWLRQV DQG PXOWLYDULDEOH OLQHDU UHJUHVVLRQ WR WHVW 5HFHQWO\ZHGHPRQVWUDWHGWKDWWKH.USSHOOLNHIDFWRUVDFRQVHUYHG associations between biomarker concentrations and clinical and VXEIDPLO\RI]LQF¿QJHUWUDQVFULSWLRQIDFWRUVDUHERQD¿GHUHJXODWRUV KLVWRORJLF¿QGLQJV RIDJLQJLQZRUPVDQGDOVRLQÀXHQFHFDUGLRYDVFXODUDJLQJLQPLFH :HPHDVXUHG.,0DQG0&3LQSDWLHQWVZLWKDYDLODEOHSODVPD +HUHZHVKRZWKDWDORQJOLYHGZRUPRYHUH[SUHVVLQJNOIis resistant VDPSOHV7KHPHDQDJHZDV\HDUVZHUHIHPDOHDQG WRDJHUHODWHGQHXURGHJHQHUDWLRQLQDPRGHORI3DUNLQVRQ¶VGLVHDVH ZHUHQRQZKLWH7KHPRVWFRPPRQUHDVRQVIRUELRSV\ZHUH RYHUH[SUHVVLQJ PXWDQW ĮV\QXFOHLQ ,QWHUHVWLQJO\ ZH ¿QG WKDW WKH SURWHLQXULD DEQRUPDO H*)5 DQG KHPDWXULD 7KH PRVW FRPPRQ QHXURSURWHFWLYHHႇHFWRINOI is localized to the intestine, as intestine clinicopathological diagnoses were proliferative glomerulonephritis VSHFL¿FRYHUH[SUHVVLRQRINOILVVXႈFLHQWWRSKHQRFRS\V\VWHPLF QRQSUROLIHUDWLYH JORPHUXORQHSKULWLV DQG GLDEHWLF RYHUH[SUHVVLRQ )XUWKHU XVLQJ 51$VHT DQDO\VLV ZH LGHQWLI\ D QHSKURSDWK\.,0OHYHOVZHUHLQYHUVHO\FRUUHODWHGZLWKH*)5 U VHFUHWHG&W\SHOHFWLQFOHF, which is required for and mediates P DQGGLUHFWO\FRUUHODWHGZLWKSURWHLQXULD U WKH QHXURSURWHFWLYH HႇHFW RI LQWHVWLQDO NOI 6\VWHPLF GHOHWLRQ RU P < 0.001) and highest in patients with diabetic nephropathy and LQWHVWLQHVSHFL¿FNQRFNGRZQRIFOHF completely abolishes NOI tubulointerstitial disease. After adjusting for estimated glomerular PHGLDWHG QHXURSURWHFWLRQ ZKLOH GRSDPLQH VSHFL¿F NQRFNGRZQ RI ¿OWUDWLRQUDWHDQGSURWHLQXULD.,0OHYHOVZHUHKLJKHULQWKRVHZLWK FOHFKDVQRHႇHFW6HTXHQFHDQDO\VLVRI&HOHJDQV NOI points PRUH$7,PHVDQJLDOPDWUL[H[SDQVLRQDQGLQWHUVWLWLDO¿EURVLVWXEXODU to the complement protein COLEC11 as a mammalian ortholog. DWURSK\ ,)7$ 0&3OHYHOVZHUHQRWDVVRFLDWHGZLWKH*)5RU &2/(&LVGHWHFWDEOHLQUDWEUDLQVDQG&6)DQGVWXGLHVFXUUHQWO\ proteinuria but were elevated in patients with more tubulointerstitial ongoing will assess a conserved neuroprotective role for COLEC11 LQÀDPPDWLRQ in mammals. Collectively, these observations identify a mechanism +LVWRSDWKRORJLFDO¿QGLQJVIURPNLGQH\ELRSVLHVFDQEHQRQLQYDVLYHO\ PHGLDWLQJQHXURSURWHFWLRQYLDDJXWQHXURQD[LVZKHUHE\LQWHVWLQDO GHWHUPLQHG IURP SODVPD ELRPDUNHUV 3ODVPD .,0 DQG 0&3 NOI regulation of the secreted complement protein FOHF could be used to provide diagnostic information and to track response modulates distant neuronal responses to proteotoxic stress due to to therapies in patients with a variety of kidney diseases. PLVIROGHG ĮV\QXFOHLQ 2XU ¿QGLQJV DGGLWLRQDOO\ VKHG OLJKW RQ WKH mechanisms coupling longevity with extension of healthspan and 128 0RXVH HQGRWKHOLDO FHOO WUDQVFULSWRPHV LQ KHDOWK\ DQG KDYHLPSOLFDWLRQVIRUWDUJHWLQJWKHXQGHUO\LQJDJLQJELRORJ\LQDJH diseased states dependent diseases, which currently pose an enormous burden on Jennifer C. W. Hu healthcare systems worldwide. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, USA 127 Plasma kidney injury molecule-1 and monocyte chemoattractant protein-1 correlations with kidney Endothelial cells line the interiors of blood and lymphatic vessels. histopathology 'HSHQGLQJRQWKHYHVVHOW\SH HJFDSLOODU\YHLQDUWHU\VLQXVRLG Isabel J. Hsu WKH\KDYHGLYHUVHPRUSKRORJLHVDQGIXQFWLRQV6RPDWLFPXWDWLRQV Princeton, Dearborn Heights, USA KDYH EHHQ LGHQWL¿HG LQ HQGRWKHOLDO FHOOV LVRODWHG IURP VSRUDGLFDOO\ occurring vascular malformations; these include: PIK3CA mutations 0RUH WKDQ RQH LQ VHYHQ DGXOWV LQ WKH 8QLWHG 6WDWHV² PLOOLRQ LQ O\PSKDWLF DQG YHQRXV PDOIRUPDWLRQV DQG *1$4 PXWDWLRQV LQ SHRSOH²KDYH FKURQLF NLGQH\ GLVHDVH &.' &.' FDQQRW EH congenital hemangiomas. How a mutation in an endothelial cell reversed, so early detection and prevention is crucial. Currently JLYHVULVHWRDVSHFL¿FW\SHRIYDVFXODUPDOIRUPDWLRQLVXQNQRZQ VHUXPFUHDWLQLQH 6&U DQGSURWHLQXULDDUHXVHGWRLQGLFDWHNLGQH\ IXQFWLRQ+RZHYHU6&UODJVLQUHVSRQVHWRNLGQH\LQMXU\RUGLVHDVH :HK\SRWKHVL]HWKDWDVRPDWLFPXWDWLRQ¶VHႇHFWGHSHQGVXSRQWKH DQG SURWHLQXULD ODFNV GLDJQRVWLF VSHFL¿FLW\ %HWWHU ELRPDUNHUVDUH transcriptome of the endothelial cell in which the mutation arose. For needed for earlier, more accurate diagnoses and for monitoring the LQVWDQFHEDVHOLQHWUDQVFULSWLRQDOGLႇHUHQFHVEHWZHHQVLQXVRLGDODQG course of kidney disease progression. DUWHULDOHQGRWKHOLDOFHOOVDFFRXQWIRUWKHDELOLW\RIDVRPDWLF*1$4 mutation to produce a hepatic hemangioma in the former and no .LGQH\ LQMXU\ PROHFXOH .,0 DQG PRQRF\WH FKHPRDWWUDFWDQW malformation in the latter. To begin testing this hypothesis, we are SURWHLQ 0&3DOVR&&/ KDYHVKRZQSURPLVHDVQHSKURORJ\ SHUIRUPLQJ 51$ VHTXHQFLQJ RQ PRXVH HQGRWKHOLDO FHOOV IUHVKO\ ELRPDUNHUV LQ DQLPDO DQG FRKRUW VWXGLHV .,0 LV D SURWHLQ UHFRYHUHGIURPGLႇHUHQWYDVFXODUFRPSDUWPHQWV highly upregulated in proximal tubular cells after acute ischemic NLGQH\ LQMXU\ ,QFUHDVHV LQ 0&3 D FKHPRNLQH WKDW UHFUXLWV 7KXV IDU ZH KDYH LPPXQRDႈQLW\ SXUL¿HG HQGRWKHOLDO FHOOV IURP VSHFL¿FOHXNRF\WHSRSXODWLRQVKDYHEHHQGHWHFWHGLQUHVSRQVHWR collagenase digested lung, liver, aorta, inferior vena cava/jugular LQÀDPPDWLRQ DV LQ DFWLYH OXSXV QHSKULWLV :H K\SRWKHVL]HG WKDW YHLQVDQGXWHUXVVDPSOHVIURPDGXOW&%/-PLFHXVLQJDQWL&' SODVPD .,0 DQG 0&3 LQGHSHQGHQW RI HVWLPDWHG JORPHUXODU DQWLERGLHV2XUKLJKHVW\LHOGFDPHIURPWKHOLYHU aPLOOLRQFHOOV DQG ¿OWUDWLRQ UDWH H*)5 DQG SURWHLQXULD ZRXOG LGHQWLI\ DFXWH WXEXODU RXUORZHVW\LHOGFDPHIURPWKHDRUWD aFHOOV ([WUDFWHG51$

www.jointmeeting.org 67 POSTER ABSTRACTS

ZDVXVHGWRFUHDWH51$VHTOLEUDULHVZKLFKZHUHFKDUDFWHUL]HGXVLQJ ends. We thus propose that MRI is an adaptor which, through its DQ,OOXPLQD0L6HT$VH[SHFWHGNQRZQHQGRWKHOLDOFHOOWUDQVFULSWV PXOWLYDOHQW LQWHUDFWLRQV LQFUHDVHV WKH DYLGLW\ RI ''5 IDFWRUV IRU HJ 9ZI ZHUH SUHVHQW LQ HYHU\ VDPSOH +RZHYHU RXU DELOLW\WR GDPDJHGFKURPDWLQWRSURPRWH1+(- GHWHFWGLႇHUHQFHVLQWKHWUDQVFULSWRPHVRIWKHGLႇHUHQWHQGRWKHOLDO cell populations was confounded by contaminating neighboring cells. 130 Age-dependent effects of apoE reduction using antisense For example, albumin transcripts (Alb) were enriched in endothelial ROLJRQXFOHRWLGHVLQDPRGHORIȕDP\ORLGRVLV cells isolated from liver and surfactant associated protein transcripts Tien-Phat V. Huynh 6IWSE ZHUHHQULFKHGLQHQGRWKHOLDOFHOOVLVRODWHGIURPOXQJ Washington University School of Medicine, Saint Louis, USA We are currently developing more stringent enrichment methods The apolipoprotein E ($32() gene is the strongest genetic risk to recover endothelial cells, applying computational methods to IDFWRU IRU ODWHRQVHW $O]KHLPHU GLVHDVH 3UHYLRXV VWXGLHV VXJJHVW eliminate contaminating transcripts from endothelial cell datasets, reduction of apoE levels through genetic manipulation can reduce DQG SHUIRUPLQJ VLQJOH FHOO 51$ VHTXHQFLQJ WR SUHFLVHO\ GH¿QH $ȕSDWKRORJ\+RZHYHULWLVQRWFOHDUKRZUHGXFWLRQRIDSR(OHYHOV GLႇHUHQWHQGRWKHOLDOFHOOWUDQVFULSWRPHV2QFHWKLVZRUNLVFRPSOHWH DIWHUELUWKZRXOGDႇHFWDP\ORLGGHSRVLWLRQ:HXWLOL]HDQDQWLVHQVH we will begin determining endothelial cell transcriptomes in mice with ROLJRQXFOHRWLGH $62 WR UHGXFH DSR( H[SUHVVLRQ LQ WKH EUDLQV RI DFRQGLWLRQDO3LNFDS+5DOOHOHWKDWKDVEHHQDVVRFLDWHGZLWK $3336 PLFH KRPR]\JRXV IRU KXPDQ $32(İ RU $32(İ YHQRXVDQGO\PSKDWLFPDOIRUPDWLRQVRUD*1$4S4/DOOHOHWKDW DOOHOH$62WUHDWPHQWVWDUWLQJDIWHUELUWKOHGWRDVLJQL¿FDQWGHFUHDVH KDVKHSDWLFPDOIRUPDWLRQV)LQDOO\HQGRWKHOLDOFHOOVIURPGLႇHUHQW LQ$ȕ SDWKRORJ\ ZKHQ DVVHVVHG DW PRQWKV RI DJH ,QWHUHVWLQJO\ YDVFXODU FRPSDUWPHQWV RI ZLOGW\SH DQG FRQGLWLRQDO PXWDQW PLFH $62WUHDWPHQWVWDUWLQJDWWKHRQVHWRIDP\ORLGGHSRVLWLRQOHGWRDQ ZLOO EH FRFXOWXUHG ZLWK ZLOGW\SH FHOOV WR GHWHUPLQH KRZ PXWDQW LQFUHDVH LQ $ȕ SODTXH VL]H DQG D UHGXFWLRQ LQ SODTXHDVVRFLDWHG HQGRWKHOLDOFHOOVDႇHFWWKHEHKDYLRURIQRQPXWDQWQHLJKERUV neuritic dystrophy, despite no change in overall plaque load. These UHVXOWVVXJJHVWWKDWPDQLSXODWLRQRIDSR(OHYHOVFDQVWURQJO\DႇHFW Completion of these experiments will elucidate the transcriptional WKHLQLWLDWLRQRI$ȕSDWKRORJ\LQYLYR, while modulating plaque size SUR¿OHVRIHQGRWKHOLDOFHOOVIURPGLႇHUHQWYDVFXODUVLWHVLQWKHDEVHQFH and toxicity during the later stages of amyloid deposition. RUSUHVHQFHRIDPDOIRUPDWLRQFDXVLQJVRPDWLFPXWDWLRQ,WZLOODOVR identify cell autonomous changes in gene expression that can recruit 131 Neutrophil extracellular traps propagate post-traumatic QRQPXWDQW FHOOV LQWR WKH PDOIRUPDWLRQ SURFHVV 7KLV NQRZOHGJH KHWHURWRSLFRVVL¿FDWLRQ could lead to therapies that halt the development or progression of Charles Hwang a vascular malformation, or promote the malformation’s regression. University of Michigan, USA 129 05,IXQFWLRQVDVD'1$GDPDJHUHVSRQVHDGDSWRUGXULQJ 1HXWURSKLO H[WUDFHOOXODU WUDSV 1(7V D FRPSRQHQW RI WKH KRVW non-homologous end joining GHIHQVH PHFKDQLVP KDYH EHHQ LPSOLFDWHG LQ SURLQÀDPPDWRU\ Putzer J. Hung conditions such as arthritis and autoimmune disorders. Heterotopic Washington University School of Medicine, New York, USA RVVL¿FDWLRQ +2 LV D SDWKRORJ\ RI LPSDLUHG PXVFXORVNHOHWDO wound healing characterized by ectopic osseous lesions that 1RQKRPRORJRXV HQG MRLQLQJ 1+(- LV WKH SULPDU\ '1$ GRXEOH FDXVH MRLQW LPPRELOLW\ GLV¿JXUHPHQW DQG SDLQ 7KLV DFXWHRQ VWUDQGEUHDN '6% UHSDLUSDWKZD\LQ*SKDVHFHOOVDQGLQYROYHV FKURQLFLQÀDPPDWRU\SURFHVVKDVERWKFOLQLFDOO\DQGH[SHULPHQWDOO\ WKH GLUHFW OLJDWLRQ RI WZR '1$ HQGV ,Q GHYHORSLQJ O\PSKRF\WHV exhibited an association between mechanical strain and increased 1+(- LV UHTXLUHG IRU WKH UHSDLU RI '6%V JHQHUDWHG E\ WKH 5$* ORFDO LQÀDPPDWLRQ :H VKRZ WKDW PHFKDQLFDOO\ GLVUXSWHG 1(7V endonuclease during the antigen receptor gene assembly process, LQGHSHQGHQWO\ LQGXFH 1(7RVLV WKHUHE\ DXJPHQWLQJ LQÀDPPDWLRQ and dysregulation of this pathway can lead not only to impaired in response to injury, and causing wound pathology. Furthermore, lymphogenesis, but also to chromosomal deletions or translocations LQWHUUXSWLQJ VLJQDOLQJ GRZQVWUHDP WR QDVFHQW 1(7V DWWHQXDWHG WKDWSUHGLVSRVHWRZDUGVO\PSKRLGPDOLJQDQFLHV1+(-LVFDUULHGRXW ectopic formations. E\DVHWRIHVVHQWLDOFRUHIDFWRUVLQFOXGLQJ.X'1$OLJDVH,9 DQG;5&&ZKLFKUHFRJQL]HEURNHQ'1$HQGVDQGFDWDO\]HWKHLU :LOGW\SH PLFH XQGHUZHQW KLQGOLPE$FKLOOHV WHQRWRP\ WR JHQHUDWH rejoining. Additionally, several other accessory factors, such as XLF, WUDXPDLQGXFHG+20LFHZHUHDOORZHGWRDPEXODWHZLWKWKHLQMXUHG $70 DQG +$; DOVR IXQFWLRQ UHGXQGDQWO\ GXULQJ 1+(- WR WHWKHU KLQGOLPE HLWKHU PRELOH RU FDVWLPPRELOL]HG 0LFH ZHUH WUHDWHG EURNHQ '1$ HQGV DQG SURWHFW WKHP IURP QXFOHRO\WLF GHJUDGDWLRQ ZLWK YHKLFOH FRQWURO LY '1DVH, WR FKHPLFDOO\ GLVUXSW 1(7V RU

68 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

WKURXJK'1DVH,DOVRVLJQL¿FDQWO\LQFUHDVHGQRUPDOL]HGQHXWURSKLO &RQFOXVLRQ3UHYDOHQFHRI$$$&1LQVLPLODULQDYHUDJHULVN%ODFN Y DQG PDFURSKDJH Y FRXQWV LQ WKH LPPRELOH DQG :KLWH VFUHHQHOLJLEOH SHUVRQV ¿QGLQJV WKDW VXSSRUW &5& KLQGOLPEDWKRXUVKRZHYHUQRGLႇHUHQFHVZHUHREVHUYHGLQWKH screening beginning at age 50, irrespective of race. PRELOHKLQGOLPE Q JURXS 7UHDWPHQWZLWK'1DVH,WRFKHPLFDOO\ GLVUXSW 1(7V DOVR OHG WR WKH SUHVHQFH RI HFWRSLF FDUWLODJH 7/5 133 8SWDNH (I¿FDF\ DQG 6XVWDLQDELOLW\ RI D )LWELW %DVHG LQWHUUXSWLRQ YLD 2'1 VLJQL¿FDQWO\ UHGXFHG LQÀDPPDWLRQ LQ Lifestyle Program for Patients with Non-Alcoholic Fatty Liver WKH PRELOH KLQGOLPEV ,Q YLWUR VWXGLHV FRQ¿UPHG WKDW PHFKDQLFDOO\ Disease (NAFLD) GLVUXSWHG 1(7V LQGXFH UREXVW VHFRQGDU\ 1(7RVLV FRPSDUHG ZLWK Donovan Inniss LQWDFW1(7V KSIYKSI 7UHDWPHQWRIVHFRQGDU\QHXWURSKLOV Saint John’s University/The College of St. Benedict, ZLWK 2'1 UHGXFHG VHFRQGDU\ 1(7RVLV KSI Y KSI Collegeville, USA YDOLGDWLQJWKHUROH7/5VVHUYHDVPDMRUUHFHSWRUVIRU1(7LQGXFHG $EVWUDFW 1RQ$OFRKROLF )DWW\ /LYHU 'LVHDVH 1$)/' LV D KLJKO\ 1(7RVLV 3RVWWUDXPDWLF WUHDWPHQW ZLWK 2'1 VXFFHVVIXOO\ SUHYDOHQWGLVHDVHDႇHFWLQJDSSUR[LPDWHO\RIWKH86SRSXODWLRQ UHGXFHGWKH&7YROXPHRIHFWRSLFERQH YPP FRQ¿UPLQJ It is associated with metabolic diseases including diabetes, WKHVLJQDOLQJDQGUHFUXLWLQJUROHRI1(7RVLVLQ+2 REHVLW\DQGKLJKFKROHVWHURO&XUUHQWO\WKHUHDUHQR)'$DSSURYHG These results strongly suggest mechanical or chemical disruption pharmacologic therapies to halt or reverse liver injury. Prior studies RI 1(7V DXJPHQWV MRLQW LQÀDPPDWLRQ DQG HQGRFKRQGUDO HFWRSLF have found that improvement of liver histology and metabolic ERQH IRUPDWLRQ E\ LQGXFLQJ IXUWKHU 1(7RVLV DPRQJ QHXWURSKLOV parameters has been achieved with increases in physical activity 7/5LQKLELWLRQYLD2'1SUHYHQWVWKLVVHFRQGDU\1(7RVLV DQGQXWULWLRQDOOLIHVW\OHLQWHUYHQWLRQV+RZHYHULWKDVEHHQGLႈFXOW and downstream development of ectopic lesions, suggestive of a for many patients to initiate and maintain these lifestyle changes. YDOXDEOHWDUJHWLQSUHYHQWLQJ1(7RWLFSDWKRORJLHVDQGG\VUHJXODWHG Hypothesis & Aims: We hypothesize that a less vigorous and LQÀDPPDWLRQ PLQLPDOO\ WLPHFRQVXPLQJ DSSURDFK WR LPSOHPHQW WKHVH OLIHVW\OH FKDQJHVZLOOVHUYHDVDQHႇHFWLYHDQGVXVWDLQDEOHRSWLRQIRUSDWLHQWV 132 Prevalence of Advanced, Precancerous Colorectal 7KHUHIRUHWKHJRDORIWKLVVWXG\LVWRDVVHVVWKHHႈFDF\IHDVLELOLW\ 1HRSODVLDLQ%ODFNDQG:KLWH3RSXODWLRQVD6\VWHPDWLF5HYLHZ and sustainability of a technology (Fitbit) based lifestyle intervention DQG0HWDDQDO\VLV SURJUDPIRUSDWLHQWVZLWK1$)/' Thomas F. Imperiale 0HWKRGV7RDVVHVVWKLVDSLORWWULDORISDWLHQWVZDVGHVLJQHG7R Indiana University School of Medicinie, Indianapolis, USA date, 23 patients have been enrolled. Baseline metabolic, physical Background: Colorectal cancer (CRC) incidence and mortality DFWLYLW\ QXWULWLRQDO DQG +HDOWK 5HODWHG 4XDOLW\ RI /LIH +542/ is higher in Blacks than in Whites. While the reason(s) for these parameters were collected for each patient, and will be compared disparities is unclear, some guidelines recommend CRC screening WRWKHVDPHPHDVXUHVWDNHQDWWKHHQGRIWKHPRQWKVWXG\2YHU LQ%ODFNVVWDUWLQJDWDJH the course of the study, patients are given weekly individualized Objective: To compare the prevalence of advanced adenoma (AA) feedback on their step counts. Results: The current approached/ RU DGYDQFHG SUHFDQFHURXV FRORUHFWDO QHRSODVLD $&1 EHWZHHQ HQUROOHG UDWLR RI LV FRPSDUDWLYH WR RWKHU OLIHVW\OH EDVHG DV\PSWRPDWLF%ODFNDQG:KLWHVFUHHQHOLJLEOHDGXOWV programs and is indicative of the general appeal of the program to this patient population. The median age of the cohort is 52.5 0HWKRGV:HSHUIRUPHGDV\VWHPDWLFUHYLHZDQGPHWDDQDO\VLVE\ \HDUVZLWKPDOHVDQGZKLWHV7KHPHGLDQEDVHOLQH%0, ¿UVWVHDUFKLQJ2YLG0('/,1(3XE0HG(0%$6(DQGWKH&RFKUDQH LV DQG KDYH GLDEHWHV 0HGLDQ EDVHOLQH$67 LV DQG Library to identify published literature from database inception to +J$FLV2QWKH)LEURVFDQWKHPHGLDQ)VFRUHLV)DQG&$3 -XQH:HLQFOXGHGVWXGLHVPHDVXULQJWKHSUHYDOHQFHRI$$RU SHUFHQWDJHRIVWHDWRVLVLV$PRQJWKHHQUROOHGSDWLHQWV $&1LQDYHUDJHULVN%ODFNDQG:KLWHSHUVRQVXQGHUJRLQJVFUHHQLQJ DUHZHDULQJWKH)LWELWRIWKHWLPH7KHEDVHOLQHZHHNO\VWHS colonoscopy. Two authors independently assessed study quality and FRXQWZDVVWHSVDQGRISDWLHQWVKDGVWDEOHRULQFUHDVLQJ ULVNIRUELDVXVLQJDPRGL¿HG1,+TXDOLW\DVVHVVPHQWLQVWUXPHQWIRU step counts thus far over the course of the study. Conclusion: As FURVVVHFWLRQDO VWXGLHV DQG LQGHSHQGHQWO\ DEVWUDFWHG GHVFULSWLYH enrollment is ongoing, knowledge gained from the study will improve DQGTXDQWLWDWLYHGDWDIURPHDFKVWXG\$UDQGRPHႇHFWVPRGHOIRU 2 understanding of the optimal methods to help implement lifestyle PHWDDQDO\VLVZDVXVHGSURYLGLQJWKH, measure for heterogeneity, FKDQJHVIRUSDWLHQWVZLWK1$)/'7KLVVWXG\FDQWKHQEHXVHGWR ULVNGLႇHUHQFHV 5' DQGRGGVUDWLRV 25 help design larger trials comparing structured lifestyle intervention 5HVXOWV )URP WLWOHV ZH LGHQWL¿HG VWXGLHV WKDW LQFOXGHG SURJUDPVWRRWKHU1$)/'WKHUDSLHV VXEMHFWV 7KH ODUJHVW VLQJOH VWXG\ LQFOXGHG RIDOOVXEMHFWV6L[RIVWXGLHVZHUHRIKLJKPHWKRGRORJLFDO 134 The Circulatory Sialyltransferase ST6Gal-1 is a Systemic TXDOLW\DQGORZULVNIRUELDV2YHUDOOSUHYDOHQFHRI$$$&1ZDVQR 5HJXODWRURI%RQH0DUURZ%/\PSKRSRLHVLVDWWKH7UDQVLWLRQDO GLႇHUHQWEHWZHHQ%ODFNVDQG:KLWHV25 &, B cell Stage DQG 5' &, WR ,2 VKRZLQJ PRGHUDWH Eric Irons KHWHURJHQHLW\3UR[LPDO$$$&1SUHYDOHQFHZDVJUHDWHULQ%ODFNV 8QLYHUVLW\DW%X௺DOR%X௺DOR86$ WKDQ LQ :KLWHV 25 &, DQG 5' &, WR Hematopoiesis generates the cellular components of blood essential 2 0.01; I VKRZLQJ ORZ KHWHURJHQHLW\ ([FOXGLQJ WKH ODUJHVW VWXG\ WRKHDOWKGXULQJKRPHRVWDVLVDQGVWUHVV'\VUHJXODWHGKHPDWRSRLHVLV UHVXOWHG LQ QR GLႇHUHQFH LQ WKH SUHYDOHQFH RI RYHUDOO $$$&1 D IHDWXUH RI PDQ\ LQÀDPPDWRU\ DQG DXWRLPPXQH GLVHDVHV LV DQ 25 &, RUSUR[LPDO$$$&1 25 &, attractive but underutilized therapeutic target. As the interface 2.52). Including only the highest quality studies for which pathology between immune cells and their interactants, glycans are increasingly ZDVDYDLODEOH VWXG\1 VXEMHFW1 VKRZHGQRGLႇHUHQFH appreciated as critical mediators of immune cell production, turnover, LQ$$$&1SUHYDOHQFH 25 &, RUSUR[LPDO$$$&1 and function. Although canonical glycosylation is restricted to SUHYDOHQFH VWXG\1 VXEMHFW1 25 &, WKH (5*ROJL JO\FRV\OWUDQVIHUDVHV VXFK DV 67*DO DUH DOVR

www.jointmeeting.org 69 POSTER ABSTRACTS

VHFUHWHGLQWREORRGGXULQJLQÀDPPDWLRQDVSDUWRIWKHDFXWHSKDVH $20'66 PRGHO RI FRORQ FDUFLQRJHQHVLV WKH 3.* .2 DQLPDOV response. We have recently described a novel, extrinsic pathway SURGXFHGVLJQL¿FDQWO\PRUHSRO\SVWKDQZLOGW\SHFRQWUROV IROG of glycosylation by which these extracellular glycosyltransferases S :KLOHWKHSRO\SVIURP3.*.2DQLPDOVZHUHVOLJKWO\ PRGLI\FHOOVXUIDFHJO\FDQVLQDQRQFHOODXWRQRPRXVPDQQHU7KLV VPDOOHU WKDQ WKRVH IURP ZLOG W\SH WKH WUHQG ZDV QRW VLJQL¿FDQW paradigm predicts that circulating glycosyltransferases are global S :LOGW\SHDQG3.*.2PLFHUHVSRQGHGHTXDOO\WR'66 UHJXODWRUVRIJO\FDQGHSHQGHQWSURFHVVHV,QGHHGZHKDYHVKRZQ WUHDWPHQWEXWWKH3.*GH¿FLHQWDQLPDOVH[KLELWHGFU\SWK\SHUSODVLD WKDWWKHVHUXPVLDO\OWUDQVIHUDVH67*DOLQÀXHQFHV,J*VLDO\ODWLRQ and increased apoptosis in luminal epithelium relative to wild type and inhibits bone marrow granulocyte production. In this study, we DQLPDOV 7DNHQ WRJHWKHU WKHVH ¿QGLQJV VXJJHVW WKDW 3.* KDV D SUHVHQWHYLGHQFHWKDWH[WULQVLF67*DOLVDOVRDV\VWHPLFSRVLWLYH tumor suppressive role in the colon epithelium, and that reducing the UHJXODWRU RI % O\PSKRF\WH GHYHORSPHQW 67*DO GH¿FLHQF\ proliferative compartment may be part of the mechanism. impeded the development of transitional and marginal zone B cells in YLYR+RZHYHUWKHGLVFRUGDQFHEHWZHHQ67*DOH[SUHVVLRQDQG 136 Sonoreperfusion of microvascular obstruction: a step FHOO VXUIDFH ĮVLDO\ODWLRQ GXULQJ % FHOO GHYHORSPHQW VXJJHVWHG toward clinical translation that intrinsic expression could not completely account for B cell Filip Istvanic VLDO\ODWLRQ*LYHQWKHDVVRFLDWLRQRIVHUXP67*DOZLWKVWUHVVDQG University of Pittsburgh School of Medicine, USA LQÀDPPDWRU\ VWDWHV ZH K\SRWKHVL]HG WKDW VHUXP 67*DO FRXOG Microembolization during percutaneous coronary intervention for XSUHJXODWHSURGXFWLRQRI%FHOOVGXULQJLQÀDPPDWLRQLQDQWLFLSDWLRQ DFXWHP\RFDUGLDOLQIDUFWLRQFDXVHVPLFURYDVFXODUREVWUXFWLRQ 092 of imminent antigen presentation. Bone marrow transplantations :HKDYHVKRZQWKDWVRQRUHSHUIXVLRQWKHUDS\XVLQJXOWUDVRXQG 86 EHWZHHQ :7 DQG 67*DO GH¿FLHQW PLFH VKRZHG WKDW LQWULQVLF and lipid microbubbles restores microvascular perfusion in an in 67*DO H[SUHVVLRQ ZDV QHFHVVDU\ IRU PDUJLQDO ]RQH % FHOO YLWUR PRGHO RI 092 DQG WKDW UHSHUIXVLRQ HႈFDF\ LQFUHDVHV ZLWK GHYHORSPHQWEXWH[WULQVLF67*DOZDVQHFHVVDU\IRUWUDQVLWLRQDO 86SXOVHOHQJWK7RHQDEOHFOLQLFDOWUDQVODWLRQRIWKLVWHFKQLTXHZH B cell development. The cellular targets of extrinsic sialylation were FRPSDUHGWKHUHSHUIXVLRQHႈFDF\RIDQH[SHULPHQWDOORQJSXOVH86 LGHQWL¿HG DV WKH ERQH PDUURZ LPPDWXUH DQG WUDQVLWLRQDO % FHOO V\VWHP PRGL¿HG3KLOLSV(3,4 WRWKDWRIDFOLQLFDOVKRUWSXOVH86 SRSXODWLRQVZKLFKH[KLELWHGGHFUHDVHGĮVLDO\ODWLRQLQFKLPHUDV V\VWHP 3KLOLSV 6RQRV ZKLFK KDV EHHQ VKRZQ WR HQKDQFH ODFNLQJKRVW67*DO([YLYRWUHDWPHQWRILPPDWXUH%FHOOVZLWK perfusion in a rodent hindlimb arterial ligation model of ischemia. We H[WULQVLF67*DOVXSSRUWHGGLႇHUHQWLDWLRQLQWRWUDQVLWLRQDO%FHOOV K\SRWKHVL]HGWKDWWKHH[SHULPHQWDOORQJSXOVH86GHOLYHU\V\VWHP DQGLQFUHDVHG&'H[SUHVVLRQ2XU¿QGLQJVVKRZDQXQH[SHFWHG ZRXOG UHOLHYH 092 WR D JUHDWHU H[WHQW LQ D UDW KLQGOLPE PRGHO RI UROH IRU H[WULQVLF VLDO\ODWLRQ E\ 67*DO LQ % O\PSKRSRLHVLV 7KLV 092WKDQZRXOGWKHFOLQLFDOVKRUWSXOVH86GHOLYHU\V\VWHP novel axis sheds light on the long elusive function of circulating 2XUUDWKLQGOLPEPRGHORI092ZDVFUHDWHGE\LQMHFWLQJPLFURWKURPEL VLDO\OWUDQVIHUDVHV DQG DGGV FRPSOH[LW\ WR WKH JO\FDQGHSHQGHQW into the hindlimb muscle microvasculature via the contralateral FRQWURORILPPXQHFHOOSURGXFWLRQDQHPHUJLQJWKHPHLQKHPDWRORJ\ femoral artery. Lipid encapsulated microbubbles were infused As primary targets of negative selection, transitional B cells are a WKURXJKWKHIHPRUDODUWHU\ZKLOHWKHUDSHXWLF86ZDVGHOLYHUHGWRWKH ODELOH SRSXODWLRQ WKDW FDQ KDUERU VHOIUHDFWLYH FORQHV WRZDUGV WKH REVWUXFWHG PLFURYDVFXODWXUH IRU WZR PLQXWH WUHDWPHQW VHVVLRQV development of autoimmunity. Thus, our observations are consistent using either a long pulse (1600 cycles, 1.6 MHz, 1.1 MPa, 0.33 ZLWKWKHZHOOGRFXPHQWHGUROHRIVLDO\ODWLRQLQLPPXQHWROHUDQFHEXW +] IUDPHUDWH RU D ³VKRUW´ SXOVH F\FOHV UHSHDWHG WLPHV potentially represent a target more amenable to clinical manipulation MHz, 1.3 MPa, 0.33 Hz framerate). Control rats were injected with by intravenous administration of recombinant enzyme or inhibitors. PLFURWKURPELEXWGLGQRWUHFHLYH86WKHUDS\&RQWUDVWHQKDQFHG86 Future studies will determine the mechanism by which extrinsic SHUIXVLRQLPDJLQJ 6HTXRLD&360+] RIWKHPLFURYDVFXODWXUH 67*DO LQÀXHQFH % O\PSKRSRLHVLV DQG LWV FRQVHTXHQFHV IRU ZDVFRQGXFWHGDW EDVHOLQH %/ SRVW092 SRVWWUHDWPHQW autoimmunity. 7[ DQG SRVWWUHDWPHQW 7[ '(),1,7< PLFUREXEEOH 135 7\SH F*03 GHSHQGHQW SURWHLQ NLQDVH KDV D WXPRU contrast agent was infused through the jugular vein during perfusion suppressive role in the colon epithelium LPDJLQJ0LFURYDVFXODUEORRGYROXPHV 0%9 ZHUHFDOFXODWHGIURP Bianca N. Islam YLGHRLQWHQVLW\WLPH GDWD PHDVXUHG LQ KLQGOLPE PXVFOH UHJLRQV RI Augusta University, Augusta, USA LQWHUHVW'DWDDUHH[SUHVVHGDVPHDQVWDQGDUGGHYLDWLRQ 7KH F*03 OHYHO SOD\V D FHQWUDO UROH LQ UHJXODWLQJ KRPHRVWDVLV LQ 0%9ZHUHVLPLODUDWEDVHOLQHDQGPDUNHGO\UHGXFHGDIWHU092IRU the colon epithelium and is emerging as a potential target for colon DOOJURXSV,QWKHORQJSXOVHUDWV Q 0%9LQFUHDVHGWRRI FDQFHUSUHYHQWLRQ7KHVLJQDOLQJFRPSRQHQWVGRZQVWUHDPRIF*03 %/DIWHU7[ G%QVYV%/DGMSYDOXH YV092 and the tumor suppressive mechanism remain poorly understood. DGM S YDOXH YV 6KRUWSXOVH 7[ DGM S YDOXH YV 7KHSUHVHQWVWXG\KDVH[DPLQHGWKHH[SUHVVLRQRIF*03GHSHQGHQW 1R7UHDWPHQW7[ ,QWKHVKRUWSXOVHJURXS Q 0%9UHPDLQHG SURWHLQNLQDVHLVRIRUPV 3.*3.* LQQRUPDOLQWHVWLQDOPXFRVD UHGXFHGDWRI%/DIWHU7[ G%QVYV092 ,QWKH and in colon cancer from human specimens. Immunohistochemical ³1R7UHDWPHQW´JURXS Q 0%9UHPDLQHGUHGXFHGDWRI%/ DQDO\VLV GHWHFWHG 3.* LQ VXSSRUWLYH FHOOV LQ WKH ODPLQD SURSULD DIWHU7[ G%QVYV092 DQG LQ VPRRWKPXVFOH WLVVXH EXW QRW LQ WKH HSLWKHOLXP RI QRUPDO 7KHVH GDWD GHPRQVWUDWH WKH VXSHULRU UHSHUIXVLRQ HႈFDF\ RI D LQWHVWLQHDQGFRORQ,QFRQWUDVW3.*ZDVGHWHFWHGH[FOXVLYHO\LQ ORQJSXOVH F\FOHV YV VKRUWSXOVH F\FOHV 86 GHOLYHU\ WKHHSLWKHOLXP,QFRORQFDQFHU3.*ZDVUHVWULFWHGWRWKHVWURPD V\VWHP IRU WKH WUHDWPHQW RI 092 7KLV LQ YLYR REVHUYDWLRQ DOLJQV ZKHUHLWFRORFDOL]HGZLWKYLPHQWLQZKHUHDV3.*ZDVRQO\GHWHFWHG ZLWKRXUSUHYLRXVLQYLWUR¿QGLQJVVKRZLQJWKDWORQJHUSXOVHOHQJWK in the tumor epithelium where it colocalized with cytokeratin. This LV DVVRFLDWHG ZLWK JUHDWHU UHSHUIXVLRQ HႈFDF\ 5HVXOWV REWDLQHG SDWWHUQRI3.*LVRIRUPH[SUHVVLRQZDVVLPLODULQWKHPRXVHLQWHVWLQH from this study should inform clinical translation and optimization of DQGFRORQZKHUHRQO\3.*ZDVGHWHFWHGLQSXUL¿HGFRORQLFFU\SWV VRQRUHSHUIXVLRQRI092 3.* NQRFNRXW .2 PLFH ZHUH XVHG LQWHUURJDWH SRVVLEOH DQWL carcinogenic roles in the colon epithelium. When subjected to the

70 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

137 Deciphering the functional heterogeneity of the human Here, we report exquisite synergistic interactions between TMZ PDFURSKDJHUHVSRQVHWR0\FREDFWHULXPWXEHUFXORVLVLQIHFWLRQ DQG LQKLELWRUV RI D NH\ '1$ GDPDJH UHVSRQVH SURWHLQ DWD[LD Christopher Y. Itoh WHODQJLHFWDVLD DQG UDGUHODWHG SURWHLQ $75 3UHOLPLQDU\ GDWD Harvard T.H. Chan School of Public Health, USA suggest a mechanism of action which involves acute replication stress OHDGLQJWRIRUNFROODSVHDQGFRQVHTXHQWLQGXFWLRQRI'1$GRXEOH Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, VWUDQGEUHDNV70=LQGXFHVDFWLYDWLRQRI$75VSHFL¿FDOO\LQ0*07 is the leading cause of infectious death in the world. Macrophages are methylated glioma cells, and inhibition of ATR signaling sensitizes critical to both the progression and control of Mtb infection, providing the glioma cells to TMZ. The magnitude of TMZ sensitization by a protected niche for the bacterium in some cases but clearing the $75LQKLELWLRQLVPDUNHG²RYHUIROG²DQGHQWLUHO\GHSHQGHQWRQ EDFWHULXPLQRWKHUV:HXQGHUVWDQGOLWWOHDERXWKRZGLႇHUHQFHVLQ 0*07VWDWXV7KHVHGDWDOD\WKHIRXQGDWLRQIRUIXWXUHFOLQLFDOWULDOV macrophage antimicrobial capacity are established and maintained. WHVWLQJWKLVFRPELQDWLRQVSHFL¿FDOO\LQ0*07PHWK\ODWHGJOLRPDDQG Canonically, M1 macrophages are thought to be antimicrobial and they challenge previously described mechanisms of action proposed M2 macrophages are immunoregulatory. However, several lines of IRUWKHGLႇHUHQWLDOVHQVLWLYLW\RI70=LQ0*07PHWK\ODWHGWXPRUV evidence now indicate that there is extensive transcriptional and functional heterogeneity within macrophage populations that is not 139 The role of Teneurins in neurodevelopmental disorders FDSWXUHGE\WKHVHFODVVL¿HUV7RGH¿QHWKHG\QDPLFVRIPDFURSKDJH Hudin N. Jackson PHPRU\ DQG SODVWLFLW\ZH GHYHORSHG +(50(6 +LJKGLPHQVLRQDO University of Connecticut School of Medicine, USA (YDOXDWLRQRI5HVSRQVHWR0DFURSKDJH(QYLURQPHQWDO6WLPXOL DQ 1HXURGHYHORSPHQWDO GLVRUGHUV 1'' HQFRPSDVV FRQGLWLRQV LQ in vitro platform to characterize macrophage responses and assess which development of the central nervous system is perturbed and their phenotypic stability. This assay captures both static and dynamic manifest as neuropsychiatric problems or impaired motor function, features of macrophage state, including surface marker expression, OHDUQLQJ ODQJXDJH RU QRQYHUEDO FRPPXQLFDWLRQ 7KH XQGHUO\LQJ F\WRNLQHSURGXFWLRQDQGDQWLPLFURELDOFDSDFLW\+(50(6LQYROYHVD etiologies for these disorders are highly complex, but increasing tiered checkerboard assay in which we polarized macrophages with HYLGHQFH KDV VKRZQ WKDW GLႇHUHQW UDUH DQG FRPPRQ JHQHWLF DSULPDU\GLႇHUHQWLDWLRQVWLPXOL0&6)RU*0&6)PRGXODWHGWKHLU alterations can contribute to similar disease mechanisms underlying VWDWHZLWK/36,)1Ȗ,/,/RU,/DQGPHDVXUHGWKHLUUHVSRQVH shared clinical phenotypes. This suggests that determining the WR GLႇHUHQW 7/5 VWLPXOL 0DFURSKDJHV ZHUH LQGLVWLQJXLVKDEOH E\ genetic basis and pathogenic mechanisms of rare monogenic canonical surface markers; however, by using a strategy that is both disorders has the potential to provide critical insights for many highly FRPELQDWRULDODQGVWDWHVSHFL¿FZHXQFRYHUHGURXWHVRIPDFURSKDJH SUHYDOHQW1''7KHUHIRUHZHGHYHORSHGDODUJHVFDOHFROODERUDWLYH state modulation that are both terminal and plastic as indicated HႇRUWWRLGHQWLI\LQGLYLGXDOVZLWKHLWKHUUDUHFRQGLWLRQVRUUDUHJHQHWLF WKURXJK WKHLU F\WRNLQH UHOHDVH SUR¿OHV )XUWKHUPRUH ZH REVHUYHG etiologies and to determine the functional consequences of the WKDWSRODUL]HGPDFURSKDJHVKDGGLႇHUHQWLDOFDSDFLW\WRFRQWURO0WE KXPDQJHQHDOWHUDWLRQVLQDKLJKWKURXJKSXW'URVRSKLODV\VWHP growth indicating that macrophage antimicrobial programs were also GLႇHUHQWLDOO\ HQJDJHG ,Q FRQFOXVLRQ PDFURSKDJH H[SRVXUH DQG 7KURXJK PXOWLLQVWLWXWLRQDO FROODERUDWLRQV VHYHUDO LQGLYLGXDOV ZLWK stimulation history give rise to combinatorial plasticity, as well as QHXURGHYHORSPHQWDO GLVRUGHUV ZHUH LGHQWL¿HG ZLWK FDQGLGDWH GLႇHUHQWLDOUHVSRQVHLQ0WEFRQWURO+(50(6DOORZVXVWRLQYHVWLJDWH pathogenic variants in vertebrate teneurin genes. These individuals WKHFRPSOH[LW\RIPDFURSKDJHSODVWLFLW\DQGKHOSGH¿QHVWUDWHJLHV H[KLELWDUDQJHRIQHXURORJLFDOGH¿FLWVWKDWZHUHQRWSUHYLRXVO\VKRZQ FDSDEOHRIDFWLYDWLQJDSDWKZD\IRUWKHPRVWHႇHFWLYHPDFURSKDJH to be associated with this gene family. The evolutionarily conserved state to control disease. teneurins encode transmembrane proteins involved in a number of processes integral to the proper development of the nervous system, 138 Elucidation of an exquisite synthetic lethal interaction including neuronal outgrowth, synaptic organization, and synaptic EHWZHHQ $75 LQKLELWRUV DQG DON\ODWLQJ DJHQWV LQ 0*07 WUDQVPLVVLRQ3UHYLRXVVWXGLHVRIWKHÀ\WHQHXULQVWHQDDQGWHQP methylated glioma cells GHPRQVWUDWHGWKDWNQRFNGRZQRIWHQPDQGWHQDFDXVHVV\QDSWLF Christopher B. Jackson ORVV LPSDLUHG DSSRVLWLRQ RI SUH DQG SRVWV\QDSWLF SDUWQHUV DQG Yale University, USA GHIHFWLYHV\QDSWLFWUDQVPLVVLRQ7HQHXULQNQRFNGRZQLQÀLHVUHVXOWV *OLREODVWRPD LV WKH PRVW FRPPRQ SULPDU\ EUDLQ WXPRU LQ DGXOWV LQORFRPRWRUGH¿FLWVPDUNHGE\SRRUFUDZOLQJ6WXGLHVLQYHUWHEUDWHV The current standard of care for this condition consists of surgery GHPRQVWUDWHG WKDW 7(10 NQRFNRXW PLFH GLVSOD\ LPSDLUHG RGRU with maximal resection followed by concurrent temozolomide (TMZ) GLVFULPLQDWLRQDQG7(10NQRFNRXWPLFHH[KLELWWUHPRUV7(10 and radiation therapy. TMZ belongs to a class of alkylating agents knockdown also causes hypomyelination of small axons and ZKLFKDUHWKRXJKWWRH[HUWWKHLUPDLQF\WRWR[LFHႇHFWVRQFHOOVYLD LQKLELWLRQRIROLJRGHQGURF\WHGLႇHUHQWLDWLRQZLWKLQWKHVSLQDOFRUGRI PHWK\ODWLRQRI'1$EDVHVLQFOXGLQJJXDQLQHEDVHVDWWKH2SRVLWLRQ 7(10PXWDQWPLFH 2PH* 2PHWK\OJXDQLQH'1$ PHWK\OWUDQVIHUDVH 0*07 LV D In order to determine the pathogenic nature of the rare human VXLFLGHHQ]\PHWKDWUHSDLUV70=LQGXFHG'1$GDPDJHE\UHPRYLQJ variants, we employed a genetic system where the endogenous these alkyl adducts. ORFXVIRUWKHÀ\KRPRORJLVGLVUXSWHGUHVXOWLQJLQDORVVRIIXQFWLRQ 7KHSURPRWHUUHJLRQRI0*07FRQWDLQV&S*LVODQGUHJLRQVWKDWDUH allele that simultaneously expresses the yeast transactivator PHWK\ODWHG LQ DSSUR[LPDWHO\ RI JOLREODVWRPD FDVHV 3DWLHQWV JHQH *$/ XQGHU WKH VDPH VSDWLRWHPSRUDO UHJXODWLRQ RI WKH ZLWK PHWK\ODWLRQ RI WKH 0*07 SURPRWHU UHVSRQG PRUH UHDGLO\ WR endogenous locus. To study the human teneurins, we generated 70=DQGVXUYLYHDSSUR[LPDWHO\PRQWKVORQJHUWKDQSDWLHQWVZLWK DQRYHOWHQD7$*$/DOOHOHDQGREWDLQHGWKHWHQP*DODOOHOH DQXQPHWK\ODWHG0*07SURPRWHU'HVSLWHWKLVSURJQRVWLFEHQH¿W Z3%DF ,7*$/ 7HQP*70%7E 7KHWHQD7$ WKHVH SDWLHQWV VWLOO KDYH D PHGLDQ VXUYLYDO RI RQO\ PRQWKV *DODQGWHQP*DODOOHOHVDUHXVHGLQFRQMXQFWLRQZLWKWUDQVJHQLF Ample opportunity still exists to better understand the relationship À\ DOOHOHV H[SUHVVLQJ ZLOGW\SH DQG YDULDQW À\ DQG KXPDQ WHQHXULQ EHWZHHQ0*07DQG70=DQGWRLQWURGXFHWUHDWPHQWVWKDWIXUWKHU F'1$V KF'1$ XQGHU WKH UHJXODWLRQ RI 8SVWUHDP $FWLYDWLQJ extend survival in these patients. 6HTXHQFHV 8$6 7KH 8$6*$/ V\VWHP DOORZV XV WR SHUIRUP

www.jointmeeting.org 71 POSTER ABSTRACTS

a KLJKWKURXJKSXW LQ YLYR DQDO\VLV RI WKH FRQVHTXHQFHV RI KXPDQ organisms, and with limited lower organism model systems available gene variants on nervous system development and function. These to provide the necessary developmental roadmaps to guide in vitro ¿QGLQJVKDYHWKHSRWHQWLDOWRHOXFLGDWHWKHUROHRIWHQHXULQVLQKXPDQ GLႇHUHQWLDWLRQ 1''DQGLGHQWLI\VKDUHGSDWKRJHQLFPHFKDQLVPVWKDWPD\SURYLGH +HUH ZH UHSRUW WKH VXFFHVVIXO GLUHFWHG GLႇHUHQWLDWLRQ LQ YLWUR RI insight into novel therapeutic avenues. KXPDQ36&VLQWR$(&VWKHIDFXOWDWLYHSURJHQLWRUVRIOXQJDOYHROL 8VLQJ JHQH HGLWLQJ WR HQJLQHHU PXOWLFRORUHG ÀXRUHVFHQW UHSRUWHU 140 %DVDOLQWHUIHURQVWLPXODWHGJHQHH[SUHVVLRQLQÀXHQFHV *)3 tdTomato the productive infection of oncolytic HSV in malignant peripheral 36&OLQHV 1.; 6)73& ), we track and purify human nerve sheath tumor cells SFTPC+ DOYHRODU SURJHQLWRUV DV WKH\ HPHUJH IURP 1.; endodermal developmental precursors in response to stimulation Joshua Jackson RI:QWDQG)*)VLJQDOLQJ3XUL¿HG36&GHULYHGSFTPC+ cells are Univeristy of Alabama at Birmingham, Birmingham, USA able to form monolayered epithelial spheres (“alveolospheres”) in ,QWURGXFWLRQ0DOLJQDQWSHULSKHUDOQHUYHVKHDWKWXPRUV 03167V 'FXOWXUHVZLWKRXWWKHQHHGIRUPHVHQFK\PDOFRFXOWXUHVXSSRUW DUH DJJUHVVLYH FDQFHUV RI WKH QHUYH VKHDWK 1HDUO\ KDOI DULVH H[KLELW H[WHQVLYH VHOIUHQHZDO FDSDFLW\ DQG GLVSOD\ DGGLWLRQDO VSRUDGLFDOO\ZKLOHWKHRWKHUKDOIDUHDVVRFLDWHGZLWKQHXUR¿EURPDWRVLV canonical AEC2 functional capacities, including innate immune W\SH 1) $PRQJ DOO SDWLHQWV PHGLDQ VXUYLYDO LV D GLVPDO responsiveness, the production of lamellar bodies able to package PRQWKV IROORZLQJ GLDJQRVLV 03167V DUH W\SLFDOO\ UHIUDFWRU\ WR VXUIDFWDQWDQGWKHDELOLW\WRXQGHUJRVTXDPRXVFHOOGLႇHUHQWLDWLRQ traditional chemotherapy and radiotherapy, with surgical resection while upregulating type 1 alveolar cell markers. Importantly, despite DVWKHRQO\GHPRQVWUDEOHEHQH¿WWRVXUYLYDOWKHUHIRUHRQFRO\WLF+69 weeks to months of LQ YLWUR culture, these cells exhibit a normal virotherapy has been suggested as a therapeutic alternative. NDU\RW\SH*XLGHGE\WLPHVHULHVJOREDOWUDQVFULSWRPLFSUR¿OLQJZH 2EMHFWLYH 'HWHUPLQH WKH H[WHQW WR ZKLFK 03167 FHOOV UHVLVW WKH ¿QGWKDW$(&PDWXUDWLRQLQYROYHVGRZQUHJXODWLRQRI:QWVLJQDOLQJ SURGXFWLYHLQIHFWLRQRIRQFRO\WLFKHUSHVVLPSOH[YLUXV R+69 WKURXJK DFWLYLW\ DQG WKH KLJKHVW GLႇHUHQWLDOO\ H[SUHVVHG WUDQVFULSWV LQ WKH DFWLYDWLRQRIWKH-$.67$7SDWKZD\DQGUHVXOWDQWXSUHJXODWLRQRI resulting SFTPC+ cells encode genes associated with lamellar body LQWHUIHURQ VWLPXODWHG JHQHV ,6*V ,6*V HQFRGH GLYHUVH SURWHLQV and surfactant biogenesis. Finally, we apply this novel model system that mediate intrinsic antiviral resistance in infected cells. WR JHQHUDWH SDWLHQWVSHFL¿F $(&V IURP LQGXFHG 36&V L36&V 121ins2 0HWKRGV7ZHQW\RQHKXPDQDQGPRXVH03167FHOOVZHUHXVHGWR carrying homozygous surfactant mutations (6)73% ), and we H[SORUHWKHUHODWLRQVKLSEHWZHHQ67$7DFWLYDWLRQDQGWKHSURGXFWLYH HPSOR\ IRRWSULQWIUHH &5,635EDVHG JHQH HGLWLQJ WR REVHUYH WKDW LQIHFWLRQRIǻȖR+69V correction of this genetic lesion restores surfactant processing in the cells responsible for their disease. Thus, we provide an approach for 5HVXOWV67$7DFWLYDWLRQLQUHVSRQVHWRR+69LQIHFWLRQZDVIRXQG disease modeling and future functional regeneration of a cell type WRDVVRFLDWHZLWKGLPLQLVKHGǻȖR+69VUHSOLFDWLRQDQGVSUHDG XQLTXHWRDLUEUHDWKLQJRUJDQLVPV 0XOWLGD\ SUHWUHDWPHQW EXW QRW FRWUHDWPHQW ZLWK D -$. 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This protection leads GHFUHDVHGEDVDO67$7WUDQVFULSWLRQDQG,6*H[SUHVVLRQ to persistence of malignant cells, development of resistance and &RQFOXVLRQ :KLOH FDQFHUDVVRFLDWHG ,6* H[SUHVVLRQ KDV EHHQ GLVHDVH UHODSVH :H SUHYLRXVO\ LGHQWL¿HG ¿EUREODVW JURZWK IDFWRU previously reported to impart resistance to chemotherapy and )*) DV D SURWHFWLYH VLJQDO LQ ERWK FKURQLF P\HORLG OHXNHPLD UDGLRWKHUDS\ WKHVH GDWD VKRZ WKDW EDVDO ,6* H[SUHVVLRQ DOVR &0/ DQG DFXWH P\HORLG OHXNHPLD $0/ ZLWK )/7 ,7' DIWHU FRQWULEXWHVWRRQFRO\WLF+69UHVLVWDQFH W\URVLQHNLQDVHLQKLELWRU 7., WKHUDS\)*)LVH[SUHVVHGLQERQH PDUURZ VWURPDO FHOOV DQG )*) H[SUHVVLRQ LQFUHDVHV GXULQJ Generation of functional lung alveolar epithelial cells 141 H[SRVXUHWRWKHUDS\+HUHZHGHPRQVWUDWHWKDW)*)LVGHOLYHUHG from human pluripotent stem cells from stromal cells to leukemia cells via exosomes, and stromal Anjali Jacob exosomes protect leukemia cells during TKI exposure. Expression Boston University School of Medicine, Boston, USA RI)*)DQGLWVUHFHSWRU)*)5DUHERWKLQFUHDVHGLQDVXEVHWRI Pulmonary alveolar epithelial type II cell (AEC2) dysfunction has VWURPDOFHOOOLQHVDQGSDWLHQWGHULYHG$0/VWURPD)*)5LQKLELWLRQRU been implicated as a primary cause of pathogenesis in many JHQHVLOHQFLQJLQVWURPDOFHOOVDEURJDWHV)*)PHGLDWHGDXWRFULQH SRRUO\ XQGHUVWRRG OXQJ GLVHDVHV WKDW ODFN HႇHFWLYH WKHUDSLHV JURZWK VLJQDOLQJ DQG VLJQL¿FDQWO\ GHFUHDVHV VHFUHWLRQ RI )*) LQFOXGLQJ LQWHUVWLWLDO OXQJ GLVHDVH ,/' DQG HPSK\VHPD $(&V containing exosomes. This results in decreased stromal protection are inaccessible to study in the developing human embryo and RIOHXNHPLDFHOOV,QDPRXVHPRGHORI%&5$EOOHXNHPLD)*) GLႈFXOW WR VWXG\ LQ SDWLHQWV 7KH\ SUROLIHUDWH SRRUO\ DQG UDSLGO\ PLFHVXUYLYHVLJQL¿FDQWO\ORQJHUWKDQZWFRXQWHUSDUWVZKHQWUHDWHG WUDQVGLႇHUHQWLDWH LQWR RWKHU FHOO W\SHV ZKHQ LVRODWHG DQG FXOWXUHG with TKI. Exosomes from wt mouse stroma supported increased VHYHUHO\OLPLWLQJUHVHDUFKLQDOYHRODUGHYHORSPHQWDQGGLVHDVH8VLQJ %&5$EOFRORQ\IRUPDWLRQXQGHU7.,H[SRVXUHFRPSDUHGWR)*) L36&WHFKQRORJ\DQGGLUHFWHGGLႇHUHQWLDWLRQWRJHQHUDWH$(&VGH H[RVRPHV:HFRQFOXGHWKDWH[RVRPHVDUHLPSRUWDQWSXUYH\RUV novo would provide novel opportunities to study both normal AEC2 of protective signaling in the leukemia microenvironment and their development and the pathogenesis of monogenic alveolar diseases. SURGXFWLRQLVUHJXODWHGLQSDUWE\)*))*)5DXWRFULQHVLJQDOLQJLQ AEC2s have been challenging to generate in vitro from pluripotent ERQHPDUURZVWURPD,QKLELWLRQRI)*)5FDQLQWHUUXSWWKLVSURWHFWLYH VWHPFHOOV 36&V KRZHYHULQSDUWEHFDXVHDOYHROLDUHDWLVVXHW\SH VWURPDOHXNHPLDLQWHUDFWLRQDQGUHVWRUH7.,VHQVLWLYLW\WROHXNHPLD WKDW DURVH ODWH LQ HYROXWLRQDU\ WLPH H[LVWLQJ RQO\ LQ DLUEUHDWKLQJ cell in the bone marrow niche.

72 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

143 “TIPSTer” to the rescue: A rapid and sensitive method for UHWLFXOXP FDOFLXP VHQVRU 67,0 DQG WKH SODVPD PHPEUDQH GHWHFWLQJWXPRUFHOOVLQSOHXUDOÀXLGIURPOXQJFDQFHUSDWLHQWV SURWHLQ2UDLDFWLYDWH62&(:KLOH2UDL2UDL67,0DQGWKH LQÀDPPDWRU\ PHGLDWRU OHXNRWULHQH& (LTC DFWLYDWHV QRQ62&( 6DPXHO5-HDQ%DSWLVWH University of Pennsylvania, Philadelphia, USA :H KDYH SUHYLRXVO\ VKRZQ WKDW 62&( LV DXJPHQWHG LQ DVWKPD +RZHYHUWKHUROHRIQRQ62&(LQFOXGLQJ67,02UDLDQG2UDL 3OHXUDO HႇXVLRQV 3( LV D SRWHQWLDOO\ OLIHWKUHDWHQLQJ FRQGLWLRQ LQ$60UHPRGHOLQJLVXQFOHDU,WKDVEHHQVKRZQLQYDVFXODUVPRRWK DႉLFWLQJXSWRPLOOLRQSHRSOHLQWKH86HDFK\HDU7KHHWLRORJ\ PXVFOH 960 UHPRGHOLQJWKDWXSUHJXODWLRQRI2UDLDQGQRQ62&( RI3(FDQUDQJHIURPLQÀDPPDWLRQLQIHFWLRQWRFDQFHULWLVHVSHFLDOO\ FDXVHVHQKDQFHGPLJUDWLRQWKURXJKDFWLYDWLRQRIP725$.7$60 HVVHQWLDOWRGHWHUPLQHZKHWKHUDQHႇXVLRQLVRIPDOLJQDQWRULJLQGXH UHPRGHOLQJVKDUHVPDQ\IHDWXUHVZLWK960UHPRGHOLQJ to profound implications for staging and treatment. Analysis of PE YLD VWDQGDUG F\WRORJ\ LV KRZHYHU ODERULQWHQVLYH ODFNV VHQVLWLYLW\ 7KURXJK FXOWXUHG $60 REWDLQHG IURP SRVWPRUWHP KXPDQ OXQJ GRQRUV +$60 WKH &D VLJQDOLQJ RI 2UDL 2UDL DQG 67,0 RUUHTXLUHVODUJHVDPSOHVIRUDFFXUDWHLGHQWL¿FDWLRQRIFDQFHUFHOOV +HUHZHGHVFULEHDQRYHOPHWKRGWRLGHQWLI\FDQFHUFHOOVHႈFLHQWO\ in airway remodeling was investigated. Intracellular Ca in DQGDFFXUDWHO\LQVPDOOVDPSOHVRISOHXUDOÀXLG +$60 ZDV PHDVXUHG XVLQJ IXUD$0 62&( DQG QRQ62&( ZDV demonstrated using the CaRႇ&Don protocol in the presence of We have developed a new diagnostic methodology, which we refer to thapsigargin and physiological agonists. Three normal and asthmatic as Tumor cell IGHQWL¿FDWLRQLQPOHXUDOÀXLGYLD6ize and TelomERase KXPDQGRQRUVGLVSOD\HG62&(DQGZHUHUHYHUVHGWKURXJK62&( DFWLYLW\ RU7,367HU IRUGHWHFWLQJUDUHFDQFHUFHOOVLQOLPLWHGDPRXQWV LQKLELWRUV+$60UHPRGHOLQJWKURXJKFHOOXODUPLJUDWLRQZDVVWXGLHG RI SOHXUDO DQG RWKHU ERGLO\ ÀXLGV 7,367HUHPSOR\V D PLFURÀXLGLF XVLQJWKHZRXQGKHDOLQJDVVD\+$60PLJUDWLRQZDVFRPSDUHGDW EDVHGV\VWHP &HO6HHFKLS WRLVRODWHFDQFHUFHOOVEDVHGRQVL]H DQGKRXUVLQVL2UDLVL2UDLVL67,0DQGQRQWDUJHWLQJVL51$ FHOOVODUJHUWKDQȝP DQGGHIRUPDELOLW\ FDQFHUFHOOVDUHUHODWLYHO\ 7RH[SORUHDPHFKDQLVPSKRVSKRU\ODWLRQRI$.7LQVL67,0VL2UDL more rigid than monocytes) in conjunction with an adenoviral probe DQGVL2UDL+$60ZDVPHDVXUHGZKHQVWLPXODWHGZLWKJURZWKIDFWRUV WKDWGULYHV*)3H[SUHVVLRQLQWKHSUHVHQFHRIWKHHOHYDWHGKXPDQ telomerase promoter activity that is characteristic of almost all cancer ,Q FRQFOXVLRQ WKHVH UHVXOWV HOXFLGDWH D QRYHO FDOFLXPVLJQDOLQJ FHOOV EXW QRW QRUPDO FHOOV 7XPRU FHOOV H[SUHVVLQJ *)3 DUH WKHQ SDWKZD\ WKURXJK QRQ62&( DQG P725$.7 WKDW DOORZV +$60 LGHQWL¿HGEDVHGRQVL]HVKDSHDQGÀXRUHVFHQFHLQWHQVLW\ remodeling and pathogenesis of asthma. Further studies unraveling this pathway will reveal novel therapeutic targets in asthma. :H ¿UVW WHVWHG DQG YDOLGDWHG7,367HULQ KXPDQ OXQJ FDQFHU FHOOV LQFXOWXUHDQGVSLNHGLQWRFRQWUROEORRG7RFRQ¿UPWKDWWKH*)3 145 &KDUDFWHUL]DWLRQ RI 7UDQVIRUPLQJ 175. DQG 175. H[SUHVVLQJ WXPRU FHOOV LVRODWHG YLD 7,367HUZHUH RI WXPRU RULJLQ 0XWDWLRQVLQ/HXNHPLD ZH DVVHVVHG IRU WK\URLG WUDQVFULSWLRQ IDFWRU 77) DQG 1DSVLQ Sunil K. Joshi $ H[SUHVVHG UHVSHFWLYHO\ E\ ZHOO DQG SRRUO\ GLႇHUHQWLDWHG OXQJ Knight Cancer Institute, Oregon Health & Science University, DGHQRFDUFLQRPD 7KH XVHIXOQHVV RI 77) DQG 1DSVLQ $ IRU Portland, USA WKLV SXUSRVH ZDV SUHYLRXVO\ FRQ¿UPHG YLD ZHVWHUQ EORWWLQJ DQG ,QWURGXFWLRQ 7KH QHXURWURSKLF W\URVLQH UHFHSWRU NLQDVHV 175. LPPXQRÀXRUHVFHQFH VWDLQLQJ RI SRVLWLYH DQG QHJDWLYH FRQWURO FHOO are a family of neuronal transmembrane receptors that comprise of OLQHV 7R VLPXODWH D SDWLHQW 3( VDPSOH 8 FHOOV WDJJHG ZLWK an: extracellular domain for ligand binding, transmembrane domain, P&KHUU\ZHUHVSLNHGLQWRÀXLGVRIKXPDQRULJLQDQGWKHQLVRODWHG and intracellular domain with kinase activity. These receptors signal YLDD&HO6HHPLFURÀXLGLFFKLSWRYDOLGDWHLWVDSSOLFDELOLW\LQFDSWXULQJ WKURXJKVHYHUDOSDWKZD\VLQFOXGLQJ-$.67$73,.$.7DQG0(. tumor cells. Finally, we show that malignant cells can be successfully (5.WRSURPRWHSUROLIHUDWLRQGLႇHUHQWLDWLRQDQGVXUYLYDO$OWKRXJK LGHQWL¿HGLQPO3(VDPSOHVIURPSDWLHQWVZLWKQRQVPDOOFHOOOXQJ much of the literature has focused on the importance of these FDQFHUYLDWKH7,367HUPHWKRG receptors in neuronal development, over the past decade, gene We present promising preclinical and clinical results with this method. IXVLRQV FRQWDLQLQJ 175. IDPLO\ PHPEHUV KDYH EHHQ LPSOLFDWHG This method should be useful for rapidly assessing if PE (or other in driving tumor growth in salivary gland, breast, lung, colon, and ERGLO\ÀXLGV DUHGXHWRPDOLJQDQWGLVHDVH)XUWKHUPRUHGRZQVWUHDP neuronal cancers. molecular analysis such as for next generation genetic sequencing 0RUHRYHU H[SUHVVLRQ RI 175. DQG 175. KDV EHHQ UHSRUWHG UHTXLUHFHOOVRIVXEVWDQWLDOTXDOLW\DQGTXDQWLW\ZKLFK7,367HUFRXOG in lymphoid and myeloid malignancies (Li, Z HW DO %ORRG provide. We describe future plans for further validation including ,QWHUHVWLQJO\ 175. H[SUHVVLRQ KDV EHHQ DVVRFLDWHG ZLWK SRRUHU WRLGHQWLI\WDUJHWDEOHSUHH[LVWLQJPXWDWLRQ V RIGULYHUPXWDWLRQVLQ prognosis (Hillis, J HW DO &HOOXODU DQG 0ROHFXODU /LIH 6FLHQFHV JHQHVVXFKDV.5$6DQG()*5LQWXPRUFHOOVLVRODWHGIURP3(DQG 'HVSLWH WKHVH LQLWLDO VWXGLHV WKH UROH RI 175. UHFHSWRUV matched blood samples. ODUJHO\ UHPDLQV XQGHULQYHVWLJDWHG LQ WKH VHWWLQJ RI KHPDWRORJLF 144 The Role of STIM1, Orai1 and Orai3 in Regulating ASM PDOLJQDQFLHV +HUHLQ ZH GHVFULEH VRPDWLF PXWDWLRQV LQ 175. Remodeling in Asthma DQG175.WKDWZHUHLGHQWL¿HGXVLQJQH[WJHQHUDWLRQVHTXHQFLQJ 0DUWLQ-RKQVRQ of primary leukemia patient samples. We evaluated changes in Penn State, Hummelstown, USA downstream signaling driven by these mutations in our previously validated Ba/F3 transformation model system. Lastly, we demonstrate $VWKPDLVDFKURQLFREVWUXFWLYHSXOPRQDU\GLVHDVHWKDWDႇHFWV WKDWVHOHFWLYHLQKLELWLRQRI175.DQG175.ZLWKHQWUHFWLQLEDZHOO million people worldwide. A major pathological hallmark of asthma is YDOLGDWHG175.LQKLELWRUFXUUHQWO\LQFOLQLFDOWULDOVIRU175.IXVLRQ DLUZD\VPRRWKPXVFOH $60 UHPRGHOLQJZKLFKLVFKDUDFWHUL]HGE\ positive cancers, can inhibit proliferation and induce apoptosis of $60SUROLIHUDWLRQDQGPLJUDWLRQ&DOFLXP &D ) is a major regulator 175.WUDQVIRUPHGFHOOV RI$60UHPRGHOLQJ&D entry channels including those activated by depletion of internal CaVWRUHV 6WRUHG2SHUDWHG&DOFLXP(QWU\ 5HVXOWV :H IRXQG WZR SRLQW PXWDWLRQV LQ 175. WKDW ZHUH 62&( DQGWKRVHLQGHSHQGHQWRI&DGHSOHWLRQ QRQ62&( KDYH transforming — one in the extracellular domain (A203T) and one UHFHQWO\ EHHQ LPSOLFDWHG LQ $60 UHPRGHOLQJ 7KH VDUFRSODVPLF LQ WKH MX[WDPHPEUDQH GRPDLQ 5* 6LPLODUO\ ZH IRXQG WZR

www.jointmeeting.org 73 POSTER ABSTRACTS

SRLQWPXWDWLRQVWKDWZHUHWUDQVIRUPLQJLQ175.2QHZDVLQWKH WKHVHFHOOVFRQWDLQSURPLQHQWF\WRSODVPLF³VWUHVV´¿EHUVSLQRF\WLF H[WUDFHOOXODUGRPDLQ (' DQGWKHRWKHUZLWKLQWKHWUDQVPHPEUDQH vesicles, lysosomes, phagocytosed cells and debris. GRPDLQ /) The morphologic appearance as well as presence of a unique Immunoblot results suggest that expression of total and spectrum of antigens on LCs, support the hypothesis that LCs serve SKRVSKRU\ODWHG 175. DQG 175. LV LQFUHDVHG LQ PXWDQW DVDPDMRU¿OWHURIFLUFXODWLQJFHOOVDQGSDWKRJHQVGHWHUPLQLQJZKLFK WUDQVIRUPHG %D) FHOOV UHODWLYH WR ZLOGW\SH FHOOV )XUWKHUPRUH products will return to the general circulation. The mechanisms that 175. DQG 175. PXWDQWGULYHQ FHOOV H[KLELWHG HQKDQFHG they use to achieve to process circulating pathogens, altered cells, SKRVSKRU\ODWLRQRI$.765&DQG(5.FRPSDUHGWRZLOGW\SHFHOOV aged erythrocytes, and other debris (e.g. directly (phagocytosis, :KLOHSKRVSKRU\ODWLRQRI67$7ZDVVLJQL¿FDQWO\LQFUHDVHGLQ%D) entosis) or by presenting them to the neighboring T cells and the FHOOVWUDQVIHFWHGZLWKERWK175.PXWDQWVLWZDVLQFUHDVHGRQO\LQ macrophages) are entirely unknown. Our current work is focused on RQHRIWKH175.PXWDQWV $7 establishment of a platform for characterization of LCs in situ and 8SRQWUHDWLQJ175.PXWDQWWUDQVIRUPHG%D)FHOOVZLWKHQWUHFWLQLE HOXFLGDWLQJWKHFHOOXODUPHFKDQLVPVWKH\XWLOL]HWRSURFHVVGLႇHUHQW Q0 ZH REVHUYHG D GRVHGHSHQGHQW GHFUHDVH LQ cells, pathogens and particles. Work on visualization of LCs in WRWDODQGSKRVSKRU\ODWHG175.DQG175.LQDOOPXWDQWVH[FHSW VLWXWKURXJKDGYDQFHGPLFURVFRS\SXUL¿FDWLRQDQGFXOWXULQJXVLQJ IRU175.PXWDQW5*:LWK5*WRWDODQGSKRVSKRU\ODWHG VSHFLDOL]HGPHGLDWRVXSSRUWH[YLYRVXUYLYDOZLOOEHUHSRUWHGDVD 175. H[SUHVVLRQ GHFUHDVHG XS WR Q0 RI HQWUHFWLQLE EXW WKDW prelude to experiments that address the mechanism(s) by which HႇHFWZDVGLPLQLVKHGDWQ0 GLႇHUHQWFHOOW\SHVDUHSURFHVVHGE\/&V Conclusions: Taken together, our data demonstrates mutations 147 6WUXFWXUDOWRROVIRUFOLQLFDOSUREOHPV8ELTXLWLQVSHFL¿F LQ 175. DQG 175. KDYH WUDQVIRUPDWLYH SRWHQWLDO WR SURPRWH protease 7 and p53, a critical regulatory complex in cancer downstream survival signaling and leukemogenesis. More Timofey Karginov importantly, these activated pathways can be pharmacologically Department of Molecular Biology and Biophysics, University of DWWHQXDWHG XVLQJ HQWUHFWLQLE 2XU ¿QGLQJV FRQWULEXWH WR RQJRLQJ Connecticut Health Center, New Britain, USA HႇRUWV WR XQGHUVWDQG PROHFXODU FKDQJHV WKDW GULYH KHPDWRORJLFDO 8ELTXLWLQVSHFL¿FSURWHDVH 863 LVDGHXELTXLWLQDVHUHJXODWLQJ malignancies and could potentially alter current treatment modalities. WXUQRYHU RI SURWHLQV LQYROYHG LQ WXPRU VXSSUHVVLRQ '1$ GDPDJH 146 Littoral Cells of the Human Spleen: A Specialized Barrier DQG LPPXQH UHVSRQVH 863 FRQVLVWV RI D WXPRU QHFURVLV IDFWRU Cell? UHFHSWRUDVVRFLDWHGIDFWRU 75$) OLNHGRPDLQDWLWV1WHUPLQXVD Sandeep Jubbal FDWDO\WLFGRPDLQDQG¿YH8ELTXLWLQOLNHUHJLRQV 8EO 6WUXFWXUHV University of Massachusetts Medical School, Marlborough, RI DOO LQGLYLGXDO GRPDLQV RI 863 KDYH EHHQ UHVROYHG +RZHYHU USA WKHWHUWLDU\IROGLQJRIWKHIXOOOHQJWKSURWHLQLVFXUUHQWO\XQNQRZQD IXOOOHQJWK VWUXFWXUH RI 863 FRXOG VXEVHTXHQWO\ KHOS WR HOXFLGDWH Human spleen was historically viewed as a vestigial organ that WKLVIROGLQJSDWWHUQDVZHOODVELQGLQJRI863WRLWVVXEVWUDWHV7KH was not critical for survival, thus early studies were limited. In the 75$)OLNHGRPDLQRI863LVNQRZQWRELQGWRWKHWUDQVFULSWLRQIDFWRU VDYLWDOUROHLQWKHUHJXODWLRQRI5%&WXUQRYHUDQGSUHYHQWLRQ p53, a tumor suppressor involved in cell cycle arrest and apoptosis of sepsis was established. More recently, functions in the prevention WKDWLVRIWHQIRXQGPXWDWHGLQFDQFHUV,QRUGHUWRLQYHVWLJDWH863¶V RILVFKHPLFKHDUWGDPDJHVHYHUDOFDQFHUVDXWRLPPXQHDQGHYHQ IXOOOHQJWK VWUXFWXUH ZH VXFFHVVIXOO\ SXUL¿HG IXOOOHQJWK 863 DQG metabolic diseases have been revealed based on epidemiologic observed complex formation with a recombinant p53 construct. We research. further conducted both negative stain electron microscopy as well The spleen is the largest secondary lymphoid organ in humans though DV FU\RHOHFWURQ PLFURVFRS\ H[SHULPHQWV WR HOXFLGDWH VWUXFWXUH LWLVXQLTXHO\DFFHVVHGE\WKHFLUFXODWRU\V\VWHP8QOLNHO\PSKQRGHV DQG ELQGLQJ SDWWHUQV RI IXOOOHQJWK 863 DQG 863S FRPSOH[ WKHVSOHHQODFNVDQDႇHUHQWO\PSKDWLFVXSSO\DQGLVQRWFRQQHFWHG Here, we demonstrate supporting evidence for production of both to the lymphatic system. Only cells and pathogens that circulate are 863DQG863SFRPSOH[7KHVHUHVXOWVFDQIXUWKHUEHXVHGWR interrogated, destroyed and/or released from spleen. Human spleen GHWHUPLQHWKHVWUXFWXUHRIIXOOOHQJWK863DQGLQYHVWLJDWHELQGLQJRI is highly vascularized and has a unique open microcirculation. SWR863*LYHQ863¶VUHJXODWLRQDQGELQGLQJRISDVZHOODV 6SOHQLFDUWHULROHVDQGWKHFDSLOODULHVGRQRWGUDLQLQWRYHQXOHVEXW LWVUROHLQFDQFHUVFKDUDFWHUL]DWLRQRI863VWUXFWXUHDQGVXEVWUDWH instead release blood directly into an open meshwork of reticular binding would help to elucidate interactions that could be targeted for ¿EHUV%ORRGLVWKHQFROOHFWHGLQWRVPDOOFDYLWLHVFDOOHGWKHYHQRXV inhibition and subsequent use in cancer therapy. sinuses lined by a uniquely human cell population known as littoral FHOOV /&V /&V UHJXODWH WKH LQWHUFHOOXODU VOLW VL]H WKDW IDFLOLWDWHV 148 $FWD 5& PXWDWLRQ FDXVHV DWKHURVFOHURVLV YLD return of passenger cells and particles to the circulation. The precise SUROLIHUDWLYHDQGLQÀDPPDWRU\SDWKZD\V mechanism(s) through which this is achieved is unknown. RBCs Kaveeta Kaw DQGRWKHUFHOOVPXVWGHIRUPWRVTXHH]HWKURXJKWKHVHQDUURZLQWHU University of Texas Health Science Center at Houston, cellular slits from outside to inside the venous sinuses or many pass Houston, USA through these cells in a process known as transcytosis. +HWHUR]\JRXV PLVVHQVH PXWDWLRQV LQ $&7$ DFFRXQW IRU RI LCs emerged late in evolution only in higher primates. They exhibit IDPLOLDODVFHQGLQJWKRUDFLFDRUWLFDQHXU\VPVDQGGLVVHFWLRQV 7$$' a unique phenotype as they express antigens common not only to 3DWLHQWVFDUU\LQJWKH$&7$5YDULDQWDUHSUHGLVSRVHGWRERWK HQGRWKHOLDO FHOOV &' EXW DOVR WR PDFURSKDJHV PDFURSKDJH 7$$'DQGHDUO\RQVHWFRURQDU\DUWHU\GLVHDVH7RXQGHUVWDQGZK\ PDQQRVHUHFHSWRUVLJQDOUHJXODWRU\SURWHLQDOSKD6,53Į VPRRWK this mutation leads to two distinct disease processes and which PXVFOHFHOOV IRUPLQKRPRORJ\SURWHLQ)+2' DQGO\PSKRLGFHOOV molecular mechanisms underlie the pathology, our lab utilized &'Į WKRXJKWKH\ODFNWKHFRPPRQOLQHDJHDVVRFLDWHGPDUNHUV &5,635&DVWHFKQRORJ\WRJHQHUDWHDWUDQVJHQLFPRXVHPRGHO &' HQGRWKHOLDO DQG &' KHPDWRSRLHWLF 0RUSKRORJLFDOO\ $FWD5& 7KH $FWD5& PRXVH GRHV QRW VKRZ DRUWLF

74 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

enlargement; however the mouse has increased atherosclerotic Methods: &PDKGH¿FLHQW&PDK-/- and WT mice were bred into an SODTXH EXUGHQ ZKHQ FURVVHG LQWR DQ$SR( EDFNJURXQG DQG IHG Ldlr-/-EDFNJURXQGDQGIHGD1HX*FIUHHKLJKIDWGLHW +)' WRLQGXFH DKLJKIDWGLHW,QWHUHVWLQJO\WKHUHLVQRVLJQL¿FDQWGLႇHUHQFHLQOLSLG DWKHURJHQHVLVDQGDVVHVVWKHLPSDFWRI&0$+ORVV1H[WCmah-/- OHYHOV EHWZHHQ WKH$SR( PRXVH DQG WKH$SR($FWD5F Ldlr-/-PLFH ZHUH LPPXQL]HG ZLWK FRQWURO DQWLJHQV RU ZLWK 1HX*F double mutant. Both smooth muscle cell proliferation and EHDULQJ DQWLJHQV WR JHQHUDWH KXPDQOLNH OHYHOV RI DQWL1HX*F LQÀDPPDWLRQ KDYH EHHQ VKRZQ WR EH LQYROYHG LQ DWKHURVFOHURWLF DQWLERGLHVDQGVXEVHTXHQWO\IHGD1HX*FULFKGLHWWRGHWHUPLQH SODTXHSDWKRJHQHVLV$FWD5&VPRRWKPXVFOHFHOOV 60&V DUH WKHFRQWULEXWLRQRIGLHWLQGXFHG[HQRVLDOLWLVRQDWKHURJHQHVLV PRUHSUROLIHUDWLYHWKDQZLOGW\SHFHOOVLQFXOWXUH7KH$FWD5& Result: Cmah-/- Ldlr-/-PLFHKDGLQFUHDVHGDWKHURJHQHVLVRQD+)' mouse does not have reduced contractile gene expression or altered compared to Cmah+/+Ldlr-/-mice. This was not associated with ORFDOL]DWLRQ RI 057)$ VXJJHVWLQJ WKDW SUROLIHUDWLRQ LV QRW GXH WR cytokine levels in plasma, but increased cytokine expression was FODVVLFSKHQRW\SLFLFVZLWFKLQJ:HSUHYLRXVO\LGHQWL¿HGDSDWKZD\ seen in Cmah-/-Ldlr-/- macrophages in comparison to Cmah+/+Ldlr-/-. involving focal adhesion kinase, altered cellular p53 localization, The baseline relative hyperglycemia of the Cmah-/-Ldlr-/-mice was DQG LQFUHDVHG H[SUHVVLRQ RI 3'*)5 DV WKH PHFKDQLVP GULYLQJ also enhanced on a HF diet. When such mice were immunized LQFUHDVHG SUROLIHUDWLRQ LQ$FWD 60&V$FWD5& FHOOV DOVR WR GHYHORS KXPDQOLNH OHYHOV RI DQWL1HX*F DQWLERGLHV WKH\ have altered focal adhesions, but it is not yet established whether KDG D IROG LQFUHDVH LQ DWKHURVFOHURVLV RQ D 1HX*FULFK +)' the same pathway drives proliferation in these cells. Additionally, we FRPSDUHG WR FRQWURO 1HX$FULFK RU VLDOLF DFLGIUHH +)' IHHGLQJ KDYHIRXQGLQFUHDVHGLQÀDPPDWRU\PDUNHUVLQ$FWD5&DRUWDV 'UDVWLFDOO\DGYDQFHGOHVLRQVZLWKLQFUHDVHGQHFURWLFFRUHDUHDVDQG DWVL[PRQWKVRIDJH60&VFDQWUDQVGLႇHUHQWLDWHLQWRPDFURSKDJHV LQ¿OWUDWLRQ RI PDFURSKDJHV DQG 7FHOOV DFFRPSDQLHG LQFUHDVHV LQ in atherosclerotic plaques; to model this in culture we conducted a DWKHURVFOHURWLFDUHDDQGOHVLRQYROXPH1RQHRIWKHVHGLႇHUHQFHV FKROHVWHUROORDGLQJH[SHULPHQWDQG$FWD5&FHOOVZHUHIRXQG ZHUHH[SODLQHGE\FKDQJHVLQOLSRSURWHLQSUR¿OHVRULQVXOLQVHQVLQJ to express macrophage markers at a much lower cholesterol dose WKDQZLOGW\SHFHOOV7DNHQWRJHWKHURXUGDWDVXJJHVWVWKDWPXWDQW Conclusion: Human evolutionary loss of &0$+ likely contributes to 60&V DUH SURQH WR ERWK LQFUHDVHG SUROLIHUDWLRQ DQG LQÀDPPDWLRQ atherosclerosis propensity, via both intrinsic mechanisms such as DQG ERWK PHFKDQLVPV PD\ H[SODLQ ZK\ $FWD5& PLFH DUH DPSOL¿HG FKURQLF LQÀDPPDWRU\ UHVSRQVH DQG K\SHUJO\FHPLD DQG SURQHWRDWKHURVFOHURVLV)XWXUHVWXGLHVZLOOLQYHVWLJDWHWKHVSHFL¿F H[WULQVLF PHFKDQLVPV VXFK DV UHG PHDWGHULYHG 1HX*FLQGXFHG PHFKDQLVPVOLQNLQJWKH5PXWDWLRQLQDFWLQZLWKSUROLIHUDWLRQDQG xenosialitis. LQÀDPPDWLRQWRGHWHUPLQHKRZWKLVPXWDWLRQFDXVHVDWKHURVFOHURVLV 150 High resolution immune function analyses reveal 149 +XPDQ VSHFLHVVSHFL¿F ORVV RI WKH &03N- markedly attenuated IL-7 signaling function restricted to the acetylneuraminic Acid Hydroxylase fuels atherosclerosis &'7FHOOFRPSDUWPHQWLQDQLPPXQHFRPSURPLVHGQHRQDWH development via intrinsic and extrinsic mechanisms Aaruni Khanolkar Kunio Kawanishi Ann and Robert H. Lurie Children’s Hospital of Chicago; Department of Cellular and Molecular Medicine, University of Northwestern University, Chicago, USA California, San Diego, La Jolla, USA A female infant was referred to our institution on day nine of life ,QWURGXFWLRQ &DUGLRYDVFXODU GLVHDVH &9' HYHQWV GXH WR following a T cell receptor excision circle count of zero (normal value atherosclerosis are very common in humans, but rarely occur ȝ/RIEORRG REVHUYHGGXULQJWKHPDQGDWRU\VWDWHZLGHQHZERUQ spontaneously in other mammals, absent experimental manipulation. VFUHHQIRUVHYHUHFRPELQHGLPPXQRGH¿FLHQF\ 6&,' /RQJLWXGLQDO &9'HYHQWVDUHUDUHHYHQLQFORVHO\UHODWHGFKLPSDQ]HHVLQFDSWLYLW\ analyses of circulating lymphocytes revealed a persistent paucity of T GHVSLWHKXPDQOLNHDWKHURJHQLFEORRGOLSLGSUR¿OHVK\SHUWHQVLRQDQG FHOOV &'7FHOOV &'7FHOOV ZKLOHWKH%FHOODQG1.FHOOFRXQWV VHGHQWDU\OLIHVW\OH$OOKXPDQVH[KLELWDVSHFLHVVSHFL¿FGH¿FLHQF\ ZHUHFRQVLVWHQWO\ZLWKLQWKHDJHDVVRFLDWHGQRUPDOUDQJHVDVZHUH of the common mammalian sialic acid NJO\FRO\OQHXUDPLQLF DFLG WKHDVVHVVPHQWVIRUVHUXPLPPXQRJOREXOLQV6WULQJHQWDQWLPLFURELDO 1HX*F GXHWRSVHXGRJHQL]DWLRQRIWKH&03NDFHW\OQHXUDPLQLF prophylaxis was initiated from the time of initial referral and the patient’s DFLG 1HX$F K\GUR[\ODVH &0$+ JHQH ZKLFK RFFXUUHG LQ FDUHJLYHUV ZHUH LQVWUXFWHG WR DYRLG OLYHYDFFLQH DGPLQLVWUDWLRQ KRPLQLQDQFHVWRUVDERXWPLOOLRQ\HDUVDJR+XPDQOLNHCmah- Maternal T cell engraftment was ruled out by chimerism analyses /-PLFHWKDWH[SUHVVRQO\WKHSUHFXUVRUVLDOLFDFLG1HX$FDUHPRUH DV ZHUH 'L*HRUJH 6\QGURPH E\ PXOWLSOH[ OLJDWLRQGHSHQGHQW prone to insulin resistance and have more reactive macrophages SUREHDPSOL¿FDWLRQ DQG%DUH/\PSKRF\WH6\QGURPHV7\SHV,DQG DQG 7 FHOOV +XPDQ GLHWDU\ FRQVXPSWLRQ RI 1HX*F SULPDULO\ ,,E\ÀRZF\WRPHWU\0LWRJHQLQGXFHGO\PSKRF\WHSUROLIHUDWLRQZDV from red meat), can acts as a foreign “xenoantigen” in humans that normal albeit lower compared to the control sample assessed in gets metabolically incorporated into endogenous glycoproteins. SDUDOOHO*LYHQWKHFULWLFDOUROH,/SOD\VLQ7FHOOGHYHORSPHQWDQG +XPDQV ZLWK FLUFXODWLQJ DQWL1HX*F ³[HQRDXWRDQWLERGLHV´ FDQ KRPHRVWDVLVZHQH[WLQYHVWLJDWHGDEHUUDWLRQVLQWKH,/VLJQDOLQJ WKXVSRWHQWLDOO\GHYHORSORFDOFKURQLFLQÀDPPDWLRQRU³[HQRVLDOLWLV´ D[LV:HGHWHFWHGKLJKHUWKDQQRUPDOOHYHOVRISODVPD,/OHYHOV DW VLWHV RI 1HX*F DFFXPXODWLRQ VXFK DV HQGRWKHOLDO FHOOV DQG LQ LQ WKH SDWLHQW DQG PDUNHG GRZQUHJXODWLRQ RI ,/ UHFHSWRU Į ,/ DWKHURVFOHURWLF SODTXHV 1RWDEO\ GLHWDU\ UHG PHDWDVVRFLDWHG 5Į &' H[SUHVVLRQ VSHFL¿FDOO\ RQ WKH SDWLHQW¶V &' 7 FHOOV HQKDQFHPHQW RI &9' LV QRW VHHQ LQ RWKHU FDUQLYRURXV PDPPDOV DVZHOODOPRVWFRPSOHWHDEURJDWLRQRI&'7FHOODVVRFLDWHGVLJQDO and the human risk is typically explained by increased cholesterol WUDQVGXFHU DQG DFWLYDWRU RI WUDQVFULSWLRQ 67$7 SKRVSKRU\ODWLRQ and saturated fat in red meat, conversion of choline and carnitine into E\ SKRVÀRZ DQDO\VLV IROORZLQJ WUHDWPHQW RI WKH SDWLHQW¶V ZKROH WULPHWK\ODPLQH1R[LGHDQGRUR[LGDQWGDPDJHGXHWRGLHWDU\KHPH EORRG VDPSOH ZLWK UHFRPELQDQWKXPDQ ,/ 6LPLODU WUHDWPHQW RI iron. However, none of these mechanisms fully explain the human WKH SDWLHQW VDPSOH ZLWK ,/ GLG QRW UHYHDO DQ LQKLELWLRQ RI 67$7 SURSHQVLW\IRUDWKHURVFOHURVLVQRUWKHUHGPHDWVSHFL¿FQDWXUHRIWKH SKRVSKRU\ODWLRQ WKHUHE\ UXOLQJ RXW DQ\ LQWULQVLF IXQFWLRQDO GH¿FLWV dietary component of risk. LQ WKH VLJQDOLQJ FRPSRQHQWV VKDUHG E\ WKH WZR SDWKZD\V >67$7 FRPPRQȖFKDLQDQG-DQXV.LQDVH -$. @)ORZF\WRPHWU\DOVR +\SRWKHVLV+XPDQ&0$+GH¿FLHQF\FRQWULEXWHVWR&9'YLDPXOWLSOH revealed normal cytosolic expression of the JAK3 protein in the intrinsic and extrinsic mechanisms.

www.jointmeeting.org 75 POSTER ABSTRACTS

patient’s T cells. However, whole exome sequencing revealed that rates may arise from distinct mechanisms in each disease subtype. the patient was a compound heterozygote for two -$. variants [the Together, the results from the cardiomyocyte and skeletal muscle SDWHUQDOO\GHULYHGF&!7 S5& DQGWKHPDWHUQDOO\GHULYHG PRGHOVWRJHWKHULPSOLFDWHWKDW'0DQG'0ZKLOHERWKQXFOHRWLGH F*!$ S(. YDULDQWV@Homozygous5&-$. variant repeat expansion disorders, have distinct pathogenetic mechanisms. KDVEHHQGHVFULEHGWREHDVVRFLDWHGZLWKDW\SLFDO7%1.6&,' DQG (. LV SUHGLFWHG WR EH D YDULDQW RI XQFHUWDLQ VLJQL¿FDQFH 152 Combinations of Health Status, Access, and Demographic 7 FHOO DVVRFLDWHG ,/5Į H[SUHVVLRQ DQG ,/ VLJQDOLQJ DQDO\VHV Variables that Predict Cancer History performed on samples from the patient’s parents and siblings failed Uriel Kim to demonstrate similar aberrations thereby casting doubt on the role Case Western Reserve University, Cleveland, USA of the JAK3 variants in inducing the immunopathology observed Traditional research in disparities employs parametric regression LQ RXU SDWLHQW ,W LV OLNHO\ WKDW XQLGHQWL¿HG YDULDQWV LQ WKH UHOHYDQW methods that identify independent risk factors for disparities. regulatory regions of the genome could likely be contributing to the 8VLQJ WKLV UHGXFWLRQLVW DSSURDFK PDQ\ LQGHSHQGHQW ULVN IDFWRUV REVHUYHGLPPXQRORJLFDO¿QGLQJVLQRXUSDWLHQW7KHSDWLHQWUHFHQWO\ IRU FDQFHU GLVSDULWLHV KDYH EHHQ LGHQWL¿HG LQFOXGLQJ UDFHHWKQLFLW\ XQGHUZHQWDKHPDWRSRLHWLFVWHPFHOOWUDQVSODQW +6&7 DQGLVEHLQJ socioeconomic status, health behavior, and health care access. followed up in the stem cell clinic at our institution. In reality, risk factors occur in constellations, and distinct patterns of risk may emerge because of the intersection, interaction, and 5HSURJUDPPHGKXPDQFHOOVLGHQWLI\GLVWLQFWSDWKRJHQLF 151 interdependence of many factors. Thus, this study aimed to identify mechanisms in myotonic dystrophy disease subtypes FRPELQDWLRQV RI ULVN IDFWRUV WKDW SUHGLFW FDQFHU KLVWRU\ 'DWD IURP Ellis Y. Kim WKH 2KLR 0HGLFDLG$VVHVVPHQW 6XUYH\ 20$6 D FRPSOH[ University of Chicago, Chicago, USA GHVLJQHG GXDOIUDPH UDQGRP GLJLW GLDO WHOHSKRQH VXUYH\ ZDV 0\RWRQLFG\VWURSKLHVW\SHDQGW\SH '0DQG'0UHVSHFWLYHO\ DQDO\]HG )RU D UHSUHVHQWDWLYH VDPSOH RI DOO 2KLRDQV DUHQXFOHRWLGHUHSHDWH[SDQVLRQGLVRUGHUVZKHUH'0LVFKDUDFWHUL]HG $GXOWV WKH 20$6 UHSRUWHG RQ WKH UHVSRQGHQWV¶ KHDOWK VWDWXV JHQHWLFDOO\E\&7*WULQXFOHRWLGHUHSHDWH[SDQVLRQLQWKH'03. gene insurance status, and use of preventive and other health services. DQG'0E\&&7*WHWUDQXFOHRWLGHUHSHDWH[SDQVLRQLQWKH&1%3 7KH DQDO\VLV XVHG D PDFKLQHOHDUQLQJ QRQSDUDPHWULF WHFKQLTXH JHQH ,Q '0 WUDQVFULSWLRQ RI QXFOHRWLGH UHSHDW VHTXHQFHV OHDGV FDOOHG FODVVL¿FDWLRQ DQG UHJUHVVLRQ WUHH &$57 DQDO\VLV ZKLFK WRWKHIRUPDWLRQRILQWUDQXFOHDUGRXEOHVWUDQGHG51$IRFLWKDWELQG H[DPLQHG DOO WKH PDLQ HႇHFWV DQG SRVVLEOH LQWHUDFWLRQV RI VSOLFLQJIDFWRUVLQFOXGLQJWKHPXVFOHEOLQGOLNH 0%1/ IDPLO\RI51$ FRYDULDWHV7KHFRYDULDWHVZHUHEURDGO\FODVVL¿HGLQWRPHDVXUHVRI ELQGLQJ SURWHLQV UHVXOWLQJ LQ D IXQFWLRQDO GHSOHWLRQ LQ 0%1/ DQG health care access, health status, health behavior, and demographic PLVVSOLFLQJ RI GRZQVWUHDP JHQHV 6SHFL¿F PLVVSOLFLQJ HYHQWV DUH characteristics. There were ultimately 25 unique combinations of WKRXJKW WR FRQWULEXWH WR GLVWLQFW DVSHFWV RI SDWKRJHQHVLV LQ '0 covariates (termed “phenotypes”) associated with cancer history including muscle myotonia and cardiac dysfunction. The degree (“never diagnosed with cancer” or “diagnosed with cancer”). WR ZKLFK WKLV VDPH SDWKRJHQHWLF PHFKDQLVP FDXVHV '0 LV QRW *HQHUDOO\WKHORZULVNSKHQRW\SHVZHUHFRQVWLWXWHGE\³\RXQJHU´DJH NQRZQ DV WKH YHU\ ODUJH UHSHDWV WKDW FKDUDFWHUL]H '0 KDYH QRW LQGLYLGXDOV XQGHU\HDUVROG DQGWKHKLJKULVNSKHQRW\SHVZHUH EHHQHႇHFWLYHO\PRGHOHG7RHYDOXDWHZKHWKHUWKHVHPHFKDQLVPV FRQVWLWXWHGE\³ROGHU´DJHLQGLYLGXDOV RYHU\HDUVROG 7KHUHZDV DUHVKDUHGRUGLVWLQFWEHWZHHQ'0DQG'0ZHXVHGGLUHFWDQG a “negative deviant phenotype” associated with many more cancer LQGLUHFWO\ UHSURJUDPPHG XULQHGHULYHG FHOOV IURP KXPDQ SDWLHQWV cases than expected. This phenotype was constituted by younger, with myotonic dystrophy, evaluating both skeletal muscle and cardiac rural Appalachian females reporting fair health without disabling PXVFOH PRGHOV &DUGLRP\RF\WHV ZHUH GLႇHUHQWLDWHG IURP LQGXFHG mental conditions. In the highest risk phenotype, approximately SOXULSRWHQWVWHPFHOOV L36&V FRQWUROQ '0Q '0Q RI WKH LQGLYLGXDOV KDYH EHHQ GLDJQRVHG ZLWK FDQFHU 7KLV DQG VNHOHWDO P\RF\WHV ZHUH GLႇHUHQWLDWHG IURP FHOOV XVLQJ 0\R' phenotype was constituted by “older” age, widowed individuals who RYHUH[SUHVVLRQ FRQWURO Q '0 Q '0 Q %RWK '0 VHOIUHSRUWHG IDLU RU SRRU KHDOWK KDYH QRW KDG PDMRU PHGLFDO ELOOV cardiomyocytes and skeletal muscles demonstrated intranuclear recently, and have had at least one emergency visit in the past year. 0%1/FOXVWHUVZKHUHDVQRGLVWLQFW0%1/FOXVWHUVZHUHREVHUYHGLQ In conclusion, there is considerable variation in the “phenotypes” that '0DQGFRQWUROFHOOV:KHQ0%1/WDUJHWJHQHVLQFDUGLRP\RF\WHV SUHGLFWFDQFHUKLVWRU\0RGHOLQJWKHFRPELQDWRU\HႇHFWVRIFRYDULDWHV ZHUHSUREHGXVLQJ573&5'0GLVSOD\HGPLVVSOLFLQJLQ6&1$, advances the understanding of the subpopulations at the highest risk $1., and 5<5 ZKLOH '0 FHOOV KDG VSOLFLQJ SDWWHUQV VLPLODU of cancer history, and can inform precision public health interventions WR FRQWURO FHOOV 6LPLODUO\ ZKHQ VNHOHWDO PXVFOHV ZHUH SUREHG IRU aimed at reducing cancer disparities. PLVVSOLFHGJHQHV'0EXWQRW'0FHOOVVKRZHGDVKLIWWRZDUGV embryonic splicing pattern in genes such as INSR, mTTN, ]771, 153 5HYHUEĮ G\QDPLFDOO\ PRGXODWHV FKURPDWLQ ORRSLQJ WR 6(5&$, and =$63 7KHVH ¿QGLQJV VXJJHVW GLVWLQFW SDWKRJHQHWLF control circadian gene transcription PRGHOVIRU'0DQG'0ZKHUH0%1/VHTXHVWUDWLRQDQGPLVVSOLFLQJ Yong Hoon Kim HYHQWV FKDUDFWHUL]H '0 EXW QRW '0 :H DOVR VWXGLHG FDOFLXP Perelman School of Medicine at the University of KDQGOLQJSURSHUWLHVZLWK,QGRG\HE\SDFLQJWKHFDUGLRP\RF\WHVDW Pennsylvania, Philadelphia, USA IRXUGLႇHUHQWIUHTXHQFLHV DQG+]DYHUDJHRI 0DPPDOLDQ SK\VLRORJ\ H[KLELWV KRXU F\FOLFLW\ GXH WR FLUFDGLDQ transient measurements per frequency). Compared to control cells, rhythms of gene expression controlled by transcription factors '0 FHOOV GLVSOD\HG VLJQL¿FDQWO\ GHFUHDVHG GLDVWROLF FDOFLXP DQG 7) WKDW FRPSULVH PROHFXODU FORFNV 7KH FORFN RUFKHVWUDWHV DOO increased calcium release and reuptake rates at every frequency. encompassing aspects of physiological homeostasis. As such, 2Q WKH RWKHU KDQG '0 FHOOV VKRZHG VLPLODU GLDVWROLF FDOFLXP WR genetic and enviromental perturbation of the clock can result in control cells, but increased calcium release and reuptake rates devasting health consequences, including neuropsychiatric disorders WUHQGLQJ WRZDUGV VLJQL¿FDQFH p= DW ORZHU IUHTXHQFLHV and metabolic derangements. Core clock TFs bind to the genome at +] 7KHGLႇHUHQFHLQGLDVWROLFFDOFLXPEHWZHHQ'0DQG enhancer sequences to regulate circadian gene expression, but not '0VXJJHVWVWKDWWKHLQFUHDVHVLQFDOFLXPUHOHDVHDQGUHXSWDNH all binding sites are equally functional. Here we demonstrate that

76 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

circadian gene expression in mouse liver is controlled by rhythmic mitochondrial activity and imprinted methylation in oocytes and FKURPDWLQLQWHUDFWLRQVEHWZHHQHQKDQFHUVDQGSURPRWHUV5HYHUEĮ embryos from mice of advanced maternal age. a core repressive TF of the clock, opposes functional loop formation EHWZHHQ 5HYHUEĮUHJXODWHG HQKDQFHUV DQG FLUFDGLDQ WDUJHW JHQH 155 8QGHUVWDQGLQJ 0DUEXUJ YLUXV SURWHFWLRQ WKURXJK SURPRWHUVE\UHFUXLWPHQWRIWKH1&R5+'$&FRUHSUHVVRUFRPSOH[ WKHUDSHXWLFDQWLERG\05 KLVWRQHGHDFHW\ODWLRQDQGHYLFWLRQRIWKHHORQJDWLRQIDFWRU%5'DQG Liam King WKHORRSLQJIDFWRU0('7KXVDUHSUHVVLYHDUPRIWKHPROHFXODU University of California San Diego, San Diego, USA clock operates by rhythmically modulating chromatin loops to control 7KH ¿ORYLUXV IDPLO\ FRQWDLQV (EROD YLUXV (%29 0DUEXUJ YLUXV circadian gene transcription. 0$59 DQG RWKHU SDWKRJHQV WKDW FDQ FDXVH VHYHUH GLVHDVH LQ humans. Ebola virus caused a sustained outbreak in West Africa with Oocytes and embryos from mice of advanced maternal 154 !IDWDOLWLHVIURP!FDVHV0DUEXUJYLUXVKDVDVLPLODU age show decreased mitochondrial mass but no changes in RXWEUHDNSRWHQWLDO7KH0DUEXUJYLUXVRXWEUHDNLQ$QJROD imprinted methylation FDXVHGOHWKDOLW\,WUHHPHUJHGLQDQGLQWUDYHOHUV Audrey J. Kindsfather WR8JDQGDZHUHKRVSLWDOL]HGLQWKH8QLWHG6WDWHVDQG(XURSHZLWK University of Pittsburgh School of Medicine, USA severe Marburg virus disease. A large panel of antibodies was 2YHUWKHODVWVHYHUDOGHFDGHVWKHDYHUDJHDJHRI¿UVWWLPHPRWKHUV LVRODWHG IURP WKH$PHULFDQ SDWLHQW E\ WKH &URZH ODE DW 9DQGHUELOW KDV ULVHQ VWHDGLO\$GYDQFHG PDWHUQDO DJH GH¿QHG LQ KXPDQV DV 8QLYHUVLW\DQGFKDUDFWHUL]HGIRUELQGLQJDQGQHXWUDOL]DWLRQ2QHRI above 35 years old, is known to increase the risk of spontaneous WKHDQWLERGLHVLQWKLVSDQHOLV05ZKLFKSURWHFWVRIQRQ abortion, stillbirth, preterm birth, aneuploidy, and other chromosomal KXPDQSULPDWHVDJDLQVW0$59FKDOOHQJHDQGLVDFDQGLGDWHIRUDQ abnormalities and birth defects. As a woman ages, molecular HPHUJHQF\SRVWH[SRVXUHLPPXQRWKHUDSHXWLF+HUHZHSUHVHQWWKH FKDQJHVRFFXULQKHURRF\WHVWKDWFDQDႇHFWWKHDELOLW\RIWKHRRF\WHV FU\VWDOVWUXFWXUHRI05LQFRPSOH[ZLWKWKHWULPHULFSUHIXVLRQ to be fertilized and the viability of the embryo. These changes XQFOHDYHG 0DUEXUJ YLUXV VXUIDFH JO\FRSURWHLQ *3 7KLV FU\VWDO include oxidative stress, which is known to damage mitochondria. structure and accompanying biochemistry illuminates the precise In addition to other cellular processes, mitochondria likely play a role interactions made by this extremely potent antibody and illustrates in regulating epigenetic mechanisms, such as genomic imprinting. how it neutralizes infection by binding to the receptor binding site *HQRPLF LPSULQWLQJ LV DQ HSLJHQHWLF SKHQRPHQRQ WKDW UHVWULFWV DWWKHDSH[RI*37KLVVLWHLVODUJHO\FRQVHUYHGDFURVVWKH¿ORYLUXV expression to predominantly one parental allele through various genus. The structure explains how a candidate immunotherapeutic mechanisms including cytosine methylation. Mitochondria provide functions, and provides a template by which interactions could be both the ATP and methyl groups used for imprinted methylation PRGL¿HGWRLPSURYH¿ORYLUXVFURVVUHDFWLYLW\ acquisition in germ cells and imprinted methylation maintenance in preimplantation embryos as the rest of the genome is demethylated. 156 ,5)FRQWUROV7FHOOVXUYLYDODQGWKH&'RVWHRSRQWLQ 7KHDLPRIWKLVSURMHFWLVWRGHWHUPLQHZKHWKHUPDWHUQDODJHDႇHFWV axis to regulate T cell antitumor activity PLWRFKRQGULDODFWLYLW\DQGPHWK\ODWLRQRIWKHLPSULQWHGJHQHV6QUSQ John Klement +DQG.FQTRWLQPRXVHRRF\WHVDQGSUHLPSODQWDWLRQHPEU\RV Augusta University, Augusta, USA )HPDOH&%/ &$67 PLFHIURPYHU\\RXQJ PRQWKV \RXQJ 7KHWUDQVFULSWLRQIDFWRULQWHUIHURQUHJXODWRU\IDFWRU ,5) SOD\VDQ PRQWKV PLGGOH PRQWKV DQG DGYDQFHG ! PRQWKV HVVHQWLDOUROHLQOLQHDJHGLႇHUHQWLDWLRQDQGIXQFWLRQRIKHPDWRSRLHWLF DJHJURXSVZHUHPDWHGZLWK&%/PDOHV0RUXODDQGEODVWRF\VWV FHOOV/RVVRI,5)OHDGVWRGHIHFWLYH1.FHOODFWLYLW\SHUWXUEDWLRQV ZHUH FROOHFWHG DW GD\ ( E\ ÀXVKLQJ WKH XWHUXV DQG RYLGXFWV in B cell development and, in mouse models, an accumulation of with M2 medium. Oocytes were collected by treating the ovaries &'E *U LPPDWXUHP\HORLGFHOOV+RZHYHUWKHUROHRI,5)LQ ZLWKFROODJHQDVHDQGWU\SVLQ('7$$OOVDPSOHVZHUHVWDLQHGZLWK T cell development and antitumor activity remains unclear. Here, we 0LWRWUDFNHU5HGWRYLVXDOL]HDFWLYHPLWRFKRQGULD0LWRWUDFNHU*UHHQ DLPHGWRWHVWWKHK\SRWKHVLVWKDW,5)SOD\VDFULWLFDOUROHLQKRVW to visualize total mitochondria, and Hoechst to visualize nucleic acids, cancer immunosurveillance by regulating T cell homeostasis and and imaged with confocal microscopy. Total and active mitochondria activation. ,QYLWUR T cell responses were assayed by stimulation with OHYHOVZHUHTXDQWL¿HGE\WKHJUHHQDQGUHGLQWHQVLW\UHVSHFWLYHO\,Q DQWL&'&'DQWLERGLHV7RH[DPLQHWKHUROHRI,5)LQ7FHOOVD oocytes, total and active mitochondrial patterning was characterized SHSWLGHEDVHGYDFFLQHZDVXWLOL]HGWRPHDVXUH LQYLYR responses. as perinuclear, peripheral, homogenous, or aggregated. Individual 0L[HGFKLPHUDPLFHZHUHJHQHUDWHGE\OHWKDOLUUDGLDWLRQRIUHFLSLHQW RRF\WHV PRUXOD DQG EODVWRF\VWV ZHUH VXEMHFWHG WR ELVXO¿WH KRVWIROORZHGE\UHFRQVWLWXWLRQZLWK&' :7DQG&' ,5) PXWDJHQHVLVDQGDVVHVVHGIRU6QUSQ+DQG.FQTRWLPSULQWHG .2 ERQH PDUURZ7RIXUWKHU HOXFLGDWH7FHOO LQWULQVLF UROH RI ,5) methylation levels. ,5)7FHOOVSHFL¿FNQRFNRXW ,5)7.2 PLFHZHUHJHQHUDWHGE\ FURVVLQJ,5)ÀÀPLFHZLWKOFNFUH mice. 2XU GDWD VKRZ WKDW WKHUH ZDV D VLJQL¿FDQW GHFUHDVH LQ DFWLYH mitochondrial mass in both oocytes and blastocysts with increasing /RVVRIKHPDWRSRLHWLF,5)DOORZHGIRUHQJUDIWPHQWRIDQDOORJHQLF maternal age. While the mitochondria in oocytes from young and mouse breast tumor and enhanced the growth of a spontaneous PLGGOHDJHG PRWKHUV ZDV XVXDOO\ DUUDQJHG LQ SHULQXFOHDU DQG sarcoma model, and, similarly, iQ YLYR VWLPXODWLRQ RI &' T cells homogenous patterns, oocytes from mothers of advanced age GHPRQVWUDWHGGHIHFWLYH7FHOOSUROLIHUDWLRQLQ,5).2PLFH+RZHYHU show peripheral and aggregated patterns more frequently. However, LVRODWHG7FHOOVIURP,5).2PLFHGLVSOD\HGQRGH¿FLHQF\IROORZLQJ RXUGDWDWRGDWHKDYHQRWVKRZQDQ\GLႇHUHQFHEHWZHHQLPSULQWHG LQ YLWUR polyclonal stimulation or an LQ YLYR mixed chimera model. hi PHWK\ODWLRQ OHYHOV RI 6QUSQ + DQG .FQTRW LQ RRF\WHV DQG /RVVRI,5)OHGWRWKHDFFXPXODWLRQRID&' &' population blastocysts between mice of any of the age groups. Future studies LQ ,5).2 PLFH WKDW ZDV QRW SUHVHQW LQ D PL[HGFKLPHUD PRGHO will determine the consequences of the observed mitochondrial RU ,5)7.27KLV ZDV DFFRPSDQLHG E\ D WZHOYHIROG LQFUHDVH LQ dysfunction, as well as examine how assisted reproductive WKH,5).2VSOHQRF\WHH[SUHVVLRQRIWKH&'OLJDQGRVWHRSRQWLQ WHFKQRORJLHV VXFK DV VXSHURYXODWLRQ DQG HPEU\R FXOWXUH DႇHFW which we showed to be a potent inhibitor of T cell proliferation in

www.jointmeeting.org 77 POSTER ABSTRACTS

YLWUR 6XUSULVLQJO\ UHFRQVWLWXWHG ,5):7 PL[HG FKLPHUD PLFH 158 Discovery and Characterization of VU0529331, the First demonstrated preferential engraftment and survival of T cells 6PDOO0ROHFXOH$FWLYDWRURI*3URWHLQJDWHG,QZDUGO\UHFWLI\LQJ GHULYHG IURP :7 UDWKHU WKDQ ,5).2 ERQH PDUURZ ZLWK IXUWKHU 3RWDVVLXP *,5. 6XEXQLW&RQWDLQLQJ&KDQQHOV DQDO\VLVVKRZLQJDSURJUHVVLYHORVVRI,5).27FHOOVGXULQJWKHLU Krystian Kozek PDWXUDWLRQDQGGHYHORSPHQWSURFHVV*LYHQWKDW,5)UHJXODWHVD Vanderbilt University, Nashville, USA YDULHW\ RI SUR DQG DQWLDSRSWRWLF PROHFXOHV LQ WXPRU DQG P\HORLG FHOOVZHK\SRWKHVL]HGWKDW,5)FRQWUROVWKHSHULSKHUDOVXUYLYDORI7 The nationwide opioid epidemic claims tens of thousands of lives each cells. To test this hypothesis, resting and in vitro stimulated WT and year as people addicted to opiates overdose on them. The cravings .27FHOOYLDELOLW\ZDVPHDVXUHGE\$QQH[LQ93,VWDLQLQJ,5).2 RIDGGLFWLRQDUHH[WUHPHO\GLႈFXOWWRLJQRUHDEHKDYLRUGHSHQGHQWLQ FHOOVEXWQRW:7GHPRQVWUDWHGDSURDSRSWRWLFSKHQRW\SH SDUWRQGRSDPLQHVLJQDOLQJ$GGLFWLRQDVVRFLDWHGGRSDPLQHUJLF '$ QHXURQVH[LVWLQVSHFL¿FEUDLQDUHDVVXFKDVWKHVXEVWDQWLDQLJUD 7KHUHIRUH ,5) LQWULQVLFDOO\ UHJXODWHV 7 FHOO VXUYLYDO WR PHGLDWH 7 DQGWKHYHQWUDOWHJPHQWDODUHD 97$ ,QDGGLWLRQWRVLJQDOLQJYLDWKH FHOO GLႇHUHQWLDWLRQ DQG KRPHRVWDVLV ZKLOH H[WULQVLFDOO\ UHJXODWLQJ QHXURWUDQVPLWWHUGRSDPLQHWKHVHQHXURQVGLႇHUIURPWKHPDMRULW\RI osteopontin in myeloid cells to mediate T cell activation and FHQWUDOQHUYRXVV\VWHP &16 QHXURQVLQWKHH[SUHVVLRQRIVSHFL¿F H[SDQVLRQ 7RJHWKHU WKHVH LQWULQVLFH[WULQVLF PHFKDQLVPV RI ,5) * SURWHLQJDWHG LQZDUGO\UHFWLI\LQJ SRWDVVLXP *,5. FKDQQHOV control T cell function in the context of the tumor microenvironment. 7KURXJKRXW PRVW RI WKH &16 *,5. FKDQQHOV DUH FRPSRVHG RI 157 Aspirin use predicts successful outcomes after WKH *,5. *,5. DQGRU *,5. VXEXQLWV ZKLFK DVVHPEOH LQWR SHUFXWDQHRXVDQJLRSODVW\RIDUWHULRYHQRXV¿VWXODVDQGJUDIWV KRPRWHWUDPHUVDQGKHWHURWHWUDPHUV0RUHVSHFL¿FDOO\'$QHXURQV used for hemodialysis LQWKH97$H[SUHVVRQO\QRQ*,5.FRQWDLQLQJ*,5. QRQ*,5.[ 0DOJRU]DWD$.RFKDQHN FKDQQHOV QDPHO\ *,5. DQG *,5. ([SHULPHQWV ZKHUH QRQ University of Chicago, Oak Park, USA *,5.[ FKDQQHO H[SUHVVLRQ ZDV PRGXODWHG KDYH GHPRQVWUDWHG that these channels are implicated in the regulation of substance $UWHULRYHQRXV ¿VWXODV $9) DQG DUWHULRYHQRXV JUDIWV $9* PD\ DEXVH LQ URGHQWV 7R IXUWKHU LQYHVWLJDWH ZKHWKHU *,5. FKDQQHO GHYHORS YHQRXV VWHQRVHV FDXVHG E\ QHRLQWLPDO K\SHUSODVLD 1+ PRGXODWLRQLQ'$QHXURQVFDQDႇHFWGUXJDEXVHLQZLOGW\SHDQLPDOV which may be treated with percutaneous transluminal angioplasty ZH VRXJKW PHDQV RI SKDUPDFRORJLFDOO\ PRGXODWLQJ QRQ*,5.[ (PTA). While the standard criteria for treatment of a clinically channels. However, small molecules that modulated the activity of VLJQL¿FDQWYHQRXVVWHQRVLVLVHVWLPDWHGDWWKHUHLVDSDXFLW\RI QRQ*,5.[FKDQQHOVGLGQRWH[LVW7KHUHIRUHZHGLVFRYHUHGDQG GDWDWKDWGH¿QHVIDFWRUVDVVRFLDWHGZLWKFOLQLFDOVXFFHVVDIWHU37$ FKDUDFWHUL]HGWKH¿UVWVPDOOPROHFXOHPRGXODWRUVRI*,5.FKDQQHOV We prospectively evaluated the associations of clinical characteristics and procedural measurements with one month outcomes of PTA to )URPDKLJKWKURXJKSXWVFUHHQRI!FRPSRXQGVZHLGHQWL¿HG ¿QGSRWHQWLDOSUHGLFWRUVRISDWHQF\ 98 98 WR EH WKH PRVW HႈFDFLRXV VPDOO PROHFXOH DFWLYDWRU RI *,5. FKDQQHOV 8VLQJ KLJKWKURXJKSXW WKDOOLXP $OOSHUVRQVUHIHUUHGIRU37$RIDSDWHQW$9)RU$9*IURP ÀX[ DVVD\V ZH GHWHUPLQHG WKDW 98 DFWLYDWHV ERWK *,5. ZKRFRQVHQWHGZHUHLQFOXGHGLQWKHVWXG\'HPRJUDSKLFDQG DQG *,5. FKDQQHOV 98 KDV D SRWHQF\ RI a ȝ0 RQ ERWK clinical data were obtained from records; indication for PTA and the FKDQQHOVDQGWKHDFWLYLW\RI98KDVEHHQYDOLGDWHGXVLQJZKROH type and location of each lesion were collected. Each stenosis was FHOO SDWFKFODPS HOHFWURSK\VLRORJ\ 98 DSSOLFDWLRQ LQFUHDVHG evaluated in two orthogonal planes so percentage of stenosis could *,5.FXUUHQWVLQERWK*,5.DQG*,5.RYHUH[SUHVVLQJ+(. be calculated, compared to a reference vessel, before and after PTA. cells; these currents are sensitive to barium ion inhibition. Because Clinical outcomes were ascertained from dialysis units one month *,5. FKDQQHOV DUH JDWHG E\ WKH DFWLYDWHG * ȕȖVXEXQLW ZKLFK DIWHU37$6XFFHVVZDVGH¿QHGDVGLDO\]HUEORRGÀRZVRIP/ i/o LV DQ HႇHFWRU RI * SURWHLQFRXSOHG UHFHSWRU *3&5 VLJQDOLQJ ZH min during dialysis, without: prolonged bleeding, cannulation pain, H[DPLQHGZKHWKHULQKLELWLRQRI*3&5VLJQDOWUDQVGXFWLRQSHUWXUEV KLJKYHQRXVSUHVVXUHORZDUWHULDOSUHVVXUHSXOOLQJFORWVLQ¿OWUDWLRQV 98DFWLYLW\:HGHPRQVWUDWHGWKDWLQKLELWLRQRI*3&5VLJQDOLQJ poor clearance, infections, or swelling of the arm neck or head. 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We could QRW GHPRQVWUDWH DQ\ VLJQL¿FDQW DVVRFLDWLRQV EHWZHHQ SURFHGXUDO success and any anatomic features or measurements. Future work is needed to examine longer term outcomes, validate the current ¿QGLQJVDQGLQYHVWLJDWHWKHEHQH¿FLDOELRORJLFPHFKDQLVPRIDVSLULQ use in patients with hemodialysis vascular access.

78 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

159 &KDUDFWHUL]LQJWKHFRQVHTXHQFHVRI'(3'&GH¿FLHQF\ 160 Dissecting the genetic regulatory elements of cold in cortical neurons differentiated from patient-derived induced sensation in white fat pluripotent stem cells as a model of epileptogenesis Daniel J. Kramer Lindsay K. Kozek Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional Vanderbilt University, Nashville, USA MD-PhD Program, New York, USA 'HVSLWHQXPHURXVDYDLODEOHDQWLFRQYXOVDQWGUXJVRYHURQHWKLUGRI 7KH EUDLQ FDQ VWLPXODWH KHDWSURGXFWLRQ WKHUPRJHQHVLV LQ epilepsies are refractory to treatment. Pathogenic mutations in '(3 adipocytes in response to cold temperatures. This occurs via GRPDLQFRQWDLQLQJ SURWHLQ ('(3'& DUH D VLJQL¿FDQW FDXVH RI QRUHSLQHSKULQH UHOHDVHG E\ QHXURQV WR IDW FHOOV7KH HႇHFW RI WKLV IRFDO HSLOHSVLHV HSLOHSVLHV ZKLFK DUH ERWK GUXJUHVLVWDQW DQG DUH VLJQDOLQJLVLQFUHDVHG8FSWUDQVFULSWLRQ6WLPXODWLRQRIWKLVSDWKZD\ OLQNHGWRVXGGHQXQH[SHFWHGGHDWKLQHSLOHSV\ 68'(3 '(3'& can promote weight loss, but the amount of cold required makes negatively regulates mTORC1 activity when amino acid levels are low, it less feasible on a large scale. Further, therapeutic activation of GHFUHDVLQJSURWHLQWUDQVODWLRQDQGGLVLQKLELWLQJDXWRSKDJ\'(3'& this pathway by added norepinephrine is limited by the ubiquity of mutations are proposed to cause impaired nutrient sensing, resulting adrenergic signaling and catecholamines across cell types whose in dysregulation of both mTORC1 and autophagy. Hyperactivation of alteration is undesired. Recent work suggests white and beige fat can mTORC1 and impairment of autophagy are independently linked to increase thermogenic gene expression by alternative mechanisms of epileptogenesis, thus suggesting possible pathogenic mechanisms activation. These mechanisms are incompletely understood, and if IRU'(3'&PXWDWLRQV:HXVHSDWLHQWGHULYHGLQGXFHGSOXULSRWHQW elucidated could provide a novel therapeutic target for treatment of VWHPFHOOV L36&V GLႇHUHQWLDWHGLQWRFRUWLFDOQHXURQVWRGH¿QHWKH obesity and the metabolic syndrome. H[WHQWWRZKLFK'(3'&KDSORLQVXႈFLHQF\DOWHUVQHXURGHYHORSPHQW :HDUHFKDUDFWHUL]LQJWKLVSKHQRW\SHXVLQJDJHQRPHZLGH&5,635 and metabolism and to link these changes to the pathogenesis of based phenotypic screen using reporters for thermogenic gene epilepsy. H[SUHVVLRQ&HOOVFDQEHVRUWHGE\TXDQWL¿HGUHSRUWHUH[SUHVVLRQDQG 0HWKRGV L36&V ZHUH GHULYHG IURP ¿EUREODVWV IURP D SDWLHQW ZLWK ÀRZF\WRPHWU\XVLQJVXUIDFHPDUNHUVDVVRFLDWHGZLWKWKHUPRJHQLF HSLOHSV\DQG'(3'&PXWDWLRQYLDLQWHJUDWLRQIUHHUHSURJUDPPLQJ capacity. Cells will then be sequenced to determine which guide XVLQJ 6HQGDL YLUXV $Q LVRJHQLF FRQWURO OLQH ZDV FUHDWHG XVLQJ 51$VDUHGLVSURSRUWLRQDWHO\SUHVHQWDPRQJWKHORZH[SUHVVLRQFHOO &5,635&DVPHGLDWHG JHQRPLF HGLWLQJ YLD KRPRORJ\GLUHFWHG population. This method will give us a preliminary set of candidate UHSDLU WR FRUUHFW WKH '(3'& SRLQW PXWDWLRQ L36&V ZHUH JHQHVDQGJDLQDQGORVVRIIXQFWLRQVWXGLHVZLOOWKHQEHSHUIRUPHG GLႇHUHQWLDWHG LQWR H[FLWDWRU\ FRUWLFDO QHXURQV XVLQJ D WKUHHVWDJH to determine the intermediate steps of this mechanism. SURFHVV EDVHG RQ GXDO60$' LQKLELWLRQ WKDW PLPLFV FRUWLFDO 7KLVQRYHOSKHQRW\SHKDVEHHQYDOLGDWHGLQFHOOVGLႇHUHQWLDWHGIURP GHYHORSPHQW&RUWLFDOLQWHUQHXURQVZHUHGLႇHUHQWLDWHGLQDSURFHVV LPPRUWDOL]HG)$SUHDGLSRF\WHOLQHVDVZHOODVFXOWXUHGSULPDU\ XWLOL]LQJ GXDO60$' LQKLELWLRQ IROORZHG E\ :QW DQWDJRQLVP DQG subcutaneous white adipocytes. Transgenic and knockout mouse 6RQLF KHGJHKRJ DFWLYDWLRQ 1HXURQV ZHUH ¿[HG DQG VWDLQHG DW lines have been developed with increased and decreased expression various timepoints during development to characterize expression of of PR domain containing 16 (Prdm16), a factor complexed with key QHXURQDOGLႇHUHQWLDWLRQPDUNHUVP725&DFWLYDWLRQZDVDVVD\HG UHJXODWRUVRI8FSWUDQVFULSWLRQLQFODVVLFDOWKHUPRJHQHVLV7KHHႇHFW E\TXDQWLI\LQJSKRVSKR6H[SUHVVLRQYLDLPPXQREORW of Prdm16 expression is currently being measured. Establishing the 5HVXOWV'(3'&PXWDQWL36&VDUHDEOHWRGLႇHUHQWLDWHLQWRPDWXUH potential roles of known transcriptional regulators in a novel process excitatory and inhibitory neurons, as determined by staining for will help us determine where in the architecture of thermogenic gene 9*OX7 DQG 36' RU *$%$ DQG *$' UHVSHFWLYHO\ (DUO\ LQ H[SUHVVLRQFROGH[SRVXUHH[HUWVLWVHႇHFWV&OXHVVXFKDVWKHVHZLOO GLႇHUHQWLDWLRQ FHOOV H[SUHVV QHXUDO SURJHQLWRU FHOO 13& PDUNHUV be important for developing our list of candidate genes that will come 3D[ DQG 1HVWLQ$IWHU GD\V FHOOV H[SUHVV PDUNHUV RI PDWXUH RXWRIWKHJHQRPHZLGHVFUHHQ)XUWKHUVWXGLHVDUHDOVRXQGHUZD\WR QHXURQVVXFKDV7XM0$3DQG1HX1$WEDVHOLQH'(3'& GHWHUPLQHWKHSK\VLRORJLFUROHRIWKLVPHFKDQLVPLQYLYRE\SUR¿OLQJ and control cells show equivalent levels of mTORC1 activation, but WUDQVFULSWLRQDOFKDQJHVLQIDWDQGIDWDGMDFHQWFHOOV not during starvation. 162 $OWHUHG FHUHEURVSLQDO ÀXLG ÀRZ SDWWHUQV LQ D PRXVH &RQFOXVLRQV :H FUHDWHG DQ L36&EDVHG PRGHO RI '(3'& model of chronic neuropathic pain KDSORLQVXႈFLHQWHSLOHSV\XVLQJH[FLWDWRU\DQGLQKLELWRU\QHXURQVWR Benjamin T. Kress LQYHVWLJDWHWKHFRQQHFWLRQEHWZHHQ'(3'&GH¿FLHQF\GHIHFWVLQ University of Rochester Medical Center, USA DXWRSKDJ\DQGHSLOHSV\:H¿QGWKDW'(3'&L36&VDUHDEOH to go through a neuroprogenitor phase to form mature excitatory Altered neuronal connectivity and hyperexcitability of nociceptive and inhibitory neurons with similar levels of mTORC1 activation in neurons is generally believed to represent the causal substrate of DQXWULHQWULFKHQYLURQPQHQW)XUWKHUVWXGLHVZLOOH[DPLQHVLJQDOLQJ persistent neuropathic pain. It is now accepted that, in addition, activity following nutrient deprivation and also evaluate neuronal a deviation from the normal supportive functions of glial cells, in morphology and dendritic arborization. Improving our understanding particular astrocytes and microglia, contributes to both the initial RI KRZ '(3'& KDSORLQVXႈFLHQF\ FRQWULEXWHV WR HSLOHSWRJHQHVLV rewiring of spinal pain pathways, as well as the maintenance of the may suggest new drug targets and provide fundamental knowledge hypersensitivity believed to underlie the persistent component of about the pathogenic mechanisms driving the development of neuropathic pain. To date, the exact impairment of the supportive epilepsy. functions of glial cells that contributes to the establishment and maintenance of neuropathic pain remains unknown. Here we tested the hypothesis that peripheral nerve injury triggers functional and structural changes in astrocytes that results in pathologically VLJQL¿FDQWDOWHUDWLRQVLQFHUHEURVSLQDOÀXLG &6) ÀRZSDWWHUQV:H WKHRUL]HGWKDWLPSDLUHGFOHDUDQFHRILQWHUVWLWLDOÀXLGDQGVROXWHVPD\

www.jointmeeting.org 79 POSTER ABSTRACTS

OHDGWRWKHDFFXPXODWLRQRIH[FLWDWRU\RUSURLQÀDPPDWRU\PHGLDWRUV of 6R[ in neural crest cell development and migration by crossing (e.g., cytokines, ATP, or glutamate), which could subsequently the 6R[5)3 WUDQVJHQLF OLQH ZKLFK ÀXRUHVFHQWO\ ODEHOV QHXUDO contribute to maladaptive synaptic plasticity and the sensitization of crest cells) with the 6R[ mutant lines and performing live imaging QRFLFHSWLYHQHXURQV7RWHVWWKLVK\SRWKHVLVZHXVHGÀXRUHVFHQFH of neural crest cell dynamics. These experiments will provide a better LPDJLQJ WR PRQLWRU ÀRZ SDWWHUQV RI WUDFHUV LQIXVHG LQWR WKH &6) understanding of the potential role of 6R[ in the pathogenesis of of awake mice that had (i) received either the spared nerve injury &+$5*(V\QGURPH 61, PRGHORISHULSKHUDOQHXURSDWKLFSDLQRU LL VKDPLQMXU\7KH accumulation of tracers from the brain and spinal cord parenchyma, 165 A pharmacological neuroprotective approach to severe traumatic brain injury: targeting mitochondria and lipid DV ZHOO DV WKH H[SUHVVLRQ RI PDUNHUV RI DVWURJOLRVLV JOLDO ¿EULOODU\ peroxidation DFLGLF SURWHLQ >*)$3@ DQG DTXDSRULQ >$43@ RU PLFURJOLRVLV &' ZHUH WKHQ TXDQWL¿HG DIWHU PXOWLFKDQQHO ÀXRUHVFHQFH Jacqueline Kulbe LPDJLQJRIH[YLYREUDLQDQGVSLQDOFRUGVOLFHV,QWKH61,PRGHO University of Kentucky College of Medicine, Lexington, USA neuropathic pain behavior, including thermal hyperalgesia and ,QWKH8QLWHG6WDWHVRYHU¿YHPLOOLRQSHRSOHOLYHZLWKD7%,UHODWHG PHFKDQLFDODOORG\QLDSHDNHGDWGD\VIROORZLQJ61,$FFXPXODWLRQ disability. Currently, acute treatment for severe TBI entails supportive of tracers within the parenchyma was markedly altered between FDUH 7R GDWH WKHUH DUH QR )'$DSSURYHG SKDUPDFRWKHUDSLHV PLFH WKDW UHFHLYHG 61, YV VKDPLQMXU\$OWHUHG &6) ÀRZ SDWWHUQV available to prevent the devastating neurologic consequences of ZHUH GHWHFWHG DV HDUO\ DV GD\V IROORZLQJ 61, DQG SRVLWLYHO\ 7%,'XHWRWKHFRPSOH[SDWKRSK\VLRORJ\ZKLFKRFFXUVIROORZLQJ7%, correlated with both pain behavior and astrogliosis, determined by innovative targeting strategies must be developed. LQFUHDVHGH[SUHVVLRQRI*)$3$437KHHDUO\DGPLQLVWUDWLRQRIWKH )ROORZLQJ7%,PLWRFKRQGULDWDNHXSLQFUHDVHVLQLQWUDFHOOXODU&D analgesics pregabalin and clonidine, but not morphine, prevented LQDQDWWHPSWWRPDLQWDLQKRPHRVWDVLVKRZHYHULQFUHDVHVLQLQWUD the suppression of glymphatic clearance. We are currently evaluating PLWRFKRQGULDO &D OHDG WR JHQHUDWLRQ RI UHDFWLYH R[\JHQ DQG &6)ÀRZLQDZDNHQHUYHLQMXUHGYVVKDPLQMXUHGPLFHLQYLYRXVLQJ QLWURJHQ VSHFLHV 526516 LQGXFWLRQ RI OLSLG SHUR[LGDWLRQ /3 VHULDOFRQWUDVWHQKDQFHGFRPSXWHGWRPRJUDSK\2XUUHVXOWVVXJJHVW DQGIRUPDWLRQRI/3GHULYHGQHXURWR[LFDOGHK\GHVZKLFKFRYDOHQWO\ DOWHUHGJOLDOFHOOIXQFWLRQDQG&6)ÀRZSDWWHUQVPD\FRQWULEXWHWRWKH bind mitochondrial proteins, exacerbating mitochondrial dysfunction. onset and maintenance of chronic neuropathic pain. Eventually, mitochondrial dysfunction leads to opening of the mitochondrial permeability transition pore (mPTP), cessation of ATP 163 3URJUHVVWRZDUGVGHYHORSLQJ]HEUD¿VKPRGHOVWRVWXG\ SURGXFWLRQ H[WUXVLRQ RI &D EDFN LQWR WKH F\WRVRO F\WRVNHOHWDO WKH OLQN EHWZHHQ 6R[& WUDQVFULSWLRQ IDFWRUV DQG &+$5*( and neuronal degeneration, and neurologic impairment. Therefore, syndrome mitochondria make promising therapeutic targets for prevention Laura A. Krueger of cellular death and dysfunction following TBI. Here we evaluate University of Kentucky, Lexington, USA WKH QHXURSURWHFWLYH HႇHFWV RI F\FORVSRULQH$ &V$ RQ V\QDSWLF &+$5*( V\QGURPH coloboma, heart defects, choanal atresia, DQG QRQV\QDSWLF PLWRFKRQGULD WKH QHXURSURWHFWLYH HႇHFWV RI D growth retardation, genital abnormalities, and ear abnormalities) is continuous infusion of CsA combined with phenelzine (PZ) and 3) the a complex congenital genetic disorder resulting in severe defects in QHXURSURWHFWLYHHႇHFWVRI3=K\GUDOD]LQH += DQGSDUJ\OLQH 3* PXOWLSOH RUJDQ V\VWHPV ZLWK DQ RFFXUUHQFH RI OLYH Mitochondria are heterogeneous, consisting of both synaptic and ELUWKV0XWDWLRQVLQFKURPRGRPDLQKHOLFDVHELQGLQJSURWHLQ &+') QRQV\QDSWLF SRSXODWLRQV ZKLFK KDYH GLVWLQFW SURSHUWLHV LQFOXGLQJ and defects in neural crest cell development and migration have been GLႇHUHQWLDO UHVSRQVHV WR SKDUPDFRWKHUDS\ 2XU UHVXOWV LQGLFDWH LPSOLFDWHG LQ WKH SDWKRJHQHVLV RI &+$5*( V\QGURPH KRZHYHU WKDWFRPSDUHGWRQRQV\QDSWLFPLWRFKRQGULDV\QDSWLFPLWRFKRQGULD the mechanisms underlying the ocular birth defects observed in VXVWDLQ JUHDWHU GDPDJH K IROORZLQJ VHYHUH FRQWUROOHG FRUWLFDO &+$5*(SDWLHQWVKDYHQRWEHHQLGHQWL¿HG2XUODERUDWRU\VWXGLHV impact injury (CCI) in young male rats, and are protected to a greater WKH GHYHORSPHQW RI WKH YHUWHEUDWH YLVXDO V\VWHP XVLQJ ]HEUD¿VK GHJUHHE\ &V$ DQ)'$DSSURYHGLPPXQRVXSSUHVVDQWFDSDEOHRI ('DQLRUHULR). Previous work from our lab has shown that knockdown inhibiting mPTP. of 6R[DPHPEHURIWKH6R[&IDPLO\RIWUDQVFULSWLRQIDFWRUVLQ Additionally, because the TBI secondary injury cascade is complex, ]HEUD¿VK UHVXOWV LQ PLFURSKWKDOPLD FRORERPD EUDLQ WUXQN DQG FRPELQDWLRQDO WKHUDSLHV VKRXOG RႇHU JUHDWHU QHXURSURWHFWLRQ WKDQ KHDUW GHIHFWV DOO SKHQRW\SHV REVHUYHG LQ &+$5*( V\QGURPH VLQJOH DJHQWV 7KH ¿UVW K IROORZLQJ 7%, DUH FULWLFDO DV SHDN Furthermore, a duplication of 6R[KDVEHHQLGHQWL¿HGLQDSDWLHQW PLWRFKRQGULDOG\VIXQFWLRQDQG/3RFFXUKIROORZLQJ7%,7KHUHIRUH FOLQLFDOO\GLDJQRVHGZLWK&+$5*(V\QGURPHDQG&+' has been FRQWLQXRXVGHOLYHU\RIGUXJRYHUWKH¿UVWKIROORZLQJ7%,PD\RႇHU shown to directly interact with 6R[ and 6R[ in neural stem cells. WKHEHVWFKDQFHDWQHXURSURWHFWLRQ:HXWLOL]HGDKVXEFXWDQHRXV 7DNHQ WRJHWKHU WKHVH GDWD VWURQJO\ VXJJHVW WKDW ORVV RI 6R[& continuous dosing paradigm to evaluate the combination of CsA expression contributes to the ocular and other phenotypes observed DQG WKH DOGHK\GH VFDYHQJHU 3= DQ )'$DSSURYHG PRQRDPLQH LQ &KGDVVRFLDWHG &+$5*( V\QGURPH ,Q WKLV VWXG\ ZH EHJLQ R[LGDVH 0$2 LQKLELWRUFODVVDQWLGHSUHVVDQW2XUUHVXOWVLQGLFDWH to further investigate the role that 6R[ plays in the phenotypes that individually both CsA and PZ are able to attenuate mitochondrial VHHQLQ&+$5*(V\QGURPHE\JHQHUDWLQJ6R[PXWDQW]HEUD¿VK DOGHK\GLF PRGL¿FDWLRQ 3= LV DEOH WR PDLQWDLQ PLWRFKRQGULDO XVLQJWKH&5,635&DVV\VWHP=HEUD¿VKKDYHWZRFR±RUWKRORJVRI respiratory control ratio, a general measure of mitochondrial health, SOX11, VR[D and VR[E &5,635 WDUJHW VLWHV ZHUH FKRVHQ WR and cytoskeletal integrity, but together, PZ and CsA, are unable to GLVUXSWWKHKLJKPRELOLW\JURXS +0* '1$ELQGLQJGRPDLQDQGWKH PDLQWDLQQHXURSURWHFWLYHHႇHFWV transactivation domain of VR[D and VR[E. Corresponding single Finally, although PZ was chosen for these experiments based on its VWUDQG JXLGH 51$V VJ51$V ZHUH JHQHUDWHG DQG PLFURLQMHFWHG aldehyde scavenging properties, the fact that it is capable of inhibiting ZLWK &DV SURWHLQ LQWR IHUWLOL]HG ]HEUD¿VK HPEU\RV DW WKH RQHFHOO the mitochondrial enzyme MAO, must not be overlooked. Therefore, stage. The resulting 6R[ mutant lines will be characterized for ZHDUHFXUUHQWO\HYDOXDWLQJWKHHႇHFWVRI3= DOGHK\GHVFDYHQJHU SKHQRW\SHVUHODWHGWR&+$5*(V\QGURPHDQGZLOOEHFRPSDUHGWR 0$2LQKLELWRU += DOGHK\GHVFDYHQJHU DQG 3* 0$2LQKLELWRU an established &+' mutant line. We will also characterize the role RQFRJQLWLYHGH¿FLWVIROORZLQJ7%,

80 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

166 5DSLGDSSURDFKWRGHULYLQJDVDIHDQGLPPXQRJHQLFOLYH $Q LPSRUWDQW PDUNHU RI VDUFRPHUH IXQFWLRQ LV %W\SH QDWULXWUHWLF attenuated Zika viral strain SHSWLGH %13 ZKLFK LV VHFUHWHG E\ WKH YHQWULFOHV LQ UHVSRQVH WR Swee Sen Kwek H[FHVVLYH VWUHWFKLQJ RI FDUGLRP\RF\WHV )XUWKHUPRUH %13 LV D Duke-NUS Medical School, Singapore, Singapore FOLQLFDOELRPDUNHUIRUKHDUWIDLOXUHSURJQRVLVDQGHႈFDF\RIWUHDWPHQW 7KHXQGHUVWDQGLQJRIKRZ%13H[SUHVVLRQLVUHJXODWHGLVVWLOOYHU\ The microcephaly outbreak in Brazil between late 2015 and early 2016 OLPLWHGDQGWKHUHIRUHRXU&5,635VFUHHQZLOODOORZXVWRLGHQWLI\QRYHO EURXJKW=LNDYLUXV =,.9 WRWKHZRUOG¶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ႇHUHQWVXEVWUDWHVWLႇQHVV ORQJWHUP KXPRUDO DQG FHOOXODU LPPXQLW\ LV HVVHQWLDO WR SUHYHQW when cardiomyocytes are plated on polyacrylamide gels of varying WKH UHHPHUJHQFH RI HSLGHPLF =LND DQG WKH DVVRFLDWHG FRQJHQLWDO VWLႇQHVV =LND V\QGURPH 7KH \HOORZ IHYHU ' <)' YDFFLQH UHPDLQV RQHRIWKHEHVW/$9VWRGDWHDQGVHUYHVDVDEHQFKPDUNIRU/$9 2XU QH[W VWHS LV WR XWLOL]H WKH %13 UHSRUWHU DVVD\ WR FRQGXFW D development: a single dose confers lifelong immunity. However, in &5,635&DVJHQRPHZLGHVFUHHQE\WUDQVGXFLQJDOHQWLYLUDOJ51$ DGGLWLRQWRGLVSOD\LQJWKHVDPHSKHQRW\SHDV<)'DQ\=,.9/$9 library into our cells. We will be using the Brunello library, which candidate must also be attenuated in causing persistent infection LQFOXGHV DURXQG J51$V WKDW WDUJHW KXPDQ JHQHV LQ RUJDQV DVVRFLDWHG ZLWK VHYHUH GLVHDVH DQG QRQYHFWRU HJ This screen will help us identify novel genes that regulate cardiac VH[XDO WUDQVPLVVLRQ :H GHPRQVWUDWH KHUH WKDW =,.9 VWUDLQV ZLWK IXQFWLRQLQKRSHRI¿QGLQJQHZWKHUDSHXWLFWDUJHWVIRUKHDUWIDLOXUH desired attenuation phenotypes can be isolated and screened from 168 Lysosomal calcium stores mediate ultraviolet light a genetically heterogeneous viral population that arose during in responsiveness in human melanocytes YLWUR FXOWXUH RI =,.97KLV VKRUWHQV WKH /$9 GHYHORSPHQW SURFHVV %UDQGRQ0/DZ FRQVLGHUDEO\ DV FRPSDUHG WR WKH WLPHFRQVXPLQJ WUDGLWLRQDO Massachusetts General Hospital, USA DSSURDFKRIVHULDOSDVVDJLQJLQHLWKHUFHOOFXOWXUHRUODERUDWRU\UHDUHG DQLPDOV :H SODTXHSXUL¿HG DQG UHVFXHG D VPDOOSODTXH YDULDQW 0XWDWLRQV LQ JHQHV HQFRGLQJ O\VRVRPHUHODWHG RUJDQHOOHV DUH '1XVLQJDQLQIHFWLRXVFORQH6LPLODUWR<)''1GLVSOD\HG implicated in impaired pigmentation, but the exact mechanism of ,5)UHVWULFWHG SODTXH VL]H DQG DOVR LQGXFWLRQ RI LQQDWH LPPXQH this relationship remains poorly understood. Pigment production by UHVSRQVHVLQSULPDU\PRQRF\WHGHULYHGGHQGULWLFFHOOV$GGLWLRQDOO\ KXPDQHSLGHUPDOPHODQRF\WHVRFFXUVLQUHVSRQVHWRXOWUDYLROHW 89 '1VKRZHGGHFUHDVHGLQIHFWLYLW\LQERWKPDWXUHHQGRWKHOLDOFHOOV light. In this study, we hypothesize that lysosomes in melanocytes (ECs) and endothelial progenitor cells, likely due to a concomitant SOD\DFULWLFDOUROHLQPHGLDWLQJ89UHVSRQVH7RTXHU\WKLVK\SRWKHVLV HDUO\DFWLYDWLRQRIDW\SH,LQWHUIHURQ ,)1 UHVSRQVHDQGLQFUHDVHG ZH XVH OLYHFHOO LPDJLQJ WR SUREH IRU 89 OLJKWHYRNHG UHVSRQVH LQ VXVFHSWLELOLW\ WR W\SH ,,, ,)1 7KLV DWWHQXDWHG LQIHFWLYLW\ LQ (&V FXOWXUHGSULPDU\KXPDQPHODQRF\WHV:HVKRZWKDW89OLJKWHYRNHV translated to decreased organ infection and vertical transmission rapid lysosomal calcium release. Pharmacologic pathway modulation ZKHQ'1ZDVWHVWHGLQDW\SH,,)1UHFHSWRUGH¿FLHQW$PRXVH LQGLFDWHVWKDWWKLVFDOFLXPUHOHDVHLV*3&5PHGLDWHGDQGUHTXLUHV PRGHO)XUWKHUPRUHDOOPLFHVXUYLYHGLQLWLDOLQRFXODWLRQZLWK'1 the presence of a retinaldehyde chromophore, suggesting that a which elicited a protective response against a lethal challenge with SKRWRWUDQVGXFWLRQFDVFDGHPHGLDWHVWKLV89UHVSRQVHUDWKHUWKDQD WKH +3) VWUDLQ 2XU ¿QGLQJV WKXV VXJJHVW WKH SRVVLELOLW\ RI QRQVSHFL¿FFHOOGDPDJHSDWKZD\$FWLRQVSHFWUXPVWXGLHVVKRZWKDW UDSLGO\GHULYLQJVDIHDQGLPPXQRJHQLF/$9FDQGLGDWHVIRU=,.9DQG calcium response robustly corresponds to the wavelength sensitivities RWKHUÀDYLYLUXVHVIURPDJHQHWLFDOO\GLYHUVHSRRORIWKHWDUJHWYLUXVE\ RINQRZQ89VSHFL¿FSKRWRUHFHSWRUV89LQGXFHGO\VRVRPDOFDOFLXP VFUHHQLQJIRUGH¿QHGPROHFXODUFKDUDFWHULVWLFVRIDWWHQXDWLRQ release is attenuated by pharmacologic blockade of lysosomal DFLGL¿FDWLRQ RU GHSOHWLRQ RI O\VRVRPDO FDOFLXP VWRUHV IXUWKHU 167 Genetic determinants of heart failure in human induced LPSOLFDWLQJWKHUROHRIO\VRVRPDOLRQKRPHRVWDVLVLQ89UHVSRQVH pluripotent stem cell model $GGLWLRQDOVWXGLHVXVLQJ&5,635&DVWRJHQHWLFDOO\HGLWFDQGLGDWH Feria Ladha lysosomal ionic transporter genes in primary human melanocytes University of Connecticut, New Britain, USA derived from individuals with light, medium, and dark skin tones are Genetic determinants of heart failure in a human induced RQJRLQJ7DNHQWRJHWKHUWKHVH¿QGLQJVVXJJHVWDJHQHUDOSDUDGLJP pluripotent stem cell model WKDWO\VRVRPHVVHUYHDVFULWLFDOVLJQDOLQJRUJDQHOOHVIRU89UHVSRQVH and provide additional mechanistic evidence for the emerging role of Heart failure is a leading cause of premature death and cardiac O\VRVRPHUHODWHGRUJDQHOOHVLQGLVHDVHVRISLJPHQWDWLRQ WUDQVSODQW DQG KDV EHHQ GH¿QHG DV D JOREDO SDQGHPLF DႇHFWLQJ DSSUR[LPDWHO\WZHQW\VL[PLOOLRQLQGLYLGXDOVZRUOGZLGH8QIRUWXQDWHO\ 170 0LFURJOLDO LQÀDPPDVRPH DFWLYDWLRQ DIWHU SHQHWUDWLQJ only four new heart failure medications have been approved since ballistic-like brain injury GXHLQSDUWWRODFNRIGUXJWDUJHWV7KHJRDORIRXUUHVHDUFK Stephanie Lee is to better understand the mechanisms of inherited cardiovascular University of Miami Miller School of Medicine, Miami, USA GLVRUGHUVHVSHFLDOO\WKRVHWKDWOHDGWRKHDUWIDLOXUH0RUHVSHFL¿FDOO\ 3HQHWUDWLQJWUDXPDWLFEUDLQLQMXU\ 37%, UHPDLQVDVLJQL¿FDQWFDXVH this study is focused on identifying novel genes involved in heart RIGHDWKDQGGLVDELOLW\LQWKH8QLWHG6WDWHVZLWKRXWHႇHFWLYHWKHUDSLHV function in order to provide mechanistic insights into heart failure $URGHQW37%,PRGHOSHQHWUDWLQJEDOOLVWLFOLNHEUDLQLQMXU\ 3%%, KDV pathogenesis and identify a platform for potential drug targets. uncovered several secondary pathophysiological mechanisms such :H ZLOO EH XWLOL]LQJ &5,635&DV JHQRPHZLGH SRROHG VFUHHQLQJ DVUHGXFHGJOXFRVHXSWDNHQHXURGHJHQHUDWLRQLQÀDPPDWLRQDQG PHWKRGVWRLGHQWLI\JHQHWLFPRGL¿HUVRIVDUFRPHUHIXQFWLRQLQKXPDQ apoptosis that magnify the primary injury. Targeting components of L36GHULYHG FDUGLRP\RF\WHV L36&0V ODEHOHG ZLWK ÀXRUHVFHQW these mechanisms may help improve PTBI outcomes. Activators of markers for sarcomerogenesis.

www.jointmeeting.org 81 POSTER ABSTRACTS

innate immunity contribute to secondary injury mechanisms following $ SUHOLPLQDU\ PDVV VSHFWURPHWU\ DQDO\VLV FRQ¿UPHG WKDW WDX WUDXPDWLFEUDLQLQMXU\ 7%, ,QÀDPPDVRPHVDUHWKHNH\UHJXODWRUV interacts with a large segment of the cellular ribonucleoproteome RILQWHUOHXNLQȕ ,/ȕ PHGLDWHGLQÀDPPDWLRQDIWHU7%,DQGSUHVHQW DQG FKDSHURQHV 'DWD FROOHFWHG WR GDWH HVWDEOLVK WKH VXFFHVVIXO DVFOLQLFDOO\UHOHYDQWWDUJHWVIRUWKHUDS\7KHUROHRILQÀDPPDVRPHV LPSOHPHQWDWLRQ RI DQ LQGXFLEOH WDX(*)3 H[SUHVVLRQ V\VWHP WKDW in PBBI pathophysiology has yet to be determined. Towards this, ZLOODOORZXVWRGLVVHFWWKHWLPHFRXUVHRIDEHUUDQWWDXLQWHUDFWLRQV DGXOWPDOH6SUDJXH'DZOH\UDWVZHUHVXEMHFWHGWRXQLODWHUDOVKDP underlying proteotoxic stress. RU3%%,VXUJHU\DQGVDFUL¿FHGDWYDULRXVWLPHSRLQWV7LVVXHVZHUH 7DUJHWHG LQVHUWLRQ PLQLPL]HV WKH GHOHWHULRXV HႇHFWV RI UDQGRP DVVHVVHG IRU H[SUHVVLRQ RI F\WRNLQHV ,/ȕ LQWHUOHXNLQ ,/ LQWHJUDWLRQV DQG WKH ÀH[LEOH WZRVWHS SURFHVV FDQ SRWHQWLDOO\ DQG FRPSRQHQWV RI WKH LQÀDPPDVRPH FDVSDVH DSRSWRVLV accommodate any genes of interest. In the future, we can use this associated speck like protein containing a caspase activation and FHOO PRGHO WR ¿QG VXLWDEOH WLPH LQWHUYDOV IRU LQ GHSWK LQWHUURJDWLRQ UHFUXLWPHQW GRPDLQ $6& ;OLQNHG LQKLELWRU RI DSRSWRVLV SURWHLQ and also polish the system to express both the three and four repeat ;,$3 12'OLNH UHFHSWRU SURWHLQ 1/53 DQG JDVGHUPLQ' tau domains to even better recapitulate the endogenous pathological *6'0' E\ LPPXQREORW DQDO\VLV DQG DVVHVVHG IRU $6& FHOO brain state. W\SHH[SUHVVLRQE\LPPXQRKLVWRFKHPLVWU\&RUWLFDO,/ȕDQG,/ H[SUHVVLRQLQFUHDVHGKKDQGKKUHVSHFWLYHO\DIWHULQMXU\ 172 Small molecule activation of Protein Phosphatase 2A 3%%,DOVRLQFUHDVHGFDVSDVH$6&;,$3DQG1/53H[SUHVVLRQ functions through regulation of the c-terminal tail of the catalytic IURP KK %UDLQ SURWHLQ O\VDWHV IURP 37%, DQLPDOV VKRZHG subunit S\URSWRVRPH IRUPDWLRQ HYLGHQFHG E\ $6& ODGGHULQJ DQG DOVR Daniel Leonard FRQWDLQHGLQFUHDVHGH[SUHVVLRQRI*6'0'DWKDIWHULQMXU\$6& Cleveland Clinic Lerner College of Medicine at Case Western positive immunoreactive neurons within the perilesional cortex were Reserve University, Cleveland Heights, USA REVHUYHGDWK$WKPLFURJOLDOQXPEHUVVLJQL¿FDQWO\LQFUHDVHG The success of molecularly targeted therapies for the treatment of in the ipsilateral cortex compared to sham and contralateral cortices select cancers has revolutionized our diagnostic and therapeutic DQG$6&H[SUHVVLRQZDVSUHGRPLQDQWO\LQFUHDVHGLQPRUSKRORJLFDOO\ DSSURDFKWRFDQFHURYHUDOO8QIRUWXQDWHO\WKHJHQHWLFKHWHURJHQHLW\ DFWLYDWHG PLFURJOLD 7KLV H[SUHVVLRQ RI$6& LQ DFWLYDWHG PLFURJOLD and activation of multiple molecular drivers in even a single persisted until 12 weeks following PBBI in the cortex and internal tumor often results in incomplete therapeutic responses and/ FDSVXOH7KLVLVWKH¿UVWUHSRUWRILQÀDPPDVRPHDFWLYDWLRQDIWHU3%%, or the development of treatment resistance. This heterogeneity 2XU UHVXOWV GHPRQVWUDWH FHOOVSHFL¿F SDWWHUQV RI LQÀDPPDVRPH and therapeutic hurdle present in cancer highlights the need for activation and pyroptosis predominantly in microglia suggesting a continued pursuit of novel treatment approaches. Contrary to the VXVWDLQHGSURLQÀDPPDWRU\VWDWHIROORZLQJ3%%,WKDWFRXOGXQGHUOLH ZHOOVWXGLHG RQFRJHQH WDUJHWHG WKHUDSLHV UHDFWLYDWLRQ RI WXPRU WKH ORQJWHUP VHTXODH RI 3%%, ,QKLELWLRQ RI WKH LQÀDPPDVRPH LQ suppressors has not been fully characterized. Enhancing the activity PBBI will evaluate its therapeutic potential for PTBI. of tumor suppressors provides an endogenous cellular mechanism 171 ,QWHUDFWLQJZLWKWKHZURQJFURZGD&5,635&DVHGLWHG to simultaneously inhibit multiple oncogenic targets, enhancing inducible human cell system designed to reveal the chronology WKHJHQHUDOL]DELOLW\DQGHႈFDF\RIWKLVDSSURDFK2QHPDMRUFODVV of events leading to proteotoxic stress in tauopathies of tumor suppressor enzymes, Protein Phosphatase 2A (PP2A), 0DFNHQ]LH/HPLHX[ is functionally inactivated in the majority of human malignancies, Cornell University, Ithaca, USA highlighting its potential as a therapeutic target. PP2A consists of a FRUHGLPHULQFOXGLQJDUHTXLVLWHVFDႇROGVXEXQLWDQGDQHQ]\PDWLF $ NH\ RSHQ TXHVWLRQ LQ WKH WDXRSDWK\ ¿HOG LV KRZ WDX SURWHLQV catalytic subunit, coupled to one of four classes of regulatory aggregate and cause proteotoxic stress in neurons. We recently subunits; creating the functional heterotrimer and enabling a broad SXEOLVKHGD¿UVWLQGHSWKWDXLQWHUDFWRPHZKLFKUHYHDOHGWKDW WDX UDQJHRIWXPRUVXSSUHVVLYHIXQFWLRQV'HVSLWHWKHORZRYHUDOOUDWH carrying the P301L frontotemporal dementia mutation exhibits of somatic mutation of PP2A, cancer employs several mechanisms reduced interactions with heat shock proteins and the proteasome. to dysregulate PP2A function including increased expression of 2XU SUHYLRXV ZRUN FDSWXUHG VWHDG\VWDWH LQWHUDFWLRQV RI D VSHFL¿F HQGRJHQRXV LQKLELWRUV HSLJHQHWLF VLOHQFLQJ DQG SRVWWUDQVODWLRQDO PXWDWHG DQG SODVPLGHQFRGHG WDX LVRIRUP +RZHYHU DV GLVHDVH PRGL¿FDWLRQVRIYDULRXVVXEXQLWV2XUODEKDVHQJLQHHUHGDQRYHO evolves dynamically, critically needed are next generation models FODVVRIVPDOOPROHFXOHV 60$3V ZKLFKELQGWRWKHVFDႇROGLQJVXEXQLW that can be induced to reveal the chronology of events underlying of PP2A to drive PP2A dependent tumor inhibition in mouse models tau’s aggregation and proteotoxicity. of both solid and hematologic malignancies. Mechanistic insight :H DUH SRLVHG WR ¿OO WKLV XQPHW QHHG ZLWK QRYHO &5,635&DV LQWR60$3GULYHQUHJXODWLRQRI33$LVFULWLFDOIRULGHQWLI\LQJ60$3 generated cell models that can be induced to express human tau VHQVLWLYHSDWLHQWSRSXODWLRQVIRUHႇHFWLYHFOLQLFDOWUDQVODWLRQRIWKLV DOOHOHV6SHFL¿FDOO\LQGXFLEOHWDX,05KXPDQQHXUREODVWRPDFHOOV approach. Evidence presented here, including molecular modeling, ZHUHFUHDWHGLQDWZRVWHSJHQHHQJLQHHULQJZRUNÀRZ¿UVWDSDLURI K\GUR[\OUDGLFDOIRRWSULQWLQJDQGFU\RHOHFWURQPLFURVFRS\KLJKOLJKW IRXQGDWLRQOR[VLWHVZDVLQVHUWHGLQWRWKH$$96KXPDQJHQRPHVDIH WKHDELOLW\RIWKHVH60$3VWRSURWHFWWKHUHJXODWRU\FWHUPLQDOWDLORI KDUERUORFXVYLDD&5,635&DVQLFNDVHVWUDWHJ\6HFRQGZLOGW\SH WKHFDWDO\WLFVXEXQLW3RVWWUDQVODWLRQDOPRGL¿FDWLRQRIWKLVFWHUPLQDO RU 3/ WDX &WHUPLQDOO\ IXVHG WR WKH HQKDQFHG JUHHQ ÀXRUHVFHQW region has been shown to direct holoenzyme assembly, regulate SURWHLQZHUHLQVHUWHGLQWRWKHSULPHG$$96ORFXVYLD&UHUHFRPELQDVH VXEVWUDWH VSHFL¿FLW\ DQG LQÀXHQFH SURWHLQ VWDELOLW\ &HOOXODU DQG mediated heterologous gene exchange using the foundation lox sites. WXPRU [HQRJUDIW FRLPPXQRSUHFLSLWDWLRQ VWXGLHV VXJJHVW WKDW WKLV 7KHV\VWHPFDQEHXVHGIRUWLPHFRXUVHWUDQVFULSWRPHDQGSURWHRPH 60$3LQGXFHGSURWHFWLRQRIWKH&WHUPLQDOWDLORIWKHFDWDO\WLFVXEXQLW DQDO\VHV $FFXUDWH WUDQVJHQH LQVHUWLRQ ZDV FRQ¿UPHG E\ JHQRPLF UHJXODWHVWKHPHWK\ODWLRQRIWKHXQLTXHWHUPLQDOOHXFLQH / WKXV PCR and sequencing. Marked induction and tight leakage control of LQÀXHQFLQJKRORHQ]\PHFRPSRVLWLRQDQGVXEVWUDWHGLUHFWHGFDWDO\VLV the inducible model were validated by Western blotting after treating ,PSRUWDQWO\FDQFHU GHULYHG PXWDWLRQV LQ WKH VFDႇROGLQJ VXEXQLWRI WKHFHOOVZLWKGR[\F\FOLQHIRUKRXUV 33$ VXFK DV 5: GHPRQVWUDWH UHVLVWDQFH WR 60$3 WKHUDS\

82 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

in tumor xenograft models, further highlighting the importance of these ICs were used to predict cognitive control performance in our identifying an appropriate clinical population for the utilization of SV\FKRVLVVDPSOH6HFRQGP&&$M,&$ZDVDSSOLHGGHQRYRWRWKH these small molecules. Future studies aimed at identifying the tumor SUHVHQWGDWDVHWUHVXOWDQW,&VZHUHYLVXDOO\H[DPLQHGDQGVXEMHFW VXSSUHVVLYH 33$ UHJXODWRU\ VXEXQLWV HQKDQFHG E\ WKLV 60$3 VSHFL¿FZHLJKWVZHUHFRUUHODWHGZLWKFRJQLWLYHFRQWUROSHUIRUPDQFH dependent protection of the catalytic subunit will better inform the %RWK DQDO\VHV FRUUHFWHG IRU JURXS GLႇHUHQFHV LQ FRJQLWLYH FRQWURO clinical placement of these small molecules and direct future drug SHUIRUPDQFH DQG )'5 ZDV XVHG WR FRUUHFW IRU PXOWLSOH VWDWLVWLFDO GHYHORSPHQWHႇRUWVWRHQKDQFH33$DFWLYLW\LQFDQFHU comparisons. 173 Transcriptional regulation of wound healing over time in 3DUWLDOFRUUHODWLRQVXVLQJWKHWZRDSULRUL,&VSUHGLFWHGVLJQL¿FDQW human gingiva and skin. relationships between working memory imaging and cognitive FRQWUROLQSV\FKRVLV U S U S RWKHU Trevor Leonardo PRGDOLWLHVQRWVLJQL¿FDQW 'HQRYRP&&$M,&$LGHQWL¿HGDVLQJOH University of Illinois - Chicago, Chicago, USA JURXSGLVFULPLQDWLYH,&3RVWKRFSDUWLDOFRUUHODWLRQVLGHQWL¿HG Injury of epidermal barriers initiates a highly complex set of events WKDWWKHVDPH,&DOVRVLJQL¿FDQWO\RUWUHQGOHYHOFRUUHODWHGZLWK to contain, cover, and prevent contamination of the wound site. FRJQLWLYHFRQWUROSHUIRUPDQFH VWUXFWXUDOU S UHVWLQJ While most wounded tissues eventually form a scar, wounded VWDWHU S ZRUNLQJPHPRU\WDVNU S oral epithelium exhibits reduced scarring, less angiogenesis, a Highly contributing structural regions included insular, somatomotor, GHFUHDVHG LQÀDPPDWRU\ UHVSRQVH DQG GHFUHDVHG ZRXQG FORVXUH cingulate, and medial visual areas; task regions included precentral, WLPHDVFRPSDUHGWRVNLQ8VLQJDELRLQIRUPDWLFVEDVHGDSSURDFK posterior parietal, cingulate, and visual areas. ZHVRXJKWWRGH¿QHWKHWUDQVFULSWLRQDOUHJXODWRU\QHWZRUNVRIZRXQG 7KHSUHVHQWDQDO\VHVSDUWLDOO\UHSOLFDWHGDSULRULQRUPDWLYHUHVXOWV healing in each tissue over time. A microarray dataset was generated LQ LQGLYLGXDOV ZLWK SV\FKRVLV 'HQRYR DQDO\VHV LGHQWL¿HG D VLQJOH IURPKXPDQIXOOWKLFNQHVVH[FLVLRQDOELRSVLHVLQJLQJLYDOPXFRVDDQG JURXSGLVFULPLQDWLYH ,& WKDW ZDV VLJQL¿FDQWO\ UHODWHG WR FRJQLWLYH YHQWUDOIRUHDUPZLWKVXEVHTXHQWELRSVLHVGRQHDWVL[DQG control performance and points towards joint contributions of KRXUV$QDO\VLVRIWKHGDWDVKRZHGWKDWRUDODQGVNLQZRXQGV LGHQWL¿HGUHJLRQVLQVXSSRUWLQJFRJQLWLYHFRQWURODFURVVWKHKHDOWK\ KDYH VSHFL¿F GLႇHUHQFHV LQ WKHLU WUDQVFULSWLRQDO UHVSRQVH WR LQMXU\ WRSV\FKRVLV VSHFWUXP 7KHVH UHVXOWV VXSSRUW WUDQVGLDJQRVWLF WKDWPLJKWH[SODLQWKHGLႇHUHQWLDORXWFRPHVLQZRXQGKHDOLQJ2XU FRQFHSWXDOL]DWLRQVRISV\FKRVLVDQGPD\DLGLQIXWXUHHႇRUWVWRPRYH analysis will provide new information about the factors involved that EH\RQGWKH'60LQGLDJQRVLVDQGWUHDWPHQWRIPHQWDOGLVRUGHUV make wound healing in oral tissue unique in its ability to heal rapidly and to produce less scarring compared to other tissue sites. 175 .LGQH\ UHVLGHQW PDFURSKDJHV GHFUHDVH 0+&,, expression after acute kidney injury 174 7UDQVGLDJQRVWLF 0XOWLPRGDO 1HXUDO &RUUHODWHV RI Cognitive Control in Psychosis: Dimensions of Alteration from -HUHPLH0/HYHU Healthy to Disease University of Alabama at Birmingham, Birmingham, USA Hi Low Dov B. Lerman-Sinkoff .LGQH\ UHVLGHQW PDFURSKDJHV ) &'E ) arise from the Washington University in St. Louis, SAINT LOUIS, USA IHWDO \RON VDF UDWKHU WKDQ ERQH PDUURZGHULYHG SUHFXUVRUV DQG are thought to promote organ development during embryonic and Psychosis, classically the hallmark of schizophrenia, is nonetheless postnatal life and recovery, secondary to acute kidney injury (AKI), in present in numerous other disorders. Mounting evidence suggests adults. We previously demonstrated that resident macrophages are that psychosis may consist of multiple dimensional traits that span not exchanged with the peripheral blood in uninjured kidneys. We the spectrum from normative to disordered. Here, we expand our hypothesized that kidney resident macrophages are not replaced by prior work in the normative population by using multimodal image H[WUDUHQDO SUHFXUVRUV DIWHU LQMXU\ and that they promote recovery analysis to examine the replicable transdiagnostic patterns of by recapitulating a developmental program, with respect to the neural variation in psychosis related to cognitive control. Cognitive transcriptome and epigenome, after AKI. control refers to the set of neural functions employed to perform FRRUGLQDWHG SXUSRVHIXO GHFLVLRQPDNLQJ SURFHVVHV LQ VXSSRUW RI To test the hypotheses that: 1) kidney resident macrophages are task demands. Persons with psychosis frequently exhibit alterations QRWUHSODFHGE\PRQRF\WHGHULYHGPDFURSKDJHVIURPWKHSHULSKHUDO in cognitive control performance and many imaging studies have blood after AKI, and 2) kidney resident macrophages recapitulate a LGHQWL¿HGUHODWLRQVKLSVEHWZHHQFRJQLWLYHFRQWUROSHUIRUPDQFHDQG developmental phenotype in the adult after AKI. QHXUDODOWHUDWLRQVLQVWUXFWXUDOUHVWLQJVWDWHDQGIXQFWLRQDOLPDJLQJ To address hypothesis 1, parabiosis was established between However, many of these studies only examine a single type of &' DQG &' &%/ FRQJHQLF SDLUV RI PLFH UHVXOWLQJ LQ imaging and thus provide a limited view of neural function. stable immune cell chimerism in the peripheral blood and kidney. ,QWKHSUHVHQWZRUNVWUXFWXUDOUHVWLQJVWDWHZRUNLQJPHPRU\WDVN $IWHU G RQH SDLU PHPEHU ZDV VXEMHFWHG WR ELODWHUDO UHQDO functional MRI, and cognitive control performance data were collected LVFKHPLDUHSHUIXVLRQ ,5 LQMXU\ 7KH SUHVHQFH RI FKLPHULVP LQ D DQG DQDO\]HG IRU KHDOWK\ FRQWUROV SHUVRQV ZLWK SV\FKRWLF JLYHQLQWUDUHQDOFHOOVXEVHWDIWHU$.,E\ÀRZF\WRPHWU\DQGFRQIRFDO ELSRODUDQGSHUVRQVZLWKVFKL]RSKUHQLDVSHFWUXPGLVRUGHUV'DWD ,) PLFURVFRS\ LQGLFDWHG LQ¿OWUDWLRQ RI FHOOV IURP WKH SHULSKHUDO were collected and processed identically to the Human Connectome blood. To address hypothesis 2, we determined the phenotype of Project (HCP) enabling assessment of relationships with prior NLGQH\UHVLGHQWPDFURSKDJHVDVDIXQFWLRQRIDJH (3 DQG replicable multimodal correlates of cognitive control in the HCP. Two compared those to the same subpopulations after AKI in adults. main analyses were performed: First, two replicable independent $IWHU,5$.,LQSDUDELRWLFPLFHFKLPHULVPDPRQJ)Hi&'ELow components (ICs) derived using multiset canonical correlation UHVLGHQWPDFURSKDJHVUHPDLQHGORZ LQMXUHGYVVKDP DQDO\VLVMRLQWLQGHSHQGHQWFRPSRQHQWDQDO\VLV P&&$M,&$ WKDW S LQGLFDWLQJ WKDW HYHQ LQ WKH VHWWLQJ RI LQMXU\LQGXFHG were predictive of cognitive control in the HCP were directly applied LQÀDPPDWLRQNLGQH\UHVLGHQWPDFURSKDJHVDUHPLQLPDOO\UHSODFHG WR WKH SUHVHQW GDWDVHW 7KH UHVXOWDQW VXEMHFWVSHFL¿F ZHLJKWV RQ by renewing precursors from the peripheral blood. Confocal IF

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PLFURVFRS\GSRVWLQMXU\UHYHDOHGDSUHGRPLQDQWO\PHGXOODU\DQG ZLWK + DV WKH SRVLWLYH FRQWURO 7KH VFUHHQ LQFOXGHG FORVH SHULWXEXODU ORFDOL]DWLRQ IRU ) PDFURSKDJHV DQG ) SURWHLQ WR FRPSRXQGV 7KH SRVLWLYH WKUHVKROG ZDV VHW WR FRORFDOL]HGZLWKWKHQDWLYH&'DOORW\SHDWDKLJKHUUDWHWKDQWKH QRUPDOL]HGSHUFHQWDJHLQKLELWLRQZLWKD]VFRUH7KHUHZHUH FKLPHULF&'DOORW\SH S ,QGHYHORSLQJ&%/PLFHZH FRPSRXQGVWKDWPHWWKLVFXWRႇ6HFRQGDU\VFUHHQVRIWKHVH³KLWV´ observed that the proportion of resident macrophages positive for are in process, and these will ultimately be tested in cells and mouse 0+&,,H[SUHVVLRQLQFUHDVHGIURPDW(WRDW3DQG PRGHOVRI)/+&& H[SUHVVLRQZDVPDLQWDLQHGLQKHDOWK\DGXOWV:LWKLQGDIWHU,5$., MHCII)Hi kidney macrophages reappeared and increased in 177 Examining the role of Dyrk1a in the development and SURSRUWLRQXSWRGSRVWLQMXU\ S 0+&,,)Hi cells function of inhibitory neurons. do not appear to have arrived from the peripheral blood, because 5DFKHO9/HY\ in injured parabiotic mice, their chimerism remained low, increasing University of Florida, Plantation, USA RQO\VOLJKWO\DIWHULQMXU\ YVS 'XDOVSHFL¿FLW\ W\URVLQH SKRVSKRU\ODWLRQUHJXODWHG NLQDVH $ Kidney resident macrophages are not replaced by renewing '\UND KDV D FUXFLDO UROH LQ EUDLQ GHYHORSPHQW DQG VWXGLHV precursors from the peripheral blood after AKI. They do not express KDYHUHYHDOHGOLQNVWR'RZQ6\QGURPH '6 DQGDXWLVPVSHFWUXP MHCII during embryonic and neonatal life, but gain expression as the GLVRUGHUV $6'V 7KH SXUSRVH RI WKLV VWXG\ ZDV WR GHWHUPLQH PLFHSURJUHVVWRDGXOWKRRG1RWDEO\NLGQH\UHVLGHQWPDFURSKDJHV ZKHWKHU GHOHWLRQ RI '\UND DOWHUV WKH QXPEHU DQG GLVWULEXWLRQ RI lose expression of MHCII after AKI, suggesting that they recapitulate SDUYDOEXPLQ 39 QHXURQVLQWKHFRUWH[DQGLQQHUYDWLRQRIQHXURQV a developmental genetic program after injury. E\ 39 QHXURQV 7KH RYHUDOO JRDO ZDV WR UHYHDO KRZ WKLV JHQHWLF PXWDWLRQSOD\VDUROHLQWKHGHYHORSPHQWRI$6' Development of a novel chemotherapeutic agent for 176 &UHOR[ WHFKQRORJ\ ZDV XVHG WR SURGXFH WKH JHQHWLFDOO\ PXWDWHG ¿EURODPHOODUKHSDWRFHOOXODUFDUFLQRPD PLFHFDUU\LQJKHWHUR]\JRXVGHOHWLRQRI'\UNDLQLQKLELWRU\QHXURQV Solomon N. Levin 3HUIXVLRQZDVSHUIRUPHGRQERWKPXWDQWDQGFRQWUROPLFHDWZHHNV The Rockefeller University, USA old. After perfusion, the mice were dissected, and their brains were )LEURODPHOODU +HSDWRFHOOXODU &DUFLQRPD )/+&& LV D UDUH DQG VHFWLRQHGDQGWUHDWHGZLWKLPPXQRÀXRUHVFHQWVWDLQLQJIRU39DQG OHWKDO OLYHU FDQFHU WKDW SULPDULO\ DႇHFWV DGROHVFHQWV DQG \RXQJ *$'7KH\ZHUHWKHQDQDO\]HGWKURXJKÀXRUHVFHQWDQGFRQIRFDO DGXOWV 6XUJLFDO UHVHFWLRQ LV WKH PDLQVWD\ RI WUHDWPHQW KRZHYHU microscopy, with a focus on the cerebral cortex. GXHWRWKHQRQVSHFL¿FQDWXUHRIWKHGLVHDVHV\PSWRPV HJZHLJKW 'DWDDQDO\VLVVKRZHGWKDW'\UNDPXWDWLRQGLVUXSWVWKHGHYHORSPHQW ORVV DEGRPLQDO SDLQ )/+&& LV RIWHQ GLDJQRVHG DW D IDLUO\ ODWH RI39QHXURQV7KHVHWUHQGVZHUHSUHVHQWLQWKHGHQVLW\DQGVL]HRI stage, at which point the tumor has often metastasized and surgery 39QHXURQVDVZHOODVLQWKHGLVWULEXWLRQRIV\QDSWLFWHUPLQDOV7KLV is no longer an option. There is a lack of systemic therapies for the VWXG\FRXOGVHUYHDVDEDVHIRUIXWXUHUHVHDUFKLQWR$6'LQKXPDQV GLVHDVHDQGWKHPRUWDOLW\UDWHLVKLJKZLWKD¿YH\HDUVXUYLYDORIRQO\ including potential for treatment and preventative measures. Previously, our lab discovered a recurrent genetic mutation found in 178 Xylose donor transport is critical for fungal virulence DOO)/+&&WXPRUVDPSOHVVHTXHQFHG7KHPXWDWLRQLVDQLQIUDPH Lucy X. Li GHOHWLRQRIDSSUR[LPDWHO\NLOREDVHVRQRQHFRS\RIFKURPRVRPH Washington University School of Medicine, Saint Louis, USA 7KLVGHOHWLRQUHVXOWVLQDIXVLRQJHQHWKDWFRQWDLQVWKH¿UVWH[RQ &U\SWRFRFFXV QHRIRUPDQV, an opportunistic fungal pathogen, IURP '1$-% ZKLFK HQFRGHV IRU D PHPEHU RI WKH KHDW VKRFN infects more than one million people annually and kills two hundred SURWHLQ IDPLO\ DQG H[RQV IURP 35.$&$ ZKLFK HQFRGHV IRU WKRXVDQG LQGLYLGXDOV ZRUOGZLGH HDFK \HDU *O\FRFRQMXJDWHV DUH WKH FDWDO\WLF VXEXQLW Į RI 3URWHLQ .LQDVH$ 3.$F 7KLV FKLPHULF crucial mediators of cryptococcal metabolism and determinants JHQHOHDGVWRDFKLPHULFP51$DQGXOWLPDWHO\DFKLPHULFSURWHLQ of pathogenesis, making these carbohydrate structures attractive that retains the full catalytic activity compared to the native kinase. WKHUDSHXWLFWDUJHWV*O\FDQPRGL¿FDWLRQVRIFU\SWRFRFFDOSURWHLQVDQG More recently, we have found that creating the deletion, and the OLSLGVLQFRUSRUDWHVLJQL¿FDQWDPRXQWVRI[\ORVH7KLVPRQRVDFFKDULGH UHVXOWLQJIXVLRQJHQHZLWK&5,635&DVLQPRXVHOLYHULVVXႈFLHQW DOVRFRQVWLWXWHVRYHURQHIRXUWKRIWKHPDVVRIWKHSRO\VDFFKDULGH to produce the tumor. The tumor is not the result of the deletion, or FDSVXOHWKHGH¿QLWLYHFU\SWRFRFFDOYLUXOHQFHIDFWRUWKDWVXUURXQGVWKH loss of a tumor suppressor, since when a transposon containing the cell. Incorporation of sugar moieties into cryptococcal carbohydrate chimera is hydrodynamically transfected into the liver of mice, the structures requires activated donors, usually nucleotide sugars mice also develop the tumor. When the same chimera is expressed OLNH WKH 8'3[\ORVH WKDW VHUYHV DV WKH [\ORVH GRQRU IRU V\QWKHWLF with a point mutation to kill the kinase activity, no tumors are formed. reactions. While nucleotide sugars are generally synthesized in 7RJHWKHU WKHVH GDWD LPSOLFDWH WKH NLQDVH DFWLYLW\ RI WKH '1$-% the cytosol, only a small fraction of these precursors is consumed PRKACA as the oncogenic driver for this cancer. there. Most nucleotide sugars are translocated into the secretory Here we initiate the discovery and development of a novel drug to pathway, where the majority of glycan biosynthesis occurs, to modify WDUJHWWKHNLQDVHDFWLYLW\RIWKHFKLPHULFSURWHLQYLDDKLJKWKURXJKSXW FULWLFDOSURWHLQVOLSLGVRUFDSVXOHSRO\VDFFKDULGHV1XFOHRWLGHVXJDU GUXJVFUHHQ7KHFKLPHULFSURWHLQZDVSURGXFHGLQ%/&RGRQ3OXV WUDQVSRUWHUV 167V DUHWKXVUHTXLUHGWRWUDQVSRUWWKHUDZPDWHULDOV '( 5,/(FROLFHOOV7KHSURWHLQZDVSXUL¿HGLQDVLQJOHDႈQLW\ to the site of glycan synthesis. However, despite their key role in VWHS XVLQJ D UHVLGXH SHSWLGH GHULYHG IURP 3URWHLQ .LQDVH glycan synthesis, the identity and regulation of the complete set of Inhibitor, a naturally occurring inhibitor of PKAc. This allowed for the FU\SWRFRFFDO167VUHPDLQVHOXVLYH SXUL¿FDWLRQRIWKHFKLPHUDZLWKRXWWKHXVHRIDQDႈQLW\WDJ7KHSXUH :H LGHQWLILHG WZR SXWDWLYH 8'3[\ORVH WUDQVSRUWHUV LQ protein was found to have comparable activity to the native kinase, & QHRIRUPDQV8[WDQG8[WZKLFKH[KLELWHGGLVWLQFWVXEFHOOXODU DQGZDVLQKLELWHGE\+DNQRZQSRWHQWLQKLELWRURI3.$F localization, expression patterns, and kinetic parameters. We 7KH NLQDVH DFWLYLW\ VFUHHQ ZDV RSWLPL]HG DQG KDG D =IDFWRU RI IXUWKHU GHPRQVWUDWHG WKDW 8[W DQG 8[W DUH UHTXLUHG IRU [\ORVH incorporation into capsule polysaccharides and glycoproteins; they

84 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

were also necessary for &QHRIRUPDQV to cause disease in mice, SUHIURQWDOQHXURQVLQ6+$1.PLFHGLVSOD\HGPDUNHGO\GLႇHUHQW although surprisingly not for fungal viability in the context of infection. UHVSRQVHSUR¿OHVFRPSDUHGWRWKDWRI:76SHFL¿FDOO\QHXURQVLQ:7 7KHVH¿QGLQJVDGYDQFHGRXUXQGHUVWDQGLQJRIJO\FDQELRV\QWKHVLV mice demonstrated integration of both the identity of the paired mouse setting the stage for further studies of fundamental glycobiology and DQG WKH YDOHQFH RI WKH FRQGLWLRQ ZKHUHDV QHXURQV RI WKH 6+$1. cryptococcal pathogenesis. PLFHGLVVRFLDWHGWKHVHWZRIHDWXUHV2XUVWXG\UHYHDOVVRPHRI WKHEDVLFQHXURQDOFRGLQJPHFKDQLVPVWKDWDUHGLVUXSWHGLQ$6',Q 179 Translational machinery heterogeneity in circulating particular, they demonstrate that, at the cellular level, autistic mice tumor cells separately encode social and conditional stimuli. This selective lack of Selena S. Li UHVSRQVHWRRWKHU¶VH[SHULHQFH LHµZKDW¶WKH\DUHH[SHULHQFLQJ LV Harvard Medical School, USA DVVRFLDWHGZLWKDQLQDELOLW\WRGLVWLQJXLVKEHWZHHQRWKHUDQGVHOIEXW Metastasis is the primary cause of morbidity and mortality in GRHVQRWDGYHUVHO\DႇHFWWKHLUDELOLW\WRHQFRGHWRWKHRWKHU¶VLGHQWLW\ FDQFHUSDWLHQWVDQGWKHPRVWLPSRUWDQWSURJQRVWLFLQGLFDWRU'XULQJ LHµZKR¶LVH[SHULHQFLQJLW &UHÀH[PHGLDWHGUHVWRUDWLRQRI6KDQN metastatic progression, a cancer cell must detach from the primary expression reverses this cellular imbalance in the mPFC of adult mice site, intravasate into a blood vessel, survive in the circulation, and temporally precedes an increase in prosocial behavior. Our study extravasate from the bloodstream, survive and proliferate in a VXJJHVWVDQHXURQDOHQFRGLQJVXEVWUDWHIRU$6'DQGGHPRQVWUDWHV distant location. Circulating tumor cells (CTCs) are neoplastic cells that it may be possible to functionally restore social encoding within that have accessed the circulation and are a critical intermediate in mature adult cells. Taken together, this neuronal response provides a WKHPHWDVWDWLFFDVFDGH6XUYLYDORI&7&VLQWKHEORRGVWUHDPLVD putative neural mechanism for disrupted capacity for theory of mind, a major determinant of metastatic spread as the majority of CTCs are KDOOPDUNFKDUDFWHULVWLFRI$6'DQGVXJJHVWVDEDVLFPRGHOIRUWHVWLQJ eliminated in the harsh conditions of the bloodstream. Although CTC neurobiologically plausible treatments for individuals with autism. KHWHURJHQHLW\ LV WKRXJKW WR XQGHUOLH WKH GLႇHUHQWLDO VXUYLYDO RI WKH 7KH5ROHRI7ZLVWLQ5HJXODWLQJ0\RJHQHVLV WXPRULQLWLDWLQJFHOOVWKHNH\GLႇHUHQFHVRI&7&KHWHURJHQHLW\DQG 181 their potential contribution to survival remain unclear. Stephen Li University of Texas Southwestern Medical Center, Dallas, USA 6LQJOHFHOO51$VHTXHQFLQJDQGFOXVWHULQJRISDWLHQWGHULYHG&7&V ZDVFRQGXFWHGWRGHWHUPLQHWKHPRVWGLႇHUHQWLDOO\UHJXODWHGJHQHV $JLQJUHODWHGPXVFOHDWURSK\ VDUFRSHQLD LVDSURFHVVWKDWDႇHFWV DQGRXUUHVXOWVVKRZHGGLVWLQFWSRSXODWLRQVGH¿QHGE\KLJKDQGORZ nearly every person, contributing to debilitations and reductions in ribosomal protein (RP) expression. Interestingly, this translational TXDOLW\RIOLIH'XULQJDJLQJIDVWWZLWFKPXVFOH¿EHUVDUHVHOHFWLYHO\ signature correlated with worse prognosis of patients from whom DWURSKLHGUHVXOWLQJLQPRWRUZHDNQHVV1RUPDOO\PXVFOHUHJHQHUDWHV the CTCs were acquired. We hypothesize that the dramatic shift through a population of stem cells called satellite cells, which in cell phenotype that occurs as tumor cells undergo metastasis GLႇHUHQWLDWH DQG QRQVHOHFWLYHO\ IXVH WR H[LVWLQJ P\R¿EHUV LQ RUGHU likely requires equally dynamic changes in protein synthesis and to repair the damaged muscle tissue. Thus, it’s possible that loss of translational machinery. To better understand the dynamics of DQDOWHUQDWLYHPXVFOHSUHFXUVRUWKDWIXVHVVSHFL¿FDOO\WRIDVWWZLWFK ribosomal protein regulation, we fused three ribosomal protein ¿EHUVPD\EHDPHFKDQLVPE\ZKLFKDJLQJUHODWHGPXVFOHDWURSK\ JHQH SURPRWHUV 536 53/D 53/ WR D GHVWDELOL]HG JUHHQ RFFXUV 7KURXJK WKH WHFKQLTXH RI OLQHDJHWUDFLQJ IDWHPDSSLQJ RI ÀXRUHVFHQW SURWHLQ *)3 JHQH DOORZLQJ TXDQWL¿FDWLRQ RI *)3 WKH WUDQVFULSWLRQ IDFWRU 7ZLVW ZH KDYH LGHQWL¿HG D QRYHO PXVFOH ÀXRUHVFHQFHWRVHUYHDVDG\QDPLFUHDGRXWRI53H[SUHVVLRQ:H SURJHQLWRUWKDWIXVHVVSHFL¿FDOO\WRW\SH,,E[ IDVWWZLWFKJO\FRO\WLF stably infected both a breast cancer CTC line and an immortalized PXVFOH¿EHUVGXULQJERWKDJLQJDQGUHJHQHUDWLYHFRQGLWLRQV7KHVH breast epithelial cell line to study temporal changes in ribosomal 7ZLVW FHOOV DUH WUDQVFULSWLRQDOO\ GLVWLQFW IURP VDWHOOLWH FHOOV DQG protein expression at both a single cell and bulk population level. We DUH LQWULQVLFDOO\ P\RJHQLF$GGLWLRQDOO\ORVV RI7ZLVW FHOOV LQ YLYR are currently investigating the regulation of the protein biosynthetic UHVXOWVLQVSHFL¿FDWURSK\RIIDVWWZLWFKP\R¿EHUV:HDUHFDSDEOH SDWKZD\DQGLWVSRWHQWLDOUROHLQPHGLDWLQJ&7&VXUYLYDO8OWLPDWHO\ RILVRODWLQJ7ZLVWFHOOVDQGGLႇHUHQWLDWLQJWKHPLQFXOWXUH7KURXJK this study aims to characterize the regulation of translational IXUWKHULQYLWURDVVD\VZHLGHQWL¿HG7ZLVWDVDUHJXODWRURIP\RJHQLF machinery and its contribution to CTC biology, expanding our GLႇHUHQWLDWLRQ :H FRQ¿UPHG WKHVH ¿QGLQJV WKURXJK 51$VHT DQG understanding of metastasis and identifying potential novel targets &K,36HT ZKHUH IRXQG WKDW 7ZLVW RYHUH[SUHVVLRQ GULYHV JOREDO for inhibition. UHSUHVVLRQRIWKHP\RJHQLFSURJUDP$GGLWLRQDOO\ZHLGHQWL¿HGVHYHUDO LQWHUHVWLQJ 7ZLVW WDUJHW JHQHV VXFK DV 1HXURSLOLQ ZKLFK PD\ 180 5HVWRUDWLRQRIVRFLDOHQFRGLQJE\LQGLYLGXDOQHXURQVLQ PHGLDWHWKH¿EHUW\SHVSHFL¿FLW\WKURXJKUHSXOVLYHLQWHUDFWLRQVZLWK an adult mouse model of Autism 6HPDSKRULQD2XUGDWDVRIDUVXJJHVWV7ZLVWSOD\VDPXOWLIDFHWHG Songjun W. Li UROHLQUHJXODWLQJWKHELRORJ\RI7ZLVWGHSHQGHQWSURJHQLWRUV Boston University School of Medicine, Boston, USA 183 Tumor-induced immunosuppression promotes brain 6RFLDOG\VIXQFWLRQLVDPRQJWKHPRVWSURPLQHQWIHDWXUHVRIDXWLVP metastasis in patients with non-small cell lung cancer VSHFWUXPGLVRUGHU $6' DVZHOODVPDQ\RWKHUGHYHORSPHQWDODQG Yuping D. Li neuropsychiatric conditions. The precise neuronal mechanisms that Feinberg School of Medicine, Northwestern University, USA DUHGLVUXSWHGLQ$6'KRZHYHUUHPDLQXQNQRZQ7KHJRDORIWKLVVWXG\ LVWRSURYLGHDEDVLFFHOOXODUOHYHOXQGHUVWDQGLQJDQGWUHDWPHQWPRGHO %UDLQPHWDVWDVHVDUHDVLJQL¿FDQWVRXUFHRIPRUELGLW\DQGPRUWDOLW\IRU IRU$6'7RWKLVHQGZHGHYHORSHGDQDOWHUQDWLQJDSSHWLWLYHDYHUVLYH SDWLHQWVZLWKOXQJFDQFHU:KLOHHႇHFWLYHLQQDWHLPPXQHUHVSRQVHV SDUDGLJPLQZKLFKVRFLDOO\SDLUHGPLFHH[SHULHQFHGERWKDFXWHVWUHVV can combat early malignancy, many cancers have the potential to and food reward while we simultaneously recorded neuronal activity induce local and systemic immunosuppression, promoting tumor IURP WKH PHGLDO SUHIURQWDO FRUWH[ :H FRPSDUHG ZLOGW\SH :7 WR growth and metastasis. One mechanism of immunosuppression is 6+$1.PLFHDVDPRGHORI$6'WRH[SORUHWKHQHXURQDOFRUUHODWHV WKHWXPRULQGXFHGH[SDQVLRQRISURJUDPPHGGHDWKOLJDQG 3' of socially relevant information and its dysfunction. Individual medial L1) positive suppressive myeloid cells. We recently demonstrated that in patients with glioblastoma, circulating monocytes have

www.jointmeeting.org 85 POSTER ABSTRACTS

LQFUHDVHG 3'/ VXUIDFH H[SUHVVLRQ ZKLFK ZDV DVVRFLDWHG ZLWK This is a prospective, observational study that uses a telemedicine worse survival in patients receiving a vaccine immunotherapy. Here QHWZRUN WKDW FRQQHFWV D XQLYHUVLW\ EDVHG EHG WHUWLDU\ FDUH ZH HYDOXDWH WKH UROH RI WXPRULQGXFHG VXSSUHVVLYH P\HORLG FHOO 3HGLDWULF,QWHQVLYH&DUH8QLWZLWKUHPRWH('V3HGLDWULFWUDQVIHUV expansion on the development of brain metastases in patients with IURPRXWVLGH('VDUHHOLJLEOHLIWKHQXUVHUHFHLYLQJUHSRUWLVDOVRWKH QRQVPDOOFHOOOXQJFDUFLQRPD DGPLWWLQJQXUVHXSRQDGPLVVLRQ5HFHLYLQJQXUVHVFRPSOHWHDWKUHH Peripheral blood was collected from patients undergoing resection SDJHVXUYH\WKDWLQFOXGHVWKHYDOLGDWHG+DQGRႇ&OLQLFDO(YDOXDWLRQ RI OXQJ PHWDVWDWLF EUDLQ WXPRUV Q ,PPXQRVXSSUHVVLYH ([HUFLVH +DQGRႇ &(; LQVWUXPHQW IRU KDQGRႇ TXDOLW\ DGGLWLRQDO PRQRF\WHV &' &'E &' 3'/ DQG P\HORLG items on nursing preparedness and the technology acceptance GHULYHGVXSSUHVVRUFHOOV 0'6&V &'E&'+/$'5OR3' model. This study was approved by the local institutional review / ZHUH TXDQWL¿HG WKURXJK ÀRZ F\WRPHWU\ 7XPRU WLVVXH ZDV board. obtained from resection of brain metastases and used to generate 7RGDWH GDWD KDYH EHHQ FROOHFWHG RQ QXUVHSDWLHQW G\DGV FHOOFXOWXUHV Q IURPZKLFKWXPRUFRQGLWLRQHGPHGLD 7&0 ZDV by telemedicine and 16 by telephone. Before commencing the collected. TCM was analyzed for immunosuppressive cytokines, study, preliminary data were collected on three transfers during LQFOXGLQJ LQWHUOHXNLQ ,/ E\ HQ]\PHOLQNHG LPPXQRVRUEHQW the study implementation phase: two telemedicine reports and DVVD\ (/,6$ 1DwYH PRQRF\WHV ZHUH VWLPXODWHG ZLWK 7&0 IRU RQHWHOHSKRQHUHSRUW'XULQJERWKWHOHPHGLFLQHUHSRUWVUHFHLYLQJ KRXUV LQ WKH SUHVHQFH RI DQWLERGLHV WDUJHWLQJ WKH ,/ UHFHSWRU nurses visually assessed the patient and communicate with the WRFLOL]XPDE ,/ VLOWX[LPDE RU,J*FRQWURO family whereas in the telephone report, neither of these occurred. Patients with brain metastatic lung carcinoma demonstrated In one telemedicine report, the use of telemedicine was particularly LQFUHDVHGSHULSKHUDOPRQRF\WH3'/FRPSDUHGWRKHDOWK\FRQWUROV helpful in determining the severity of illness of the patient; which S ZLWK DQ DYHUDJH IROG LQFUHDVH$OO SDWLHQWV H[KLELWHG ZDVSUHYLRXVO\QRWDVVHVVDEOHLQWKHSUHFHGLQJSK\VLFLDQSK\VLFLDQ DQ LQFUHDVHG DEXQGDQFH RI 0'6&V S ZLWK DQ DYHUDJH UHSRUWRYHUWHOHSKRQH'DWDFROOHFWLRQDQGDQDO\VLVZLOOEH¿QLVKHGE\ IROG LQFUHDVH (OHYDWHG SODVPD ,/ ZDV DVVRFLDWHG ZLWK 0DUFK:HH[SHFWWRHQUROOWUDQVIHUVZLWKRYHUVDPSOLQJRI LQFUHDVHGSHULSKHUDOP\HORLG3'/LQSDWLHQWVZLWKEUDLQPHWDVWDWLF telemedicine transfers. lung carcinoma (p<0.05). TCM stimulated monocytes expressed This prospective study assesses the feasibility of implementing LQFUHDVHG3'/FRPSDUHGWRXQVWLPXODWHGFRQWUROV YV WHOHPHGLFLQHIRUQXUVHOHGFRPPXQLFDWLRQEHWZHHQGLVWDQWKRVSLWDOV 3'/SRVLWLYHS &RUUHODWLRQRI7&0,/OHYHOVZLWK3' In the planned analyses, we will evaluate the impact of telemedicine /H[SUHVVLRQLQ7&0VWLPXODWHGPRQRF\WHVGHPRQVWUDWHGDGRVH RQSHUFHLYHGSUHSDUHGQHVVDQGWKHTXDOLW\RILQWHUIDFLOLW\KDQGRႇV GHSHQGHQW UHODWLRQVKLS 5 S ,Q DGGLWLRQ WUHDWPHQW XWLOL]LQJ PL[HGPRGHO ORJLVWLF UHJUHVVLRQ :H SODQ WR XVH WKLV GDWD ZLWKDQWL,/DQGDQWL,/UHFHSWRUDQWLERGLHVLQKLELWHGWKHLQFUHDVH to demonstrate a feasible model of care that can be scaled across LQPRQRF\WH3'/ healthcare systems nationwide to improve care coordination during Patients with lung cancer and brain metastases exhibit signs patient transfers. RI SHULSKHUDO LPPXQRVXSSUHVVLRQ LQFOXGLQJ LQFUHDVHG 3'/ 185 7KH5ROHRI([RVRPHVLQ5HQDO&HOO&DUFLQRPD,PPXQH PRQRF\WHV DQG 0'6&V ,/ ZDV IRXQG WR VWLPXODWH LQGXFWLRQ Suppression of immunosuppressive myeloid cells. Monitoring of these $DURQ5/LP immunosuppressive factors in peripheral blood may be used as a Vanderbilt University School of Medicine, Nashville, USA biomarker to predict patients at greater risk for brain metastases and suggest a new target for therapeutic intervention. 5HQDOFHOOFDUFLQRPD 5&& LVRQHRIWKHOHDGLQJFDXVHVRIFDQFHU UHODWHGGHDWKVLQWKH8QLWHG6WDWHV$OWKRXJKDFWLYDWLQJWKHLPPXQH 184 Evaluating Use Of Telemedicine For Interfacility Transfer V\VWHP ZLWK DQWLSURJUDPPHG GHDWK 3' LPPXQRWKHUDS\ ZDV Handoffs UHFHQWO\ DSSURYHG WR WUHDW PHWDVWDWLF 5&& RQO\ RI SDWLHQWV 0RQLFD/LHQJ respond to this treatment. Previous work in our labs demonstrated University of California, Davis, Sacramento, CA 95817, USA WKDW5&&KDVWKHKLJKHVWLQ¿OWUDWLRQRI&'7O\PSKRF\WHVZKLFK ,QWHUIDFLOLW\WUDQVIHUV±WUDQVLWLRQVLQFDUHEHWZHHQGLႇHUHQWKRVSLWDOV KDYHEHHQNQRZQWRSOD\DQDQWLWXPRUUROHRIDOOVROLGWXPRUVLQ — have been associated with serious adverse events, many of WKH &DQFHU *HQRPH$WODV +RZHYHU ZH IRXQG WKDW &' WXPRU ZKLFK VWHP IURP EUHDNGRZQV RU LQHႈFLHQFLHV LQ FRPPXQLFDWLRQ LQ¿OWUDWLQJO\PSKRF\WHVLVRODWHGIURPIUHVKO\UHVHFWHG5&&SDWLHQW 1XUVLQJUHSRUWVEHWZHHQRXWVLGHHPHUJHQF\GHSDUWPHQWV ('V DQG WXPRUV KDYH HOHYDWHG H[SUHVVLRQ RI 3' DQG DUH IXQFWLRQDOO\ receiving inpatient wards may include inaccuracies regarding the exhausted. Thus, understanding how RCC evades our immune severity of illness of the patient, which may lead to a mismatch in the V\VWHP LV FULWLFDO WR LPSURYH WKH HႈFDF\ RI LPPXQRWKHUDS\ 2QH level of resource preparation and utilization upon admission. One potential mechanism by which tumors can evade the immune solution to improve care coordination between nurses at referring system is the release of exosomes, nanosized extracellular vesicles hospitals with nurses at receiving hospitals is through telemedicine. secreted by most tissues. These particles, which carry protein cargo, 8WLOL]LQJ WHOHPHGLFLQH LQVWHDG RI WHOHSKRQH IRU UHSRUW PD\ DOORZ DUHJDLQLQJFRQVLGHUDEOHDWWHQWLRQLQWKH¿HOGRIFDQFHUELRORJ\IRU nurses to interact with patients and their families prior to their transfer WKHLUUROHVDVLQWHUFHOOXODUFRPPXQLFDWRUVDQGELRPDUNHUV6WXGLHV while enabling direct visual assessment of the patient and illness of plasma exosomes from cancer patients revealed cargo that are severity. While the use of telemedicine has been investigated during NQRZQWRVXSSUHVVWKHLPPXQHV\VWHPVXFKDVSURJUDPPHGGHDWK physician communication during interfacility transfers,no studies have OLJDQG 3'/ DQG71)UHODWHGDSRSWRVLVLQGXFLQJOLJDQG 75$,/ evaluated the use of telemedicine for nursing communication during However, the role of exosomes in RCC has been understudied. We WKHVHKDQGRႇV:HK\SRWKHVL]HWKDWKDQGRႇVXVLQJWHOHPHGLFLQHZLOO K\SRWKHVL]HG WKDW 5&& VHFUHWHV H[RVRPHV FRQWDLQLQJ 3'/ DQG LPSURYHKDQGRႇTXDOLW\DQGQXUVLQJSHUFHSWLRQRISUHSDUHGQHVVDW 75$,/ WR VXSSUHVV WKH IXQFWLRQ RI WXPRULQ¿OWUDWLQJ O\PSKRF\WHV SDWLHQWDGPLVVLRQFRPSDUHGWRKDQGRႇVXVLQJWHOHSKRQHWKHFXUUHQW and thus create an immunosuppressive environment. To test this standard of care. K\SRWKHVLVZHXVHGGLႇHUHQWLDOXOWUDFHQWULIXJDWLRQDQGDQ2SWLSUHS

86 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

density gradient to isolate and purify exosomes from the culture media mimicking environments. The relationship of systemic delivery RI2FHOOVDKXPDQ5&&FHOOOLQH8VLQJQDQRSDUWLFOHWUDFNLQJ challenges and the behaviors of these nanoparticles will be further DQDO\VLV DQG WUDQVPLVVLRQ HOHFWURQ PLFURVFRS\ ZH FRQ¿UPHG WKDW discussed. 2FHOOVVHFUHWHYHVLFOHVFRQVLVWHQWZLWKH[RVRPHVL]H aQP and morphology. With western blot, we found that these exosomes 188 An immunogenomics approach to neoantigen FRQWDLQ ERWK LPPXQRVXSSUHVVLYH SURWHLQV 3'/ DQG 75$,/ ,Q LGHQWL¿FDWLRQLQSUHFOLQLFDOPRGHOVRIJOLREODVWRPD DGGLWLRQÀRZF\WRPHWULFPHDVXUHPHQWRIDFWLYDWLRQPDUNHUVVKRZHG Connor J. Liu WKDW 5&&GHULYHG H[RVRPHV GHFUHDVHG WKH DFWLYDWLRQ RI KXPDQ Washington University School of Medicine, USA &'7FHOOV7DNHQWRJHWKHURXUUHVXOWVLQGLFDWHWKDW5&&UHOHDVHV *OLREODVWRPD *%0 UHPDLQVWKHPRVWFRPPRQDQGOHWKDOPDOLJQDQF\ H[RVRPHV ZLWK LPPXQRVXSSUHVVLYH FDUJR VXFK DV 3'/ DQG RI WKH FHQWUDO QHUYRXV V\VWHP &16 LQ DGXOWV 7KH SDVW GHFDGH TRAIL, that can suppress the immune system. RI *%0 UHVHDUFK KDV VHHQ OLPLWHG SURJUHVV LQ LPSURYLQJ SDWLHQW VXUYLYDO EH\RQG WKH FXUUHQW VWDQGDUGRIFDUH VXUJLFDO UHVHFWLRQ (JUGHSHQGHQW PLFUR51$ LV GLVSHQVDEOH IRU 186 followed by radiation and temozolomide chemotherapy. However, peripheral nerve myelination recent success in the use of immunotherapy to treat other solid and Hsin-Pin Lin blood malignancies, in addition to experimental evidence challenging University of Florida, Gainesville, USA WKHQRWLRQRIWKH&16DVDQLPPXQRORJLFDOO\SULYLOHJHGHQYLURQPHQW 5HFHQW VWXGLHV KDYH HOXFLGDWHG WKH FUXFLDO UROH RI PLFUR51$V KDVJHQHUDWHGQHZLQWHUHVWLQXVLQJLPPXQHEDVHGWUHDWPHQWVIRU in peripheral nerve myelination by ablating components of the *%0SDWLHQWV,QSDUWLFXODUµFDQFHULPPXQRJHQRPLFV¶GHVFULEHVDQ PLFUR51$ V\QWKHVLV PDFKLQHU\ )HZ VWXGLHV KDYH IRFXVHG RQ DSSURDFKWRLPPXQRWKHUDS\GHVLJQDLPHGDWOHYHUDJLQJWKHWXPRU WKH UROH RI LQGLYLGXDO PLFUR51$V 7R¿OO WKLV JDS ZH IRFXVHG WKLV VSHFL¿FPXWDQWSHSWLGHVSUHVHQWHGRQDSDWLHQW¶VLQGLYLGXDOKXPDQ VWXG\ RQ PL5 ZKLFK ZDV VKRZQ WR EH GUDVWLFDOO\ UHGXFHG LQ leukocyte antigen (HLA) molecules, as therapeutic targets. These 'LFHUDQG'JFUNQRFNRXWPLFHZLWKK\SRP\HOLQDWLQJSKHQRW\SHV WXPRU VSHFL¿F PXWDQW SHSWLGHV FDOOHG QHRDQWLJHQV KDYH FRPH DQG SRWHQWLDOO\ WDUJHW WKH QHJDWLYH UHJXODWRUV RI 6FKZDQQ FHOO XQGHULQWHQVHIRFXVDVWKHLPPXQRGRPLQDQWWDUJHWVPHGLDWLQJDQWL GLႇHUHQWLDWLRQ+HUHZHVKRZHGWKDWRIWZRPL5HQFRGLQJORFL tumor responses to immunotherapy. PLU LV WKH SUHGRPLQDQW ORFXV WUDQVFULEHG LQ 6FKZDQQ FHOOV 0RVW UHFHQWO\ XVLQJ '1$ ZKROH H[RPH VHTXHQFLQJ 51$ PLU LV WUDQVFULSWLRQDOO\ XSUHJXODWHG GXULQJ P\HOLQDWLRQ DQG sequencing, and computational algorithms to prioritize neoantigens GRZQUHJXODWHG XSRQ QHUYH LQMXU\ (*5 LV UHTXLUHG IRU PLU predicted to bind major histocompatibility complexes (MHC), WUDQVFULSWLRQ GXULQJ GHYHORSPHQW DQG ERWK 62; DQG (*5 RXU JURXS LVRODWHG QHRDQWLJHQVSHFL¿F &' 7FHOOV IURP WXPRU ELQG WR DQ DFWLYH HQKDQFHU QHDU WKH PLU ORFXV %DVHG RQ LQ¿OWUDWLQJ O\PSKRF\WHV 7,/ LQ WZR FKHFNSRLQW VHQVLWLYH PRXVH H[SUHVVLRQDQDO\VHVZHK\SRWKHVL]HGWKDWPL5IDFLOLWDWHVWKH JOLRPD PRGHOV */ DQG 60$ 7R DVVHVV WKH DQWLJOLRPD WUDQVLWLRQ EHWZHHQ XQGLႇHUHQWLDWHG 6FKZDQQ FHOOV DQG P\HOLQDWLQJ immune response following neoantigen vaccination, here we 6FKZDQQ FHOOV +RZHYHU LQ FRQGLWLRQDO NQRFNRXWV ZH FRXOG QRW demonstrate that peptide vaccination with a mutant Imp3 neoantigen GHWHFW VLJQL¿FDQW FKDQJHV LQ 6FKZDQQ FHOO SUROLIHUDWLRQ FHOO F\FOH FRQIHUVDVLJQL¿FDQWVXUYLYDODGYDQWDJHLQPLFHEHDULQJLQWUDFUDQLDO H[LWRUP\HOLQDWLRQ2YHUDOORXUUHVXOWVGHPRQVWUDWHWKDWPL5LV */ 7R RXU XQGHUVWDQGLQJ WKHVH ¿QGLQJV UHSUHVHQW WKH ¿UVW DQ(JUGHSHQGHQWPLFUR51$EXWLVGLVSHQVDEOHIRU6FKZDQQFHOO GRFXPHQWDWLRQRIDSHUVRQDOL]HGµPXWDWLRQWRYDFFLQH¶SLSHOLQHLQD myelination. SUHFOLQLFDO*%0PRGHODQGSURYLGHVDIUDPHZRUNIRUVWXG\LQJWKH 187 Biomimetic stimuli-responsive glucose-based polymeric cellular basis of neoantigen dependent responses to immunotherapy. nanocarriers for cancer therapeutics Additionally, we show that the CT2A syngeneic mouse glioma model recapitulates the highly aggressive and checkpoint blockade resistant Yen-Nan Lin SKHQRW\SH VHHQ LQ WKH KXPDQ *%0 VHWWLQJ$SSO\LQJ '1$ ZKROH Texas A&M University, Bryan, USA H[RPH VHTXHQFLQJ ZH LGHQWL¿HG QRQV\QRQ\PRXV PXWDWLRQV 1DQRFDUULHUVWKDWLPSURYHWKHHႈFDF\RIFKHPRWKHUDS\DUHHVVHQWLDO LQWKH&7$WXPRUJHQRPHRIZKLFKZHUHDOVRH[SUHVVHGLQ to the control of cancer progression. This talk will focus on the 51$VHTXHQFLQJ :H XVHG WKH RSHQVRXUFH LQ VLOLFR QHRDQWLJHQ GHYHORSPHQW RI QRYHO ELRPLPHWLF FHOOXODU PHPEUDQHFDPRXÀDJHG SUHGLFWLRQ VRIWZDUH S9$&VHT WR LGHQWLI\ WRSUDQNLQJ +.E DQG VWLPXOLUHVSRQVLYH JOXFRVHEDVHG QDQRFDUULHUV WKDW RYHUFRPH +'E UHVWULFWHG &7$ FDQGLGDWH QHRDQWLJHQV IRU V\QWKHVLV DQG various biological barriers during systemic chemotherapeutics LPPXQRJHQLFLW\VFUHHQLQJE\,)1J(/,63277KXVE\GHWHUPLQLQJ GHOLYHU\ 8SRQ V\VWHPLF DGPLQLVWUDWLRQ QDQRFDUULHUV HQFRXQWHU the immunogenicities of high priority neoantigens in CT2A, we a series of biological challenges, including protein adsorption, extend our neoantigen discovery pipeline to a third and highly PRQRQXFOHDU SKDJRF\WH V\VWHP XSWDNH RႇWDUJHW DFFXPXODWLRQ immunosuppressive glioma model. In conjunction with our work DQG GUXJ UHOHDVH GUXJ HႉX[ DQG H[FUHWLRQ 1DQRFDUULHUV VKRXOG LQ */ DQG 60$ FKDUDFWHUL]DWLRQ RI WKH &7$ QHRDQWLJHQ be designed to avoid these obstacles in order to maximize ODQGVFDSH ZLOO KHOS HVWDEOLVK D *%0 LPPXQRWKHUDS\ PRGHO WKDW ELRDYDLODELOLW\ RI GUXJV WR WXPRUV DQG UHGXFH RႇWDUJHW WR[LFLW\ captures clinically relevant biology and that will provide a platform to 2UJDQRFDWDO\]HGVHTXHQWLDOFRQWUROOHGULQJRSHQLQJSRO\PHUL]DWLRQ IXUWKHUVWXG\FRPELQDWLRQLPPXQRWKHUDSLHVLQ*%0 of cyclic glucose monomer and cyclic lactide monomer, followed by SRVWSRO\PHUL]DWLRQ PRGL¿FDWLRQ YLD WKLRO\QH FOLFN FKHPLVWU\ OHG 189 $FWLYDWLRQRI$NWE\:QWDVD1RYHO5HJXODWRURI8WHULQH WR IXQFWLRQDO DPSKLSKLOLF SRO\PHUV 2SWLPL]DWLRQ RI JOXFRVHEDVHG Leiomyoma Stem Cell Function polymer assemblies and cell membrane coating led to biomimetic Shimeng Liu VWLPXOLUHVSRQVLYHVXJDUEDVHGSRO\PHULFQDQRSDUWLFOHV7KHLPSDFW Northwestern University, Chicago, USA RI FHOO PHPEUDQH FRDWLQJV RQ WKH S+UHVSRQVLYH EHKDYLRU RI WKH ,QWURGXFWLRQ8WHULQHOHLRP\RPDV /0 UHSUHVHQWWKHPRVWFRPPRQ VXJDUEDVHG SRO\PHULF QDQRSDUWLFOHV ZLOO EH GLVFXVVHG WKURXJK tumor in women. 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WKHSURWHLQOHYHOVRIDFWLYHEFDWHQLQ,QWHUHVWLQJO\:QWLQDWLPH dependent manner, dramatically increased AKT phosphorylation 191 $'$06KHGV,&26/LJDQGRQ%&HOOVDQGLV1HFHVVDU\ S$.7 SHDNLQJ DW PLQ 1 $GGLWLRQDOO\ :QW VLJQL¿FDQWO\ IRU 3URSHU 7 &HOO ,&26 5HJXODWLRQ DQG 7 )ROOLFXODU +HOSHU LQFUHDVHGF0\FDQGF\FOLQ' GRZQVWUHDPWDUJHWVRI$NWSDWKZD\ 5HVSRQVHV SURWHLQOHYHOVDWKKDQGKDIWHUWUHDWPHQW5HDOWLPH3&5DVVD\ Joseph C. Lownik FRQ¿UPHGWKDWP51$OHYHOVRIERWKF0\FDQGF\FOLQ'ZHUHDOVR Virginia Commonwealth University, Richmond, USA XSUHJXODWHGE\:QW 1 3 /RQJWHUPWUHDWPHQW GD\V ZLWK:QWQRWRQO\LQFUHDVHGSURWHLQOHYHOVRIF0\FDQG&\FOLQ' Introduction: $ 'LVLQWHJULQ DQG 0HWDOORSURWHLQDVHV $'$0V EXW DOVR WKRVH RI 3&1$ D FHOO SUROLIHUDWLRQ PDUNHU DQG WKHVH are a family of zinc dependent proteinases which can mediate VWLPXODWRU\HႇHFWVZHUHUHYHUVHGE\FRWUHDWPHQWZLWK0. 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Our studies represent a key step towards the better understanding of stem cell regulation and indicate potential novel therapeutic targets Methods: 7RH[DPLQHWKHUROHRI$'$0RQ%FHOO,&26/UHJXODWLRQ % WRUH¿QHWKHWUHDWPHQWIRU/0 ZHXWLOL]HGD%FHOOFRQGLWLRQDONQRFNRXWRI$'$0 $'$0 ). )ORZ F\WRPHWU\ DQG ,PDJH6WUHDP DQDO\VLV ZHUH XVHG WR H[DPLQH 190 Protein o,o’-Dityrosine Cross-Linking Disrupts Cystic ,&26DQG,&26/OHYHOV)ROOLFXODUKHOSHU7FHOO 7FH) and antibody )LEURVLV0XFXV9LVFRHODVWLF'\QDPLFV UHVSRQVHV ZHUH H[DPLQHG XVLQJ 13./+ LPPXQL]DWLRQV $OOHUJLF 0RUJDQ/RF\ airway responsiveness was examined using a house dust mite University of Alabama at Birmingham, Birmingham, USA +'0 PRGHOLQZKLFK+'0H[WUDFWLVLQWUDQDVDOO\DGPLQLVWHUHGIRU 5DWLRQDOH &\VWLF ¿EURVLV &) LV D PXOWLRUJDQ GLVHDVH ZLWK OXQJ IRXUGD\VIROORZHGE\LQWUDQDVDOFKDOOHQJHZLWK+'0H[WUDFWWHQGD\V morbidity being the primary cause of early mortality. Cardinal features later. Autoimmune responses were examined using the experimental of CF airway disease include increased viscosity and decreased allergic encephalomyelitis (EAE) model. FOHDUDQFHRIQHXWURSKLOODGHQPXFXV$OWKRXJKR[LGDWLYHVWUHVVKDV Results: A'$0% PLFH H[KLELWHG D IROG LQFUHDVH LQ VXUIDFH been implicated in CF pathogenesis, its role in mucus viscoelasticity OHYHOV RI ,&26/ RQ % FHOOV ZKLOH 7 FHOOV H[KLELWHG DQ DOPRVW DUHQRWZHOOXQGHUVWRRG2[LGDWLYHW\URVLQHPRGL¿FDWLRQVLQFOXGLQJ FRPSOHWHORVVRIVXUIDFH,&267FHOOVGRZQUHJXODWHGVXUIDFH,&26 RR¶GLW\URVLQH KDYH EHHQ VKRZQ WR EH LQFUHDVHG LQ VSXWXP RI levels through internalization and lysosomal degradation following CF patients. RR¶'LW\URVLQH LV D VWDEOH FRYDOHQW LUUHYHUVLEOH LQWHUDFWLRQ ZLWK ,&26/ 3K\VLRORJLFDOO\ LQDELOLW\ WR VKHG ,&26/ PRGL¿FDWLRQWKDWLVFDWDO\]HGE\K\GURJHQSHUR[LGH + 2O2 PHGLDWHG FDXVHG GLVUXSWLRQ RI WKH ,&26,&26/ D[LV DQG FDXVHG VHYHUH oxidation of a heme peroxidase (hPx), such as myeloperoxidase defects in T GHYHORSPHQW%ORFNDGHRIHOHYDWHG,&26/UHVFXHG (MPO) produced by neutrophils and macrophages. In this study, FH 7FHOO,&26VXUIDFHH[SUHVVLRQDQGUHVFXHGERWK7FH numbers and ZH H[SORUHG WKH PHFKDQLVPV E\ ZKLFK SURWHLQDVVRFLDWHG RR¶ the abnormal antibody production in these mice. Additionally, using dityrosine contributes to disease pathogenesis.

88 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

WKH +'0 PRGHO RI DOOHUJLF DLUZD\ LQÀDPPDWLRQ ZH GHPRQVWUDWHG 193 'H¿QLQJWKHUROHRIWKHLPPXQHV\VWHPLQDQHXSORLGFHOO WKDW ,&26,&26/ G\VUHJXODWLRQ WKURXJK$'$0 GHOHWLRQ FDXVHG clearance GHIHFWLYH 7K SRODUL]DWLRQ ,Q FRQWUDVW 7K DQG 7K UHVSRQVHV (PLO\&0DF'XI¿H ZKLFK DUH OHVV GHSHQGHQW RQ ,&26,&26/ DUH LQFUHDVHG 7KLV Warren Alpert Medical School of Brown University, USA FKDQJHZDVH[HPSOL¿HGLQWKDWDXWRLPPXQHUHVSRQVHVLQWKH($( model were clearly more severe both with respect to symptomology Aneuploidy, the loss or gain of one or more chromosomes, is a and percent of mice developing disease. hallmark of oncogenic transformation. Although aneuploidy is rare LQ QRUPDO WLVVXHV RI FHOOV LW LV HVWLPDWHG WR EH SUHVHQW LQ Conclusions:2YHUDOOWKLVVWXG\QRWRQO\FRQ¿UPVWKHLPSRUWDQFH RIVROLGFDQFHUV'HVSLWHLWVSHUYDVLYHQHVVLQFDQFHURXVWLVVXH RI ,&26/ VKHGGLQJ LQ ,&26/,&26 IXQFWLRQ EXW LW DOVR LGHQWL¿HV H[SHULPHQWDOO\GHULYHGDQHXSORLGFHOOVKDYHDVLJQL¿FDQWSUROLIHUDWLYH $'$0 DV WKH PRVW LPSRUWDQW VKHGGDVH IRU WKLV IXQFWLRQ 2XU disadvantage compared to euploid cells both in vitro and in vivo. ZRUN DOVR GH¿QHV D QRYHO SRVWWUDQVODWLRQDO PHFKDQLVP IRU ,&26 UHJXODWLRQQDPHO\LQWHUQDOL]DWLRQLQUHVSRQVHWR,&26/LQWHUDFWLRQ 7R DVVHVV WKH HႇHFWV RI DQHXSORLG\ RQ FHOOXODU ¿WQHVV DQG DVZHOODVGLႇHUHQFHVLQHQGRVRPDOVKXWWOLQJSDWKZD\VZKHQ7&5 tumorigenesis, mouse models were developed that lack a functional VWLPXODWLRQRFFXUVFRQFRPLWDQWO\FRPELQHGZLWK,&26/,QVXPPDU\ VSLQGOHDVVHPEO\FKHFNSRLQW 6$& :LWKRXWDIXQFWLRQLQJFKHFNSRLQW WKHVH ¿QGLQJV SUHVHQW D QRYHO SDWKZD\ WR PRGXODWH ,&26/ DQG cells initiate anaphase before correct kinetochore attachments ,&26H[SUHVVLRQDQGDOWHUWKHKXPRUDOLPPXQHUHVSRQVH are made, resulting in aneuploid daughter cells. Mouse models of FKURPRVRPDOLQVWDELOLW\ &,1 GXHWRGLVUXSWLRQRIWKH6$&VKRZKLJK 192 (SLWKHOLDOVSHFL¿FSĮ.2$IIRUGV6XUYLYDO$GYDQWDJH levels of aneuploidy in tissues that are formed during embryogenesis $IWHU5DGLDWLRQ,QMXU\7KURXJK(QKDQFHG&U\SW5HVLOLHQFH such as brain. However, tissues that regenerate during adulthood, Evan B. Lynch such as skin, intestine, and peripheral blood harbor very low levels of University of Kentucky College of Medicine, Lexington, USA aneuploidy. It is unknown how aneuploid cells are selected against in these tissues. We tested the possibility that aneuploid cells are +LJKGRVH UDGLDWLRQ WDUJHWV KLJKO\ SUROLIHUDWLYH FRPSDUWPHQWV FOHDUHGYLDDSRSWRVLV:HTXDQWL¿HGFOHDYHGFDVSDVHDPDUNHU making radiation an attractive option for aggressive cancers. RIDSRSWRVLVLQWKHLQWHVWLQHRI&,1PRXVHPRGHOVEXWGHWHFWHGQR However, radiation exerts stress on high cycling cells, including increase in apoptotic cells compared to control mice, suggesting that LQWHVWLQDOHSLWKHOLDOFHOOV ,(& ZKHUHLWFDXVHVVLJQL¿FDQWGHELOLWDWLQJ other mechanisms may be responsible for aneuploid cell elimination. VLGH HႇHFWV GLDUUKHD EOHHGLQJ HWF +HUH ZH H[DPLQH WKH UROH We hypothesized that aneuploid cells exhibit immunogenic stress RI 3,.LQDVH 3,. VLJQDOLQJ LQ SURPRWLQJ HSLWKHOLDO UHSDLU DIWHU responses that are recognized by the immune system and result in radiation injury. Previously, we found that reductions in class IA PI3K their ultimate removal. (SLNU UHJXODWRU\VXEXQLWSĮ LQGXFHVWKHDQWLDSRSWRWLFSURWHLQ survivin and promotes IEC expansion in an ileocecal resection To test the above hypothesis, we optimized a protocol to generate repair model. Preliminary data obtained in histopathologic sections arrested aneuploid cells with complex karyotypes from RPE1 IURP UDGLDWLRQ SURFWLWLV SDWLHQWV UHYHDO D HQKDQFHPHQW RI FHOOV %URDG SURWHLQ SUR¿OLQJ RI VHFUHWHG F\WRNLQHV LQ WKH FHOOXODU VXUYLYLQQXFOHLFRPSDUHGWRQRUPDOFRORQLFELRSVLHV7RLQWHUURJDWH VXSHUQDWDQW UHYHDOHG LQFUHDVHG OHYHOV *0&6) ,/ DQG &&/ the role of IEC PI3K in radiation injury, we utilized 9LOOLQ&UHSÀ LQÀDPPDWRU\F\WRNLQHVNQRZQWRDWWUDFWFHOOVLQYROYHGLQERWKLQQDWH À S.2 DQG 9LOOLQ&UHS+/+ VXEMHFWHG WR KLJK GRVH *\ DQG DGDSWLYH LPPXQLW\ &RFXOWXUHV RI DQHXSORLG 53( FHOOV DQG UDGLDWLRQ,(&:HVWHUQEORW :% GDWDRIXQSHUWXUEHGS.2PLFH QDWXUDONLOOHU 1. FHOOVKDYHSUHYLRXVO\GHPRQVWUDWHG1.PHGLDWHG UHYHDOHGDFRPSOHWHDEODWLRQRISĮZLWKVXEVHTXHQWLQFUHDVHVLQ cell killing. Continuing investigations are exploring the interactions S$NW6HUDORQJZLWKS37(1S*6.ȕ6HUDVZHOODVSS6. between aneuploid cells and phagocytic cell types including and survivin compared to WT controls, suggesting a deregulation macrophages and dendritic cells. RI3,.PDFKLQHU\573&5VWXGLHVSHUIRUPHGDWEDVHOLQHUHYHDOHG To determine if immune mediated clearance of aneuploid cells LQFUHDVHVLQ7$HQULFKHG:QWWDUJHWJHQHV$[LQ DQGc-myc RFFXUV LQ YLYR WLVVXH LQÀDPPDWLRQ ZDV DVVHVVHG LQ WZR PRXVH DQGUHVHUYHLQWHVWLQDOVWHPFHOO ,6& PDUNHUVHopX PRGHOVH[SUHVVLQJPXWDWHGFRPSRQHQWVRIWKH6$&,QWHVWLQHVNLQ and %PL DWWKHH[SHQVHRIWKHDFWLYHF\FOLQJ/JUVWHPFHOOV kidney, liver, and brain tissue were stained with immune cell markers +LVWRSDWKRORJLFVHFWLRQVKLJKOLJKWDGLVWLQFWVKLIWLQWKH]RQH DQGWKHQXPEHURILPPXQHFHOOVSHUDUHDZDVTXDQWL¿HG3UHOLPLQDU\ RISUROLIHUDWLRQZLWKPRUHWKDQDIROGLQFUHDVHLQ%UG8FHOOVDWWKH experiments suggest that macrophages are more abundant in the UHVHUYHVWHPFHOOSRVLWLRQFRPSDUHGWRFRQWUROVFollowing lethal UHJHQHUDWLQJ WLVVXHV RI &,1 PRGHOV EXW WKDW WKH QXPEHU RI &' radiationGRVDJHS.2PLFHH[KLELWHGDLQFUHDVHLQVXUYLYDO KHOSHU 7 FHOOV GRHV QRW GLႇHU EHWZHHQ &,1 PRGHOV DQG FRQWUROV as compared to wildtype (WT) littermates along with increased 2QJRLQJ H[SHULPHQWV DUH HYDOXDWLQJ TXDQWLW\ RI 1. FHOOV &' FU\SWVXUYLYDO SURSRUWLRQRIFU\SWVZLWK!%UG8FHOOVFU\SW:7YV F\WRWR[LF7FHOOVDQGGHQGULWLFFHOOVLQ&,1WLVVXHV S.29VS6HUS37(1 ,QS.2PLFH UDGLDWLRQLQGXFHGORZHUOHYHOVRI:%380$DQGFOHDYHGFDVSDVH 8QGHUVWDQGLQJLPPXQHV\VWHPUHFRJQLWLRQRIWKHVHQRQFDQFHURXV 3 compared to WT controls. Concomitantly, crypt lengths increased DQHXSORLGFHOOVLVWKH¿UVWVWHSWRZDUGVWKHGHYHORSPHQWRIWKHUDSLHV LQS.2 FRPSDUHGWR:7 7DNHQWRJHWKHURXUGDWD that can augment the immune system’s response to cancerous suggest PI3K signaling enhances recovery from radiation injury aneuploid cells. WKURXJKH[SDQVLRQRIUHVHUYH,6&SRSXODWLRQVFDSDEOHRIFUHDWLQJ 194 &7 6FDQ )LQGLQJV LQ 0LFURFHSKDO\ &DVHV 'XULQJ SUROLIHUDWLYH /JU ,6& DQG DFFHOHUDWLQJ FU\SW ,(& UHFRYHU\ IURP 2016 Zika Outbreak: A Cohort Study UDGLDWLRQLQGXFHGFHOOGHDWK:HSRVLWWKLVSDWKZD\OLPLWVDSRSWRVLV -HVVLND7GD60DLD and enhances survival of proliferating progenitor populations which &HQWUR&OLQLFRGD'RU1DWDO%UD]LO LQFUHDVHVRYHUDOOFU\SWVXUYLYDO*LYHQUHVXOWVVXJJHVWLQJSĮ.2 ,(&LQFUHDVH3,.VLJQDOLQJZHSURSRVHSĮDVDSRWHQWLDOGUXJ 2EMHFWLYH7KLV VWXG\ DLPHG WR HYDOXDWH &7 VFDQ ¿QGLQJV LQ OLYLQJ able target capable of enhancing recovery from radiation therapy. EDELHVZKRVHPRWKHUVKDGH[DQWKHPDWRXVGLVHDVHV (' FRPSDWLEOH ZLWK=,.9LQIHFWLRQGXULQJWKHLUSUHJQDQF\

www.jointmeeting.org 89 POSTER ABSTRACTS

%DFNJURXQG 6WXGLHV KDYH GHPRQVWUDWHG UDGLRORJLFDO ¿QGLQJV LQ 196 Evaluation of non-random X-inactivation in blood cells PLFURFHSKDO\ 0&3 UHODWHG WR =LND YLUXV =,.9 7KH as a marker for cardiovascular disease and adverse health risk =,.9HSLGHPLFOHDGHGWRDQLQFUHDVHLQWKHSUHYDOHQFHRI0&3LQ (PLO\$0DUUH WKHQRUWKHDVWUHJLRQRI%UD]LO5LR*UDQGHGR1RUWH6WDWH 51 D Rosalind Franklin University of Medicine and Science, USA Brazilian northeast state, was highly impacted by this outbreak. $JHUHODWHGFORQDOKHPDWRSRLHVLV &+ LVDFRPPRQFRQGLWLRQWKDWLV 'HVLJQ0HWKRGV :H HYDOXDWHG WKH &7 EUDLQ VFDQ LPDJHV RI associated with an increased risk of hematologic malignancies (HM) VXEMHFWVXSWRPRQWKVZKRVHPRWKHUVKDG('GXULQJSUHJQDQF\ DQGFDUGLRYDVFXODUGLVHDVH &9' 7KHPDMRULW\RIFDQGLGDWHGULYHU All these MCP cases were followed at a reference center for children PXWDWLRQV RFFXU LQ HSLJHQHWLF UHJXODWRU\ JHQHV VXFK DV $6;/ UHKDELOLWDWLRQLQ51&RKRUWHQUROOPHQWRFFXUUHGZLWKLQEDELHVERUQ '107$ DQG 7(7 JHQHV +RZHYHU D VLJQL¿FDQW SURSRUWLRQ RI between January 2015 and May 2016. older people harbor clonal hematopoiesis without candidate driver Results: All subjects had brain volume reduction, followed by mutations. In older women, clonal hematopoiesis can be detected by LQWUDFUDQLDO FDOFL¿FDWLRQ 1 /LVVHQFHSKDO\ DQG YHQWULFXODU WKHKXPDQDQGURJHQUHFHSWRU$JHQH +80$5$ DVVD\UHJDUGOHVV GLODWDWLRQZHUHIRXQGLQFDVHV3DFK\J\ULDZDVREVHUYHGLQ of the presence or absence of candidate driver mutation(s). The VXEMHFWV DQGFHUHEHOODUDWURSK\ZDVREVHUYHGLQVXEMHFWV +80$5$ DVVD\ HYDOXDWHV QRQUDQGRP ; LQDFWLYDWLRQ 15;, DV $OO VXEMHFWV UHSRUWHG ZLWK SDFK\J\ULD KDG OLVVHQFHSKDO\,Q a marker for clonal hematopoiesis. The purpose of this study is to DGGLWLRQ DOO VXEMHFWV REVHUYHG ZLWK LQWUDFUDQLDO FDOFL¿FDWLRQVKDG HYDOXDWH WKH DVVRFLDWLRQ EHWZHHQ 15;, DQG FDUGLRYDVFXODU ULVN pachygyria. factors and other health correlates. Conclusions: It is a large and well detailed case series of CT brain :HVFUHHQHGIRU15;,LQZRPHQDJHVDQGROGHUSDUWLFLSDWLQJ VFDQ SHUIRUPHG LQ OLYLQJ EDELHV ZLWK 0&3 UHODWHG WR =,.97KHVH in an ongoing, prospective cohort study in Oregon (Women Engaged ¿QGLQJVREVHUYHGDUHVXSSRUWLYHHYLGHQFHWRSURYHWKHVHYHULW\RI in Advancing Health Research [WEAR] study). This approach was EUDLQGDPDJHVFDVHGE\=,.9GXHWRLWVQHXURWURSLVP7KLVSDWWHUQRI XVHG WR HQKDQFH WKH HႈFLHQF\ RI LGHQWLI\LQJ D VXESRSXODWLRQ RI CT scan images should be compared with CT brain images observed ZRPHQKDUERULQJLPSDFWIXOKLJKULVNPXWDWLRQV:HH[DPLQHGWKH LQ RWKHUV VWXGLHV LQ 0&3 FDVHV UHODWHG WR =,.9)XUWKHUPRUH RXU +80$5$ UHVXOWV DQG DQ\ DVVRFLDWLRQ ZLWK SUHYLRXV KHDOWK KLVWRU\ results might be compared with CT brain scan images from MCPs XVLQJ D FURVVVHFWLRQDO VWXG\ GHVLJQ $QDO\VLV RI YDULDQFH DQG UHODWHG WR RWKHU LQIHFWLRXV GLVHDVHV 6725&+ SRVLWLYH WKDW FDQ logistic regression analyses were used to examine the relationship also lead to central nervous system alterations. It will certainly help EHWZHHQ+80$5$DVVD\UHVXOWVDQGEDVHOLQH&9'ULVNFRQWUROOLQJ GLႇHUHQWLDWLQJWKHHWLRORJ\RI0&3V for age and race. 195 5HSXUSRVLQJ WULFORVDQ DV DQ DPLQRJO\FRVLGH DGMXYDQW :RPHQGLVSOD\LQJKLJKO\VNHZHG15;,ZHUHWLPHVDVOLNHO\WR IRUWKHHUDGLFDWLRQRI3VHXGRPRQDVDHUXJLQRVDELR¿OPV UHSRUWDKLVWRU\RIGLDEHWHVFRQWUROOHGZLWKLQVXOLQLQMHFWLRQ SYDOXH &, FRPSDUHGWRZRPHQZLWKRXW15;,7KH\ 0LFKDHO0DLGHQ ZHUH WLPHV DV OLNHO\ WR UHSRUW K\SHUFKROHVWHUROHPLD SYDOXH Michigan State University/MSUCOM, Lansing, USA &, DQG WLPHV DV OLNHO\ WR UHSRUW XV RI $ PDMRU SUREOHP LQ WKH PDQDJHPHQW RI F\VWLF ¿EURVLV &) LV FKROHVWHUROORZHULQJPHGLFDWLRQ SYDOXH&, DQWLELRWLFWUHDWPHQWIDLOXUHGXHWRELR¿OPVSURGXFHGE\3VHXGRPRQDV :RPHQZLWK15;,ZHUHWLPHVDVOLNHO\WRUHSRUWDKLVWRU\RI aeruginosa. The current Pseudomonas eradication protocol is 300 P\RFDUGLDOLQIDUFWLRQ SYDOXH&, :RPHQ PJ RI DHURVROL]HG WREUDP\FLQ WZLFH D GD\ IRU GD\V LQ RQRႇ ZLWK15;,ZHUHWLPHVPRUHOLNHO\WRUHSRUWGDLO\DVSLULQXVH F\FOHVUHDFKLQJPHDQVSXWXPFRQFHQWUDWLRQVRIJJ a SYDOXH &, WKDQ ZRPHQ ZLWKRXW 15;, 0SHUGRVH +RZHYHUGHVSLWHWKHURXWLQHXVHRIWKLVSURWRFROE\ :RPHQZLWKDQGZLWKRXW1;5,ZHUHQRWIRXQGWRGLႇHUZLWKUHVSHFW HDUO\DGXOWKRRGQHDUO\RI&)SDWLHQWVDUHFKURQLFDOO\FRORQL]HG to race, age, body mass index, smoking history, hypertension, family with P. aeruginosa. The ability of this pathogen to survive eradication KLVWRU\RI&9'RUSUHYLRXVKLVWRU\RIWUDQVLHQWLVFKHPLFDWWDFNDQG E\WREUDP\FLQDQGSDWKRDGDSWLQWRDK\SHUELR¿OPVWDWHOHDGLQJWR stroke. chronic infections is key to its success. Retrospective studies have Prediction of major adverse cardiac events is based the presence demonstrated that preventing this pathoadaptation by improving of traditional risk factors including high blood pressure, high eradication is essential to extend the lives of CF patients. To identify cholesterol, uncontrolled diabetes, smoking, and family history. Yet adjuvants that enhance tobramycin eradication of P. aeruginosa, we WKHUHLVVLJQL¿FDQWUHVLGXDOULVNPDQ\ZLOOVWLOOGLHIURP&9'ZLWKRXW SHUIRUPHGDKLJKWKURXJKSXWVFUHHQ +76 RIFRPSRXQGVIURP WKHVHULVNIDFWRUV15;,LQDGGLWLRQWRHQULFKLQJIRUPXWDWLRQVNQRZQ IRXUGUXJUHSXUSRVLQJOLEUDULHV:HLGHQWL¿HGWKDWWKH)RRGDQG'UXJ WR FRQIHU &9' DQG +0 ULVN PD\ EH D PDUNHU IRU DGGLWLRQDO DQG $GPLQLVWUDWLRQ )'$ DSSURYHGFRPSRXQGWULFORVDQFRPELQHGZLWK XQLTXHKHDOWKULVN$QDVVRFLDWLRQEHWZHHQ15;,DQG'0DVZHOO WREUDP\FLQUHVXOWHGLQDORJUHGXFWLRQRIYLDEOHFHOOVZLWKLQELR¿OPV as hypercholesterolemia, supports the current biological hypothesis DW VL[ KRXUV EXW QHLWKHU FRPSRXQG KDG VLJQL¿FDQW DQWLPLFURELDO that clonal hematopoiesis, perhaps irrespective of the cause or DFWLYLW\ DJDLQVW ELR¿OPV RQ WKHLU RZQ 7KLV V\QHUJLVWLF WUHDWPHQW XQGHUO\LQJGULYHUPXWDWLRQLVDGULYHURI&9' VLJQL¿FDQWO\DFFHOHUDWHGNLOOLQJRIELR¿OPVFRPSDUHGWRWREUDP\FLQ WUHDWPHQW DORQH DQG WKH FRPELQDWLRQ ZDV HႇHFWLYH DJDLQVW 197 $W\SLFDO ;LVW 51$ ORFDOL]DWLRQ WR WKH LQDFWLYH ; LQ D CF clinical isolates tested including a tobramycin resistant strain. female-biased murine model of systemic lupus erythematosus Further, triclosan and tobramycin killed persister cells, causing $QQD50DUWLQ D ORJ UHGXFWLRQ E\ KUV DQG HUDGLFDWLRQ E\ KUV$GGLWLRQDOO\ Perelman School of Medicine, University of Pennsylvania, USA triclosan synergized with other aminoglycosides such as gentamicin or streptomycin. Triclosan is an aminoglycoside adjuvant that could 6\VWHPLF OXSXV HU\WKHPDWRVXV 6/( LV D VHYHUH DXWRLPPXQH improve current Pseudomonas eradication protocols. GLVHDVHWKDWDႇHFWVZRPHQDWDUDWHQLQHWLPHVKLJKHUWKDQPHQ7KH JHQHWLFEDVLVIRUWKLVELDVLVWKH;FKURPRVRPHZKHUHWKHJUHDWHVW concentration of immunity related genes on any chromosome can

90 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

be found. Females have two X chromosomes (XX), and through a compounds and tested them in cellular assays to assess their SURFHVVNQRZQDV;FKURPRVRPHLQDFWLYDWLRQ ;&, VLOHQFHRQHRI UHODWLYH SRWHQFLHV WRZDUGV DFWLYDWLQJ WKH * SURWHLQ DQG ȕDUU WKHLU ;FKURPRVRPHV UDQGRPO\ WR KDYH D VLPLODU OHYHO RI ;OLQNHG signaling pathways. 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RI6/(OLNHGLVHDVHWKDWDOVRGLVSOD\VDIHPDOHELDV7KHK\SRWKHVLV RIRXUVWXG\LVWKDWWKH;LLQVSOHQLF%FHOOVRI1=%:)PLFHGXULQJ 199 0DVW FHOOV SURPRWH WKURPERF\WRSHQLD GXULQJ GHQJXH disease progression will exhibit compromised silencing due to virus infection. UHGXFHGHSLJHQHWLFPRGL¿FDWLRQVUHVXOWLQJLQLQFUHDVHGH[SUHVVLRQ 0RKDPDG)DGKOL0DVUL RI;OLQNHGJHQHV3UHOLPLQDU\UHVXOWVLQGLFDWHWKDWWKHSURWHLQDQG Duke-NUS Medical School, Singapore, Singapore P51$OHYHOVRI<<ZKLFKLVUHTXLUHGIRU;LVW51$ORFDOL]DWLRQWR 'HQJXH IHYHU DQ LQIHFWLRQ FDXVHG E\ GHQJXH YLUXV '(19 KDV WKH;LLVUHGXFHGDFURVVDOOVWDJHVRIGLVHDVHLQIHPDOH1=%:) become an increasing health concern worldwide. Thrombocytopenia, ZKHQ FRPSDUHG WR DJHPDWFKHG ZLOG W\SH :7 PLFH 8VLQJ ;LVW a reduction in platelet counts, is a classical trait of dengue fever. 51$),6+ZHKDYHREVHUYHGWKDWWKHDFWLYDWHG%FHOOVRIODWHVWDJH 2XU SUHYLRXV VWXGLHV KDYH KLJKOLJKWHG WKDW '(19 FDQ DFWLYDWH GLVHDVH1=%:)PLFHKDYHGHFUHDVHGORFDOL]DWLRQRI;LVW51$WR mast cells, resulting in the release of mast cell mediators which the Xi when compared to WT, suggestive of compromised silencing FDQ LQÀXHQFH WKH VHYHULW\ RI GHQJXH :H K\SRWKHVL]H WKDW PDVW RIWKH;L,QDGGLWLRQZHREVHUYHGWKDWWKHH[SUHVVLRQRI7OUDQG FHOOGHULYHGSURGXFWVFRQWULEXWHWRWKURPERF\WRSHQLDGXULQJ'(19 &[FUWZRLPSRUWDQWLPPXQLW\UHODWHG;OLQNHGJHQHVLVLQFUHDVHG LQIHFWLRQ 8VLQJ DQ LQ YLWUR model, we have shown that activated LQ GLVHDVHG 1=%: ) ZKHQ FRPSDUHG WR DJHPDWFKHG :7 :H PDVWFHOOVUHOHDVHPHGLDWRUVWKDWUHVXOWLQSODWHOHWDFWLYDWLRQ'(19 conclude that there is evidence of perturbations with XCI in the infection of wild type (WT) mice induced thrombocytopenia, which IHPDOHELDVHGOXSXVPRXVHPRGHOWKDWFRXOGH[SODLQKRZ;OLQNHG was characterized by increased platelet activation and phagocytosis. JHQHVEHFRPHDEQRUPDOO\RYHUH[SUHVVHGLQ%FHOOVGXULQJ6/( 8VLQJ PDVW FHOOGH¿FLHQW 6DVK PLFH DV ZHOO DV SKDUPDFRORJLFDO 198 Toward the Discovery of a Novel, Functionally Selective inhibition of mast cell activation with ketotifen, we have been able 'RSDPLQH5HFHSWRU$JRQLVWIRUWKH7UHDWPHQWRI3DUNLQVRQ¶V WR GHPRQVWUDWH D UHGXFWLRQ LQ '(19LQGXFHG WKURPERF\WRSHQLD Disease Reduction in thrombocytopenia was characterized by a reduction 0LFKDHO0DUWLQL LQSODWHOHWDFWLYDWLRQDQGSKDJRF\WRVLV5HFRQVWLWXWLRQRIWKH6DVK Icahn School of Medicine at Mount Sinai, New York, USA mice with mast cells restored the phenotype of thrombocytopenia VHHQLQZLOGW\SHPLFH)XUWKHUPRUHSODWHOHWVRIERWK:7DQG6DVK 3DUNLQVRQ¶V 'LVHDVH 3' LV WKH VHFRQG PRVW FRPPRQ mice could be activated H[ YLYR, suggesting no intrinsic activation neurodegenerative disease in the world with a prevalence estimated GH¿FLWLQWKHSODWHOHWVRIPDVWFHOOGH¿FLHQWPLFH2XU¿QGLQJVSRLQW WREHDSSUR[LPDWHO\LQSHRSOHRYHUWKHDJHRIPDNLQJLWDQ WR PDVW FHOOV SURPRWLQJ WKURPERF\WRSHQLD GXULQJ '(19 LQIHFWLRQ increasingly important medical problem in our aging population. through the release of mediators, increasing platelet activation and /'23$ LV WKH FXUUHQW VWDQGDUG RI FDUH IRU 3' DQG IXQFWLRQV E\ phagocytosis. One mediator released by mast cells that is known to LQFUHDVLQJ OHYHOV RI GRSDPLQH FHQWUDOO\ LQ WKH GRSDPLQHGHSOHWHG EHDEOHWRDႇHFWSODWHOHWVLVVHURWRQLQ3KDUPDFRORJLFDOLQKLELWLRQRI QLJURVWULDWDOSDWKZD\'HVSLWHLWVVXFFHVVLQPDQDJLQJ3'/'23$ serotonin with the 5HT2AUHFHSWRUDQWDJRQLVWNHWDQVHULQLQ'(19 LV NQRZQ WR LQGXFH PRWRU ÀXFWXDWLRQV WHUPHG /'23$LQGXFHG infected WT mice reduced thrombocytopenia compared to vehicle G\VNLQHVLDV /,'V LQ SDWLHQWV FKURQLFDOO\ UHFHLYLQJ LW /,'V DUH WUHDWHG PLFH &RQYHUVHO\ WUHDWPHQW RI '(19LQIHFWHG 6DVK PLFH HVWLPDWHG WR RFFXU LQ RYHU RI SDWLHQWV DIWHU WR \HDUV RI with exogenous serotonin restored the thrombocytopenic phenotype treatment and present a considerable limitation to the viability of WKDWLVDEVHQWLQ6DVKPLFH7KXVZHKDYHLPSOLFDWHGPDVWFHOOV XVLQJ /'23$ ORQJ WHUP DV SDWLHQW IXQFWLRQ DQG TXDOLW\ RI OLIH DUH DVDSUHYLRXVO\XQLGHQWL¿HGFRPSRQHQWRIWKURPERF\WRSHQLDGXULQJ compromised while individual and societal costs rise. '(19IHYHUUHYHDOLQJDSRWHQWLDOWKHUDSHXWLFWDUJHWRIGLVHDVH 5HFHQW UHVHDUFK KDV HOXFLGDWHG WKDW LQ DGGLWLRQ WR * SURWHLQ + signaling, dopamine receptors are also capable of signaling through 200 Electrophysiological Effects of NAD Supplementation D GLVWLQFW ȕDUUHVWLQ ȕDUU GHSHQGHQW SDWKZD\7KLV SDWKZD\LV and Depletion on the Cardiac Sodium Channel LPSRUWDQW LQ UHJXODWLQJ GRZQVWUHDP UHVSRQVHV DW WKH 'RSDPLQH 'DQLHO0DWDVLF 5HFHSWRU '5 DQGSOD\VDVLJQL¿FDQWUROHLQFRQYHUWLQJGRSDPLQH The University of Iowa, Iowa City, USA signaling into motor function. Importantly, previous studies have also %DFNJURXQG 1LFRWLQDPLGH $GHQLQH 'LQXFOHRWLGH 1$') is a VKRZQ WKDW JHQHWLF PRGXODWLRQ RI ȕDUUPHGLDWHG '5 VLJQDOLQJ central mediator of metabolism within the heart. Previous studies UHVXOWVLQLPSURYHGPRWRUIXQFWLRQLQJZKLOHSUHYHQWLQJ/,'V GHPRQVWUDWHGWKDWWKHPHWDEROLFVWDWHRIWKHKHDUWLQÀXHQFHVFDUGLDF 7KHVH SURPLVLQJ UHVXOWV LQVSLUHG WKLV SURMHFW ZKLFK LV WKH ¿UVW WR electrophysiology and the propagation of arrhythmias. 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www.jointmeeting.org 91 POSTER ABSTRACTS

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92 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

WKDW ,'+Į UHJXODWHV F6+07 DFWLYLW\ SURPRWLQJ WK\PLG\ODWH 204 &RPSRVLWLRQDO 'DWD $QDO\VLV ZLWK VOHXWK$/5 V\QWKHVLVDWWKHQXFOHDUODPLQD,QWKHDEVHQFHRI,'+ĮH[SUHVVLRQ LPSOLFDWLRQVIRUUHLQWHUSUHWLQJ51$6HTGDWD we observed decreased proliferation, increased sensitivity to the :DUUHQ0F*HH DQWLIRODWH FKHPRWKHUDSHXWLF PHWKRWUH[DWH 07; DQG LQFUHDVHG Northwestern University, Chicago, USA ÀX[RIIRODWHPHWDEROLWHVWKURXJKWKHPHWKLRQLQHSDWKZD\OHDGLQJWR DQLQFUHDVHLQ'1$PHWK\ODWLRQ7KHVHHႇHFWVUHVXOWHGLQGHFUHDVHG 0ROHFXODU SURELQJ 6HT WHFKQLTXHV HJ 51$6HT JHQHUDWH tumor growth and increased survival in vivo. The epigenetic changes “compositional” datasets, where the number of fragments sequenced FDXVHG D GHFUHDVH LQ P51$ IRU JHQHV UHODWHG WR D[RQDO JURZWK LV QRW GLUHFWO\ SURSRUWLRQDO WR WKH WRWDO 51$ LQ WKH FHOO SRSXODWLRQ DQGWKH:QWȕFDWHQLQSDWKZD\7KXVZHGLVFRYHUHGDQRYHOUROH but rather directly proportional to other experimental factors. Thus, IRU,'+ĮLQ*%0SDWKRJHQHVLVDQGLQJHQHUDOFHOOXODUSK\VLRORJ\ the dataset carries only relative information constrained by the 7KHUHIRUH,'+ĮDSSHDUVWREHDQRYHOPHWDEROLFWDUJHWIRUIXWXUH arbitrary dataset size, even though absolute copy numbers are WKHUDSLHVWKDWPD\LPSURYH*%0SDWLHQWRXWFRPHV 1RFRQÀLFWVRI RIWHQ RI LQWHUHVW 8QOHVV H[WHUQDO LQIRUPDWLRQ LV DGGHG HJ VSLNH interest to declare.) ins), or unless there is no change to the overall composition (i.e. only a few features change), then conclusions drawn from the relative 203 0DQLSXODWLQJWKHEUHDVWWXPRUPLFURHQYLURQPHQWZLWK information can be misleading. Critically, many datasets do not histone deacetylase inhibitors for more robust and durable have external information available and have contexts where many T cell responses features are expected to change (e.g. cancer cells versus control 7\OHU0F&DZ cells; knockout of a transcription factor). University of Alabama at Birmingham, Birmingham, USA We propose a new approach that combines an “additive logratio (ALR) Malignant cells harbor an imbalance in histone acetyltransferase transformation” from compositional data analysis with the strengths DQGKLVWRQHGHDFHW\ODVH +'$& DFWLYLW\HSLJHQHWLFDOO\FRQWULEXWLQJ of the current pipeline using the R package sleuth, which we call WR DOWHUHG FHOOXODU SURJUDPV +'$& LQKLELWRUV GLVUXSW WKLV EDODQFH VOHXWK$/5$/5 WUDQVIRUPDWLRQ LV DQDORJRXV WR WKH QRUPDOL]DWLRQ to impact both cellular transcription and protein function, changing ZLWK D UHIHUHQFH JHQH XVHG LQ T3&5 6LPXODWLRQV GHPRQVWUDWHG the phenotype of tumor cells as well as responding immune cells, VOHXWK$/5SHUIRUPVMXVWDVZHOODVSUHYLRXVPHWKRGVZKHQRQO\D LQFOXGLQJ WXPRULQ¿OWUDWLQJ 7 FHOOV :H K\SRWKHVL]HG WKDW +'$& few changes occur but outperforms previous methods when many LQKLELWLRQFRXOGEHXVHGWRERRVWDQWLWXPRU7FHOOUHVSRQVHVWKURXJK changes dramatically shift the composition. This approach was used inducing expression of immunomodulatory proteins on tumor cells WRUHDQDO\]HVHYHUDO51$6HTGDWDVHWVVWXG\LQJWKH51$%LQGLQJ DV ZHOO DV GLUHFWO\ DOWHULQJ WKH WUDQVFULSWLRQDO SURJUDPV RI WXPRU 3URWHLQ )86 1RUPDOL]LQJ WKH GDWD XVLQJ $/5 DQG *$3'+ WKH VSHFL¿F7 FHOOV7RWHVW WKLV ZH WUHDWHG WZR PXULQH EUHDVW FDQFHU UHIHUHQFHJHQHXVHGE\WKH)86¿HOGOHGWRGUDPDWLFDOO\GLႇHUHQW PRGHOV 76$ DQG 7 ZLWK +'$& LQKLELWRUV UHSUHVHQWLQJ FODVV SDWWHUQVRIJHQHVGHWHFWHGDVGLႇHUHQWLDOO\H[SUHVVHG,PSOLFDWLRQV , VSHFL¿FLW\ HQWLQRVWDW RU SDQVSHFL¿FLW\ SDQRELQRVWDW LQ YLWUR IRU XQGHUVWDQGLQJ )86 ELRORJ\ DQG DSSO\LQJ VOHXWK$/5 WR RWKHU and in vivo. Culture of tumor cells with either inhibitor increased ELRORJLFDOSUREOHPVZLOOEHGLVFXVVHG6OHXWK$/5FDQEHIRXQGRQ surface expression of molecules involved in T cell recognition and github: https://www.github.com/warrenmcg/sleuthALR. VWLPXODWLRQLQFOXGLQJ0+&,0+&,,&'%%&'DQG,&26/ DV ZHOO DV WKH 7 FHOO FKHPRDWWUDFWDQW &;&/ 7UHDWLQJ WXPRU 205 Lower axon density in residual temporal white matter EHDULQJPLFHZLWK+'$&LQKLELWRUUHVXOWHGLQDVLJQL¿FDQWUHGXFWLRQLQ is related to semantic paraphasia prevalence tumor growth that was absolutely dependent on adaptive immunity. (PLOLH70F.LQQRQ 8VLQJGHSOHWLQJDQWLERGLHVZHQH[WVKRZHGWKDW,)1ȖDQG&'7 Medical University of South Carolina, Charleston, USA FHOOVEXWQRW&'7FHOOVRU%FHOOVDUHQHFHVVDU\IRUWKHDQWLWXPRU Introduction: Wallerian degeneration after ischemic stroke is a HႇHFWV RI HQWLQRVWDW ,QWHUHVWLQJO\ WXPRU LQ¿OWUDWLRQ RI &' 7 FHOOV recognized phenomenon, although, the importance of residual ZDV UHGXFHG IROORZLQJ WUHDWPHQW DQG WKHLU HႇHFWRU IXQFWLRQV ZHUH white matter (WM) integrity in aphasia remains poorly understood. ODUJHO\XQFKDQJHG+RZHYHU&'7FHOOLQ¿OWUDWLRQZDVGUDPDWLFDOO\ 'LႇXVLRQ 05, G05, LV LGHDOO\ VXLWHG WR SUREH :0 LQWHJULW\ QRQ LQFUHDVHGDVZDVWKHLUSURGXFWLRQRI,)1Ȗ71)ĮDQGJUDQ]\PH% invasively, admitting, traditional dMRI results can be hard to interpret HYHQDWODWHUWLPHSRLQWV7KLVXSUHJXODWLRQRIHႇHFWRUIXQFWLRQZDV as they characterize underlying general physical processes and SDUDOOHOHGE\DVLJQL¿FDQWLQFUHDVHLQWKHWUDQVFULSWLRQIDFWRU7EHW QRW WLVVXHVSHFL¿F PLFURVWUXFWXUDO SURSHUWLHV %LRSK\VLFDO PRGHOV while Eomes actually decreased over time, trends opposite those D VLPSOL¿FDWLRQ RI FRPSOH[ ELRORJLFDO V\VWHPV DUH QHFHVVDU\ WR VHHQ LQ &' 7 FHOOV IURP YHKLFOH WUHDWHG WXPRUV DQG WKDW ZRXOG overcome this drawback. In this study, we use the white matter tract suggest entinostat treatment can imprint T cells with a transcriptional integrity model (WMTI), which provides a physically meaningful SURJUDP OHVV VXVFHSWLEOH WR H[KDXVWLRQ 6WULNLQJO\ ZH DOVR IRXQG LQWHUSUHWDWLRQ WR GLႇXVLRQDO NXUWRVLV LPDJHV '., 6SHFL¿FDOO\ ZH that simply adjusting the timing of entinostat dosing relative to T focused on the modeling parameter labeled axonal water fraction FHOODFWLYDWLRQFRXOGDEROLVKDQWLWXPRUHႇHFWVRUOHDGWRUHMHFWLRQLQ (AWF), describing the amount of water in the axons relative to the total QHDUO\RIPLFH7KHVHHႇHFWVFRUUHVSRQGHGZLWKDVLJQL¿FDQW DPRXQWRIZDWHU D[RQDOH[WUDFHOOXODUVSDFH :HK\SRWKHVL]HWKDW shift in the responding T cell repertoire. Collectively, our data Wallerian degeneration results in a decreased AWF, caused by the VXJJHVWVWKDW+'$&LQKLELWLRQKDVLPSRUWDQWHႇHFWVRQERWKWXPRU GLPLQLVKHGD[RQFRXQW$GGLWLRQDOO\ZHSUREHUHJLRQDOGLႇHUHQFHVLQ FHOOV DQG 7 FHOOV VSHFL¿FDOO\ DOWHULQJ WXPRU FHOO JHQH H[SUHVVLRQ AWF and their relationship to the number of semantic paraphasias leads to a repolarization of the tumor microenvironment more PDGHGXULQJWKH3KLODGHOSKLDQDPLQJWHVW 317 IDYRUDEOHWRDQWLWXPRULPPXQLW\DQGUHSURJUDPPLQJWUDQVFULSWLRQDO 0HWKRGV 7ZHQW\IRXU VXEMHFWV DJH \ PDOH 05, WLPH SUR¿OHVRIDFWLYDWHG7FHOOVLPSURYHVHႇHFWRUIXQFWLRQVDQGUHGXFHV SRVWVWURNH P:$%$4 VHPDQWLFSDUDSKDVLDV susceptibility to exhaustion. Thus, appropriately timed administration ZLWK FKURQLF SRVWVWURNH DSKDVLD XQGHUZHQW WKH 317 DQG 05, RI +'$& LQKLELWRUV PD\ V\QHUJLVWLFDOO\ SRWHQWLDWH FXUUHQW WXPRU LPDJLQJ6WUXFWXUDOLPDJHV 7DQG7 DQG'., E immunotherapies, especially adoptive cellular transfer and T cell s/mm2 ZHUH DFTXLUHG 'LႇXVLRQDO .XUWRVLV (VWLPDWRU ZDV XVHG reinvigoration strategies.

www.jointmeeting.org 93 POSTER ABSTRACTS

WR HVWLPDWH GLႇXVLRQ DQG NXUWRVLV WHQVRUV IURP ZKLFK $:) ZDV &;&5H[SUHVVLQJ013VLVDOVRQHFHVVDU\IRU09' FDOFXODWHG XVLQJ LQKRXVH VRIWZDUH$ SUREDELOLVWLF :0 PDVN ZDV Conclusions +HUH ZH GH¿QHG WKH LQ YLYR mechanism by which FUHDWHGXVLQJWKHFOLQLFDOWRROER[LQ6307KH:0PDVNDQGWKH FLUFXODWLQJ DXWRDQWLERGLHV DFWLYDWH D &' SKDJRF\WHPHGLDWHG -+8 :0 DWODV ZHUH ZDUSHG LQWR QDWLYH GLႇXVLRQ VSDFH XVLQJ WKH LPPXQHUHVSRQVHWRLQLWLDWH09LQÀDPPDWLRQ2XUVWXGLHVXQFRYHUHG QRQOLQHDU GHIRUPDWLRQ ¿HOG FDOFXODWHG E\ WKH FOLQLFDO WRROER[7KH multiple targets for therapeutic intervention that could readily be IROORZLQJ UHJLRQV RI LQWHUHVW 52, ZHUH GH¿QHG IRU ERWK LSVL DQG translated to a clinical setting. FRQWUDODWHUDO VLGHV ZKROHKHPLVSKHUH :0 WHPSRUDO OREH :0 GH¿QHGE\WKHLQIHULRUORQJLWXGLQDOIDVFLFXOXV DQGSDULHWDOOREH:0 207 Erosive rheumatoid arthritis is associated with a GH¿QHG E\ WKH VXSHULRU ORQJLWXGLQDO IDVFLFXOXV 7KH 52,V ZHUH limited B cell receptor gene segment repertoire FUHDWHGDVVXFKWRH[FOXGHOHVLRQHGZKLWHPDWWHU6LPSOHFRUUHODWLRQV .R¿$0HQVDK DQGWWHVWVZHUHSHUIRUPHGWRVWXG\$:)EHKDYLRU$GGLWLRQDOSDUWLDO Yale School of Medicine, New Haven, USA correlations were run to control for lesion size. There is normally a diverse repertoire of B cell receptors (BCRs) 5HVXOWV$YHUDJH$:)LVVLJQL¿FDQWO\ORZHUWKURXJKRXWWKHZKROH generated via random recombination of variable, diversity, and joining OHIWKHPLVSKHUHWKHOHIWWHPSRUDODQGWKHOHIWSDULHWDOOREHV S 9 ' - JHQH VHJPHQWV RQ WKH LPPXQRJOREXOLQ KHDY\ FKDLQ ,J+ U S! &RQWUROOLQJIRUOHVLRQVL]HIXUWKHUVWUHQJWKHQHGWKH DQGNDSSD ț RUODPEGD Ȝ OLJKWFKDLQJHQHV,QVRPHUKHXPDWRLG correlation between temporal lobe AWF and semantic paraphasia DUWKULWLV 5$ SDWLHQWVWKHUHLVDVNHZHG%&5țOLJKWFKDLQUHSHUWRLUH SUHYDOHQFH U S Conclusion: Biophysical models ZLWK XQGHUUHSUHVHQWDWLRQ RI XSVWUHDP 9ț JHQH VHJPHQWV IRXQG such as the WMTI are promising techniques to study WM integrity WRZDUGWKH¶UHJLRQRIWKH%&5țJHQHORFXV DQGGRZQVWUHDP-ț since they provide us with physically meaningful and interpretable gene segments (found in the 3’ region). Whether this BCR phenotype parameters. Our results suggest widespread left hemisphere axonal relates to erosive joint disease in RA is unclear. GHJHQHUDWLRQDVTXDQWL¿HGE\$:),PSRUWDQWO\$:)VKRZVUHJLRQDO $ FURVVVHFWLRQDO DQDO\VLV ZDV SHUIRUPHG RQ SHULSKHUDO EORRG % VSHFL¿FLW\DVDUHGXFWLRQLQWHPSRUDOOREHD[RQGHQVLW\LVUHÀHFWHG cells obtained from 36 consecutively enrolled, seropositive, RA by an increase in the number of semantic paraphasias. These results SDWLHQWV%&59țDQG-țJHQHVHJPHQWH[SUHVVLRQZHUHGHWHUPLQHG SRVVLEO\UHÀHFWWKHZLGHVSUHDGSURFHVVRI:DOOHULDQGHJHQHUDWLRQ occurring after ischemic incidents. using PCR assays. Patients were grouped according to extent of 9țDQG-țJHQHVHJPHQWXVDJHDQGZHH[DPLQHGWKHDVVRFLDWLRQ 206 &'E0*/+ mononuclear phagocytes orchestrate between gene segment usage and the presence of joint erosions. DXWRLPPXQHFDUGLDFYDOYHLQÀDPPDWLRQDQG¿EURVLV Flow cytometry and gene expression assays were used to further /HH0HLHU FKDUDFWHUL]H % FHOOV WR GHWHUPLQH GLႇHUHQFHV WKDW PD\ LPSO\ D University of Minnesota, Minneapolis, USA mechanism for an association to erosive disease. Background&DUGLDFYDOYHGLVHDVHLVFRPPRQDQGDႇHFWVWKH 'LYHUVLW\ LQ H[SUHVVLRQ RI WKH a 9ț DQG -ț JHQH VHJPHQWV PLWUDOYDOYH 09 PRVWIUHTXHQWO\'HVSLWHLWVSUHYDOHQFHUHODWLYHO\ allowed for subgrouping of RA patients. The expression of upstream little is known about its cellular and molecular pathogenesis. Herein, 9țDQGGRZQVWUHDP-țJHQHVHJPHQWVZDVVLJQL¿FDQWO\FRUUHODWHGLQ ZHGLVVHFWWKHPHFKDQLVPVE\ZKLFKDXWRLPPXQH09LQÀDPPDWLRQ 5$SDWLHQWV U 3 EXWQRWLQKHDOWK\GRQRUV +' U DQG¿EURVLVDUHLQLWLDWHGLQYLYR. 3 ,QDVXEJURXSRI5$SDWLHQWV%FHOOVZHUHFKDUDFWHUL]HG E\ GHFUHDVHG XSVWUHDP 9ț DQG GRZQVWUHDP -ț JHQH VHJPHQW 0HWKRGV.%JPLFHGHYHORSIXOO\SHQHWUDQW09GLVHDVH 09' H[SUHVVLRQ 7KLV LQGLFDWHV OLPLWHG XVH RI WKH IXOO %&5 ț JHQH LQWKHVHWWLQJRIV\VWHPLFDXWRDQWLERG\DVVRFLDWHGDXWRLPPXQH repertoire; hence, we designated these patients as BCR.ltd. Among disease. We used complementary approaches including histological %&5OWGSDWLHQWVKDGHURVLYHGLVHDVHFRPSDUHGWRRIQRQ staining, LQYLYR monoclonal antibody blockade, constitutive and BCR.ltd patients (P<0.05). Additionally, the non%&5OWG VXEJURXS conditional gene deletion, bone marrow (BM) chimeric mice, FRQWDLQHGRIDOOSDWLHQWVZLWKRXW erosions (P<0.05). There were GLSKWKHULDWR[LQPHGLDWHGFHOODEODWLRQPXOWLSDUDPHWHUÀRZ QR VLJQL¿FDQW GLႇHUHQFHV LQ DJH GLVHDVH GXUDWLRQ DXWRDQWLERG\ F\WRPHWU\PXOWLSOH[LPPXQRÀXRUHVFHQFH ,) DQGLPDJHDQDO\VLV WLWHUVRUWUHDWPHQWEHWZHHQ%&5OWGDQGQRQ%&5OWGSDWLHQWV:H WRVWXG\WKHFHOOXODUDQGPROHFXODUPHGLDWRUVRI09'LQWKLVPRGHO IRXQGDVLJQL¿FDQWO\LQFUHDVHGIUHTXHQF\RIDW\SLFDO&'ORZ B cells 9DOYHVDPSOHVWDNHQIURPSDWLHQWVZLWKUKHXPDWLFKHDUWGLVHDVH LQWKH%&5OWGVXEJURXS>PHDQ 6(0 @FRPSDUHGWR 5+' ZHUHXVHGWRFRUUHODWHRXU¿QGLQJVZLWKKXPDQSDWKRORJ\ QRQ%&5OWGSDWLHQWV>PHDQ 6(0 3 @DQG+' 5HVXOWV: Through characterization of the immune cell milieu >PHDQ 6(0 3 @&'ORZ B cells have been LQ LQÀDPHG .%J 09V ZH GHWHUPLQHG WKDW &'E0*/ VKRZQWRH[SUHVVHOHYDWHGOHYHOVRI5$1./ZKLFKVWLPXODWHVERQH PRQRQXFOHDUSKDJRF\WHV 013V DUHUHTXLUHGIRU09'SURJUHVVLRQLQ HURGLQJ RVWHRFODVW IRUPDWLRQ &'ORZ B cells showed increased .%JPLFHDQGGHSHQGRQIUDFWDONLQH &;&/ UHFHSWRU &;&5 levels of TNFR2 and decreased IL4R compared to conventional VLJQDOLQJ)XUWKHUPRUHZHLGHQWL¿HGDQDORJRXVFHOOVLQKXPDQ5+' &' mature naïve B cells (P<0.01). This indicates increased ability YDOYHV,Q.%JPLFHWKHYDOYHLQ¿OWUDWLQJ&'E0*/ 013V RI&'ORZ%FHOOVWRUHVSRQGWR71)ĮZKLFKSURPRWHV5$1./ H[SUHVVWLVVXHUHSDUDWLYHPROHFXOHVVXFKDVDUJLQDVH $UJ DQG H[SUHVVLRQRYHU,/ZKLFKLQKLELWV5$1./H[SUHVVLRQ UHVLVWLQOLNHPROHFXOHDOSKD 5(/0D 'HSOHWLRQRI&'E0*/ /LPLWHG H[SUHVVLRQ RI WKH IXOO %&5 ț OLJKW FKDLQ UHSHUWRLUH LV FHOOV SURWHFWV PLFH IURP YDOYH SDWKRORJ\ 6SOHHQ W\URVLQH NLQDVH DVVRFLDWHG ZLWK DQ HOHYDWHG IUHTXHQF\ RI &'ORZ B cells and 6\N VLJQDOLQJ GRZQVWUHDP RI ,J*UHFRJQL]LQJ )F UHFHSWRUV RQ increased prevalence of erosive RA. Identifying patients with the &'E0*/013VLQ09SURPRWHVWXPRUQHFURVLVIDFWRU 71) BCR.ltd phenotype has implications for prognosis and early treatment DQGLQWHUOHXNLQ ,/ SURGXFWLRQDQGERWKDUHUHTXLUHGIRU09' to prevent irreversible joint destruction. 71) DFWV WKURXJK 71) UHFHSWRU 71)5 H[SUHVVHG RQ YDOYH UHVLGHQW FHOOV WR SURPRWH 09' WKURXJK XSUHJXODWLRQ RI YDVFXODU FHOO DGKHVLRQ PROHFXOH 9&$0 H[SUHVVLRQ &RUUHVSRQGLQJO\ ZHVKRZWKDWYHU\ODWHDQWLJHQ 9/$ H[SUHVVLRQE\FLUFXODWLQJ

94 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

208 0LFURYDVFXODU3DWKRORJ\,Q3HULSKHUDO$UWHU\'LVHDVH 209 Examining the merits of engaged department cohorts: &RQVWDQFH-0LHWXV Where to begin and how to proceed? University of Nebraska Medical Center, Omaha, USA *ORULD0LOHYD Grand Valley State University, Allendale, USA Background: 3HULSKHUDO $UWHU\ 'LVHDVH 3$' LV FDXVHG E\ DWKHURVFOHURWLFQDUURZLQJRIDUWHULHVVXSSO\LQJWKHOHJV3$'LQGXFHG I hope to explore the conditions under which engaged department P\RSDWK\LVFKDUDFWHUL]HGE\P\R¿EHUGHJHQHUDWLRQDQGSURGXFHV LQLWLDWLYHV (',V DUH HႇHFWLYH VWDUWLQJ SRLQWV IRU IRVWHULQJ functional limitations. Furthermore, work from our laboratory (Ha FROODERUDWLYH VFDႇROGHG DQG VXVWDLQHG FLYLF HQJDJHPHQW DFURVV HW DO - 7UDQVO 0HG KDV HVWDEOLVKHG D SURJUHVVLYH ¿EURVLV RQH¶V LQVWLWXWLRQV *LYHQ WKDW GHSDUWPHQWV DUH DQ LQWHJUDO XQLWRI LQ WKH DႇHFWHG FDOI PXVFOHV RI SDWLHQWV ZLWK 3$' 4XDOLWDWLYH power within the current infrastructures of higher education, some histological review suggests systematic pathological changes in leading scholars argue that they are one of the best starting points WKHPLFURYDVFXODWXUHRI3$'PXVFOHLQDVVRFLDWLRQZLWKDGYDQFLQJ IRU VKLIWLQJ IURP H[SHUWGULYHQ ³RQHRႇ´ FRPPXQLW\EDVHG SURMHFWV ¿EURVLV ,Q WKLV VWXG\ ZH WHVWHG WKH K\SRWKHVLV WKDW PLFURYHVVHO to collaborative and sustainable engagement opportunities that span DUFKLWHFWXUH FROODJHQ SUR¿OHV DQG WLVVXH GHQVLW\ V\VWHPDWLFDOO\ programs of study. Building upon this research, I will share lessons change with advancing disease and are consistent with advancing learned from two initiatives beginning in the spring of 2015. microvascular pathology. These initiatives encompass ten engaged departments across three institutions of higher education (a large, public; a small private; and a 0HWKRGV DQG 5HVXOWV &DOI PXVFOH ELRSVLHV RI 3$' SDWLHQWV DW ORFDOFRPPXQLW\FROOHJH LQ*UDQG5DSLGV0,)LQGLQJVHPHUJHIURP )RQWDLQH6WDJH,, Q DQG,9 Q DQGFRQWUROV Q ZHUH a systemic action research approach and harness mixed methods, ODEHOHGZLWK:KHDW*HUP$JJOXWLQLQ :*$ DQGDQWLERGLHVVSHFL¿F including traditional surveys, interviews, and comparison analyses IRU&ROODJHQ,DQG&ROODJHQ,9,PDJHVZHUHDFTXLUHGZLWKDZLGH RI UHSRUWLQJ GRFXPHQWV ,QLWLDO ¿QGLQJV LQGLFDWH FRKRUWV²ZKHQ ¿HOG ÀXRUHVFHQFH PLFURVFRSH DQG SURFHVVHG ZLWK $XWR4XDQW intentionally supported by a number of other structures (like civic GHFRQYROXWLRQVRIWZDUHDQG,PDJH3UR3OXVVRIWZDUH&ROODJHQ,9 action plans, committed administrative and faculty leadership, etc.)— label was used to measure thickness of the basement membrane FDQEHDSDUWLFXODUO\HႇHFWLYHPHFKDQLVPIRUJHQHUDWLQJLQVWLWXWLRQDO %0 DQGOXPHQGLDPHWHURIDSSUR[LPDWHO\PLFURYHVVHOV FDSDFLW\&RKRUWVFDQJHQHUDWHRQFDPSXVOHDGHUVKLSLQDGGLWLRQWR P WRWDO GLDPHWHU SHU ELRSV\ VSHFLPHQ ZLWK D FXVWRP 0DW/DE IRVWHULQJ D FRPPXQLW\ RI UHÀHFWLYH SUDFWLFH HVVHQWLDO IRU SURYLGLQJ program. Regions of interest were generated around microvessels support, fostering accountability, and expanding narrow disciplinary DQG&ROODJHQ,GHQVLW\ DUHDZHLJKWHGPHDQÀXRUHVFHQFHLQWHQVLW\ frameworks. In addition, they have the potential to catalyze more ZDV PHDVXUHG :*$ ODEHO ZDV XVHG WR PHDVXUH WRWDO WLVVXH pervasive and sustained institutional change. For instance, the area and microvessel density was calculated as a ratio of number implementation of successive cohorts over time and across the RI PLFURYHVVHOV SHU WRWDO WLVVXH DUHD VDPSOHG 0HDQV DQG campus can nurture transdisciplinary collaboration and generate FRQ¿GHQFH LQWHUYDOV ZHUH GHWHUPLQHG IRU HDFK PHDVXUHPHQW SDWKZD\VWRZDUGVLQVWLWXWLRQZLGHFKDQJH 6LJQL¿FDQWGLႇHUHQFHVZHUHGHWHUPLQHGZLWKRQHZD\$129$DQG 'HVLJQHGWRIDFLOLWDWHGLVFXVVLRQUHOHYDQWWRHDFKSDUWLFLSDQWV¶ZRUN post hocSDLUZLVHFRPSDULVRQVXVLQJ6WXGHQW¶V77HVWZLWK%RQIHUURQL this poster will highlight critical challenges across departments and correction. Correlations were determined by linear regression institutions along with key recommendations for shifting academic DQDO\VLV7KLFNQHVVRIWKH%0ZDVJUHDWHULQ6WDJH,,SDWLHQWV culture and structures towards an environment that inspires and P FRPSDUHGFRQWUROV P S DQGLQ6WDJH,9 sustains collaborative engagement. P FRPSDUHGWR6WDJH,,SDWLHQWV S 0LFURYDVFXODUOXPHQ GLDPHWHU ZDV LQFUHDVHG S LQ 6WDJH,9 SDWLHQWV P 210 Characterizing the Effects of TiO2 Nanotubes on FRPSDUHGWRFRQWURO P DQG6WDJH,,SDWLHQWV P %0 WKH 9DVFXODU 5HVSRQVH WR ,QÀDPPDWRU\ &\WRNLQHV LQ ,Q6WHQW thickness correlated positively with microvascular lumen diameter 5HVWHQRVLV (R2 S 0LFURYDVFXODUGHQVLW\ZDVLQFUHDVHGLQ3$' $QYLWD0LVKUD SDWLHQWV FRPSDUHG WR FRQWUROV S DQG LQ 6WDJH,9 SDWLHQWV California Institute of Technology, Pasadena, USA FRPSDUHG WR 6WDJH,, S &ROODJHQ, GHSRVLWLRQ DURXQG Cardiovascular diseases are the leading cause of death globally, WKH PLFURYDVFXODWXUH ZDV JUHDWHU LQ 6WDJH,9 SDWLHQWV FRPSDUHG estimated to cost over $320 billion in annual healthcare costs in WR 6WDJH,, SDWLHQWV S 3HULPLFURYDVFXODU &ROODJHQ, DORQH0DQ\FDVHVRIFDUGLRYDVFXODUGLVHDVHVDUHWUHDWHGZLWK deposition correlated positively with microvascular lumen diameter SHUFXWDQHRXVFRURQDU\LQWHUYHQWLRQ 3&, KRZHYHUQHDUO\RI 2 (R S WKHVHSDWLHQWVVXႇHUIURPUHVWHQRVLVZLWKLQD\HDURIWUHDWPHQW Conclusions: Increases in microvessel density and lumen diameter Restenosis is characterized by arterial wall remodeling and LQ 3$' PXVFOH UHSUHVHQW DGYDQFLQJ PLFURYDVFXODU GLVHDVH neointimal hyperplasia or the uncontrolled proliferation of vascular since they occurred in association with increased perivascular smooth muscle cells and endothelial cells after injury. Previous GHSRVLWLRQRI&ROODJHQ,DQG%0WKLFNHQLQJ/RVVRUG\VIXQFWLRQRI UHVHDUFKLQWKH'HVDLODEKDVVKRZQWKDWQDQRVWUXFWXUHG7L2VWHQW microvascular pericytes has been shown to produce microvascular surfaces can lower the rate of restenosis. However, the mechanism lumen hyperdilation and altered collagen composition of the BM. of attenuation in the experimental model of Human Coronary Artery Thus, pericyte loss may produce the changes observed and will be (QGRWKHOLDO &HOOV +&$(& DQG +XPDQ &RURQDU\ $UWHU\ 6PRRWK evaluated in future studies. 0XVFOH &HOOV +&$60& LV QRW \HW XQGHUVWRRG :H EHOLHYH WKDW LQÀDPPDWRU\ F\WRNLQHV VXFK DV 7XPRU 1HFURVLV )DFWRU Į 71)Į DQG3ODWHOHW'HULYHG*URZWK)DFWRU 3'*) PD\SOD\DQLPSRUWDQW role in mediating vascular restenosis, In this project, we developed a PRGHORIYDVFXODULQÀDPPDWLRQE\FRPSDULQJWKHYDVFXODUUHVSRQVH to various cytokines with quantitative PCR. Ongiong studies are XVLQJ WKLV PRGHO WR XQGHUVWDQG WKH SRWHQWLDO SURWHFWLYH HႇHFWV RI nanostructured TiO2 surfaces against restenosis.

www.jointmeeting.org 95 POSTER ABSTRACTS

211 Ultrasound Oncotripsy: Targeting Cancer Cells 212 Characterization of two E. coli bacteriophages isolated 6HOHFWLYHO\9LD5HVRQDQW+DUPRQLF([FLWDWLRQ from the bladder of adult females 'DYLG50LWWHOVWHLQ &HVDU0RQWHORQJR+HUQDQGH] Caltech, Pasadena, USA Loyola University - Stritch School of Medicine, North Riverside, 7KHUDSHXWLF XOWUDVRXQG LV D SURPLVLQJ QRQLQYDVLYH PHWKRG WR USA ablate tumors. Clinical trials demonstrate that high intensity focused It is now established that the bladder is not sterile; it contains a resident XOWUDVRXQG +,)8 FDQLPSURYHFOLQLFDORXWFRPHVLQSURVWDWHEUHDVW community of bacteria, which we now know contains an abundance OLYHU SDQFUHDV ERQH DQG EUDLQ WXPRUV +RZHYHU +,)8 XVHV of bacteriophages. Bacteriophages (phages) are abundant in nature thermal ablation or acoustic cavitation to destroy tissue in a target and interact with bacteria in a complex manner. Phages can alter DUHDDQGDVVXFKLVODUJHO\QRQVSHFL¿F6DIHO\LPSOHPHQWLQJ+,)8 microbial population dynamics by lysing bacteria, conferring traits via is an involved procedure that demands costly MRI tumor tracking to horizontal gene transfer, and protecting hosts against infection from SUHYHQWRႇWDUJHWDEODWLRQDQGVWLOOPD\LQGXFHFROODWHUDOGDPDJH RWKHUSKDJHV2XUJURXSKDVLGHQWL¿HGSURSKDJHVHTXHQFHVLQWKH $Q HPHUJLQJ ¿HOG RI UHVHDUFK LQ ORZ LQWHQVLW\ IRFXVHG XOWUDVRXQG genomes of phylogenetically diverse bladder bacteria, and isolated /,)8 PD\ DOORZ IRU PRUH WDUJHWHG XOWUDVRXQG WKHUDS\ 3XOVHG seven Escherichia coli phages from the bladders of adult women with ultrasound at 2 does not cause heating or cavitation, but can induce urinary incontinence. In terms of host range and propagation ability, ELRHႇHFWVWKURXJKDPHFKDQLVPWKDWLVFXUUHQWO\QRWZHOOXQGHUVWRRG ZHKDYHEHJXQWRFKDUDFWHUL]HWZRRIWKHVHSKDJHV*UHHGDQG/XVW $W&DOWHFKDFURVVGLVFLSOLQDU\FROODERUDWLRQLQYHVWLJDWHVWKHLQKHUHQW In terms of its genome, Lust is similar to other phages isolated from FHOOXODUHႇHFWRI/,)8:HKDYHGHYHORSHGDFRPSXWDWLRQDOPRGHO WKHEODGGHU (QY\*OXWWRQ\3ULGH6ORWK DQGERWKWKH*UHHGDQG that predicts that ultrasound pulsing patterns at target frequencies /XVWJHQRPHVUHVHPEOHWKRVHRISKDJHVLGHQWL¿HGLQFDWWOHVOXUU\ can induce resonant oscillation in the membranes of target cells. 7RDVVHVVKRVWUDQJHIRU*UHHGDQG/XVWZHXWLOL]HGDVSRWWLWUDWLRQ ³8OWUDVRXQGRQFRWULSV\´LQYROYHVDSSO\LQJWKHVHZDYHIRUPVWRO\VH assay, which was also used to screen for phage resistant mutant FDQFHUFHOOVZLWKRXWDႇHFWLQJKHDOWK\FHOOV:HKDYHH[SHULPHQWDOO\ bacteria. To assess phage propagation in E. coli strains, we used YDOLGDWHGWKDWWKLVWHFKQLTXHFDQHႇHFWVHOHFWLYHFHOOWDUJHWLQJZLWK D IXOO SODWH WLWUDWLRQ DVVD\ *UHHG DQG /XVW VKDUH OLWWOH VHTXHQFH LQ YLWUR DQG LQ YLYR OHXNHPLD O\PSKRPD PRGHOV DQG XVHG KLJK identity, apart from 15 small genetic segments ranging from 10 to speed imaging to quantify cell membrane deformation and verify the EDVHSDLUVORQJ

96 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

VWHDWRKHSDWLWLV 1$6+ D PRUH SURJUHVVLYH IRUP RI 1$)/' WKDW Therefore, future experiments will focus on eliminating exosome LQYROYHVOLYHULQÀDPPDWLRQDQGGDPDJH VHFUHWLRQ E\ XVLQJ VL51$5DE LQKLELWLRQ DQG WKH VPDOO GUXJ The functional impact of this suppression was examined in mice FRPSRXQG FDPELQRO FRQFXUUHQWO\ ZLWK DQWL3' RU DQWL3'/ ZLWK &UHPHGLDWHG OLYHUVSHFL¿F GHOHWLRQ RI $ULGD $ULGD /.2 PRQRFORQDODQWLERG\LQHႇRUWVWRLQFUHDVHSURJUHVVLRQIUHHVXUYLYDO ZKLFK GHYHORS DJHGHSHQGHQW IDWW\ OLYHU GLVHDVH DV PHDVXUHG YLD IRUFDQFHUSDWLHQWV)XUWKHULQYHVWLJDWLRQDVWRWKHUROHȖį7FHOOVSOD\ WKH1$)/'DFWLYLW\VFRUH 1$6 7KHVH$ULGD/.2PLFHH[KLELWD in lupus is another main objective of this project. phenotype marked by increased liver weight, elevated cholesterol, 215 Local action of monocyte chemoattractant protein-1 and and increased markers of liver damage. They are also more osteopontin in aneurysm healing VXVFHSWLEOHWRKLJKIDWGLHWLQGXFHGOLYHUVWHDWRVLVDQGLQÀDPPDWLRQ .DUWLN0RWZDQL 51$VHTXHQFLQJ DQDO\VLV RI $ULGDGH¿FLHQW OLYHU WLVVXH UHYHDOHG University of Florida, Gainesville, USA XSUHJXODWLRQ RI OLSRJHQHVLV JHQHV VXFK DV 6UHEI DQG )DVQ DQG downregulation of fatty acid oxidation genes, including Acsl1. Background: Asymptomatic cerebral aneurysms occur in up to &KURPDWLQ LPPXQRSUHFLSLWDWLRQ VHTXHQFLQJ &K,3VHT VWXGLHV RI DGXOWV ,Q DQHXU\VP WKHUDS\ WKRXJK FRPSOLFDWLRQ UDWHV DUH corroborated these results, demonstrating direct binding of Arid1a lower for endovascular coiling than for operative clipping, aneurysm WR WKH SURPRWHUV RI GLႇHUHQWLDOO\ UHJXODWHG JHQHV LQYROYHG LQ OLSLG recurrence is a limitation of coiling. Recurrence is attributed to handling and fatty acid metabolism. recanalization of the aneurysm neck following coil embolization, whereas the goal is to establish durable occlusion from the parent To better study the later stages of fatty liver disease progression, we artery. Coiling therapy is limited by lack of mechanistic knowledge FRPELQHGDGHQRYLUDO&DVPHGLDWHG3WHQGHOHWLRQZLWKRXU$ULGD regarding aneurysm healing. In previous work in our lab, we have LKO model, which synergistically drove fatty liver development. FKDUDFWHUL]HG ELRORJLFDO PROHFXOHUHOHDVLQJ SODWLQXP FRLOV WR HOXWH ,QKLELWLRQRIOLSRJHQHVLVXVLQJ&$7DSRWHQW65(%3LQKLELWRU LQÀDPPDWRU\UHJXODWRUVVXFKDVPRQRF\WHFKHPRDWWUDFWDQWSURWHLQ showed improvements in markers of fatty liver disease progression 0&3 LQDPXULQHFDURWLGDQHXU\VPPRGHOWRPHGLDWHGXUDEOH in this Arid1a/Pten double knockout model. Collectively, our data aneurysm healing. n our murine aneurysm model, sustained local VKRZWKDW$5,'$SOD\VDUROHLQWKHHSLJHQHWLFUHJXODWLRQRIKHSDWLF HOXWLRQ RI PRQRF\WH FKHPRDWWUDFWDQW SURWHLQ 0&3 LQFUHDVHV lipid homeostasis, and its suppression contributes to fatty liver tissue ingrowth into the aneurysm sac which requires osteopontin pathogenesis. 231 PHGLDWHG VLJQDOLQJ +\SRWKHVLV /RFDO 0&3 DFWLYLW\ LV 214 The development and utilization of exosome driven QHFHVVDU\ IRU PXULQH DQHXU\VP KHDOLQJ 231 PHGLDWHV KHDOLQJ polarization of PD-L1+ gamma delta T cells in cancer by reparative (M2) macrophage interaction with lymphocytes and 6DPDQWKD0RUULVVH\ SODWHOHWVE\&'RULQWHJULQSDWKZD\V0HWKRGV&DURWLGDQHXU\VPV University of Louisville, Louisville, USA DUHFUHDWHGLQZLOGW\SH :7 0&3NQRFNRXW .2 RU&&5.2 PLFHXVLQJRXUHVWDEOLVKHGPRGHO0&3HOXWLQJ231HOXWLQJRU 3XUSRVH 'HWHUPLQH LI WXPRU GHULYHG H[RVRPHV 7'( FDQ GULYH FRQWURO3/*$FRDWHGSODWLQXPFRLOVDUHLPSODQWHGLQWRWKHDQHXU\VP cancer progression through polarization of immunosuppressive VDF 6\VWHPLF QHXWUDOL]LQJ DQWLERG\ LV DSSOLHG WR LQKLELW 0&3RU FHOO SKHQRW\SHV FDSDEOH RI UHVWULFWLQJ Įȕ 7 FHOO IXQFWLRQLQJ 231 SDWKZD\V &\WRNLQH OHYHOV RI 231FRLOHG DQHXU\VP O\VDWH 3UHOLPLQDU\ GDWD VKRZV WKDW H[RVRPH VWLPXODWLRQ GLႇHUHQWLDOO\ are assayed in early days of aneurysm healing. Coiled aneurysm XSUHJXODWHV 3'/ SURJUDPPHGGHDWKOLJDQG H[SUHVVLRQ RQ tissue is measured for percent tissue ingrowth into aneurysm lumen SHULWRQHDO PDFURSKDJHV DQG OXQJ UHVLGHQW Ȗį 7 FHOOV ZKLOH DOVR DQG LPPXQRKLVWRFKHPLVWU\ IRU HႇHFWRU FHOO SRSXODWLRQV 5HVXOWV XSUHJXODWLQJ3'H[SUHVVLRQRQĮȕ7FHOOV$GGLWLRQDOO\JLYHQWKH :LWK 0&3FRLOLQJ V\VWHPLF GHSOHWLRQ RI 0&3 RU &&5 E\ immunosuppressive nature of these cells, we hypothesize that they QHXWUDOL]DWLRQ RU RU.2 RU DWWHQXDWHVOXPLQDO FDQUHVWULFWSUROLIHUDWLRQDQGHႇHFWRUIXQFWLRQLQJRIDXWRUHDFWLYH7 LQJURZWKYHUVXV:7 S 0PDFURSKDJHVWDLQHGDUHD cells in a LPR lupus model as a potential new cell based therapy. LVLQFUHDVHGLQ:7 YHUVXV0&3&&5.2 RU The ultimate goal of this project is develop new therapies based RULQKLELWRU RU JURXSV6\VWHPLF0&3DGPLQLVWUDWLRQ on the utilization or elimination of tumor derived exosomes for the UHYHDOVQRGLႇHUHQFHLQLQJURZWKYHUVXVYHKLFOH&\WRNLQHDUUD\VDW WUHDWPHQW RI DXWRLPPXQLW\ RU FDQFHU UHVSHFWLYHO\ 0HWKRGV 7'( SRVW231FRLOLQJGD\VDQGUHYHDOXSUHJXODWLRQRIQXPHURXV were isolated using serial ultracentrifugation from Lewis Lung F\WRNLQHVLQFOXGLQJ3)DQG,/YHUVXVFRQWURO&RQFOXVLRQ/RFDO Carcinoma cells. Exosome stimulated peritoneal macrophages and GHOLYHU\ RI 0&3 LV FULWLFDO IRU PXULQH DQHXU\VP KHDOLQJ 231 Ȗį 7 FHOOV ZHUH FRFXOWXUHG ZLWK RYDWUDQVJHQLF , &' 7FHOOV may further activate lymphocyte subsets and platelets to promote WR DVVD\ IRU VXSSUHVVLYH IXQFWLRQ$QWL3' DQWLERG\ ZDV DGGHG aneurysm healing, which merits future study. WR WKH FXOWXUH WR FRQ¿UP WKDW WKH 3'3'/ D[LV PHGLDWHV WKH LPPXQH VXSSUHVVLRQ 7KH HႇHFW RI 7'( RQ Ȗį 7 FHOO PHWDEROLVP 216 7KH/.%0,7)SDWKZD\G\VUHJXODWLRQLQ was also investigated. Human peripheral blood samples from lung melanomagenesis FDQFHUDQGDQWL3'WUHDWHGOXQJFDQFHUSDWLHQWVZHUHFRPSDUHG 1LVPD0XMDKLG YLD ÀRZ F\WRPHWU\ IRU Ȗį3'/ H[SUHVVLRQ SUR¿OLQJ /DVWO\ 7'( Boston University School of Medicine; Massachusetts General VWLPXODWHGȖį7FHOOVZHUHDGRSWLYHO\WUDQVIHUUHGLQWRį7&5/35 Hospital; Cutaneous Biology Research Center, Boston, USA PLFHWRGHWHUPLQHWKHLUDELOLW\WRUHVWULFWĮȕ7FHOOLQGXFHGGLVHDVH Background: 8SRQ 89 H[SRVXUH VLJQDOV IURP NHUDWLQRF\WHV SDWKRJHQHVLV5HVXOWV7KHUHVXOWVVXJJHVWWKDW7'(SOD\DUROHLQ stimulate melanocytes through melanocortin 1 receptor, leading WXPRUPHWDVWDVLVE\SRODUL]LQJȖį7FHOOVDQGPDFURSKDJHVWRDQ to downstream activation of the cAMP response element binding LPPXQRVXSSUHVVLYH 3'/ SKHQRW\SH FDSDEOH RI UHVWULFWLQJ Įȕ SURWHLQ &5(% WUDQVFULSWLRQ IDFWRU DQG PLFURSKWKDOPLDDVVRFLDWHG 7FHOOHႇHFWRUIXQFWLRQLQJ$GGLWLRQDOO\WKHVHFHOOVGLVSOD\DVWURQJ transcription factor (MITF), the master regulator of pigmentation. 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www.jointmeeting.org 97 POSTER ABSTRACTS

WUDQVIRUPDWLRQRIPHODQRF\WHV2QO\RIPHODQRPDVFDUU\DQ K\SRWKHVL]HWKDWLQKLELWLRQRI525ȖDFWLYLW\XVLQJV\QWKHWLFOLJDQGV 0,7)DPSOL¿FDWLRQHPSKDVL]LQJWKHQHHGWRLGHQWLI\SDWKZD\VWKDW FDQ UHJXODWH WKH 1/53 LQÀDPPDVRPH DQG KDYH D SRWHQWLDO modulate 0,7) expression. Recent genetic data in mice suggest the WKHUDSHXWLFEHQH¿WIRU1/53GHSHQGHQWGLVHDVHV SUHVHQFH RI D SDWKZD\ LQ ZKLFK &5(%UHJXODWHG WUDQVFULSWLRQ FR 8VLQJ DQ LQ YLWUR PRGHO RI PDFURSKDJH SRODUL]DWLRQ DQG ELR DFWLYDWRU &57& DQGVDOWLQGXFLEOHNLQDVH 6,. UHJXODWH0,7) PROHFXODUWHFKQLTXHVZHGHPRQVWUDWHGWKDWVXSSUHVVLQJ525ȖZLWK H[SUHVVLRQ/LYHUNLQDVH% /.% UHJXODWHVPDQ\FDQFHUUHOHYDQW V\QWKHWLF LQYHUVH DJRQLVWV DWWHQXDWHV ERWK 1/53 DQG ,/ȕ JHQH FHOOSKHQRW\SHVDQGLVDNQRZQ6,.LQGXFHU+RZHYHUWKHLQWHUDFWLRQ H[SUHVVLRQ DQG VXSSUHVVHV WKH UHOHDVH RI PDWXUH ,/ȕ 3UHYLRXV RIWKH/.%6,.SDWKZD\DQG0,7)LQPHODQRPDIRUPDWLRQLVQRW VWXGLHV GHPRQVWUDWH WKDW WKH 1/53,/ȕ SDWKZD\ LV VLJQL¿FDQWO\ fully understood. XSUHJXODWHGLQPRXVHPRGHOVRI/36LQGXFHGVHSVLVDQGIXOPLQDQW 0HWKRGV *HQRPLF GDWD IURP VNLQ FXWDQHRXV PHODQRPD KHSDWLWLV,QYLYRUHVXOWVVKRZWKDW525ȖLQKLELWLRQUHGXFHGSODVPD,/ WXPRUVIURP7KH&DQFHU*HQRPH$WODV$QDO\VLVZDVDQDO\]HGXVLQJ ȕDVZHOODV,/ȕSURGXFWLRQE\SHULWRQHDOPDFURSKDJHVLQDQ/36 F%LR3RUWDOIRU&DQFHU*HQRPLFV1RUPDOKXPDQPHODQRF\WHVDQG LQGXFHGVHSVLV$OVR525ȖLQYHUVHDJRQLVWVUHGXFHGPRUWDOLW\UDWHLQ PHODQRPDFHOOOLQHVZHUHSUR¿OHGIRU/.%H[SUHVVLRQXWLOL]LQJ DQ/36'JDODFWRVDPLQHLQGXFHGIXOPLQDQWKHSDWLWLVPRXVHPRGHO ZHVWHUQEORWDQDO\VLV/HQWLYLUDOWUDQVGXFWLRQV\VWHPVZHUHXVHGWR 7RJHWKHUWKHVH¿QGLQJVGHPRQVWUDWHWKHIHDVLELOLW\RIWDUJHWLQJ525Ȗ RYHUH[SUHVVZLOGW\SH/.% :7 NLQDVHGHIHFWLYH/.% '$ WRVXSSUHVVWKH1/53,/ȕD[LVERWKLQYLWURDQGLQYLYR DQG&57&*)3DQGVPDOOLQWHUIHULQJ51$WUDQVIHFWLRQZDVXWLOL]HG ,Q FRQFOXVLRQ LQKLELWLRQ RI 525Ȗ YLD V\QWKHWLF OLJDQGV FRXOG EH D to knockdown /.%6,.LQKLELWLRQZDVFRQGXFWHGZLWKDSUHYLRXVO\ QHZWKHUDSHXWLFDSSURDFKLQWUHDWLQJ1/53DVVRFLDWHGGLVHDVHV SXEOLVKHGVPDOOPROHFXOHLQKLELWRURI6,.+*4XDQWLWDWLYH UHDO WLPH SRO\PHUDVH FKDLQ UHDFWLRQ T573&5 DQG ZHVWHUQ EORW 218 5HSHWLWLYH 7UDQVFUDQLDO 0DJQHWLF 6WLPXODWLRQ IRU WKH DQDO\VLVZHUHHPSOR\HGWRGHWHUPLQHP51$H[SUHVVLRQDQGSURWHLQ Treatment of Fibromyalgia levels, respectively. Cell growth was determined utilizing a cell 1LOVRQ10HQGHV1HWR viability assay. 䯠 Extension Center, University of California, Davis/School of 5HVXOWV &ROOHFWLYHO\ /.% 6,. &57& DQG 0,7) DUH DOWHUHG 0HGLFLQH8Q31DWDO51%UD]LO LQ RI WKH VNLQ FXWDQHRXV PHODQRPDV IURP 7KH &DQFHU ,1752'8&7,21 5HFXUUHQW 7UDQVFUDQLDO 0DJQHWLF 6WLPXODWLRQ *HQRPH$WODV 7&*$ GDWDVHW5HGXFHG/.%SURWHLQOHYHOVZHUH U706 LVDQRQLQYDVLYHQHXURPRGXODWLRQWHFKQLTXHWKDWKDVEHHQ observed in majority of melanoma cell lines evaluated compared XVHG WR WUHDW SDWLHQWV ZLWK ¿EURP\DOJLD )0 7KLV VWXG\ DLPHG WR WR QRUPDO KXPDQ PHODQRF\WHV :LOGW\SH /.% overexpression HYDOXDWHWKHHႈFDF\DQGVDIHW\RIU706DVDWUHDWPHQWIRU)0LQD LQKLELWV&57&*)3QXFOHDUORFDOL]DWLRQDQGNQRFNGRZQRI/.% center for diagnosis and treatment of pain. LQFUHDVHV QXFOHDU LPSRUW RI &57&*)3 2YHUH[SUHVVLRQ RI 0(7+2'6 )URP -DQXDU\ WR 0D\ SDWLHQWV ZLWK LKB1 (WT) suppresses 0,7) H[SUHVVLRQ LQ /.%GH¿FLHQW * )0ZHUHHQUROOHGLQDQRSHQODEHOXQFRQWUROOHGFOLQLFDOWULDO7R EH PHODQRPDFHOOVDQG$PHODQRPDFHOOVEXWQRFKDQJHLQ0,7) LQFOXGHGLQWKLVVWXG\SDWLHQWVVKRXOGKDYHUHFHLYHGU706LQWKHOHIW P51$H[SUHVVLRQLVVHHQZKHQNLQDVHGHIHFWLYH/.% '$ LV prefrontal cortex. The sessions were performed in a series of 3 to 5 overexpressed. /.% knockdown increases 0,7) expression in consecutive days with maximum break of 2 days between the series. :0 PHODQRPD FHOOV $ VDOWLQGXFLEOH NLQDVH LQKLELWRU UHVFXHV A minimum of 10 sessions was required. Parameters used: frequency 0,7) H[SUHVVLRQ DIWHU /.% RYHUH[SUHVVLRQ LQ /.%GH¿FLHQW (10Hz), cycles of 10 stimuli with pause of 20 seconds between them. PHODQRPDFHOOV5HVFXHRI/.% :7 EXWQRW/.% '$ LQ 20 minutes was the length of each session. Motor threshold was *PHODQRPDFHOOVVXSSUHVVHVFHOOSUROLIHUDWLRQ DGMXVWHGDFFRUGLQJWRWKHDFFHSWDQFHRISDWLHQWV9DULDEOHVVXFKDV Conclusion: 2YHUDOO RXU ¿QGLQJV HVWDEOLVK /.% DV D QHJDWLYH VLGHHႇHFWVSDLQGHSUHVVLYHV\PSWRPVLQVRPQLDIDWLJXHTXDOLW\RI UHJXODWRU RI WKH &57&&5(%0,7) SDWKZD\ WKURXJK DFWLYDWLRQ RI OLIHDQGVLGHHႇHFWVZHUHDVVHVVHGDIWHUHDFKVHVVLRQ 6,.DQD[LVDOWHUHGLQDOPRVWKDOIRI7&*$VNLQFXWDQHRXVPHODQRPD 5(68/76 $PRQJ WKH SDWLHQWV ZHUH ZRPHQ 0HDQ samples, and demonstrate how this pathway could potentially play a VDPSOHDJHRI\HDUV UDQJLQJIURP\HDUV UHSRUWHG critical role in as a tumor suppressor in melanoma oncogenesis and VLJQL¿FDQWLPSURYHPHQWRISDLQDIWHUUGU706VHVVLRQ,PSURYHPHQW PD\RႇHUQHZWDUJHWVIRUFDQFHUWKHUDS\ RIGHSUHVVLYHV\PSWRPVZDVREVHUYHGDIWHUUGVHVVLRQVLQRI 217 525Ȗ LQYHUVH DJRQLVWV VXSSUHVV WKH 1/53 patients. Improvement of insomnia and fatigue was reported after LQÀDPPDVRPH UGVHVVLRQVLQLQRISDWLHQWVUHVSHFWLYHO\,QFUHDVHG 0HJKDQ0XUUD\ TXDOLW\RIOLIHZDVVHHQLQRISDWLHQWVDIWHUWKHUGVHVVLRQ Saint Louis University School of Medicine, Saint Louis, USA Three patients reported mild and transient symptoms such as tinnitus and headache. 7KHUHWLQRLFDFLGUHFHSWRUUHODWHGRUSKDQQXFOHDUUHFHSWRUJDPPD 525Ȗ LV D OLJDQGGHSHQGHQW WUDQVFULSWLRQ IDFWRU NQRZQ WR &21&/86,21,QRXUH[SHULHQFHU706KDGDVLJQL¿FDQWLQÀXHQFH XSUHJXODWHSURLQÀDPPDWRU\JHQHH[SUHVVLRQLQPXOWLSOHOLQHDJHVRI RQ WKH UHGXFWLRQ RI GLႇXVH SDLQ LQ SDWLHQWV ZLWK )0 ,Q DGGLWLRQ LW DGDSWLYHDQGLQQDWHLPPXQHFHOOV525ȖKDVEHHQVKRZQWRUHJXODWH showed to be a good option for rapid relief of symptomatology since DGDSWLYHLPPXQLW\ UROHLQ7KGLႇHUHQWLDWLRQ EXWLWVUROHLQLQQDWH most patients reported relief of symptoms after third session. 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98 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

219 Clinical data correlations to algorithmic surgical skill H[SUHVVLRQ7KLVVWXG\GHPRQVWUDWHVWKHSRWHQWLDOHႈFDF\RI$03. assessment metrics during robotic assisted surgery LQKLELWLRQDVDFDQFHUWKHUDSHXWLFDQGVHUYHVDVSURRIRIFRQFHSWIRU Daniel Naftalovich XQELDVHG )86,21EDVHG GHWHFWLRQ RI VPDOO PROHFXOH LQKLELWRUV RI California Institute of Technology, Pasadena, USA WKHUDSHXWLFWDUJHWV7KHVHUHVXOWVKLJKOLJKWWKHSRWHQWLDOIRU)86,21 to identify novel compounds for cancer therapy development. 6XUJLFDO WHFKQLFDO VNLOO DQG HႈFLHQF\ DUH VWXGLHG LQ WKH FRQWH[W RI robotic assisted surgery using algorithmic computation of surgical 222 Investigating context-dependent integration potential skill and safety features from surgeon motion data during oncological of postnatally born interneurons VXUJHULHVSHUIRUPHGZLWKWKHGD9LQFL6XUJLFDO6\VWHP6XUJLFDOURERWV Gabriel F. Neves FDQ VHUYH DV D ULFK VRXUFH RI GDWD IRU PRWLRQ VNLOO DQG HႈFLHQF\ Duke University School of Medicine, USA data, but this has been limited to the setting of virtual simulators 8QGHUVWDQGLQJWKHSULQFLSOHVJXLGLQJQHXURQLQWHJUDWLRQLQWRQHXUDO and laboratory robots. Recent progress and industry collaborations FLUFXLWV KDYH LPSRUWDQW LPSOLFDWLRQV IRU IXQFWLRQDO UHFRYHU\ SRVW now enable study of surgeon motion data from clinical cases, as injury. Firing action potentials (AP) is a central characteristic of all well as corresponding clinical information, from which metrics for QHXURQV TXLQWHVVHQWLDO IRU FLUFXLWOHYHO FRPSXWDWLRQ 'HVSLWH RXU VDIHW\ VNLOO DQG HႈFLHQF\ FDQ EH FRPSXWHG DNLQ WR WKH VLPXODWRU mechanistic understanding of how APs are generated, how newborn and laboratory environments. The ongoing pilot study at the City of DGXOWQHXURQVGHYHORSDELOLWLHVWR¿UH$3VUHPDLQVXQNQRZQ7KLVLV Hope Comprehensive Cancer Center is presented, in which surgeon likely a key step to successfully transplant neurons as a therapy. The motion and robot kinematic data are analyzed for prostatectomies, $QN\ULQSURWHLQVRUJDQL]HYROWDJHJDWHGLRQFKDQQHOVQHFHVVDU\IRU nephrectomies, gastrectomies, and hepatectomies. AP generation in neurons. Their roles have not been studied during 220 A Functional Signature Ontology (FUSION) screen DGXOWERUQLQWHUQHXURQLQWHJUDWLRQ8VLQJDGXOWQHXURJHQHVLVLQWKH GHWHFWVDQ$03.LQKLELWRUZLWKVHOHFWLYHWR[LFLW\WRZDUGKXPDQ URGHQW VXEYHQWULFXODU ]RQH 69= DV D PRGHO IRU XQGHUVWDQGLQJ colon tumor cells neuronal integration into functional circuitry, we combined innovations Beth Neilsen in mouse genetics, microscopy, and electrophysiology to characterize University of Nebraska Medical Center, Omaha, USA Ank3 expression and function during olfactory bulb (OB) interneurons maturation. To determine developmental Ank3 expression by OB AMPK is a serine threonine kinase composed of a heterotrimer of LQWHUQHXURQVZHJHQHUDWHGDQRYHO'&;&UH(5WPWUDQVJHQLFGULYHU D FDWDO\WLF NLQDVHFRQWDLQLQJ Į DQG UHJXODWRU\ ȕ DQG Ȗ VXEXQLWV OLQH WKDW VSHFL¿FDOO\ WDUJHWV QHZERUQ QHXURQV PLJUDWLQJ IURP WKH KRZHYHU WKH VSHFL¿F FRQWULEXWLRQV RI LQGLYLGXDO VXEXQLW LVRIRUPV DGXOW69=WRWKH2%HQDEOLQJXVWRDJHWKHVHLQWHUQHXURQV8VLQJ to its function and activity are unknown and likely contribute to the this strategy, we were able to characterize Ank3’s developmental LQFRQVLVWHQWDQGFRQWH[WVSHFL¿FUROHRI$03.LQFDQFHU,QDSDQHO H[SUHVVLRQLQ2%LQWHUQHXURQV¿QGLQJ$QNXSUHJXODWLQJGXULQJWKH of colon cancer cell lines, individual AMPK subunit expression and initial phase of neuronal integration. Electrophysiological recordings UHTXLUHPHQW IRU VXUYLYDO YDULHV $03.D $03.Ȗ DQG $03.ȕ showed that Ank3 upregulation paralleled the interneurons’ ability expression was relatively consistent across colon cancer cells lines WR ¿UH $3V 8VLQJ WKH '&;&UH(5WP WUDQVJHQLF GULYHU FURVVHG DQGZDVFRPSDUDEOHWRLPPRUWDOL]HGQRQWUDQVIRUPHGKXPDQFRORQ WR D $QNÀR[ DOOHOH WDPR[LIHQLQGXFHG $QN GHOHWLRQ UHVXOWHG epithelial cells (HCECs) expression. However, the expression of LQ GHFUHDVHG GHQGULWLF FRPSOH[LW\ DV ZHOO DV UHGXFHG $3 ¿ULQJ AMPKa2 was variable between cancer cell lines with the highest IUHTXHQFLHVDQGDPSOLWXGHV6WULNLQJO\ZHHNVIROORZLQJWDPR[LIHQ H[SUHVVLRQEHLQJGHPRQVWUDWHGLQWKH6:DQG6:FDQFHU LQGXFWLRQ $QNGHOHWLRQ UHVXOWHG LQ VLJQL¿FDQWO\ IHZHU LQWHJUDWHG cells and moderate expression being demonstrated in the HCECs as interneurons compared to control littermates, revealing Ank3 as a ZHOODVWKH+&7FDQFHUFHOOV(YHQWKRXJK$03.ȖLVFRQVLVWHQWO\ critical regulator of neuronal integration into adult neural circuits. H[SUHVVHGGHSOHWLRQRIWKHȖVXEXQLWRI$03.LVWR[LFWR+&7 Together, our data demonstrated that Ank3 upregulation during FRORQ FDQFHU FHOOV EXW OHVV VR WR 6: FRORQ FDQFHU FHOOV 2Q interneuron integration in the adult brain is required for proper AP WKH RWKHU KDQG GHSOHWLRQ RI $03.Į ZKLFK LV DOVR FRQVLVWHQWO\ generation, promoting interneuron survival. expressed, does not induce cell death in any of the colon cancer cell OLQHV WHVWHG 51$LPHGLDWHG GHSOHWLRQ RI WKH RWKHU NLQDVH VXEXQLW 223 0RWRU G\VIXQFWLRQ DQG VNHOHWDO PXVFOHV DWURSK\ LQ $03.ĮLQGXFHVFHOOGHDWKLQ6:DQG+&7FRORQFDQFHU rats with spinal cord injury FHOOVWZRFHOOOLQHVH[SUHVVLQJKLJKDQGPRGHUDWHOHYHOVRI$03.Į Bich Tram Nguyen respectively. These data suggest colon cancer cells have variable Cleveland Clinic Lerner Research Institute, Brooklyn, USA UHTXLUHPHQWV IRU VSHFL¿F $03. VXEXQLW LVRIRUPV ZKLFK PD\ EH 6SLQDO FRUG LQMXU\ 6&, LV D WUDXPDWLF FRQGLWLRQ WR DQ\ OHYHO RI LQGLFDWLYHRILVRIRUPVSHFL¿FUROHVIRU$03.DFWLYLW\DQGIXQFWLRQ the spinal cord that causes impaired neurological function with Colon cancer cells are largely susceptible to decreased AMPK kinase DVVRFLDWHG GH¿FLWV LQ WKH PXVFXORVNHOHWDO V\VWHP DQG FDQ OHDG WR activity, but vary in their dependence for a given AMPK subunit. permanent disability. This study is to test the hypothesis that the These data suggest that AMPK kinase inhibition may be a useful motor dysfunction and skeletal muscle atrophy is correlated with the component of future therapeutic strategies. Therefore, Functional VHYHULW\RI6&,:HXVHGWZRGLႇHUHQW6&,PRGHOVLQFOXGLQJWKRUDFLF 6Lgnature OnWRORJ\ )86,21 ZDVXVHGWRVFUHHQDQDWXUDOSURGXFW 7 OHYHOFRPSOHWHLQMXU\RU7LQFRPSOHWHLQMXU\LQDGXOWUDWV7KH library to identify compounds that were inhibitors of AMPK to test FRPSOHWH6&,ZDVFUHDWHGE\DVXUJLFDOVFLVVRUWRWUDQVHFWVSLQDO its potential for detecting small molecules with preferential toxicity FRUG7KHLQFRPSOHWH6&,ZDVFUHDWHGE\WKHFRPSXWHUFRQWUROOHG WRZDUG KXPDQ FRORQ WXPRU FHOOV )86,21 LGHQWL¿HG K\GUR[\ impactor to generate a contusive injury. The rats were observed for 3 staurosporine, which competitively inhibits AMPK kinase activity. PRQWKVDIWHU6&,:LWKLQWKHPRQWKVWKHORFRPRWRUSDWWHUQVZHUH Human colon cancer cell lines are notably more sensitive to assessed using the Basso, Beattie, and Breshnahan (BBB) scale. K\GUR[\VWDXURVSRULQH WKDQ DUH QRQWUDQVIRUPHG KXPDQ FRORQ $QDO\VHVVKRZHGPRUHVLJQL¿FDQWGH¿FLWLQWKHWUDQVHFWLRQDQLPDOV epithelial cells, but demonstrates variable toxicity across cancer cell ZKLOHFRPSDUHGWRWKHFRQWXVLYHLQMXU\JURXS%RWK6&,JURXSVZHUH lines. This could be a consequence of increased AMPK a subunit DOVRVKRZQWKHVLJQL¿FDQWGHFUHDVHRIPRWRUIXQFWLRQZKLOHFRPSDUHG

www.jointmeeting.org 99 POSTER ABSTRACTS

WRWKHVSLQDOLQWDFWDQLPDOV$WWKHHQGRIPRQWKVWKHDQLPDOVZHUH hours or days as opposed to the weeks or months currently needed SHUIXVHGZLWKSDUDIRUPDOGHK\GH7KHVROHXVDQGWLELDOLVDQWHULRU to see measurable size changes on CT or MRI. were harvested for muscle analysis process including cryostat tissue VHFWLRQLQJ DQG KHPDWR[\OLQ HRVLQ VWDLQLQJ 7KH FURVVVHFWLRQDO 225 A novel role of phosphatidylinositol-5-phosphate, DUHDV &6$ RI ERWK KLQGOLPE PXVFOHV ZHUH SKRWRJUDSKHG DQG NLQDVHV 3,3.V DWWKHV\QDSVHDQGLQH[FLWRWR[LFLW\ PHDVXUHGLQWKHFRPSXWHU6LPLODUWRWKHPRWRUIXQFWLRQERWK6&, Evan Noch JURXSV VKRZHG WKH VLJQL¿FDQW GHFUHDVH RI &6$ ZKHQ FRPSDUHG Weill Cornell Medicine, New York, USA WRVSLQDOLQWDFWDQLPDOV7KHWUDQVHFWLRQJURXSVKRZHGVLJQL¿FDQW The phosphoinositide kinases, along with their corresponding IXUWKHUUHGXFWLRQRI&6$ZKHQFRPSDUHGWRFRQWXVLRQJURXS7KLV phosphatases and phospholipases, regulate key functions of further validates the correlation analyses between BBB score and the phosphoinositide family of lipids in cells. These functions PXVFOHPDVV7KHVH¿QGLQJVVXJJHVWWKHVSDUHGQHXUDOWLVVXHDIWHU include proliferation and migration, metabolic adaptation to growth 6&,FRQWULEXWLQJWRWKHSUHVHUYDWLRQRIPRWRUIXQFWLRQDQGVNHOHWDO acceleration, and survival in the setting of genotoxic stress. The PXVFXODUPDVVGXHWRWKHVHYHULW\RI6&, W\SH SKRVSKDWLG\OLQRVLWROSKRVSKDWH NLQDVHV 3,3.V ZKLFK FDWDO\]H WKH IRUPDWLRQ RI 3,3 (PIP2), are critical to Bionanosensors for in vivo monitoring of cancer 2 224 diverse cellular functions. Recently, the type 2 phosphatidylinositol therapeutics SKRVSKDWH NLQDVHV Į DQG 3,3.Į DQG ZKLFK FDWDO\]H Freddy T. Nguyen WKH IRUPDWLRQ RI 3,3 E\ SKRVSKRU\ODWLQJ WKH SRVLWLRQ RI Massachusetts Institute of Technology, Cambridge, USA SKRVSKDWLG\OLQRVLWRO SKRVSKDWH 3,3 KDYH EHHQ VKRZQ WR EH Brain tumors are the most common form of pediatric solid tumors upregulated in breast cancer and are essential for tumorigenesis in DႇHFWLQJaRIDOOSHGLDWULFFDQFHUV3HGLDWULFJOLRPDVPDNHXS the absence of p53, possibly through the regulation of autophagy. DSSUR[LPDWHO\ RI SHGLDWULF FHQWUDO QHUYRXV V\VWHP WXPRUV Though the expression and function of these kinases have been High grade gliomas are highly aggressive and malignant tumors explored in a host of human cancers, few studies have examined ZLWK\HDUVXUYLYDOUDWHVEHWZHHQWR&XUUHQWPDQDJHPHQW their role in the brain. In the brain, the majority of PIP2 is created follows a multipronged approach that include surgery, radiation, and WKURXJK SKRVSKRU\ODWLRQ RI 3,3 E\ WKH W\SH , 3,3 NLQDVH JDPPD FKHPRWKHUDS\6XUJHU\LVXVHGIRUWXPRUGHEXONPHQWDQGIROORZHG isoform. However, the potential role of the type II PIP kinases in by radiation and chemotherapy. Current chemotherapeutics include synaptic PIP2 function and neurotransmission has not been explored. temozolomide, bevacizumab, lomustine, cyclophosphamide, and :H¿UVWH[SORUHGWKHH[SUHVVLRQSDWWHUQVRI3,3.ĮDQG3,3. platinum complexes. There is a pressing need for a platform to in normal mouse brain through immunohistochemistry and electron provide precision chemotherapy screening to increase survival rates, microscopy. We focused our work on mouse hippocampus given the UHGXFH DGYHUVH HႇHFWV DQG ORZHU RYHUDOO FRVWV &XUUHQW VWDQGDUG potential involvement of the type II PIP kinases in oxidative stress of care utilizes imaging to assess tumor response to therapeutic and excitotoxicity as may pertain to a seizure model. We report interventions and to monitor for cancer recurrence. Endogenous WKDW3,3.ĮDQG3,3.DUHGLႇHUHQWLDOO\H[SUHVVHGWKURXJKRXW

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H2O2 during tumor initiation, progression, and regression will be DQG 3,3. LQ DVWURF\WHV LQGLFDWLQJ D SRWHQWLDO UROH IRU WKHVH crucial to better understand their dual roles in cancer metabolism NLQDVHVLQJOLDOIXQFWLRQ7RH[SORUHWKHIXQFWLRQDOLPSDFWRI3,3. and response to chemotherapeutics. We recently developed a series expression in neurotransmission, we utilized a kainic acid model of

RI Q,5 ÀXRUHVFHQW SUREHV IRU 12 DQG +2O2 XVLQJ VLQJOHZDOOHG H[FLWRWR[LFLW\LQPLFH:HVKRZWKDWPLFHGH¿FLHQWLQ3,3.%DQG FDUERQ QDQRWXEHV 6:17 WKDW KDYH EHHQ GHPRQVWUDWHG LQ YLWUR ZLWKDVWURF\WHVSHFL¿FNQRFNRXWRI3,3.$H[KLELWGHOD\HGDQGOHVV with no evidence of photobleaching, and LQYLYR with no decrease VHYHUHVHL]XUHVWKDQWKHLUZLOGW\SHFRXQWHUSDUWV51$VHTDQDO\VLV LQ VHQVRU SHUIRUPDQFH RU VLJQV RI LQÀDPPDWLRQ RYHU GD\V LQ ZKROH EUDLQV IURP WKHVH *)$33,3.$3,3.% DQLPDOV The nIR emission allows for deeper tissue penetration. We also demonstrates globally reduced synaptic and excitatory signaling, present novel bionanosensors that have been developed for some DW OHDVW SDUWO\ GXH WR FKDQJHV LQ HQGRVRPDO WUDႈFNLQJ SDWKZD\V RIWKHPDMRUFKHPRWKHUDSHXWLFGUXJVLQEUDLQFDQFHUV $PLQR This work explores the expression of the type II PIP kinases in the imidazolecarboxamide (AIC), an inactive byproduct of degradation brain and may indicate a novel role in neurotransmission and in RI WHPR]RORPLGH LULQRWHFDQ FLVSODWLQ DQG ORPXVWLQH 'XULQJ excitotoxicity. Further experiments will explore the mechanism of GHJUDGDWLRQRIȝ070='1$6:17VKRZDÀXRUHVFHQFH 3,3. LQYROYHPHQW LQ QHXURWUDQVPLVVLRQ DQG V\QDSWLF YHVLFOH LQFUHDVHZLWKQRVLJQL¿FDQWZDYHOHQJWKVKLIWDQGPRVWVHQVLWLYHWR WUDႈFNLQJ FRQFHQWUDWLRQVEHWZHHQDQGȝ00ROHFXOHVVLPLODULQVWUXFWXUH WR$,&ZHUHDOVRWHVWHGVKRZLQJQRVLJQL¿FDQWÀXRUHVFHQFHVLJQDO 226 Vemurafenib inhibits ILEI by repressing its FKDQJH FRQ¿UPLQJ WKH KLJK VSHFL¿FLW\ DFKLHYHG XVLQJ FRURQD transcriptional activator Upstream Stimulatory Factor-1 SKDVHPROHFXODUUHFRJQLWLRQWHFKQLTXHWRGHVLJQRXU6:17EDVHG Ken Noguchi ELRQDQRVHQVRUV7KHLULQRWHFDQELRQDQRVHQVRUVKRZHGDWZRVWHS Medical University of South Carolina, Charleston, USA PHFKDQLVPZLWKVWURQJLQLWLDOÀXRUHVFHQFHGHFUHDVHIROORZHGE\D ,QWHUOHXNLQOLNH(07,QGXFHU ,/(,)$0& LVDVHFUHWHGIDFWRUWKDW VLJQL¿FDQWUHGVKLIW7KHELRQDQRVHQVRUIRUFLVSODWLQDQGORPXVWLQH FRQWULEXWHVWRWKHHSLWKHOLDOWRPHVHQFK\PDOWUDQVLWLRQ (07 DFHOO VKRZHG VLJQL¿FDQW ÀXRUHVFHQFH TXHQFKLQJ UHVSRQVHV :LWK biological process that confers metastatic properties to a tumor cell. WKLV G\QDPLF DQG UHDOWLPH LQIRUPDWLRQ SK\VLFLDQV DQG SDWLHQWV We previously described the role of ILEI in melanoma phenotype will be able to quickly know more about the local delivery and VZLWFKLQJ+HUHLQZHGHVFULEHWKHUROHRI86)DVDWUDQVFULSWLRQDO GLႇXVLRQRIFKHPRWKHUDSHXWLFVLQWKHFRPSOH[KHWHURJHQHRXVWXPRU activator of ILEI. The BRAF inhibitor vemurafenib decreases ILEI microenvironment and the tumor molecular response in a matter of SURWHLQDQGP51$H[SUHVVLRQ,/(,SURPRWHUDQG¶875OXFLIHUDVH

100 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

reporter constructs were used to show that vemurafenib treatment directly stimulate sensory neurons to mediate chronic itch. UHGXFHV,/(,SURPRWHUDFWLYLW\EXWQRW¶875DFWLYLW\6XFFHVVLYH 0HWKRGV:HLQYHVWLJDWHGWKHFRQWULEXWLRQVRIQHXURQDO,/DQG,/ 5’ deletions on the ILEI promoter reporter highlighted a proximal VLJQDOLQJ WR FKURQLF LWFK XVLQJ VHQVRU\ QHXURQVSHFL¿F JHQHWLF (ER[ &$&*7* ESXSVWUHDPRIWKHWUDQVFULSWLRQDOVWDUWVLWH deletion of type 2 cytokine signaling components and pharmacologic WKDW FRQWULEXWHV WR YHPXUDIHQLEUHVSRQVLYH ,/(, SURPRWHU DFWLYLW\ EORFNDGH ZLWK -$. LQKLELWRUV LQ D PRXVH PRGHO RI $' :H DOVR 7KH(ER[ELQGLQJWUDQVFULSWLRQIDFWRUXSVWUHDPVWLPXODWRU\IDFWRU SHUIRUPHGREVHUYDWLRQDOVWXGLHVWRH[SORUHWKHDQWLLWFKSURSHUWLHVRI 86) ELQGV WR WKLV (ER[ LQ D YHPXUDIHQLE DQG VHTXHQFH JAK inhibitors in patients. GHSHQGHQW PDQQHU )LQDOO\ ZH VKRZ WKDW RYHUH[SUHVVLRQ RI 86) EORFNV WKH YHPXUDIHQLEPHGLDWHG LQKLELWLRQ RI ,/(, H[SUHVVLRQ 5HVXOWV:HIRXQGWKDW,/DQG,/GLUHFWO\DFWLYDWHLWFKVHQVRU\ Mechanistically, vemurafenib inhibits ILEI expression by repressing QHXURQV LQ PLFH 6WULNLQJO\ ZH REVHUYHG WKDW ,/ DOVR DFWLYDWHV LWVWUDQVFULSWLRQDODFWLYDWRU86) human sensory neurons, suggesting that neuronal type 2 cytokine VLJQDOLQJSURPRWHVLWFKDFURVVVSHFLHV8VLQJFRQGLWLRQDOGHOHWLRQRI 227 Changes in Brain Leukocyte Populations Instigate ,/5ĮIURPVHQVRU\QHXURQVZHGLVFRYHUHGWKDWQHXURQDO,/5Į Alterations in Cognitive and Sensorimotor Behaviors of Septic FULWLFDOO\ PHGLDWHV $'DVVRFLDWHG LWFK $GGLWLRQDOO\ ZH IRXQG WKDW 0DOH0LFH type 2 cytokine responses in neurons were dependent on JAK1, and Divine Nwafor disruption of neuronal JAK1 signaling reduced chronic itch. Finally, in West Virginia University, Morgantown, USA translational studies, we found that JAK inhibitors markedly improved itch symptoms in chronic itch patients. 6HSVLVLVDGHELOLWDWLQJV\VWHPLFLQÀDPPDWRU\SURFHVVWKDWLVRIWHQ concomitant with an infectious etiology. Although much focus in &RQFOXVLRQV7KHFODVVLFDOLPPXQHVLJQDOLQJPROHFXOHV,/5ĮDQG sepsis has been on peripheral organ insults, cognitive decline and JAK1 represent new targets within the sensory nervous system to VHSVLV DVVRFLDWHG HQFHSKDORSDWK\ 6$( DSSHDU WR EH LPSRUWDQW WUHDWLWFKLQ$'DQGRWKHUFKURQLFLWFKGLVRUGHUV factors precipitating mortality in sepsis patients. In fact, many patients 5HSURJUDPPLQJ 3OXULSRWHQW 6WHP &HOOV WRZDUG who survive sepsis are burdened with neuropsychiatric symptoms 229 Totipotency of memory loss, delirium, mood disorders and long term cognitive impairment. The mechanism through which sepsis exacerbates Sanders Oh EUDLQG\VIXQFWLRQLVXQFOHDU,QWKLVVWXG\ZHORRNHGDWGLႇHUHQFHVLQ Northwestern University, Chicago, USA immune cell populations of male mice subjected to a surgical cecal Totipotent cells have the highest developmental potential and ligation and puncture (CLP), an experimental model of sepsis, versus can only be created by nuclear transfer into oocytes. Identities their sham counterparts. We hypothesized that CLP mice would of maternal factors that can induce this reprogramming remain a H[KLELW LQFUHDVHG OHXNRF\WH H[WUDYDVDWLRQ DFURVV WKH EORRGEUDLQ mystery. In this report, we demonstrate induction of totipotency on barrier (BBB) and show altered behavioral outcomes compared to mouse embryonic stem cells by introducing six factors, Hist1h2aa, controls. Following sepsis initiation, both CLP and sham mice were +IE+IRRS1SP=VFDQGDQG8EWÀ:HREVHUYHGGRVH IROORZHGIRUGD\V6LFNQHVVEHKDYLRULQWKHVHPLFHZDVDVVHVVHG GHSHQGHQW LQFUHDVHV LQ WKH 0X(59/ HQGRJHQRXV UHWURYLUXV ZLWK D PXULQH PRGL¿HG VHSVLV VHYHULW\ VFDOH 0066 GHULYHG H[SUHVVLRQ W\SLFDOO\ VHHQ LQ WRWLSRWHQW FHOO VWDJH EODVWRPHUH IURP SUHYLRXV VWXGLHV 7KH GD\ SHULRG ZDV DOVR DFFRPSDQLHG DQG DGGLQJ S VL51$ DQG WULFKRVWDWLQ $ IXUWKHU LQFUHDVHG WKH with a series of behavioral assays to assess spatial learning and expression. These cells, which we designated iTLCs (induced memory, cognition, depression, thermal nociception and locomotion. WRWLSRWHQWOLNH FHOOV KDG XSUHJXODWLRQ RI WRWLSRWHQW JHQHV EXW 3HUIXVHGEUDLQVZHUHKDUYHVWHGRQ'D\IRULVRODWLRQRIOHXNRF\WHV GRZQUHJXODWLRQRISOXULSRWHQWDQGGLႇHUHQWLDWLRQJHQHVVXJJHVWLQJ DQG TXDQWL¿FDWLRQ E\ ÀRZ F\WRPHWU\ ,PPXQH FHOO SRSXODWLRQV RI a distinct shift towards the totipotent state. Furthermore, iTLCs LQWHUHVW LQFOXGHG PLFURJOLD &'OR&'E&'F LQ¿OWUDWLQJ displayed unusually large nuclei, a characteristic of zygotic genome PRQRF\WH &'KLJK&'E/\*/\& &16 PDFURSKDJH DFWLYDWLRQ =*$ $OVR L7/&V VKRZHG WHORPHUH OHQJWKHQLQJ DQG &'ORZ&'E&'F QHXWURSKLO &'KL/\* GHQGULWLF were able to be cultured in totipotent condition. Meanwhile, iTLCs FHOOV &'KL&'EF % FHOO &' F\WRWR[LF 7 FHOOV did not show malignant transformations as indicated by normal &'KL&' DQG7KHOSHUFHOOV &'KL&' ZLWKHPSKDVLVRQ NDU\RW\SHV LQDELOLW\ WR JURZ LQ QXWULHQWGHSULYHG FRQGLWLRQ DQG 7UHJXODWRU\FHOOSRSXODWLRQV &')R[S 7DNHQWRJHWKHUZH sensitivity to contact inhibition. iTLCs demonstrated expanded cell hope to elucidate a functional understanding of the immune system’s IDWHSRWHQWLDOE\GLႇHUHQWLDWLQJLQWRDOOWKUHHGLVWLQFWOLQHDJHVRIWKH role in neuroimmune responses and mechanisms that contribute to SUHLPSODQWDWLRQHPEU\RDQGH[SUHVVHGPDUNHUVIRUERWKHPEU\RQLF long term cognitive impairment in sepsis patients. DQG H[WUDHPEU\RQLF OLQHDJHV 51$VHT GDWD VKRZHG UHPDUNDEOH VLPLODULWLHV EHWZHHQ L7/&V DQG WRWLSRWHQW FHOOV (DUO\ =*$ JHQHV 228 1HXURQDO,/5ĮDQG-$.VLJQDOLQJFULWLFDOO\PHGLDWH were strongly upregulated in iTLCs, indicating active totipotent state. chronic itch When reprogrammed with factors only for an extended period, we Landon K. Oetjen observed cells resembling various stages of embryogenesis. These Washington University School of Medicine, St. Louis, USA data suggest that pluripotent stem cells can be reprogrammed 5DWLRQDOH $WRSLF GHUPDWLWLV $' LV D FKURQLF LQÀDPPDWRU\ VNLQ toward totipotent state without the need of oocytes and raise the disorder with itch as its most debilitating symptom. Blockade of tantalizing possibility of creating totipotent cells. WKHW\SHF\WRNLQHV,/DQG,/ZLWKGXSLOXPDEDQDQWL,/5Į DQWLERG\KDVGHPRQVWUDWHGXQSUHFHGHQWHGHႈFDF\LQWUHDWLQJ$' including rapid improvements of itch. However, how disrupting type F\WRNLQH VLJQDOLQJ LPSURYHV LWFK UHPDLQV XQNQRZQ *LYHQ WKH UHPDUNDEOHHႇHFWVRI,/5ĮEORFNDGHRQLWFKZHK\SRWKHVL]HGWKDW LQDGGLWLRQWRWKHLUNQRZQSURLQÀDPPDWRU\IXQFWLRQV,/DQG,/

www.jointmeeting.org 101 POSTER ABSTRACTS

230 7\SH'LDEHWHVDQG&DUGLRPHWDEROLF5LVN$VVRFLDWHG 231 Nanomechanics of a tip-link protein from the cochlea ZLWK,QFUHDVHLQ'1$0HWK\ODWLRQRI).%3 Aaron B. Oswald 5RELQ2UWL] Weill Cornell Medical College, USA Johns Hopkins University School of Medicine, Baltimore, USA 6RXQG WUDQVGXFWLRQ RFFXUV LQ FRFKOHDU KDLU FHOOV ZKHQ GHÀHFWLRQ It has been hypothesized that early life stress may burden the of hair bundles opens mechanically sensitive ion channels. Each K\SRWKDODPLFSLWXLWDU\DGUHQDO +3$ D[LV OHDGLQJ WR DVVRFLDWHG KDLU EXQGOH FRPSULVHV VWLႇ F\OLQGULFDO SURMHFWLRQV FDOOHG HSLJHQHWLFV FKDQJHV WKDW PD\ LQÀXHQFH FDUGLRPHWDEROLF FDQFHU VWHUHRFLOLDZKRVHGLVWDOHQGVDUHFRQQHFWHGE\WLSOLQNV¿ODPHQWRXV DQG QHXURGHJHQHUDWLYH GLVHDVH ULVN ODWHU LQ OLIH 6XEFOLQLFDO ELRSRO\PHUV FRQVLVWLQJ RI GLPHUV RI SURWRFDGKHULQ 3&'+ K\SHUFRUWLVROLVP DQG +3$ D[LV G\VIXQFWLRQ DUH VSHFL¿FDOO\ DQG FDGKHULQ &'+ 1XPHURXV SDWKRJHQLF PXWDWLRQV associated with type 2 diabetes, cardiovascular disease, and DႇHFWLQJ ERWK SURWHLQV DUH DVVRFLDWHG ZLWK 8VKHU 6\QGURPH DQG metabolic dysfunction, however, further research in this area has nonsyndromic deafness in humans. The sensitivity and dynamic been hindered by lack of a chronic total cortisol (glucocorticoid) range of mammalian hearing require a certain amount of elasticity exposure measure. Intronic epigenetic methylation of the gene in a hypothetical mechanical element, the “gating spring,” that IRU ). ELQGLQJ SURWHLQ N' ).%3 D FRFKDSHURQH RI WKH transmits tension to the transduction channels. Although tip links are glucocorticoid receptor, has been implicated as a potential indicator FDQGLGDWHV WR EH JDWLQJ VSULQJV PROHFXODUG\QDPLFV VLPXODWLRQV of chronic cortisol exposure. Our overall objective in this study was RIIUDJPHQWVRI3&'+DQG&'+VXJJHVWWKDWWLSOLQNVDUHIDU to determine the association of percent methylation of FKBP5 with WRRVWLႇIRUWKLVSXUSRVH(YHQWKRXJKWKHPHFKDQLFDOSURSHUWLHVRI JO\FRV\ODWHGKHPRJORELQ +E$F ORZGHQVLW\OLSRSURWHLQFKROHVWHURO IXOOOHQJWKWLSOLQNSURWHLQVDQGWKHLUGLPHUVUHPDLQXQNQRZQRWKHU /'/ ZDLVWFLUFXPIHUHQFHDQGERG\PDVVLQGH[ %0, LQDVDPSOH VWUXFWXUHVDUHWKHUHIRUHEHOLHYHGWRGRPLQDWHJDWLQJVSULQJHODVWLFLW\ of 65 individuals with type 2 diabetes mellitus. The Johns Hopkins We hypothesize that the mechanical properties of tip links play a Institutional Review Board approved this study and the authors had key role in the elasticity of gating springs, and that some of the QRFRQÀLFWVRILQWHUHVW'DWDZDVFROOHFWHGGXULQJFOLQLFYLVLWVXVLQJ SDWKRJHQLFPXWDWLRQVLQWLSOLQNSURWHLQVSHUWXUEWLSOLQNHODVWLFLW\7R standardized demographics questionnaires and calibrated devices test these hypotheses, we characterize the mechanics of individual to measure participants’ weight, waist circumference, height, and 3&'+ PROHFXOHV E\ FRQ¿QLQJ WKH SURWHLQV EHWZHHQ D JODVV blood pressure. Blood samples were collected and analyzed by VXEVWUDWHDQGDSRO\VW\UHQHEHDGPLQGLDPHWHU%\KROGLQJWKH Johns Hopkins Clinical Core Laboratory for HbA1c and lipid panels bead in an optical trap, we subject the protein to tensions as great as o DQG '1$ ZDV H[WUDFWHG IURP WKH EORRG DQG VWRUHG DW C. Two S17HWKHUHGE\3&'+WKHEHDGH[SORUHVDUDQJHRISRVLWLRQV VHWV RI ELVXO¿WH SRO\PHUDVH FKDLQ UHDFWLRQ 3&5 SULPHUV ZHUH in response to thermal forces. After measuring the position of the GHVLJQHG WR WDUJHW HDFK RI WZR UHJLRQV ÀDQNLQJ D JOXFRFRUWLFRLG EHDGRYHUWLPHZHXVHWKHSRVLWLRQGLVWULEXWLRQWRLQIHUWKHIRUFH response element) in the second intron of the human FKBP5 H[WHQVLRQUHODWLRQDQGHQHUJ\ODQGVFDSHRI3&'+0HDVXUHPHQWV JHQH 3HUFHQW '1$ PHWK\ODWLRQ DW HDFK RI WKH WDUJHWHG F\WRVLQH DWD&DFRQFHQWUDWLRQW\SLFDORIFRFKOHDUHQGRO\PSKGHPRQVWUDWH JXDQLQH GLQXFOHRWLGH VLWHV &S*V ZDV GHWHUPLQHG E\ ELVXO¿WH the unfolding of individual cadherin domains under physiologically pyrosequencing. Analyses were conducted by multivariable linear relevant forces. By acting as an entropic spring, the resulting regression including age, sex, and race as covariates. We observed XQVWUXFWXUHG SHSWLGH FKDLQ GLVSOD\V D JUHDWO\ UHGXFHG VWLႇQHVV WKDWJUHDWHUSHUFHQWPHWK\ODWLRQRIWKH).%3LQWURQDWRQH&S* :KHQORXGVRXQGVSXWKDLUFHOOVDWULVNRIGDPDJHWLSOLQNHORQJDWLRQ GLQXFOHRWLGHUHJLRQ &S* ZDVVLJQL¿FDQWO\DVVRFLDWHGZLWKKLJKHU DQG WKH HQVXLQJ UHGXFWLRQ LQ VWLႇQHVV PLJKW RႇHU SK\VLRORJLFDO +E$F E S DQG/'/ E S DQGDVHFRQG protection against acoustic trauma. &S* GLQXFOHRWLGH UHJLRQ &S* ZDV VLJQL¿FDQWO\ DVVRFLDWHG ZLWK KLJKHU %0, DQG ZDLVW FLUFXPIHUHQFH E S E 232 0HDVOHV SVHXGRW\SHG YHFWRUV IRU LPSURYHG JHQH S UHVSHFWLYHO\ ,QDVHFRQGDU\DQDO\VLVLWZDVREVHUYHGWKDW delivery to hematopoietic stem cells having a history of more invasive cardiovascular procedures was Stosh Ozog DVVRFLDWHGZLWKJUHDWHUSHUFHQWPHWK\ODWLRQDW&S*ZKHQDGMXVWLQJ The Scripps Research Institute, La Jolla, USA IRU/'/ E S *UHDWHUSHUFHQWPHWK\ODWLRQDW&S* 3VHXGRW\SLQJOHQWLYLUDOYHFWRUV /9V ZLWKDOWHUQDWHYLUDOHQYHORSHV was inversely associated with more days a week completing more VLJQL¿FDQWO\ZLGHQVWKHUDQJHRIWDUJHWDEOHFHOOW\SHVIRUWUDQVGXFWLRQ than 30 minutes of physical activity even when controlling for 9HVLFXODU VWRPDWLWLV YLUXV JO\FRSURWHLQ 969* SVHXGRW\SHG /9V ZDLVW FLUFXPIHUHQFH E S ,Q FRQFOXVLRQ ).%3 are the standard for human hematopoietic stem and progenitor methylation may be a marker of higher metabolic risk in type 2 FHOOV +63&V JHQH GHOLYHU\ +RZHYHU 969* SVHXGRW\SHG /9V diabetes, possibly secondary to higher exposure to cortisol. Further LQHႈFLHQWO\WUDQVGXFHORQJWHUPUHSRSXODWLQJVWHPFHOOV2XUJURXS work should aim to assess the longitudinal association of FKBP5 with KDVSURSRVHGWKDWWKLVORZHႈFLHQF\LVGXHWRDEORFNLQS+WULJJHUHG cardiovascular disease and glycemic outcomes in type 2 diabetes vector escape from the endosome and that vectors with alternate DVD¿UVWVWHSLQXQGHUVWDQGLQJSRWHQWLDOSUHYHQWLYHDQGWUHDWPHQW entry mechanisms may be able to avoid this block. related interventions targeting the HPA axis. /9V SVHXGRW\SHG ZLWK WKH (GPRQVWRQ YDFFLQH VWUDLQ PHDVOHV virus hemagglutinin (H) and fusion (F) glycoproteins have shown HQKDQFHG DELOLW\ WR WUDQVGXFH UHVWLQJ O\PSKRF\WHV DQG PRQRF\WH derived dendritic cells. Edmonston strain hemagglutinin recognizes WKH XELTXLWRXVO\ H[SUHVVHG &' SURWHLQ XQOLNH ZLOGW\SH YLUXV VWUDLQVWKDWXWLOL]H&'RU1HFWLQ +HUHLQZHVKRZWKDW+)/9VKDYHXSWRIROGHQKDQFHGFDSDELOLW\ WRWUDQVGXFH+63&VDVFRPSDUHGWR969*/9VDWDQHTXLYDOHQW PXOWLSOLFLW\ RI LQIHFWLRQ 02, PHDQ (*)3 YV

102 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

UHVSHFWLYHO\DW02, 7KLVLPSURYHGHႈFLHQF\PD\DULVHIURPWKH decreased. Eliminating senescent cells also reduced plasma levels XVH RI DQ DOWHUQDWH S+LQGHSHQGHQW HQWU\ PHFKDQLVP DV 969* RI WKH PDFURSKDJHDWWUDFWLQJ FKHPRNLQHV 0&3 DQG 0,3ȕ DV HQKDQFLQJ VPDOO PROHFXOHV VXFK DV UDSDP\FLQ DQG 3*( GLG QRW ZHOODVPDFURSKDJHFRORQ\VWLPXODWLQJIDFWRU 0&6) %\&\72) LPSURYH+)/9WUDQVGXFWLRQ S,QND SUHDGLSRF\WHV ZHUH GHFUHDVHG LQ ',2,1.$77$&PLFH However, low titers during vector production limit widespread H/F GD\V DIWHU$3 WUHDWPHQW ZKLOH PDFURSKDJHV KDG QRW \HW /9DSSOLFDELOLW\:HVKRZWKDW&'H[SUHVVLRQRQ+)WUDQVIHFWHG decreased. In addition, monocytes from donor mice injected into +(.7FHOOVLVVXႈFLHQWWRLQGXFHDGMDFHQWFHOOPHPEUDQHIXVLRQ REHVH ,1.$77$&GEGE PLFH GD\V DIWHU $3 WUHDWPHQW resulting in multinucleate syncytia and cell death prior to peak vector H[KLELWHGGHFUHDVHGPLJUDWLRQLQWR,$7FRPSDUHGWRYHKLFOHWUHDWHG production in cell supernatant. ,1.$77$&GEGE PLFH 7DNHQ WRJHWKHU RXU UHVXOWV LQGLFDWH WKDW senescent cells can cause macrophage migration into adipose &RQVHTXHQWO\ZHSXUVXHGWKH&5,635&DVPHGLDWHGNQRFNRXWRI tissue in obesity, and targeting senescent cells prevents and reduces &' LQ +(. 7 FHOOV &' .2 +) /9V SURGXFHG LQ &' WKHDGLSRVHWLVVXHPDFURSKDJHLQ¿OWUDWLRQFKDUDFWHULVWLFRIREHVLW\ .2 FHOOV SURGXFHG IROG KLJKHU WLWHU YHFWRU FRPSDUHG WR +) /9V 6XSSRUW7KLVZRUNZDVVXSSRUWHGE\1,+JUDQWV$* -/. SURGXFHG LQ ZLOG W\SH +(. 7V &' .2 +(. 7V DOVR $* -/. $* 3URMHFW-/. $* -/. demonstrated no syncytia formation and continued cell viability $* $.3 WKH &RQQRU *URXS -/. WKH *OHQQ -/. throughout vector production. Ted 1DVK/RQJ/LIH -/. DQG1RDEHU)RXQGDWLRQV -/. :KHQPDWFKHGIRU02,+)/9VJHQHUDWHGLQ&'.2FHOOVUHVXOWHG LQDSSUR[LPDWHO\IROGKLJKHUWUDQVGXFWLRQLQ+63&VFRPSDUHGWR 234 $)$&6EDVHG&5,635VFUHHQIRUKRVWGHWHUPLQDQWV YHFWRUSURGXFHGLQZLOGW\SH+(.7V PHDQ(*)3 YV of Chlamydia trachomatis invasion reveals the multiple roles of UHVSHFWLYHO\DW02, &RQIRFDOPLFURVFRS\DQDO\VLVRI+63&V COPI during infection WUDQVGXFHGZLWK+)/9VKRZHGLPSURYHGYHFWRUORDGLQJFRPSDUHG Joseph S. Park WR969*/9ZLWKOLPLWHGFRORFDOL]DWLRQWRHDUO\HQGRVRPDODQWLJHQ Harvard Medical School, USA (EEA1) positive vesicles, further indicating an alternate entry Chlamydia trachomatis, an obligate intracellular bacterium, is a mechanism. major cause of human genital and ocular infections worldwide. The 6LQFHYHFWRUSURGXFWLRQDQGTXDOLW\DUHPDMRUVRXUFHVRIFRVWDQG SDWKRJHQLVQRWHDVLO\JHQHWLFDOO\WUDFWDEOHDQGWKHDGYHQWRI&5,635 variability in clinical trials of gene therapy, we reason that the use editing in human cells enables a new approach for investigating how RI &' .2 SDFNDJLQJ FHOOV PD\ ORZHU WKH FRVW DQG LPSURYH WKH WKLV SDWKRJHQ LQWHUDFWV ZLWK KRVW 8VLQJ D ÀXRUHVFHQFHDFWLYDWLRQ HႈFLHQF\RIJHQHUDWLQJ+)/9V FHOOVRUWLQJ )$&6 DSSURDFKZHXQGHUWRRNDQXQELDVHGJHQRPH ZLGH VFUHHQ LQ D &5,635HGLWHG JHQRPHZLGH OLEUDU\ RI +7 233 Senescent cell clearance in diet-induced obese mice KXPDQHSLWKHOLDOFHOOVWKDWZHUHLQIHFWHGZLWKÀXRUHVFHQWO\ODEHOOHG decreases adipose tissue macrophage burden C. trachomatis. Enrichment of mutants that were resistant to Allyson Palmer LQYDVLRQDQGGHHSVHTXHQFLQJRIWKHLUVJ51$VOHGWRLGHQWL¿FDWLRQ Mayo Clinic College of Medicine, Rochester, USA RIPXOWLSOHKLWVLQWKH&23,YHVLFXODUWUDႈFNLQJSDWKZD\,QVL51$ %DFNJURXQG6HQHVFHQWFHOOVDFFXPXODWHLQDGLSRVHWLVVXHRIREHVH WUDQVIHFWHG RU WHPSHUDWXUHVHQVLWLYH PDPPDOLDQ FHOO OLQHV &23, mice and humans and may contribute to the development of insulin GHSOHWLRQ OHG WR D VLJQL¿FDQW UHGXFWLRQ LQ EDFWHULDO DWWDFKPHQW resistance. Obesity is also associated with accumulation of immune This was caused by a decrease in cell surface heparan sulfate, FHOOV LQFOXGLQJ PDFURSKDJHV DQG DFWLYDWHG &' O\PSKRF\WHV LQ the receptor for C. trachomatis binding. Acute inactivation of COPI adipose tissue, however the priming stimulus for this immune cell WUDႈFNLQJYLDJROJLFLGH$WUHDWPHQWZKLFKVSDUHGKHSDUDQVXOIDWH LQ¿OWUDWLRQUHPDLQVHOXVLYH,WUHPDLQVXQFOHDUZKDWHႇHFWVHQHVFHQW unmasked a defect in pathogen Type III secretion and consequent cells have on macrophage burden in adipose tissue, or what impact internalization. Furthermore, internalized bacteria were closely strategies to target senescent cells have adipose tissue macrophage DVVRFLDWHG ZLWK &23,ODEHOOHG VWUXFWXUHV LQ PLFURVFRS\ 7RJHWKHU LQ¿OWUDWLRQ LQ REHVLW\ 2EMHFWLYHV :H DLPHG WR LQYHVWLJDWHWKH WKHVH¿QGLQJVUHYHDOWKHGLYHUVHUROHVRI&23,GXULQJWKHHDUO\VWHSV relationship between senescent cell burden and adipose tissue of C. trachomatis invasion into host cells and demonstrate the utility macrophages, 2) determine the impact of senescent cell clearance RI)$&6EDVHG&5,635VFUHHQLQJLQVWXG\LQJWKHPHFKDQLVPVRI on adipose tissue macrophage burden, and 3) elucidate the role entry of intracellular pathogens. RI VHQHVFHQW FHOOV LQ PDFURSKDJH LQ¿OWUDWLRQ LQWR DGLSRVH WLVVXH 235 0D\DUR YLUDO UHSOLFDWLRQ NLQHWLFV DQG in vitro Methods. For these studies, we used two genetic mouse models F\WRSDWKRJHQLFLW\LQKXPDQGHUPDO¿EUREODVW LQZKLFKSSRVLWLYHVHQHVFHQWFHOOVFDQEHHOLPLQDWHGS05 Aum Patel PLFH LQ ZKLFK D S,QNDSURPRWHU VHTXHQFH GULYHV H[SUHVVLRQ University of Florida, Gainesville, USA RI D WULPRGDO UHSRUWHUNLOOHU IXVLRQ SURWHLQ DOORZLQJ VHQHVFHQW FHOO NLOOLQJ E\ JDQFLFORYLU DQG ,1.$77$& PLFH LQ ZKLFK D S,QND Mayaro virus (genus $OSKDYLUXV family 7RJDYLULGDH) is an emerging SURPRWHU VHTXHQFH GULYHV H[SUHVVLRQ RI D Y).%3FDVSDVH DUWKURSRGERUQH YLUXV WUDQVPLWWHG E\ +DHPDJRJXV mosquitoes )/$* IXVLRQ SURWHLQ WKDW FDQ EH DFWLYDWHG E\$3 D Y).%3 LQ V\OYDWLF UHJLRQV RI &HQWUDO DQG 6RXWK $PHULFD 6LPLODU WR dimerizer, to cause senescent cell apoptosis. Obesity was induced FKLNXQJXQ\DYLUXV0D\DURYLUXV 0$<9 LQIHFWLRQOHDGVWRIHYHUV either by diet or genetically using leptin receptor knockout (db/db) maculopapular rash and arthralgia. Many aspects of its transmission PLFH 5HVXOWV DQG &RQFOXVLRQV ) PDFURSKDJH DEXQGDQFH DQGSDWKRJHQLFLW\UHPDLQXQNQRZQLQKXPDQFHOOV6LQFHWKHYLUXV positively correlated with senescent cell burden as measured is injected into the skin by mosquitoes, cells residing in the skin are E\ WUDQVJHQH H[SUHVVLRQ LQ GLHWLQGXFHG REHVH PLFH )ROORZLQJ of particular interest in understanding early infection and antiviral VHQHVFHQWFHOOFOHDUDQFHZLWKJDQFLFORYLUIURPREHVHS05PLFH immune responses. Here, we examine viral replication kinetics H[SUHVVLRQ RI WKH PDFURSKDJH PDUNHU ) LQ LQWUDDEGRPLQDO DQG F\WRSDWKRJHQLFLW\ RI 0$<9 LQ KXPDQ GHUPDO ¿EUREODVWV DV DGLSRVH WLVVXH ,$7 ZDV UHGXFHG DQG FURZQOLNH VWUXFWXUHV ZHUH ZHOODVKXPRUDOLPPXQHUHVSRQVHV,QWUDFHOOXODU0$<9LQIHFWLRQ ZDV YLVXDOL]HG E\ LPPXQRÀXRUHVFHQFH PLFURVFRS\ DQG IXUWKHU

www.jointmeeting.org 103 POSTER ABSTRACTS

TXDQWL¿HGE\ÀRZF\WRPHWU\,)VWDLQLQJUHYHDOHGWKDWRIFHOOV 237 0\RFDUGLQ UHODWHG WUDQVFULSWLRQ IDFWRU 057) VWDLQHGSRVLWLYHIRULQWUDFHOOXODUDQWLJHQDWKRXUVDQGVWDLQLQJ constitutively active and dominant negative line analysis SRVLWLYHDWKRXUVXVLQJDQ02,RI%\ÀRZF\WRPHWU\RI Praveen Paudel cells stained positive for viral antigen at 20 hours post infection University of New Mexico, Albuquerque, USA DW 02, RI 8SRQ YLUDO LQIHFWLRQ RI ¿EUREODVWV YLUXV UHSOLFDWLRQ ZDV DVVHVVHG HYHU\ KRXUV IRU KRXUV DQG H[WUDFHOOXODU YLUDO 057)V D IDPLO\ RI FRQVHUYHG WUDQVFULSWLRQDO FRDFWLYDWRUV DUH WLWHUVZHUHTXDQWL¿HGE\SODTXHDVVD\LQ9HURFHOOV7KHVHDVVD\V expressed in cardiac and smooth muscles where they regulate cell demonstrated that peak levels of extracellular virus release occurred GLႇHUHQWLDWLRQ YLD WUDQVDFWLYDWLRQ RI GLႇHUHQWLDWLRQ PDUNHU JHQHV at 20 hours with a multiplicity of infection (MOI) of 1, at which time $V LPSRUWDQW PHGLDWRUV LQ PXVFOH GLႇHUHQWLDWLRQ 057)V KDYH WLWHUVUHDFKHG[6SIXPO&\WRSDWKLFHႇHFW &3( LQ¿EUREODVWV EHHQLPSOLFDWHGLQIUXLWÀ\ 'URVRSKLOD PHODQRJDVWHU ÀLJKWPXVFOH ZDVREVHUYHGDWYDU\LQJWLPHSRLQWV WRKRXUVSRVWLQIHFWLRQ development, and appear to have an essential role in early muscle CPE was clearly observable with crystal violet staining, resulting cell progenitor development. However, the mechanism through LQ UHGXFWLRQ LQ DGKHUHG FHOOV DW KRXUV 02, 8VLQJ which MRTF is regulating muscle development is not yet understood. ¿EUREODVWVDVWDUJHWFHOOVZHWKHQFRQGXFWHGDQWLERG\GHSHQGHQW Therefore, I have obtained and characterized the phenotypes of FHOO F\WRWR[LFLW\ DVVD\V ZLWK 0$<9 SRVLWLYH KXPDQ VHUD 7KLV transgenic 'URVRSKLOD lines that cause MRTF to be always “on” assay revealed no clear trends compared to media controls. Taken FRQVWLWXWLYHO\ DFWLYH RU DOZD\V ³Rႇ´ GRPLQDQW QHJDWLYH , XVHG WRJHWKHUWKHVH¿QGLQJVDGYDQFHRXUXQGHUVWDQGLQJRILQLWLDO0D\DUR WKH8$6*DOV\VWHPWRRYHUH[SUHVVWKHVHWUDQVJHQHVVSHFL¿FDOO\ YLUDOLQIHFWLRQLQDFULWLFDOFHOOW\SHWKHKXPDQGHUPDO¿EUREODVW LQ DGXOW PXVFOH SURJHQLWRU FHOOV WKURXJK D *DO GULYHU 7KH IXQFWLRQDOÀLJKWWHVWVKRZHGWKDWWKHWUDQVJHQLFÀLHVKDYHDZHDNHU 236 Investigating role of anti-tau antibodies in blocking tau ÀLJKW 0RUHRYHU , FU\RVHFWLRQHG DQG ÀXRUHVFHQW LPPXQRVWDLQHG seeding and spreading in vitro and in vivo WKHVH ÀLHV DQG DQDO\]HG WKH VSHFL¿F PXVFOH GLVUXSWLRQV WKURXJK Tirth Patel confocal imaging. The dominant negative MRTF appears to transform Washington University School of Medicine, St. Louis, USA LQGLUHFWÀLJKWPXVFOHVD¿EULOODUPXVFOHWRDVWUXFWXUHPRUHVLPLODU WR WKH MXPS PXVFOH D WXEXODU PXVFOH W\SH 6LPLODU WR 'URVRSKLOD Alzheimer’s disease is characterized by two main neuropathological the vertebrate muscle system comprises several types of muscle KDOOPDUNVH[WUDFHOOXODUSODTXHVRIDP\ORLGEHWDSURWHLQDQGODUJHO\ ¿EHUVLQGLFDWLQJWKDW057)PD\KDYHDQLPSRUWDQWFRQVHUYHGUROH intracellular tangles of tau protein. The microtubule associated LQ PXVFOH ¿EHU GLႇHUHQWLDWLRQ QRW RQO\ LQ 'URVRSKLOD, but also in protein tau is soluble protein, predominantly expressed in axons. vertebrates. Therefore, this project leads to a better understanding ,W LV WKRXJKW WR SOD\ D UROH LQ D[RQDO WUDႈFNLQJ E\ ELQGLQJ DQG of the role of MRTF in early muscle development. VWDELOL]LQJPLFURWXEXOHV8QGHUQRUPDOSK\VLRORJLFDOFRQGLWLRQVWDX is a soluble monomer that is released in the interstitial space by 238 0DWWHUV RI 0XFXV 0XFRFLOLDU\ 3K\VLRORJ\ LQ D neurons. In diseased state tau loses this solubility, detaches from Bleomycin-Induced Pulmonary Fibrosis Ferret microtubules, migrates to the somatodendriticcompartment and Jacelyn Peabody IRUPV LQVROXEOH DJJUHJDWHV$VLGH IURP LWV UROH LQ$' WDX LV DOVR University of Alabama at Birmingham, Birmingham, USA involved in several other neurodegenerative disorders collectively FDOOHG WDXRSDWKLHV VXFK DV SURJUHVVLYH VXSUDQXFOHDUSDOV\ 363 Introduction: ,GLRSDWKLF SXOPRQDU\ ¿EURVLV ,3) LV D SURJUHVVLYH FRUWLFREDVDOGHJHQHUDWLRQ &%' IURQWRWHPSRUDO GHPHQWLD DQG ¿EURWLF OXQJ GLVHDVH ZLWK PHGLDQVXUYLYDO UDQJLQJ IURP \HDUV DUJ\URSKLOLFJUDQGLVHDVH $*' 5HFHQWZRUNLQWKH¿HOGVHHPVWR after diagnosis. The greatest risk factor for developing IPF is a suggest that after an initial trigger event, tau pathology spreads to JDLQRIIXQFWLRQ SURPRWHU YDULDQW LQ WKH PXFLQ 08&%; however, GLႇHUHQW UHJLRQV RI WKH EUDLQ LQ D VWHUHRW\SLFDO SDWWHUQ PXFK OLNH WKHUROHRI08&%LQ,3)SDWKRJHQHVLVLVXQNQRZQ8QOLNHURGHQW D SULRQ SURWHLQ ZRXOG 8QGHU WKLV µSULRQ K\SRWKHVLV¶ DIWHU DQ LQLWLDO IPF models, ferrets airways contain submucosal glands, the major WULJJHUPLVIROGHGIRUPVRIWDXVSUHDGWKURXJKGLႇHUHQWEUDLQUHJLRQV VRXUFHRI08&%LQKXPDQV:HDUHGHYHORSLQJDQRYHOEOHRP\FLQ by seeding previously normal forms causing them to misfoldas well. LQGXFHGSXOPRQDU\¿EURVLVIHUUHWPRGHOWRHYDOXDWHWKHK\SRWKHVLV WKDWPXFRFLOLDU\SK\VLRORJ\PD\DOWHUSUR¿EURWLFPHFKDQLVPV 6LQFH SURSDJDWLRQ RI WDX DSSHDUV WR EH FULWLFDO WR SDWKRJHQHVLV of taupoathies, tau spreading is an attractive therapeutic target. 0HWKRGV$VLQJOHGRVHRIEOHRP\FLQVXOIDWHVROXWLRQ 8NJ RU 3UHYLRXV ZRUN LQ WKH ODE KDV VKRZQ WKDW WUHDWPHQW ZLWK DQWLWDX VDOLQHYHKLFOHZDVDGPLQLVWHUHGLQWUDWUDFKHDOO\YLDPLFURDHURVROL]DWLRQ DQWLERGLHV LV HႇHFWLYH DW UHGXFLQJ WDX SDWKRORJ\ LPSURYLQJ EUDLQ WRQRUPDOIHUUHWV)LEURVLVZDVDVVHVVHGZLWKȝ&7VFDQVKLVWRORJ\ DWURSK\ DQG EHKDYLRU LQ WKH 36 WDX WUDQVJHQLF PRXVH PRGHO and second harmonic imaging. Functional microanatomy of the ,WUHPDLQVWREHVHHQLIVSHFL¿FDOO\EORFNLQJVSUHDGRIWDXSULRUWR airway epithelium including airway surface morphology, ciliary onset and establishment of pathology can also work as a viable beating (CBF), and mucociliary transport (MCT) were assessed therapeutic approach. H[YLYRXVLQJPLFURRSWLFDOFRKHUHQFHWRPRJUDSK\ ȝ2&7 0XF% expression was assessed with immunohistochemistry. +HUH ZH GHVFULEH 'HYHORSPHQW RI DQ LQGXFLEOH VSUHDG PRGHO D\RXQJ36DQLPDOZKHUHWKHRQO\SDWKRORJ\SUHVHQWLVGXHWR 5HVXOWV$OOIHUUHWV 1 VXUYLYHGWRHXWKDQDVLDDWRUZHHNV VSUHDGRIWDX (ႈFDF\RIYDULRXVDQWLWDXDQWLERGLHVDWEORFNLQJ SRVWEOHRP\FLQ DGPLQLVWUDWLRQ ȝ&7 VFDQV GHPRQVWUDWHG HYLGHQFH VHHGLQJ LQ YLWUR XVLQJ WKH ZHOOHVWDEOLVKHG )5(7 EDVHG VHHGLQJ RISDWFK\DLUZD\FHQWULFDQGSHULSKHUDOJURXQGJODVVRSDFLWLHVWKDW DVVD\ DQG 3UHOLPLQDU\ UHVXOWV LQYHVWLJDWLQJ HႇHFWLYHQHVV RI was worse in the dependent lung, evident at 2 weeks, and persistent these antibodies in blocking tau spreading in vivo. 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104 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

HSLWKHOLDOL]DWLRQDLUZD\UHPRGHOLQJGLႇXVHDOYHRODUGDPDJHW\SH,, promote cancer cell survival. Future studies will employ genetic SQHXPRF\WHK\SHUSODVLDDQGSOHXUDOWKLFNHQLQJ6HFRQGKDUPRQLF approaches to manipulate canonical Wnt signaling, investigating LPDJLQJ UHYHDOHG GRVHGHSHQGHQW ¿EURVLV ZLWK DQG WKHHႇHFWRIFDQRQLFDO:QWDFWLYLW\RQWKH$&&FHOOWUDQVFULSWRPH PHDQLQWHQVLW\IRU8NJDQG8NJEOHRP\FLQIHUUHWV and characterizing the contribution of extracellular proteins to ACC respectively (P<0.05). Masson’s trichrome staining revealed distinct phenotypes. UHJLRQV RI ¿EUREODVWV DQG FROODJHQ PDWUL[ UHVHPEOLQJ ¿EUREODVWLF foci observed in humans. Proximal and distal airways had goblet cell 240 &KURPDWLQIROGLQJZLWK')5$&7 hyperplasia with increased Muc5b staining. Immunohistochemistry $ODQ3HUH]5DWKNH for Muc5b was also observed in cystic areas of metaplastic University of Illinois at Chicago, Chicago, USA HSLWKHOL]DWLRQ (YDOXDWLRQ RI PXFRFLOLDU\ WUDQVSRUW E\ ȝ2&7 1 'HFLSKHULQJ WKH GHWDLOHG PHFKDQLVPV JRYHUQLQJ JHQH UHJXODWLRQ group) following carbachol stimulation showed decreased MCT in RIWHQUHTXLUHV'UHFRQVWUXFWLRQRIWKHFKURPDWLQIROG&KURPRVRPH EOHRP\FLQWUHDWHGPDLQVWHPEURQFKL PPPLQ FRPSDUHGWR FRQIRUPDWLRQFDSWXUHWHFKQLTXHVVXFKDV+L&SURYLGHLQVLJKWLQWR FRQWUROV PPPLQ3 %OHRP\FLQWUHDWHGIHUUHWVDOVR the chromatin folding state but only give averaged spatial information KDGUHGXFHG&%)LQWKHPDLQVWHPEURQFKL +]3 LQWKHIRUPRI'FRQWDFWKHDWPDSV8VLQJWKHVHWHFKQLTXHVDORQH SULRUWRFDUEDFKROFRPSDUHGWRFRQWUROV +]UHVSHFWLYHO\ it is not possible to answer questions such as: the existence of Conclusions: %OHRP\FLQ WUHDWPHQW LQGXFHG SXOPRQDU\ ¿EURVLV LQ IXQFWLRQDOFHOOXODUVXESRSXODWLRQVWKHFRQWDFWSUREDELOLWLHVDPRQJ IHUUHWVZLWKLQÀDPPDWLRQ¿EURWLFOHVLRQVDQGUHPRGHOLQJFKDQJHV PXOWLSOH ! LQWHUDFWLQJORFLWKHFDXVDOIROGLQJUHODWLRQVKLSVDPRQJ DQDORJRXVWR,3)LQKXPDQV&RQWHPSRUDQHRXVDQDO\VLVRI¿EURVLV WKH VSDWLDOO\ LQWHUDFWLQJ JHQRPLF UHJLRQV RU WKH LGHQWL¿FDWLRQRI development and the mucociliary transport apparatus suggests GULYHULQWHUDFWLRQVJRYHUQLQJWKHIROGLQJVWDWH:HSUHVHQW')5$&7 a strong relationship and indicates that the altered airway surface 'LULFKOHW)5$FWDO&KURPD7LQ D%D\HVLDQPHWKRGXWLOL]LQJPRGHOV PLFURHQYLURQPHQWPD\DႇHFWWKHSDWKRJHQHVLVRI¿EURVLV RISK\VLFDOFKURPDWLQIROGLQJWRRႇHUSUREDELOLVWLFDQVZHUVWRWKHVH TXHVWLRQV:HGHPRQVWUDWHRXUPHWKRGRQD7$'ORFXVZLWKLQWKH 239 Canonical Wnt-associated extracellular matrix in .+L&GDWDVHWRI5DRHWDO adrenocortical carcinoma 0RUJDQ3HQQ\ 241 Functional analysis of human cardiac sarcomere University of Michigan and Sidney Kimmel Medical College, missense mutations Whitehall, USA $QWKRQ\03HWWLQDWR UConn Health and The Jackson Laboratory for Genomic Adrenocortical carcinoma (ACC) is a rare and often aggressive Medicine, New Britain, USA FDQFHU WKDW DႇHFWV SHRSOH SHU PLOOLRQ LQ WKH 8QLWHG 6WDWHV DQQXDOO\ *HQRPLF DOWHUDWLRQV DFWLYDWLQJ FDQRQLFDO :QW VLJQDOLQJ Cardiomyopathies are diseases of the myocardium that produce RFFXULQDSSUR[LPDWHO\RI$&&VDQGDUHDVVRFLDWHGZLWKSRRU abnormal cardiac structure and function. The two major forms are prognosis. However, the biological consequences of constitutive GLODWHG FDUGLRP\RSDWK\ '&0 DQG K\SHUWURSKLF FDUGLRP\RSDWK\ canonical Wnt activation in ACC are poorly understood. To better (HCM), which have estimated prevalences of 1:250 and 1:500, characterize the transcriptional programs that are engaged in ACC, UHVSHFWLYHO\%RWK'&0DQG+&0KDYHDVWURQJJHQHWLFEDVLVDQG we performed independent component analysis on The Cancer DUH VLJQL¿FDQW FDXVHV RI VXGGHQ FDUGLDF GHDWK 6&' DQG KHDUW *HQRPH$WODV$&& WUDQVFULSWRPH GDWDVHW WR LGHQWLI\ FRPSRQHQWV IDLOXUH +) DFRQGLWLRQWKDWDႇHFWVPLOOLRQSHRSOHLQWKH86DQG RIFRRUGLQDWHO\H[SUHVVHGJHQHV2QHRIWKHFRPSRQHQWVLGHQWL¿HG KDVD\HDUPRUWDOLW\RI VLPLODUWRFDQFHU 0LVVHQVHPXWDWLRQV ZDV VLJQL¿FDQWO\ HQULFKHG IRU :QW VLJQDOLQJ S DQG ZDV in thick (0<+ and 0<%3&) and thin (TNNT2 P\R¿ODPHQWVDUH strongly associated with somatic &711% ȕFDWHQLQ PXWDWLRQV S FRPPRQJHQHWLFFDXVHVRI+&0DQG'&0EXWJHQHWLFKHWHURJHQHLW\ H ,QWHUHVWLQJO\WKLV:QWHQULFKHGFRPSRQHQWDOVRVKRZHG YDULDQWVRIXQNQRZQVLJQL¿FDQFH 986 DQG VPDOO VDPSOH VL]HV HQULFKPHQW IRU H[WUDFHOOXODU PDWUL[ (&0 UHFHSWRU LQWHUDFWLRQ S PDNHLWGLႈFXOWWRSUHGLFWSDWKRJHQLFLW\DQGDVVHVVULVNRI+)DQG LQFOXGLQJ EXWQRWUHVWULFWHGWR H[SUHVVLRQRI &2/$, 6&' 2XU REMHFWLYH LV WR XQGHUVWDQG WKH IXQFWLRQDO PHDQLQJ DQG /$0&, and ,7*$VXJJHVWLQJWKDW:QWVLJQDOLQJLVUHJXODWLQJFHOO pathogenicity of all missense mutations in the sarcomere by using ECM interactions and ECM composition in ACC. To follow up on this OHQWLYLUXV WR GHOLYHU PLVVHQVH YDULDQWV WR NQRFNRXW KXPDQ L36 observation, we performed immunohistochemical staining on tissue GHULYHGFDUGLRP\RF\WHV L36&0V ZKLFKZLOOWKHQEHDQDO\]HGLQ PLFURDUUD\V 70$V FRQWDLQLQJ $&& VDPSOHV :H REVHUYHG our cardiac power and energy utilization assays. a strong correlation of COL11A1 expression in ACCs with nuclear $VSURRIRIIHDVLELOLW\RIRXUDSSURDFKZHDUH¿UVWIRFXVLQJRQ0<+, ȕFDWHQLQORFDOL]DWLRQ S VXJJHVWLQJ&2/$H[SUHVVLRQ ZKLFK HQFRGHV P\RVLQ KHDY\ FKDLQ EHWD 0+&ȕ WKH PROHFXODU may be regulated by canonical Wnt signaling. To determine whether motor of human cardiac muscle. Missense mutations in 0<+ (&0 DQG (&0UHFHSWRU JHQHV DUH UHJXODWHG E\ FDQRQLFDO :QW DFFRXQW IRU RQHWKLUG RI +&0 PXWDWLRQV DQG DUH DOVR DVVRFLDWHG DFWLYLW\ WKH +5 KXPDQ $&& FHOO OLQH KDUERULQJ DQ DFWLYDWLQJ ZLWK '&0 :H JHQHUDWHG D KRPR]\JRXV 0<+ NQRFNRXW L36& &711% PXWDWLRQ ZDV XVHG &HOOV ZHUH WUHDWHG ZLWK 3.) line (0<+ XVLQJ &5,635&DV WR LQWURGXFH D GHOHWLRQ WKDW DQLQKLELWRURIFDQRQLFDO:QWVLJQDOLQJWKDWGLVUXSWVȕFDWHQLQ OHDGV WR QRQVHQVHPHGLDWHG P51$ GHFD\ RI 0<+ transcripts. LQWHUDFWLRQZLWK7&)/()WUDQVFULSWLRQIDFWRUV3.)WUHDWPHQW )ROORZLQJ FRQ¿UPDWLRQ WKDW 0<+ L36&0V H[SUHVV QR 0+&ȕ VLJQL¿FDQWO\UHGXFHGH[SUHVVLRQRI&2/$, /$0&, and ,7*$in we generated cardiac tissues from 0<+L36&0VDQGZLOGW\SH +5FHOOV S FRQVLVWHQWZLWKRXUK\SRWKHVLVWKDWFDQRQLFDO (0<+) controls to determine impact on force generation. In Wnt signaling regulates expression of ECM components in ACC. parallel to dramatic reductions in sarcomere content, 0<+ cardiac )ROORZLQJ 3.) WUHDWPHQW +5 FHOO YLDELOLW\ GHFUHDVHG WLVVXHVJHQHUDWHQHJOLJLEOHIRUFHFRQ¿UPLQJWKDW0<+ is necessary indicating that canonical Wnt activity may regulate cell survival in for normal sarcomere structure and function. Towards reestablishing ACC. Taken together, these results suggest that canonical Wnt sarcomere content and function in a scalable method, we delivered activity in ACC contributes to expression of ECM proteins that wildtype 0<+ via lentiviral vector into 0<+ L36 &0V 7KLV

www.jointmeeting.org 105 POSTER ABSTRACTS

method restored sarcomere structure and power in 0<+ L36 LQDSSUR[LPDWHO\RIWXPRUV%HFDXVHVPDOOPROHFXOHLQKLELWLRQ CMs, as cardiac tissues generated from these 0<+ transgene RI0<&1KDVQRWEHHQFOLQLFDOO\DFKLHYHGUHFHQWLQYHVWLJDWLRQVKDYH (0<+tg L36&0V JHQHUDWHG QRUPDO IRUFH LQGLVWLQJXLVKDEOH IURP IRFXVHGRQWKHLGHQWL¿FDWLRQRIFULWLFDOWDUJHWVWKDWPRGXODWH0<&1 cardiac tissues generated from 0<+ L36&0V :H ZLOO IXUWKHU ,QDGLVHDVHZLWKIHZUHFXUUHQWVRPDWLFPXWDWLRQVDJDLQRIIXQFWLRQ FKDUDFWHUL]HRXUPRGHOXVLQJPROHFXODUVLJQDWXUHVVXFKDV%W\SH PXWDWLRQ D SKHQ\ODODQLQH WR OHXFLQH VXEVWLWXWLRQ DW FRGRQ natriuretic peptide (133%; induced by mechanical strain), telethonin exists in a gene encoding the cell surface receptor tyrosine kinase (7&$3; marker of sarcomere assembly), and mitochondrial content, $/.,QWHUHVWLQJO\WKH$/.)/PXWDQWLVSUHIHUHQWLDOO\DVVRFLDWHG ZKLFKZHZLOOXVHWRGH¿QHZLOGW\SHDQGJROGVWDQGDUG+&0'&0 ZLWK0<&1DPSOL¿FDWLRQDQGDFFRXQWVIRUDVXEVHWRISDWLHQWVZLWK mutations, with the subsequent aim of extending this approach to a particularly poor clinical outcome. In vivo studies have shown that screen all missense variants. FRQFRPLWDQW H[SUHVVLRQ RI 0<&1 DQG$/.)/ LQ QHXUDO FUHVW cells leads to development of neuroblastoma with earlier onset, higher While 0<+VHUYHVDVSURRIRIFRQFHSWZHZLOOH[WHQGRXUHႇRUWV penetrance, and enhanced lethality compared to tumors in mice to test all sarcomere genes that can be delivered by lentivirus and ZLWKLVRODWHG0<&1DPSOL¿FDWLRQ0LFHEHDULQJWXPRUVZLWK0<&1 contain missense variants, such as cardiac myosin light chains, DPSOL¿FDWLRQDQG$/.)/VKRZDGLVWLQFWWUDQVFULSWLRQDOSUR¿OH WURSRP\RVLQ DQG WURSRQLQ ZLWK NQRFNRXW L36& OLQHV FXUUHQWO\ LQ FRPSDUHG WR WKRVH ZLWK LVRODWHG 0<&1 DPSOL¿FDWLRQ VXJJHVWLQJ development. DSRVLWLYHFRRSHUDWLYHHႇHFWEHWZHHQWKHWZR+RZHYHUZHGRQRW 242 Low fat diet alters the microbiome and improves KDYH D FOHDU XQGHUVWDQGLQJ RI WKH FRQWULEXWLRQ RI $/.)/ LQ quality of life in patients with ulcerative colitis: results of a pilot, altering gene expression. cross-over design study The goal of this study is to understand the mechanism(s) underlying 0DWWKHZ&3KLOOLSV WKHDELOLW\RI$/.)/WRDႇHFWRQFRJHQLFWUDQVFULSWLRQRI0<&1 University of Miami, Miami, USA 7RLQYHVWLJDWHWKLV,SHUIRUPHGVK51$PHGLDWHGNQRFNGRZQRI$/. A diet high in animal meat and fat has been linked to an increased LQFHOOOLQHVH[SUHVVLQJ$/.)/RUZLOGW\SH :7 $/.WRJHWKHU ULVN IRU XOFHUDWLYH FROLWLV 8& DQG KLJK PHDW LQWDNH LQFUHDVHVWKH ZLWKDQGZLWKRXWDPSOL¿HG0<&1'HSOHWLRQRIRQFRJHQLF$/.)/ OLNHOLKRRGRI8&ÀDUHV'HVSLWHWKHVHFRUUHODWLRQVWKHUHKDVQHYHU UHVXOWHGLQDGHFUHDVHLQ0<&1SURWHLQOHYHOVZKLOHNQRFNGRZQRI been a controlled, prospective study to investigate the contribution of :7$/.VKRZHGQRGLVFHUQLEOHFKDQJHLQ0<&1SURWHLQH[SUHVVLRQ GLHWDU\IDWWRLQÀDPPDWLRQDQGWKHTXDOLW\RIOLIHLQSDWLHQWVZLWK8&,Q supporting a role for the mutant receptor but not its WT counterpart, WKLVSLORWFURVVRYHUGHVLJQVWXG\SDWLHQWVZLWK8&ZHUHUDQGRPL]HG LQUHJXODWLQJWKHH[SUHVVLRQRIRQFRJHQLF0<&1%\H[DPLQLQJWKH DQGJLYHQWZRZHHNLVRFDORULFGLHWDU\LQWHUYHQWLRQVZLWKDZHHN JHQRPHZLGH FKDQJHV FDXVHG E\ LQGXFLEOH RYHUH[SUHVVLRQ DQG ZDVKRXWEHWZHHQGLHWVDORZIDWGLHW /)' FRQWDLQLQJWRWDO GHOHWLRQ RI$/.)/ LQ LVRJHQLF FHOO OLQH SDLUV ZLWK DQG ZLWKRXW FDORULHV IURP IDW DQG D VWDQGDUG$PHULFDQ GLHW 6$' FRQWDLQLQJ 0<&1DPSOL¿FDWLRQZHKRSHWREHWWHUFKDUDFWHUL]HWKLVRQFRJHQLF WRWDOFDORULHVIURPIDW3DWLHQWVZHUHSURYLGHGGDLO\FDWHUHG relationship and potentially identify therapeutically targetable nodes food to ensure standardization of the diets. Patients had to be in LQKLJKULVNQHXUREODVWRPD UHPLVVLRQRURQO\PLOGO\DFWLYHDQGKDYHKDGDÀDUHZLWKLQWKHSDVW 244 Histological Analysis of the Effects of Pulsed Focused PRQWKV7RDVVHVVLPSURYHPHQWLQTXDOLW\RIOLIH 4R/ SDWLHQWV Ultrasound in the Brain FRPSOHWHG WKH ,QÀDPPDWRU\ %RZHO 'LVHDVH 4XHVWLRQQDLUH ,%'4 )DUKDQ04XUHVKL EHIRUH DQG DIWHU HDFK GLHW %LRFKHPLFDO PDUNHUV RI LQÀDPPDWLRQ University of Miami, Miami, USA were measured in the stool and serum and stool was collected for microbiome analysis. Eight patients completed both dietary 05,JXLGHG SXOVHG )RFXVHG 8OWUDVRXQG S)86 LV D QRQLQYDVLYH LQWHUYHQWLRQV3DWLHQWVH[SHULHQFHGDVLJQL¿FDQWLQFUHDVH S LQ QRQGHVWUXFWLYH WKHUDS\ ZLWK QXPHURXV DSSOLFDWLRQV :H KDYH WKHLU4R/DVPHDVXUHGE\WKH,%'4ZKLOHRQWKH/)'DVFRPSDUHG SUHYLRXVO\VKRZQWKDWS)86FRXSOHGZLWKLQWUDYHQRXVPLFUREXEEOHV WR WKH 6$' 5HVXOWV ZHUH FRQVLVWHQW UHJDUGOHVV RI WKH LQLWLDO GLHW 0% LVDQHႇHFWLYHPHWKRGRIWUDQVLHQWO\GLVUXSWLQJWKHEORRGEUDLQ 3DWLHQWVRQ/)'KDGVLJQL¿FDQWFKDQJHVLQWKHFRPSRVLWLRQRIWKHLU barrier (BBB). In the current study, we use histological analysis to PLFURELRPHLQFOXGLQJDVLJQL¿FDQWLQFUHDVHLQWKHUHODWLYHDEXQGDQFH YLVXDOL]HDQGTXDQWLI\WKHHႇHFWVRIS)86LQWKHEUDLQ RI %DFWHURLGHWHV S! &KDQJHV LQ WKH PLFURELRPH DOVR )HPDOH6SUDJXH'DZOH\UDWV Q ZHUHWUHDWHGZLWKS)86DW FRUUHODWHGZLWKSDWLHQW¶V,%'4DQGZLWKVHUXPOHYHOVRI&53,/ focal points in the anterior portion of the left hemisphere of the brain. A DQG,/E2XUGDWDLQGLFDWHWKDWD/)'LPSURYHVWKH4R/RISDWLHQWV S)86WUDQVGXFHUZDVXVHGWRDSSO\03DDFRXVWLFSUHVVXUHLQ ZLWKTXLHVFHQWRUPLOG8&DQGWKLVLPSURYHPHQWLVFRUUHODWHGZLWK PVEXUVWVȝORI2SWLVRQ0%ZHUHDGPLQLVWHUHGLQWUDYHQRXVO\ FKDQJHVLQWKHPLFURELRPH7KH/)'DOVRLQFUHDVHGWKHDEXQGDQFH VHFRQGVSUHWUHDWPHQW*GHQKDQFHG7ZHLJKWHGLPDJHVZHUH of bacteria traditionally associated with a healthy microbiome. This REWDLQHGZLWKD705,IRUSUHWUHDWPHQWSODQQLQJDQGWRDVVHVV simple dietary intervention would provide clinicians an informed VXFFHVVIXO%%%RSHQLQJSRVWWUHDWPHQW UHFRPPHQGDWLRQVWRLPSURYHWKH4R/WKHLUSDWLHQWV %UDLQVZHUHFROOHFWHGDQG¿[HGZLWKSDUDIRUPDOGHK\GHDW 243 Delineating the mechanisms underlying oncogenic DQG KRXUV SRVW WUHDWPHQW DQG HLWKHU HPEHGGHG LQ SDUDႈQ RU WUDQVFULSWLRQLQ$/.)/0<&1QHXUREODVWRPD IUR]HQEORFNVIRU,+&ȝPVOLFHVZHUHFROOHFWHGIURPWKHDQWHULRU 0RQLFD03RPDYLOOH portion of the brain and analyzed using IHC. 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106 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

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and display diametrically opposed allosteric activity in radioligand %5&$ORFDOL]DWLRQWRWKHF\WRSODVP:HQH[WLQWURGXFHGWKH(IV ELQGLQJVWXGLHV$VH[SHFWHGIRUD1$0FRPSRXQGGHFUHDVHV YDULDQWLQWRWKH,05QHXUREODVWRPDFHOOOLQHDVDPRQRDOOHOLFNQRFN ȕ$5DႈQLW\IRURUWKRVWHULFDJRQLVWVZKHUHDVWKH3$0FRPSRXQG LQYLD&5,635&DV ,05%$5':7(IV 6XFFHVVIXONQRFN HQKDQFHV DJRQLVW DႈQLW\ IRU WKH UHFHSWRU %RWK FRPSRXQGV DOVR LQZDVFRQ¿UPHGXVLQJ6DQJHUVHTXHQFLQJ%$5':7(IV,05 VKRZ XQELDVHG DOORVWHULF PRGXODWLRQ RI ȕ$5PHGLDWHG VLJQDOLQJ FHOOVDVVHPEOHGVLJQL¿FDQWO\IHZHU5$'IRFLDIWHU89LUUDGLDWLRQ LQ FHOOXODU DVVD\V PHDVXULQJ F$03 SURGXFWLRQ DQG ȕDUUHVWLQ WKDQ:7,05FHOOV YVRIQXFOHLZLWKIRFLS UHFUXLWPHQW GRZQVWUHDP RI WKH DFWLYDWHG UHFHSWRU &RPSRXQG VXJJHVWLQJUHGXFHGFDSDFLW\IRU'1$'6%UHSDLU0RUHRYHU,05 GHFUHDVHVWKHUHVSRQVLYHQHVVDQGWKHUHIRUHHႈFDF\RIRUWKRVWHULF %$5':7(IVFHOOVZHUHVL[IROGPRUHVHQVLWLYHWRSRO\ $'3 DJRQLVWVZKLOHFRPSRXQGLQFUHDVHVDJRQLVWDFWLYLW\DWWKHȕ$5 ribose) polymerase (PARP) inhibition with olaparib relative to WT ,PSRUWDQWO\ ERWK PRGXODWRUV DUH KLJKO\ VSHFL¿F IRU WKH ȕ$5 ,05FHOOV ,&RIYVQ0 as their ability to modulate agonist function at the closely related 7DNHQWRJHWKHUWKHVHGDWDVXJJHVWWKDW%$5'JHUPOLQHPXWDWLRQV ȕ$5LVJUHDWO\GLPLQLVKHG,QWHUHVWLQJO\FRPSRXQGELQGVWRWKH predispose to neuroblastoma by disrupting the stability and FDQRQLFDOLQWUDFHOOXODUWUDQVGXFHUELQGLQJVLWHRIWKHȕ$5WKHUHE\ ORFDOL]DWLRQ RI %5&$ 7KH UHVXOWDQW G\VUHJXODWLRQ RI '1$ '6% VWHULFDOO\ EORFNLQJ WUDQVGXFHU IXQFWLRQ ZKHUHDV FRPSRXQG repair and increased sensitivity to PARP inhibition may provide a SRWHQWLDWHV WUDQVGXFHU IXQFWLRQ VXJJHVWLQJ D GLႇHUHQW ELQGLQJ VLWH WKHUDSHXWLF RSSRUWXQLW\ (ႇRUWV DUH RQJRLQJ WR HQJLQHHU DGGLWLRQDO RQWKHUHFHSWRU$GGLWLRQDOO\XVLQJVWUXFWXUDOO\PRGL¿HGDQDORJVRI KHWHUR]\JRXV%$5'YDULDQWNQRFNLQVDQGWRIXUWKHUFKDUDFWHUL]H HDFKFRPSRXQGZHGH¿QHWKHUHVSHFWLYHFKHPLFDOJURXSVWKDWDUH WKHVH YDULDQWV¶ HႇHFWV RQ %$5'%5&$ KHWHURGLPHUL]DWLRQ DQG key to their biological activity. 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An activating internal tandem duplication repair ,'7 LQ)PVOLNHW\URVLQHNLQDVH )/7 SUHVHQWLQRIFDVHV 0LFKDHO35DQGDOO LVDVVRFLDWHGZLWKZRUVHQHGSUROLIHUDWLRQVXUYLYDODQGGLႇHUHQWLDWLRQ Perelman School of Medicine, University of Pennsylvania, USA E\ FRQVWLWXWLYH DFWLYLW\ RI LWV GRZQVWUHDP VLJQDOLQJ WDUJHWV )/7 1HXUREODVWRPDDQHPEU\RQDOPDOLJQDQF\RIWKHDXWRQRPLFQHUYRXV ,'7 WDUJHWHG WKHUDS\ ZLWK &UHQRODQLE KDV SURYHQ VXFFHVVIXO V\VWHP DQG WKH PRVW FRPPRQ FDQFHU GLDJQRVHG GXULQJ WKH ¿UVW however chemotherapy resistance rapidly develops. It is known \HDU RI OLIH LV D FRPSOH[ JHQHWLF GLVHDVH :KLOH D JHQRPHZLGH that AML suppress &(56 YLD KLVWRQH GHDFHW\ODVH +'$& DVVRFLDWLRQ VWXG\ *:$6 KDV LGHQWL¿HG VHYHUDO QHXUREODVWRPD EORFNLQJH[SUHVVLRQRI&HUDPLGH6\QWKDVH &HU6 ZKLFKSOD\V SUHGLVSRVLWLRQORFLHDFKLQGLYLGXDO613DVVRFLDWLRQKDVDUHODWLYHO\ an important role in mediating lethal mitophagy. 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108 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

252 7RZDUG KLJK WKURXJKSXW LPPXQH LQ¿OWUDWH DQDO\VLV 254 The role of calcineurin in normal myelination and from H&E stained images neuropathy 5LVKL5DZDW &KHOVH\5HHG University of Southern California, Los Angeles, USA +XQWHU-DPHV.HOO\5HVHDUFK,QVWLWXWH681

www.jointmeeting.org 109 POSTER ABSTRACTS

256 Immune regulation of cartilage tumors dynamic interplay between tumor cells and their microenvironment. 6SHQFHU05LFKDUGVRQ Consequently, we are interested in studying the milieu surrounding St. Jude Children’s Research Hospital, USA *%0 WXPRUV WR LGHQWLI\ IDFWRUV WKDW SHUPLW LQYDVLRQ 2QH VXVSHFW LV ('$ H[SUHVVLQJ ¿EURQHFWLQ D VSOLFH YDULDQW WKDW KDV EHHQ Osteochondromas are the most common type of benign bone tumor DVVRFLDWHGZLWKRWKHUPDOLJQDQFLHV,QRWKHUFDQFHUV('$LVWKRXJKW caused by neoplastic outgrowths of cartilage and bone. Although these to play a role in invasion and in making the tumor microenvironment tumors are benign, osteochondromas cause severe pain, deformity, more susceptible to growth. In work completed under the fellowship and constriction of tendons and neurovascular structures. Individuals WR GDWH , KDYH GHPRQVWUDWHG WKDW ('$ ¿EURQHFWLQ LV H[SUHVVHG can develop multiple osteochondromas in a condition called multiple LQ *%0 DQG KDYH DOVR VKRZQ WKDW WKLV H[SUHVVLRQ LV SDUWLFXODUO\ hereditary exostoses (MHE). MHE is linked to heterozygous HOHYDWHG LQ SHULYHQWULFXODU WXPRU ORFDWLRQV ,Q DUHDV ULFK ZLWK('$ mutations in the genes encoding exostosin glycosyltransferase 1 H[SUHVVLRQ WKLV SURWHLQ DSSHDUV WR IRUP VFDႇROGV WKDW PD\ VHUYH (EXT1) or 2 (EXT2). Although most MHE patients bear mutations a role for angiogenesis, haptotaxis and/or macrophage polarization. in either EXT1 or EXT2, studies in both mice and humans indicate :H KDYH DOVR LGHQWL¿HG WKDW FDQFHU DVVRFLDWHG ¿EUREODVWV &$)V WKDWKHWHUR]\JRXV(;7PXWDWLRQVDUHQRWVXႈFLHQWWRFDXVHGLVHDVH LQ*%0SUHIHUHQWLDOO\DFFXPXODWHLQSHULYHQWULFXODUWXPRUORFDWLRQV 0LFHZLWKDKHWHUR]\JRXVGHOHWLRQRI([WPRGHOWKHORVVRIIXQFWLRQ ZKHUHWKH\DUHWKHFHOOXODUVRXUFHRI('$¿EURQHFWLQ2QJRLQJZRUN EXT1 mutations observed in MHE patients, however these mice VHHNVWRHOXFLGDWHWKHUROHVWKDW('$¿EURQHFWLQSOD\VLQSURWXPRUDO show very limited penetrance of osteochondromas. Thus, it is not invasiveness and macrophage polarization and, in so doing, identify understood how a loss of function of one EXT allele causes such a potential therapeutic target. severe disease. We previously demonstrated that the immune system impacts the formation and severity of osteochondromas in 258 &KDUDFWHUL]DWLRQ RI WKH LQÀDPPDWRU\ LQ¿OWUDWH LQ a mouse model of multiple osteochondromas caused by genetic primed mycobacterial uveitis GHOHWLRQRI(UNDQG(UNLQ&'FHOOV7KLVZDVVXUSULVLQJDVQR .HYLQ,5ROQLFN immune regulator of osteochondroma growth had been described. University of Washington, USA Thus, we hypothesize that EXT mutations render individuals 8YHLWLVLVWKH¿IWKOHDGLQJFDXVHRIEOLQGQHVVLQWKH86KRZHYHURXU susceptible to osteochondromas, but that additional “hits” mediated understanding of its immunologic pathophysiology is only nascent. To E\ LQÀDPPDWLRQ DQG WKH LPPXQH V\VWHP DUH QHFHVVDU\ IRU WXPRU develop novel treatments for this set of diseases and to understand formation and growth. WKH UDPL¿FDWLRQV RI XYHLWLV DVVRFLDWHG ZLWK YLUDO YHFWRU PHGLDWHG To test whether activation of the immune system impacts the incidence gene therapy for retinal degeneration, a more robust understanding and severity of osteochondromas, we stimulated the innate immune RIWKHLQÀDPPDWRU\VHTXHQFHLQXYHLWLVLVUHTXLUHG%RWKLQQDWHDQG V\VWHPLQWZRGLႇHUHQWPRXVHPRGHOVRIPXOWLSOHRVWHRFKRQGURPDV adaptive immunity are implicated in uveitis. Recently, an animal model KHWHUR]\JRXV ([W ([W PLFH DQG PLFH GH¿FLHQW LQ (UN DQG incorporating innate and adaptive immunity, primed mycobacterial (UN LQ &' FHOOV (UN GRXEOH NQRFNRXW >'.2&'@ 7KH LQQDWH XYHLWLV 308 ZDVGHYHORSHG7KLVVWXG\DLPVWRGHVFULEHLQGHWDLO immune system was activated by giving the mice various adjuvants WKH LPPXQH UHVSRQVHV DVVRFLDWHG ZLWK 308 )XUWKHU ZH DLP WR LQFOXGLQJSRO\LQRVLQLFSRO\F\WLG\OLFDFLGFRPSOHWH)UHXQG¶VDGMXYDQW GHWHUPLQHLIDTXHRXVVDPSOHVUHSUHVHQWWKHLQÀDPPDWRU\UHVSRQVH and bacterial lipopolysaccharide at weekly intervals starting at three WKDWRFFXUVWKURXJKRXWWKHHQWLUHH\HLQ308DVWKLVFRXOGSRWHQWLDOO\ weeks of age. We found that the incidence of osteochondroma serve as a diagnostic approach for uveitis. formation was accelerated after sequential treatment with multiple 7RJHQHUDWHXYHLWLVLQ&%/-PLFHP\FREDFWHULDO+5DDQWLJHQ DGMXYDQWV+LVWRORJLFDODQDO\VLVRIWKHDႇHFWHGERQHVGHPRQVWUDWHG was delivered subcutaneously one week prior to unilateral intravitreal an increase in severity of osteochondromas in mice treated with LQMHFWLRQRIWKHVDPHDQWLJHQ Q ,QÀDPPDWLRQZDVFRQ¿UPHGYLD adjuvants compared to littermate controls. These data indicate that vitreoretinal and anterior chamber optical coherence tomography at stimulation of the innate immune system can impact osteochondroma GD\SRVWLQWUDYLWUHDOLQMHFWLRQ ' $W'FHOOVXVSHQVLRQVZHUH JURZWK,PSRUWDQWO\ZHVKRZWKDW([WPLFHGHYHORSODUJHUDQG JHQHUDWHGIURPLQÀDPHGH\HDTXHRXV ³,D´VDPSOH LQÀDPHGH\H more numerous tumors following innate stimulation, which supports vitreous and choroid (“Ivc” sample), as well as from fellow eye our hypothesis that the immune system can serve as an additional aqueous, vitreous, and choroid (“FE” sample). Flow cytometry “hit” resulting in tumors. The immune system may also contribute to was performed to identify ocular cells and leukocytes as well as the wide spectrum and severity of tumors observed in MHE patients. lymphocytic and granulocytic lineages. These data reveal a novel role for the immune system in development of osteochondromas. ,VRODWHG FHOOV ZHUH ¿UVW JDWHG WR LGHQWLI\ &' OHXNRF\WHV 7KH YDVWPDMRULW\RI&'FHOOVLQ,DDVZHOODV,YFZHUHJUDQXORF\WLF 257 &KDUDFWHUL]LQJWKHUROHRI¿EURQHFWLQVSOLFHYDULDQWVLQ &'&'1. ZLWKQHXWURSKLOV /\J UHSUHVHQWLQJ! glioblastoma RIWKHVHFHOOVLQ,DDQG,YF2I&'&'FHOOVDPLQRULW\ZHUH -RQDWKDQ:5LFN &' DQGLQ,D,9&DQG)(UHVSHFWLYHO\ $ University of California San Francisco, USA ODUJHUSURSRUWLRQRI&'7FHOOVDQG&'%FHOOVZHUHREVHUYHG *OLREODVWRPD *%0 LV DQ DJJUHVVLYH SULPDU\ EUDLQ FDQFHU ZLWK D LQ,YFWKDQ,D &'LQ,DLQ,YF&'LQ,D GLVPDORYHUDOOVXUYLYDORIXQGHUWZR\HDUVIURPGLDJQRVLV$GH¿QLQJ LQ,9& $VLJQL¿FDQWSRSXODWLRQRISODVPDF\WRLGGHQGULWLFFHOOV feature of these tumors is their invasiveness, which enables escape &'&'FKLJK&'EORZ ZDVIRXQGLQERWK,DDQG,YF from surgical resection and drives inevitable recurrence, with over DQGRI&'&'&'1.FHOOVUHVSHFWLYHO\ RIUHFXUUHQFHVRFFXUULQJZLWKLQFPIURPWKHRULJLQDOWXPRU 7KHVH ¿QGLQJV LOOXVWUDWH WKH FRPSOH[ PDQLIHVWDWLRQV RI LQWUDYLWUHDO Work to identify mediators of invasion and target them has thus mycobacterial exposure. Both the anterior and posterior eye far yielded little progress. This knowledge gap could be explained H[SHULHQFH D JUDQXORF\WHSUHGRPLQDQW UHVSRQVH DW ' IROORZLQJ by the fact that studies focused on cancer cells themselves are +UD H[SRVXUH )XUWKHU WKH LQÀDPPDWRU\ LQ¿OWUDWH LQ WKH DQWHULRU XQDEOHWRFDSWXUH*%0IRUZKDWLVUHDOO\LVDQRUJDQZLWKFRPSOH[ chamber is distinct from that found in the vitreous and choroid, thus a

110 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

“anterior chamber tap ” diagnostic tool may not be adequate to inform DQWLERGLHV $EV DJDLQVW=,.9DQGWKHFORVHO\UHODWHGGHQJXHYLUXV RI WKH LQÀDPPDWRU\ UHVSRQVH WKURXJKRXW WKH H\H 7KHVH ¿QGLQJV '(19 SRVHVDVLJQL¿FDQWGLDJQRVWLFFKDOOHQJH7KHFXUUHQWPHWKRG ZLOOJXLGHIXWXUHVWXGLHVXWLOL]LQJWKH308PRGHO2XUIRUWKFRPLQJ IRUGLႇHUHQWLDWLRQRI=,.9DQG'(19H[SRVXUHWKHSODTXHUHGXFWLRQ 308H[SHULPHQWVZLOOIRFXVRQHOXFLGDWLRQRIWKHLPPXQHUHVSRQVH QHXWUDOL]DWLRQ WHVW 3517 LV DQ H[SHQVLYH ODERULRXV DQG WLPH IROORZLQJ LQWUDYLWUHDO +5D H[SRVXUH ZLWK DQG ZLWKRXW V\VWHPLF consuming assay requiring sophisticated laboratory infrastructure. In SULPLQJ WR XQGHUVWDQG WKH VSHFL¿F HႇHFWV RI SULPLQJ RQ DGDSWLYH this study, we sought to develop a novel immunological diagnostic immune system activation. WHVW FDSDEOH RI GLႇHUHQWLDWLQJ =,.9 DQG '(19 VHURSRVLWLYLW\ rapidly, reproducibly, and inexpensively. We hypothesized that 259 Enucleation in induced red blood cells: a platform $EV UHFRJQL]LQJ HSLWRSHV VSHFL¿F WR WKH =,.9 HQYHORSH ZRXOG EH for autologous cell therapy and in vitro modeling of sickle cell SURGXFHG E\ LQGLYLGXDOV LQIHFWHG ZLWK =,.9 EXW QRW '(19 DQG anemia WKDWWKHVH$EVZRXOGVHUYHDVDPDUNHURISULRU=,.9H[SRVXUH7R 7ROXORSH25RVDQZR GHWHFWWKHVH=,.9VSHFL¿F$EVLQKXPDQSODVPDZHGHYHORSHGDQ Boston Children’s Hospital, USA $E FRPSHWLWLRQ (/,6$ LQ ZKLFK WKH DELOLW\ RI SODVPDERUQH$EV WR +XPDQ LQGXFHG SOXULSRWHQW VWHP FHOOV KL36&V KROG WUHPHQGRXV EORFNELQGLQJRIDSXUL¿HGODEHOHG=,.9VSHFL¿F$EWRZKROHYLUXV promise for disease modeling and the development of novel LVDVVHVVHG:HIRXQGWKDWWKHSODVPDRI=,.9H[SRVHGLQGLYLGXDOV WKHUDSHXWLF WUHDWPHQWV IRU VLFNOH FHOO DQHPLD 6&$ KL36&V FDQ EORFNHG ELQGLQJ RI WKH ODEHOHG =,.9VSHFL¿F$E WR =,.9ZKHUHDV theoretically produce all cell types including induced red blood WKH SODVPD RI '(19H[SRVHG LQGLYLGXDOV GLG QRW )XUWKHUPRUH FHOOV L5%&V 6LFNOH FHOO SDWLHQWV FRXOG EHQH¿W IURP DXWRORJRXV WKHDVVD\DFFXUDWHO\SUHGLFWHGWKH=,.9H[SRVXUHVWDWXVRI engineered red blood cells as these patients have rare blood types, EOLQGHGSODVPDVDPSOHVIURP)ODYLYLUXVH[SRVHGSDWLHQWVLQ DUHIUHTXHQWO\DOORVHQVLWL]HGWREORRGSURGXFWVDQGDWULVNRILURQ %UD]LO7KHDVVD\DOVRDFFXUDWHO\SUHGLFWHGWKH=,.9VHURQHJDWLYLW\ overload from recurrent transfusions. However, in vitro modeling of RI )ODYLYLUXVQDwYH LQGLYLGXDOV LQ WKH 86 DQG %UD]LO 6&$DVZHOODVL5%&SURGXFWLRQIURPKL36&VKDVEHHQKDPSHUHG DQGLQLQGLYLGXDOVZKRKDGUHFHLYHG\HOORZIHYHUYDFFLQDWLRQV E\ WKHLU LQDELOLW\ WR GLႇHUHQWLDWH LQWR WHUPLQDOO\PDWXUH HQXFOHDWHG Collectively, these results indicate that this Ab competition assay is EHWDJORELQH[SUHVVLQJUHGEORRGFHOOV+HUHZHGHVFULEHVWUDWHJLHV KLJKO\ VSHFL¿F IRU =,.9 DQG FDQ DFFXUDWHO\ GLႇHUHQWLDWH H[SRVXUH WR LPSURYH LQ YLWUR SURGXFWLRQ RI L5%&V :H JHQHUDWHG KL36&V WR=,.9DQGRWKHU)ODYLYLUXVHV,PSRUWDQWO\WKHVH¿QGLQJVVXJJHVW IURP VLFNOH FHOO SDWLHQWV ZLWK KHPRJORELQ 66 GLVHDVH VHHQ DW RXU WKDW DQ $E FRPSHWLWLRQEDVHG GLDJQRVWLF PHWKRG FRXOG SURYLGH D KHPDWRORJ\ FOLQLF DW %RVWRQ &KLOGUHQ¶V +RVSLWDO 8VLQJ D FRFNWDLO SURPLVLQJDSSURDFKIRUWKHHYHQWXDOGHYHORSPHQWRIDSRLQWRIFDUH RIWUDQVFULSWLRQIDFWRUVWKDWSURPRWHVHOIUHQHZDODQGPXOWLSRWHQF\ =,.9GLDJQRVWLF H[SUHVVHG XQGHU WKH FRQWURO RI D GR[\F\FOLQHUHJXODWHG SURPRWHU &RPSHWLQJ,QWHUHVWV$XWKRUV'00(*.DQG',:DUHLQYHQWRUVRQ (5* +2;$ 525$ 62; 0<% ZH JHQHUDWHG FRQGLWLRQDOO\ DSDWHQWDSSOLFDWLRQUHODWHGWRWKH=,.9VSHFL¿F$EVGHVFULEHGLQWKLV immortalized hematopoietic progenitors that serve as a renewable study. source of robust erythroid cells in vitro. Erythroid progenitors GLႇHUHQWLDWHG IURP WKHVH OLQHV XQGHUZHQW JORELQVZLWFKLQJ RQFH 261 Aging enhances the deleterious role of neutrophils in WUDQVIXVHGLQWRLPPXQRGH¿FLHQWPLFHZLWKDLQGXFWLRQRIEHWD ischemic stroke globin expression. An in vitro protocol incorporating human plasma 0HDJKDQ$5R\2¶5HLOO\ FDQ EH XVHG WR SURGXFH EHWDJORELQH[SUHVVLQJ FHOOV University of Texas Health Sciences Center at Houston, RI JHQHUDWHG L5%&V DUH DOVR HQXFOHDWHG 3UHOLPLQDU\ L5%& Houston, USA DQDO\VLVUHYHDOVQHDUO\RIWKHHQXFOHDWHGSRSXODWLRQWREH51$ Background: Ischemic stroke is a leading cause of mortality and QHJDWLYHHU\WKURF\WHVDQG51$SRVLWLYHUHWLFXORF\WHV:LWKDQ GLVDELOLW\ ZRUOGZLGH 1HXWURSKLOV H[DFHUEDWH EUDLQ LQMXU\ YLD WKH expandable source of erythroid progenitors capable of producing release of toxic products, particularly reactive oxygen species mature red cells, we hope to assess the feasibility of this platform 526 &OLQLFDO WULDOV RI DQWLLQÀDPPDWRU\ WKHUDSLHV IRU LVFKHPLF for autologous cell therapies. In future studies, we anticipate the VWURNH KDYH EHHQ XQVXFFHVVIXO GXH WR SRRU GUXJ VSHFL¿FLW\ DQG LPSURYHPHQW RI WKH VLFNOLQJ PRGHO YLD D UREXVW LQGXFWLRQ RI EHWD LQDGHTXDWHSUHFOLQLFDOPRGHOLQJ0RVWLPSRUWDQWO\DJHUHSUHVHQWV JORELQH[SUHVVLRQ7KHJHQHUDWLRQRIKL36&GHULYHG6&$PRGHOVZLOO WKHJUHDWHVWQRQPRGL¿DEOHULVNIDFWRUIRULVFKHPLFVWURNHLQFLGHQFH be critical in broadening the current understanding of the molecular and is a strong predictor of poor functional outcome. However, little mechanisms of this disease, and the development of improved LV NQRZQ UHJDUGLQJ WKH HႇHFW RI DJH RQ QHXWURSKLOGULYHQ WLVVXH SKDUPDFRORJLFDOWUHDWPHQWVIRUWKHWUHDWPHQWRI6&$ GDPDJH :H K\SRWKHVL]HG WKDW DJH HQKDQFHV SURLQÀDPPDWRU\ 260 A novel antibody-based diagnostic test for rapid neutrophil functions, driving damage and poor outcomes after differentiation of Zika and dengue seropositivity ischemic stroke, and that neutrophil depletion after ischemic stroke ZRXOGSUHIHUHQWLDOO\EHQH¿WDJHGDQLPDOV %UDQGRQ&5RVHQ University of Miami Miller School of Medicine, Miami, USA 0HWKRGV 8VLQJ ELRORJLFDO VDPSOHV DQG FOLQLFDO LQIRUPDWLRQ IURP stroke patients, we examined the associations between neutrophil 7KHHPHUJHQFHRI=LNDYLUXV =,.9 LQWKH:HVWHUQKHPLVSKHUHLQ gene expression, age and poor outcome after stroke. A mouse model 2015 precipitated a global health crisis, and hundreds of thousands ZDVWKHQXVHGWRGHWHUPLQHWKHRUJDQGLVWULEXWLRQEUDLQLQ¿OWUDWLRQ of individuals have been infected to date. The high degree of concern DQGLQÀDPPDWRU\SKHQRW\SHRIQHXWURSKLOVLQ\RXQJ PRQWK DQG VXUURXQGLQJ=,.9UHVXOWHGIURPLWVLPSOLFDWLRQDVWKHHWLRORJLFDJHQW aged (22 month) mice at baseline and following ischemic stroke. of microcephaly and other severe congenital abnormalities in the )ORZ F\WRPHWU\ ZDV XVHG WR PHDVXUH QHXWURSKLO 526 SURGXFWLRQ neonates of women infected while pregnant. Future prevention of after H[ YLYR and LQ YLYR FKDOOHQJH 1HXWURSKLOVSHFL¿F DQWL/\* =,.9LQGXFHG ELUWK GHIHFWV ZLOO UHTXLUH DFFXUDWH GLDJQRVWLF WHVWLQJ was used to deplete neutrophils after ischemic stroke, followed by WR LQIRUP SURVSHFWLYH SDUHQWV RI WKHLU =,.9 VHURVWDWXV SULRU WR assessment of functional outcomes. FRQFHSWLRQ+RZHYHUWKHKLJKGHJUHHRIFURVVUHDFWLYLW\H[KLELWHGE\

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5HVXOWV ,Q VWURNH SDWLHQWV QHXWURSKLO FRXQWV ZHUH VLJQL¿FDQWO\ bacterial adherence assay relying on Hp adherence to thick sections XSUHJXODWHG S KRXUVDIWHUVWURNHFRPSDUHGWRFRQWUROV RI¿[HGJDVWULFWLVVXHIURPXQLQMXUHGDQGPHWDSODVWLFVWRPDFKV,Q 51$VHTXHQFLQJ GHPRQVWUDWHG WKDW ROGHU VWURNH SDWLHQWV KDG addition, penetration of Hp deep within metaplastic glands in situ greater upregulation of genes involved in neutrophil degranulation FRXOGEHEORFNHGE\SUHWUHDWLQJWKH¿[HGVHFWLRQVRIPHWDSODVWLF FRPSDUHGWR\RXQJHUVWURNHSDWLHQWV,QPLFHÀRZF\WRPHWU\VKRZHG gastric tissue with neuraminidase, which cleaves exposed sialic acid that aged mice had higher proportions of neutrophils at baseline residues. DFURVV PXOWLSOH RUJDQV DQG WKDW VWURNHLQGXHG QHXWURSKLOLD ZDV Following recovery from injury, the sLex expression pattern reverts exacerbated in aged animals (p<0.0001). After stroke, aged animals to that of uninjured tissue. Accordingly, Hp is unable to penetrate were seen to experience poorer outcomes than young animals. deep within glands that have recovered from injury, suggesting ,Q¿OWUDWLQJQHXWURSKLOVLQWKHVWURNHGDPDJHGEUDLQVRIDJHGDQLPDOV that Hp’s binding is mediated in part by reversible changes in sLex KDGVLJQL¿FDQWO\KLJKHULQWUDFHOOXODU526OHYHOVFRPSDUHGWRWKRVH expression. Finally, consistent with the in situ ¿QGLQJV+SLVDEOH LQ\RXQJDQLPDOV6LPLODUO\H[YLYR stimulation of naive neutrophils to expand its topographic distribution LQ YLYR E\ PRUH HႇHFWLYHO\ VKRZHG D PRUH VHQVLWLYH DQG UREXVW SURGXFWLRQ RI 526 LQ DJHG colonizing the gastric corpus of mouse stomachs undergoing QHXWURSKLOV 'HSOHWLRQ RI QHXWURSKLOV ZLWK DQWL/\* DIWHU VWURNH metaplasia compared to uninjured stomachs, implying that Hp has a FRQIHUUHGQREHQH¿WLQ\RXQJPDOHVEXWDVLJQL¿FDQWLPSURYHPHQWLQ tropism for metaplastic gastric epithelium. Taken together, our data JURVVQHXURORJLFDOGH¿FLWVVHQVRULPRWRUIXQFWLRQDQGVWUHQJWKZDV illustrate a potential mechanism by which Hp expands its niche and VHHQLQDJHGDQLPDOVWUHDWHGZLWKDQWL/\* interacts with metaplastic gastric epithelium. Conclusions: This work demonstrates that age enhances stroke pathophysiology and neutrophil degranulation in stroke patients. 263 Centromere driven gene regulation in prostate cancer Additionally, aged animals were found to have exacerbated neutrophil Anjan Saha 526SURGXFWLRQLQWKHEUDLQDIWHUVWURNHDSKHQRPHQRQWKDWZDV University of Michigan, Ann Arbor, USA also seen in H[YLYRH[SHULPHQWVVXJJHVWLQJDQLQWULQVLFDJHUHODWHG The centromere is an essential component of the cellular machinery FKDQJHLQQHXWURSKLOELRORJ\$JHGDQLPDOVKDGVLJQL¿FDQWO\SRRUHU required for the faithful segregation of chromosomes during mitosis, RXWFRPHV DIWHU VWURNH DQG QHXWURSKLO GHSOHWLRQ ZDV VSHFL¿FDOO\ DSURFHVVWKDWLVVLJQL¿FDQWO\G\VUHJXODWHGLQFDQFHU7KHFHQWURPHUH protective in aged animals, illustrating the importance of testing + KLVWRQH YDULDQW &(13$ VHUYHV DV WKH HSLJHQHWLF PDUNHU IRU potential therapeutics in aged animals and suggesting a promising WKH FHQWURPHUH &(13$ RYHUH[SUHVVLRQ KDV EHHQ LGHQWL¿HG LQ UROH IRU QHXWURSKLOWDUJHWHG WKHUDSLHV LQ WKH IXWXUH WUHDWPHQW RI numerous malignancies, yet the functional consequences of its ischemic stroke. overexpression remain elusive. We hypothesize that centromeres represent a functionally important molecular signature that can drive Alterations in the gastric landscape and effects on 262 JHQHUHJXODWLRQLQSURVWDWHFDQFHU:HFRQ¿UPRYHUH[SUHVVLRQRI Helicobacter pylori pathogenesis &(13$LQVHYHUDOPDOLJQDQFLHVWKURXJKFDQFHUYVQRUPDODQDO\VLV Jose B. Saenz ZLWKLQ D FRPSHQGLXP RI SRO\ $ 51$VHTXHQFLQJ 51$ Washington University School of Medicine, St. Louis, USA seq) libraries containing primary cancer tissue, normal tissue, and Infection with +HOLFREDFWHUS\ORUL +S UHPDLQVWKHPRVWVLJQL¿FDQWULVN cancer cell lines. Further analysis restricted to the prostate tissue factor for the development of gastric adenocarcinoma. The sequence type cohort demonstrated an association between increased disease of events leading to gastric dysplasia begins with the gradual loss VHYHULW\ DQG KLJKHU &(13$ H[SUHVVLRQ 51$VHT ¿QGLQJV ZHUH RI DFLGVHFUHWLQJ SDULHWDO FHOOV IROORZHG E\ WKH H[SDQVLRQ RI SUH further validated via tissue microarray (TMA). Overexpression of QHRSODVWLFFKDQJHVLQWKHVHWWLQJRIFKURQLFLQÀDPPDWLRQ7KHHDUO\ &(13$P51$ZLWKLQWKHSURVWDWHFDQFHUWLVVXHW\SHFRKRUWLVWLJKWO\ mucosal response to oxyntic atrophy includes a reorganization of associated with proliferation and mitosis gene expression signatures, the gastric unit, characterized initially by an increased proliferation of GHPRQVWUDWLQJ&(13$LQYROYHPHQWZLWKSURFHVVHVLPSRUWDQWIRUFHOO JDVWULFSURJHQLWRUFHOOVDQGWKHUHSURJUDPPLQJRISRVWPLWRWLFFKLHI GLYLVLRQ)XQFWLRQDOLQWHUURJDWLRQWKURXJK51$LEDVHGGHSOHWLRQRI cells at the base of the gastric gland into a proliferating population of &(13$UHVXOWVLQUHGXFHGSUROLIHUDWLRQRI/Q&D3'8DQGUY metaplastic cells. This pattern of metaplasia is normally a transient E\LQKLELWLQJSURJUHVVWKURXJKWKHFHOOF\FOH)XUWKHUPRUH&(13$ alteration in the gastric landscape to facilitate subsequent restoration targeted chromatin immunoprecipitation followed by sequencing of normal architecture. In some cases, however, restoration is &K,3VHT UHYHDOV QXPHURXV HFWRSLF ELQGLQJ VLWHV IRU &(13$ blocked, and the lesion progresses to gastric dysplasia in the setting &(13$ELQGLQJKDVDSUHGLOHFWLRQWRZDUGVSUR[LPDOUHJLRQVRIJHQH RIFKURQLFLQÀDPPDWLRQ:KLOHLWLVNQRZQWKDW+SVWHDGLO\HVWDEOLVKHV bodies, as revealed by annotation association inquiries. In view of its gastric niche in a relatively hostile environment, it remains unclear WKH DERYH ZH VKRZ &(13$ LV LQGHHG RYHUH[SUHVVHG LQ SURVWDWH how Hp adapts to changes in the gastric metaplastic landscape. cancer and that its expression is necessary for proliferation of :H K\SRWKHVL]HG WKDW +S LQWHUDFWV GLႇHUHQWO\ ZLWK PHWDSODVWLF prostate cancer cell lines. Furthermore, cell lines overexpressing gastric epithelium and that this could explain Hp’s ability to expand &(13$ H[KLELW QRYHO &(13$ELQGLQJ FKDUDFWHULVWLFV WKDW VXJJHVW its niche within the stomach. Hp adhesion to gastric epithelium is D IXQFWLRQDO UROH IRU &(13$ LQ JHQH UHJXODWLRQ )XWXUH VWXGLHV largely mediated by the binding of two of its adhesins, BabA and LQFOXGH [HQRJUDIW WUDQVSODQWDWLRQ RI &(13$GHSOHWHG FHOO OLQHV 6DE$WRKRVW/HZLV% /Hb) and sialylated Lewis X (sLex) antigens, WUDQVFULSWRPLF DVVHVVPHQW RI &(13$GHSOHWHG FHOO OLQHV DQG respectively, epitopes expressed as terminal residues on gastric &5,635EDVHGHYDOXDWLRQRIVSHFL¿F&(13$ELQGLQJVLWHV PXFLQV 8VLQJ D PXULQH PRGHO IRU DFXWHO\ DQG UHYHUVLEO\ LQGXFLQJ PHWDSODVLD ZH ¿QG WKDW WKH RQVHW RI PHWDSODVLD UHVXOWV LQ DQ expansion of sLex expression along the length of the gastric unit axis. Hp is able to penetrate deep within metaplastic glands LQYLYR, while it is largely restricted to the surface epithelium of uninjured glands. This phenotype could be reproduced using a newly developed in situ

112 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

264 Alterations in estrogen metabolism in pulmonary WUDLQLQJLQLWLDWHGVXEDFXWHO\ PRQWKV DIWHU9VWURNHHQKDQFHV arterial hypertension: Aromatase expression in pulmonary LPSURYHPHQWLQ&%7HQVXEDFXWHDQGFKURQLF&%SDWLHQWVWUDLQHG arterial endothelial cells. with a global direction discrimination and integration task in their Sandeep Sahay EOLQG¿HOG7KUHHDGGLWLRQDOVXEDFXWHVZHUHWHVWHGEXWQRWWUDLQHG Houston Methodist Hospital, Houston, USA serving as controls. Initial discrimination performance was at chance EDVHOLQHQRUPDOL]HGGLUHFWLRQUDQJH>1'5@WKUHVKROGV IRUDOO The role of estrogen in vascular disease in general and in pulmonary VXEMHFWV $IWHUGDLO\KRPHWUDLQLQJIRUPRQWKVVXEDFXWHVDWWDLQHG DUWHULDOK\SHUWHQVLRQ 3$+ VSHFL¿FDOO\LVFRQWUDGLFWRU\3$+DႇHFWV QRUPDO1'5WKUHVKROGV DWWUDLQHGORFDWLRQVPXFKIDVWHU females more commonly than males. In animal models of pulmonary WKDQ FKURQLFV VXEDFXWHV VHVVLRQV FKURQLFV hypertension, estrogen increases nitric oxide and prostacyclin VHVVLRQV W S 0RUHRYHU XQOLNH FKURQLFV ZKRVH SURGXFWLRQ DQG GHFUHDVHV HQGRWKHOLQ UHVXOWLQJ LQ EHQH¿FLDO UHFRYHU\QHYHUWUDQVIHUUHGGHHSHULQWRWKHEOLQG¿HOGWUDLQHGVXE YDVFXODU HႇHFWV ,Q FRQWUDVW D FRPSDULVRQ RI %035 PXWDWLRQ acutes exhibited transfer of recovery up to 10 degrees deeper into carriers from families with familial PAH demonstrated that relative WKHEOLQG¿HOGWKDQWUDLQHGORFDWLRQV8QWUDLQHGVXEDFXWHVKDGQR LQFUHDVHV LQ D SURDQJLRJHQLF HVWURJHQ PHWDEROLWH 2+( ZDV VSRQWDQHRXVLPSURYHPHQWLQ1'5WKRXJKDOOVXEDFXWHVLPSURYHG highly associated with disease (PAH) expression. Elevated estrogens similarly on clinical Humphrey perimetry (luminance detection). and estrogen metabolites have been reported in males with PAH 7KXV GLVFULPLQDWLRQ WUDLQLQJ LQLWLDWHG LQ VXEDFXWH &%V JHQHUDWHV compared to matched males absent cardiovascular disease. Patients faster, more spatially distributed discrimination improvements than awaiting liver transplant have a high incidence of feminization identical training in chronic CBs. While luminance detection perimetry features and PAH (portopulmonary hypertension[POPH]). Aromatase LPSURYHG LQ ERWK WUDLQHG DQG XQWUDLQHG VXEDFXWHV RQO\ WUDLQHG &<3$ FDWDO\]HVWKHSURGXFWLRQRIHVWURJHQIURPWHVWRVWHURQH subjects recovered discrimination performance. In summary, without DQGDQGURJHQDQGKDVEHHQLGHQWL¿HGLQWKHOXQJVRISDWLHQWVZLWK DQLQWDFW9OXPLQDQFHGHWHFWLRQPD\LPSURYHVSRQWDQHRXVO\GXULQJ &23' LQSXOPRQDU\DOYHRODUPDFURSKDJHV DQGLVXSUHJXODWHGLQ WKHVXEDFXWHSHULRGEXWGHOLEHUDWHWUDLQLQJLVUHTXLUHGWRUHFRYHU pulmonary vascular smooth muscle cells in animal models of PH. visual discrimination abilities. Whether the lungs are a source of estrogen production or a site of estrogen receptor activation in PAH is unknown. 266 3HUIHFW6NHOHWDO0XVFOH5HJHQHUDWLRQ$IWHU5HSHDWHG We hypothesize that alterations in estrogen levels, estrogen ,QMXU\LQWKH$IULFDQ6SLQ\0RXVH $FRP\V metabolic byproducts, intrapulmonary estrogen receptors and/or Aaron Gabriel W. Sandoval aromatase activity in the lung and/or the liver contribute to PAH. University of Florida, Lakeland, USA Historical lung and liver specimens from autopsy or at organ Regeneration is the perfect regrowth and repair of damaged tissue. explant (lung or liver transplant) underwent aromatase staining as In most adult mammals, the body replaces damaged tissue with a RXU ¿UVW VWHSV WR DGGUHVV WKLV K\SRWKHVLV ,PPXQRKLVWRFKHPLFDO disorganized collagen matrix, better known as a scar. It is believed ,+& DURPDWDVHVWDLQLQJRQGHSDUDႈQL]HGWLVVXHVZDVXQGHUWDNHQ that the scarring response is antagonistic to the regenerative RQ DXWRSVLHG OXQJV ZLWK 323+ DQG H[SODQWHG FLUUKRWLF OLYHUV SURFHVV7KXVVWXG\LQJDQLPDOVWKDWDUHDEOHWRKHDOVFDUIUHHZLOO Controls were normal lung and liver and standard placental tissue provide insight into the mechanisms underlying regeneration. The positive and negative staining controls using primary antibodies for African spiny mouse $FRP\V is the only known mammal in the $URPDWDVH 1% 1RYXV %LRORJLFDOV /LWWOHWRQ &2 ZRUOG WKDW LV FDSDEOH RI VFDUIUHH VNLQ UHJHQHUDWLRQ DV DQ DGXOW 6HFRQGDU\ DQWLERGLHV ZHUH LQFXEDWHG ZLWK WKH WLVVXH VOLGHV +53 In the laboratory, we are using the normal lab mouse 0XV as a DQWL5DEELW ,J* DQG DQWL0RXVH ,J*Y9HFWRU /DERUDWRULHV UHDG\ WR QRQUHJHQHUDWLQJ FRQWURO WR DQDO\]H WKH WUXH H[WHQW RI $FRP\V¶V XVH DQGWKHWLVVXHZDVFRXQWHUVWDLQHGZLWKKHPDWR[\OLQ6OLGHVZHUH regenerative abilities. After an ear punch wound, Acomys fully graded for presence, absence and staining intensity for aromatase regenerated hair follicles, adipocytes, cartilage, sebaceous glands, by two pathologists blinded to the PH status of the patients. and, most notably, skeletal muscle. To further study Acomys’ skeletal Immunohistochemical staining for aromatase in the pulmonary muscle regeneration abilities, we focused on the tibialis anterior, a arterial endothelial cells of two POPH patients was demonstrated with leg muscle also found in humans. The muscles of both Acomys and no staining in normal lung tissue. Immunohistochemical aromatase 0XV ZHUH LQMHFWHG ZLWK FDUGLRWR[LQ D VQDNH YHQRPGHULYDWLYH WR staining was strongly positive in cirrhotic patients with and without induce a wounding response. The healing muscles were harvested PH but absent in normal liver. This is preliminary evidence for altered DWDQGGD\VSRVWLQMHFWLRQ7KHPXVFOHVZHUHHPEHGGHG LQWUDSXOPRQDU\ HVWURJHQ PHWDEROLVP LQ 3$+VSHFL¿FDOO\ LQFUHDVHG LQ 2&7 PHGLXP VHFWLRQHG DQG PRXQWHG RQ VOLGHV 6XEVHTXHQW aromatase expression in the pulmonary arterial endothelial cells. immunohistochemistry with a collagen I antibody showed that Further evaluation in all PAH patients undergoing autopsy or explant both 0XV and $FRP\V recovered from the single injection. It took is ongoing. approximately 11 days for the 0XV muscle to fully recover; however, the $FRP\V PXVFOH IXOO\ UHJHQHUDWHG PRUH TXLFNO\ LQ MXVW GD\V 265 Different properties of training-induced visual recovery Furthermore, immunohistochemistry with a collagen XII antibody in sub-acute versus chronic occipital stroke patients VKRZHGVLJQL¿FDQWVFDUULQJLQWKH0XVconnective tissuewhereas Elizabeth L. Saionz no scarring took place in $FRP\V 57T3&5 DQDO\VLV RI PXVFOHV University of Rochester, Rochester, USA VKRZHGGHFUHDVHGOHYHOVRI1)ț%DQG7*)b1 gene expression in 6WURNH GDPDJH WR SULPDU\ YLVXDO FRUWH[ 9 LQ DGXOW KXPDQV $FRP\V compared to 0XV VLJQLI\LQJ ORZHU OHYHOV RI LQÀDPPDWLRQ causes cortical blindness (CB). We have previously shown that DQG¿EURVLV,QRUGHUWRVWXG\UHJHQHUDWLRQLQUHVSRQVHWRUHSHDWHG YLVXDOGLVFULPLQDWLRQWUDLQLQJLQFKURQLF !PRQWKV VWURNHSDWLHQWV injury, we then injected a novel cohort of mice. After the initial GHFUHDVHV WKH GH¿FLW EXW UHFRYHUHG YLVLRQ UHPDLQV LPSDLUHG injection, the mice were given 3 weeks to heal after which they were Evidence in sensorimotor stroke suggests that earlier intervention DJDLQLQMHFWHG7KLVZDVUHSHDWHGIRUDWRWDORILQMHFWLRQKHDOLQJ promotes greater recovery. Here, we asked if visual discrimination cycles. Amazingly, $FRP\V was still able to regenerate its muscle perfectly after repeated insult. However, 0XV showed an extremely

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intriguing result: adipocytes had accumulated within the muscle. not known how the abnormal 6/&$ protein products modulate ,PPXQRKLVWRFKHPLVWU\ ZLWK D SHULOLSLQ DQWLERG\ FRQ¿UPHG WKDW IDW hearing loss and contribute to temporal bone abnormalities. The cells were indeed present throughout the 0XV muscle yet absent goal of this study was to model 6/&$associated hearing loss in the $FRP\V muscle. Although initially surprising, theabundance LQ ]HEUD¿VK DQG HOXFLGDWH D PHFKDQLVP UHVSRQVLEOH IRU KHDULQJ of fat cells throughout the 0XV muscle after repeated injections is loss in patients with pathogenic variants in 6/&$. To model the UHPLQLVFHQWRI'XFKHQQHPXVFXODUG\VWURSK\GXULQJZKLFKKXPDQ human condition, VOFDPXWDWLRQVLQ]HEUD¿VKZHUHJHQHUDWHGYLD PXVFOH FHOOV DUH UHSODFHG E\ IDW FHOOV 6LQFH $FRP\V averted this WUDQVFULSWLRQ DFWLYDWRU OLNH HႇHFWRU QXFOHDVHV 7$/(1V DW WKH VLWH G\VWURSK\OLNH SKHQRW\SH FRQWLQXHG VWXG\ RI WKH $IULFDQ VSLQ\ of the most common 6/&$ pathogenic variants. We obtained a mouse will help us to better understand ways to treat and prevent this 23bp deletion mutation in exon 10 of VOFD. We hypothesized that debilitating disease. Truly, there is much to learn about the keys to ¿VK ZLWK ELDOOHOLF VOFD mutations would closely recapitulate the VFDUIUHHWLVVXHUHJHQHUDWLRQIURPWKLVSKHQRPHQDOPRGHORUJDQLVP KXPDQSKHQRW\SHDQGKDYHVLJQL¿FDQWKHDULQJORVVDQGVWUXFWXUDO HDUPDOIRUPDWLRQV7RWHVWIRUGHDIQHVVLQ]HEUD¿VKZHGHYHORSHG 267 7KH$SSOLFDWLRQRI0HGLFDUH'DWDIRU0XVFXORVNHOHWDO DKHDULQJDVVHVVPHQWZKLFKH[SRVHVODUYDORUDGXOW¿VKWRVSHFL¿F 5HVHDUFKLQWKH8QLWHG6WDWHV$6\VWHPDWLF5HYLHZ sound stimuli while recording startle responses. To quantitatively Tiana Sarsour study the VOFDmutant ear phenotype, we took measurements of University of Toledo, Sylvania, USA the posterior and anterior otolith area and the ear area using bright Musculoskeletal disorders hinder the human body’s movement ¿HOGPLFURVFRS\5HVXOWVLQGLFDWHWKDWKRPR]\JRXVODUYDHWHVWHGDW YLD WKHLU QHJDWLYH HႇHFWV XSRQ WKH PXVFXORVNHOHWDO V\VWHP ZKLFK GD\VSRVWIHUWLOL]DWLRQWKHGD\RIKHDULQJRQVHWLQ]HEUD¿VKKDYH consists of multiple components such as muscles, tendons, KHDULQJ VLPLODU WR ZLOGW\SH +RZHYHU DGXOW ¿VK ZLWK WZR FRSLHVRI ligaments, and nerves, to name a few. These disorders can lead to mutated VOFDKDYHIUHTXHQF\VSHFL¿FUHGXFHGUHVSRQVHVDW many problems, including carpal tunnel syndrome, tendonitis, and +] GE 7KHVH UHVXOWV LQGLFDWH WKDW VOFD mutants may have HSLFRQG\OLWLV7KHFRQVHTXHQFHVRIWKHVHFRQGLWLRQVDႇHFWWKHOLYHV SURJUHVVLYHIUHTXHQF\VSHFL¿FKHDULQJORVV%ULJKW¿HOGLPDJLQJDQG of aging adults, the direct and indirect costs of their care, and the use measurement analysis showed that VOFD homozygousmutant RIGLႇHUHQWKHDOWKFDUHVHUYLFHV%\XWLOL]LQJWKH3XE0HGDQG0HGOLQH ODUYDH KDYH VLJQL¿FDQWO\ VPDOOHU VWDQGDUGL]HG SRVWHULRU RWROLWK GDWDEDVHV DV VRXUFHV IRU SHHUUHYLHZHG PDQXVFULSWV SXEOLVKHG areas, anterior otolith areas, and ear areas on average compared EHWZHHQDQGWKHVWXG\DLPHGWRH[DPLQHOLWHUDWXUHRQDOO to wildtype at 5dpf. This closely matches the human phenotype, as musculoskeletal surgical outcomes which used Medicare Claims data humans with 6/&$ pathogenic variants may have progressive LQWKH8QLWHG6WDWHVLQRUGHUWRDVVHVVWKHUHOLDELOLW\DQGXVHIXOQHVVRI hearing loss and temporal bone abnormalities. such claims data. Each study, of those observed, reported the primary 7KLQ )LODPHQW '\VUHJXODWLRQ DV D 0HFKDQLVP IRU use of Medicare claims data, involved musculoskeletal surgery, and 269 Diastolic Dysfunction in Hypertrophic Cardiomyopathy: ZDVDQRULJLQDOSHHUUHYLHZHGVWXG\%\XVLQJWKH1HZFDVWOH2WWDZD &RPSXWDWLRQDODQG([SHULPHQWDO,QYHVWLJDWLRQRI730(. $VVHVVPHQW6FDOHWKHVWXG\DVVHVVHGWKHTXDOLW\RIHDFKDUWLFOH 0XWDWLRQLQ3DWLHQW'HULYHG(QJLQHHUHG+HDUW7LVVXH 6XUJLFDOSURFHGXUHVVSHFL¿FDLPVHYDOXDWHGRXWFRPHVVWUHQJWKV and weaknesses were all extracted from each individual study for /RUHQ]R56HZDQDQ DQDO\VLV 2I WKH DUWLFOHV VHDUFKHG PHW WKH VWXG\¶V LQFOXVLRQ Yale University, New Haven, USA criteria, which focused upon various outcome measures such as 0LVVHQVHPXWDWLRQVWRDOSKDWURSRP\RVLQ 730 DUHLPSOLFDWHGLQ HSLGHPLRORJ\ DQG WUHDWPHQW YDULDWLRQ FRVW RI FDUH KRVSLWDOOHYHO the development of hypertrophic cardiomyopathy (HCM). Linking analyses, health outcomes, validity and accuracy of Medicare claims +&0WRPXWDWLRQLQGXFHGPROHFXODUFKDQJHVLVFKDOOHQJLQJEXWFULWLFDO data, disparities in healthcare, and policy evaluation. From the for improved diagnosis and treatment. A young patient diagnosed results obtained, it is concluded that Medicare claims data provide a with HCM after presenting with severe left ventricular hypertrophy, unique way for researchers to study nationally representative patient type II diastolic dysfunction, left atrium dilation, and moderate SRSXODWLRQ ORQJLWXGLQDOO\ +RZHYHU WKH UHVXOWV IRXQG D VLJQL¿FDQW LQWHUVWLWLDO¿EURVLV YLD&05/*( ZDVJHQHWLFDOO\WHVWHGDQGIRXQGWR OLPLWDWLRQ LQ WKH XVDJH RI FODLPV GDWD VSHFL¿FDOO\ WKLV OLPLWDWLRQ KDYHDVDUFRPHULF730(.YDULDQW,QRUGHUWRXQGHUVWDQGWKH LQYROYHVWKHODFNRIPHGLFDOJUDQXODULW\RQGH¿QLQJWKHVHYHULW\RID LPSDFWRIWKLVVSHFL¿F730PXWDQWRQPXVFOHIXQFWLRQDQGUHVXOWLQJ given condition. Transition to the tenth revision of the International pathophysiology leading to HCM, we have used multiscale modeling 6WDWLVWLFDO&ODVVL¿FDWLRQRI'LVHDVHVDQG5HODWHG+HDOWK3UREOHPV DQGH[SHULPHQWVDWWKHPROHFXODUP\R¿ODPHQWDQGWLVVXHOHYHOV,Q ,&'ZLOOKHOSHOLPLQDWHVRPHRIWKHVHOLPLWDWLRQV order to model the impact of the mutation, we derived measures of 730VWLႇQHVVIURPPROHFXODUG\QDPLFVVLPXODWLRQVRIPXWDQWDQG 268 =HEUD¿VK0RGHORI+XPDQSLC26A4 Deafness ZLOGW\SH SURWHLQ DQG XVHG D QRYHO 0DUNRY 0RQWH&DUOR PRGHO RI Ashley J. Scott WKHUHJXODWHGWKLQ¿ODPHQWWRWUDQVODWHWKHPROHFXODUDOWHUDWLRQRIWKH Mayo Clinic, Rochester, USA 730ÀH[LELOLW\LQWRWKHHႇHFWRQUHJXODWLRQRIPXVFOHFRQWUDFWLRQ Two out of every thousand newborns are born deaf or hard of hearing. :H IRXQG WKDW WKLQ ¿ODPHQW G\VUHJXODWLRQ DOWHUHG DFWRP\RVLQ 6L[W\SHUFHQWRIKHDULQJORVVKDVDQLGHQWL¿DEOHJHQHWLFFDXVHZLWK FRQWUDFWLRQ OHDGLQJ WR LQFUHDVH GLDVWROLF FURVVEULGJH ELQGLQJ DQG disease causing variants in 6/&$ being among the most common. UHGXFHDELOLW\RIWKLQ¿ODPHQWWRWUDQVLWLRQWRWKHEORFNHGVWDWH2XU Pathogenic variants in 6/&$ cause bilateral sensorineural model further predicted that these molecular changes would lead hearing loss, temporal bone abnormalities, and occasionally thyroid to increased systolic and diastolic twitch force production in intact goiter, known as Pendred syndrome. Pendrin, the protein product muscle. In order to understand whether these mechanisms would of 6/&$, is a solute carrier. Pendrin is expressed in the inner lead to contractile dysfunction in the context of human tissue, we ear, thyroid, and kidney. In the inner ear, Pendrin modulates the JHQHUDWHG LQGXFHG SOXULSRWHQW VWHP FHOO FDUGLRP\RF\WHV L36& transport of bicarbonate and chloride, allowing bicarbonate to leave &0V IURPWKH730(.SRVLWLYH+&0SDWLHQW(QJLQHHUHGKHDUW the supporting cells of the inner ear and chloride to enter. This helps WLVVXHV (+7V ZHUHFUHDWHGIURPSDWLHQW,36&&0VDQGFXOWXUHGIRU maintain a relatively neutral pH environment in the inner ear. It is 16 days under electrical pacing. Contractile characterization of EHTs

114 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

revealed that the peak force generated by mutant EHTs was several 271 Creation of a robust genetically engineered mouse WLPHVKLJKHUWKDQWZRLQGHSHQGHQWVHWVRIQRQPXWDQWFRQWURO(+7V model of IDH-mutant glioma &RQWUDFWLRQ NLQHWLFV ZHUH DOVR FKDQJHG H[KLELWLQJ VLJQL¿FDQWO\ Diana D. Shi VORZHUWLPHWRSHDNDQGUHOD[DWLRQWLPH)XUWKHUPRUHWKHVWLႇQHVVRI Dana-Farber Cancer Institute, USA WKHPXWDQW(+7VGXULQJGLDVWROHVLJQL¿FDQWO\LQFUHDVHG$OWRJHWKHU H[SHULPHQWDOREVHUYDWLRQVDQGPRGHOLQJLQGLFDWHWKDW(.OHDGVWR *OLREODVWRPD *%0 LVWKHPRVWFRPPRQDQGDJJUHVVLYHIRUPRIEUDLQ ORZHU70VWLႇQHVVDQGDFRQVHTXHQWLQDELOLW\RIWKHDFWLQ¿ODPHQWWR WXPRU6HFRQGDU\*%0VDUHDVXEVHWRI*%0VWKDWSURJUHVVIURPD LQKLELWP\RVLQEDVHGIRUFHSURGXFWLRQ:HSRVLWWKDWWKLVPXOWLVFDOH ORZJUDGHRUDQDSODVWLFDVWURF\WRPDDQGGLVSOD\DKLJKSUHYDOHQFH PXOWLPRGDO DSSURDFK PD\ EH JHQHUDOO\ XVHIXO IRU SUHGLFWLQJ DQG RIPXWDWLRQVLQWKHJHQHLVRFLWUDWHGHK\GURJHQDVH ,'+ understanding pathogenicity of TPM1 variants in cardiomyopathy. 7KHDELOLW\WRVWXG\,'+PXWDWLRQVLQYLYRKDVEHHQKDPSHUHG however, by a lack of faithful mouse models. The goal of this project 270 8QGHUVWDQGLQJWKHPROHFXODUIXQFWLRQRI5%)2;DQG LVWRFUHDWHDJHQHWLFDOO\HQJLQHHUHGPRXVHPRGHO *(00 RI,'+ determining the role in congenital heart disease PXWDQWJOLRPDE\LQWURGXFLQJWKHPRVWFRPPRQJOLRPDDVVRFLDWHG Harsh N. Shah ,'+PXWDWLRQ HQFRGLQJWKH,'+5+RQFRSURWHLQ LQWRPRXVH Harvard Medical School, USA brain cells in vivo concomitantly with other driver mutations that IUHTXHQWO\FRRFFXULQ,'+PXWDQWJOLRPDV &RQJHQLWDO KHDUW GLVHDVH &+' DFFRXQWV IRU QHDUO\ RQHWKLUG RI DOO PDMRU FRQJHQLWDO DQRPDOLHV DQG DႇHFWV DSSUR[LPDWHO\ 'DWD IURP ORZJUDGH JOLRPD SDWLHQWV FRPSLOHG E\ 7KH &DQFHU ELUWKVSHU\HDULQWKH8QLWHG6WDWHV$OWKRXJKFULWLFDOEUHDNWKURXJKV *HQRPH$WODV 7&*$ VKRZWKDW,'+PXWDWLRQVRIWHQFRRFFXUZLWK in cardiovascular diagnostics and surgery have led to increased activating PIK3R1 or PIK3CA mutations, together with loss of function VXUYLYDOUDWHVLQQHZERUQVZLWK&+'WKHHWLRORJLHVRIPRVW&+'V PXWDWLRQVLQ73DQG$75;:H¿UVWLQYHVWLJDWHGWKHFRRSHUDWLYLW\ remain largely unknown. Progress on this front has been recently EHWZHHQ,'+DQG3,.5PXWDWLRQVLQDKXPDQDVWURF\WLFFHOOOLQH achieved with the advent of whole exome sequencing where both immortalized via ectopic expression of telomerase (hTERT), which LQKHULWHG DQG GH QRYR PXWDWLRQV ZHUH LGHQWL¿HG LQ QHZERUQV WKDW SKHQRFRSLHVLQDFWLYDWLQJPXWDWLRQVLQ$75;DVZHOODV(DQG( VHJUHJDWH ZLWK &+'V $OWKRXJK WKHVH PXWDWLRQV DUH OLNHO\ WR EH which inactivate p53 and Rb, respectively. Lines expressing either causative for disease, this hypothesis has yet to be tested. Moreover, ,'+ RU 3,.5 PXWDQWV H[KLELWHG VLJQL¿FDQWO\ LQFUHDVHG FRORQ\ because the majority of loci discovered have not been previously VL]HDQGQXPEHULQVRIWDJDUDVVD\VFRPSDUHGWRWKHHPSW\YHFWRU linked to cardiovascular development, their mechanisms of action expressing line, and these phenotypes were enhanced further in cells DUH HOXVLYH 2QH ORFXV LGHQWL¿HG E\ WKH ZKROH H[RPH DSSURDFK expressing both mutants together. Furthermore, intracranial injection HQFRGHV 5%)2; DQ HYROXWLRQDULO\ FRQVHUYHG 51$ ELQGLQJ RI WKHVH FHOO LQWR LPPXQRGH¿FLHQW PLFH GHPRQVWUDWHG VLJQL¿FDQWO\ SURWHLQ RI XQNQRZQ IXQFWLRQ 'XULQJ P\ LQWHUQVKLS LQ WKH %XUQV increased tumor incidence and aggressiveness in mice injected with /DEDW0DVVDFKXVHWWV*HQHUDO+RVSLWDO+DUYDUG0HGLFDO6FKRRO, cells expressing both oncogenes relative to either oncogene alone. will uncover the molecular and cellular mechanisms underlying the We used this knowledge to develop our strategy for generating FDUGLRYDVFXODU SKHQRW\SHV , REVHUYH LQ D QHZ JHQHWLF ]HEUD¿VK DQ ,'+PXWDQW *(00 :H FRQVWUXFWHG DQ DGHQRDVVRFLDWHG PRGHORI5E)R[PHGLDWHG&+' YLUXV $$9 HQFRGLQJ &UHUHFRPELQDVH DQG VJ51$V WDUJHWLQJ 7KH ]HEUD¿VK JHQRPH FRQWDLQV WKUHH 5%)2; SDUDORJV LQFOXGLQJ murine isoforms of ATRX, TP53, and RB1. This virus was 5%)2; 5%)2;OLNH DQG 5%)2; 8VLQJ ZKROH PRXQW LQ LQWUDFUDQLDOO\ LQMHFWHG LQWR IRXU GLႇHUHQW HQJLQHHUHG PRXVH VWUDLQV VLWX K\EULGL]DWLRQ ZH RQO\ REVHUYHG 5%)2;OLNH DQG 5%)2; >GHVLJQDWHG /6/&DV /6/&DV /6/3,.&$+5 WUDQVFULSWVLQWKH]HEUD¿VKKHDUW%DVHGRQWKHLUH[SUHVVLRQSDWWHUQV /6/&DV /6/,'+5+ /6/&DV /6/,'+5+ ZH JHQHUDWHG QHZ ]HEUD¿VK VWUDLQV WKDW KDUERU VPDOO GHOHWLRQV LQ /6/3,.&$+5@ ZKHUH WKH LQGLFDWHG JHQHV ZHUH SODFHG 5%)2;OLNH DQG 5%)2; E\ &5,635&DV JHQRPH HGLWLQJ WR GRZQVWUHDP RI D OR[3VWRSOR[3 /6/ FDVVHWWH7KHVH PLFH KDYH learn whether they play a required role in heart development or EHHQPRQLWRUHGIRUWXPRULQLWLDWLRQZLWKVHULDO05,V2QHRIWKH¿UVW function. Compared to single mutants that develop grossly normal mice injected developed a needle track osteosarcoma, and validated hearts during embryogenesis, double mutant embryos show severe WKHLQYLYRHႈFDF\RIRXUVJ51$VDQG&UHDFWLYDWLRQHႈFLHQF\:H cardiac edema indicative of cardiovascular abnormalities. Heart beat WKHQUHHQJLQHHUHGRXU$$9VRWKDW&UHZDVFRQWUROOHGE\DWLVVXH PRQLWRULQJ UHYHDOHG D VLJQL¿FDQWO\ GHFUHDVHG UDWH RI YHQWULFXODU VSHFL¿FJOLDO¿EULOODU\DFLGLFSURWHLQ *)$3 SURPRWHUDQGLQMHFWHGLW Moreover, sarcomere structure appears highly disorganized in LQWRWKHIRXUHQJLQHHUHGPRXVHVWUDLQV$WPRQWKVSRVWLQMHFWLRQ RBFOX double mutant ventricular cardiomyocytes. Together, these RXWRI/6/&DV/6/,'+5+/6/3,.&$+5PLFH data demonstrate that RBFOX is required for normal heart function demonstrated intraparenchymal enhancement on MRI suspicious of during embryogenesis. GHYHORSLQJ*%0V)XUWKHUPRUHRXWRIGRXEOHPXWDQWPLFH /6/ In the coming months, I plan to more deeply characterize the &DV/6/3,.&$+5 VKRZHGHYLGHQFHRIWXPRUIRUPDWLRQRQ 5%)2;FDUGLDFSKHQRW\SH6SHFL¿FDOO\,ZLOODVVHVVKHDUWIXQFWLRQ 05,DWWKLVVDPHWLPHSRLQWVXJJHVWLQJWKDWPXWDQW,'+LVDFWLQJ by analyzing fractional shortening, calcium transients, and action DVDGULYHULQRXUPRGHO:HDQWLFLSDWHWKDWRXU,'+PXWDQWPLFH potential duration and heart structure by counting cardiomyocyte will develop tumors that recapitulate the histopathological, metabolic, numbers and by measuring cardiomyocyte cell size with the goal of DQGHSLJHQHWLFFKDQJHVVHHQLQKXPDQ,'+PXWDQWJOLRPDV uncovering the primary cellular mechanism underlying the observed cardiac failure. Concurrently, I plan to compare the transcriptomes of control to double mutant embryos by deep sequencing analysis to gain insight into potential molecular mechanisms underlying the KHDUWIDLOXUHSKHQRW\SH8OWLPDWHO\P\UHVHDUFKZLOOGHPRQVWUDWHWKDW mutations in RBFOX are causative for cardiovascular phenotypes in ]HEUD¿VKDQGXQFRYHUWKHPHFKDQLVPVE\ZKLFK5%)2;UHJXODWHV heart development and function.

www.jointmeeting.org 115 POSTER ABSTRACTS

272 EphA2 receptor tyrosine kinase regulates programmed XVHGEDULDWULFSURFHGXUH:HSUHYLRXVO\GHPRQVWUDWHG 1DW&RPP death ligand 2 expression in tumor cells and inhibits immune WKDWELOHGLYHUVLRQWRWKHLOHXP *%,/ KDVLGHQWLFDOPHWDEROLF LQ¿OWUDWLRQ HႇHFWVWR5<*%LQURGHQWPRGHOVRIREHVLW\:HVKRZHGWKDWWKDWWKH Eileen Shiuan metabolic improvements, particularly the enhanced insulin sensitivity, Vanderbilt University, Nashville, USA are associated with circulating bile acids (BAs). In this study we K\SRWKHVL]HWKDW%$VLQFUHDVHLQFUHWLQUHVSRQVHV:HIHG&%/ *LYHQWKHVXFFHVVRIERWKWDUJHWHGDQGLPPXQRWKHUDSLHVLQFDQFHU mice a high fat diet for 12 weeks, following which the mice were there is increasing utility for identifying targeted agents that also subjected to either bile diversion from the gall bladder to the ileum SURPRWH DQWLWXPRU LPPXQLW\ (SK$ LV D UHFHSWRU W\URVLQH NLQDVH *%,/ RU5<*%YVVKDP FRQWUROV DGGLWLRQDOO\HDFKPRXVHZDV that contributes to tumor growth and metastasis in various cancer ¿WWHG ZLWK D FKURQLF FDQQXOD LQWR WKH PHVHQWHULF O\PSKDWLFV )RXU W\SHV DQG SOD\V D UROH LQ LQÀDPPDWRU\ SURFHVVHV 3UHYLRXV ZRUN weeks following surgery, and after an overnight fast, lymph samples LQRXUODEGHPRQVWUDWHV(SK$LVDYLDEOHWDUJHWIRUQRQVPDOOFHOO ZHUHFROOHFWHGRQKRXUO\EDVLVEHIRUH K DQGDIWHU K QXWULHQW OXQJ FDQFHU 16&/& DQG EUHDVW FDQFHU +HUH ZH H[DPLQH KRZ PL[HGPHDOEROXV (QVXUH *%,/DQG5<*%PLFHKDGVLJQL¿FDQW (SK$ DႇHFWV LPPXQH FKHFNSRLQW SURWHLQ LQWHUDFWLRQV LQFOXGLQJ ZHLJKWORVVDQGUHGXFHGIRRGLQWDNHGXULQJWKH¿UVWZHHNSRVWRS$W SURJUDPPHG GHDWKOLJDQGV 3'/V DQG LPPXQH UHVSRQVH LQ WKH ZHHNVSRVWVXUJHU\ERG\IDWFRPSRVLWLRQZDVVLJQL¿FDQWO\ORZHU tumor microenvironment. LQ5<*%DQG*%,/DQGKDGVLJQL¿FDQWO\ORZHUEORRGJOXFRVHOHYHOV Our preliminary studies suggest EphA2 regulates the expression Lymph content of triglycerides and phospholipids were remarkably RI 3'/ EXW QRW 3'/ LQ KXPDQ OXQJ DQG EUHDVW FHOO OLQHV 7R KLJKHU LQ 5<*% DQG *%,/ PLFH 3ODVPD %$ OHYHOV LQ 5<*% DQG LQYHVWLJDWHWKLVZHLQGXFHG3'/H[SUHVVLRQLQYLWUR via cytokines, *%,/ ZHUH IROG DQG IROG KLJKHU IROORZLQJ FRQWUROV O\PSKDWLF RYHUH[SUHVVHGRUNQRFNHGGRZQ(SK$DQGPHDVXUHG3'OLJDQG %$VPLUURUHGWKHFKDQJHVLQSODVPD%$V3ODVPD*/3OHYHOVZHUH H[SUHVVLRQ E\ ÀRZ F\WRPHWU\ 7R HYDOXDWH WKH PHFKDQLVP E\ XQGHWHFWDEOHLQERWKJURXSVEXWO\PSKDWLFLQFUHWLQOHYHOV */3DQG ZKLFK(SK$DႇHFWHG3'/H[SUHVVLRQZHFXUDWHGWKH(1&2'( *,3 ZHUHVLJQL¿FDQWO\KLJKHULQ*%,/DQG5<*%PLFH+RZHYHU GDWDEDVHWRLGHQWLI\WUDQVFULSWLRQIDFWRU 7) ELQGLQJVLWHVQHDUWKH3' RQO\*%,/PLFHKDGVLJQL¿FDQWO\KLJKHUO\PSKDWLFOHYHOVRI&SHSWLGH L2 promoter and validated individual TF candidates with knockdown FRPSDUHGWRRWKHUVWXG\JURXSV7KHVHUHVXOWVVXJJHVWDGLႇHUHQWLDO experiments. To study LQ YLYR HႇHFWV ZH JHQHUDWHG DQ (SK$ HႇHFWRI%$VRQSDQFUHDWLFLQVXOLQDQG&SHSWLGHVHFUHWLRQZKLFK RYHUH[SUHVVLQJPXULQH16&/&FHOOOLQHIURPDSULPDU\PRXVHOXQJ PD\ EH UHVSRQVLEOH IRU D VLJQL¿FDQW FRPSRQHQW RI WKH LPSURYHG tumor. Both subcutaneous and tail vein injected lung tumor models insulin sensitivity following bariatric surgery. were used to assess the impact of EphA2 overexpression on tumor EXUGHQDQGVXUYLYDODVZHOODVLPPXQHLQ¿OWUDWLRQE\ÀRZF\WRPHWU\ 274 'LIIHUHQWLDO 5QD (GLWLQJ$FURVV Trypanosoma Brucei /LIH&\FOH 6WDJHV 5HYHDOV 8QGHUO\LQJ 0HFKDQLVPV 2I (GLWLQJ ,QKXPDQEURQFKLDODQGPDPPDU\HSLWKHOLDOFHOOV3'/ZDVLQGXFHG Coordination E\,)1ȖDQGWRDOHVVHUH[WHQW71)ĮDQG,/DQGNQRFNGRZQRI 5DFKHO06LPSVRQ (SK$ GHFUHDVHG VXUIDFH H[SUHVVLRQ RI 3'/ 7) ELQGLQJ VLWHV Department of Microbiology and Immunology, University at IRU0\FDQGSDPRQJRWKHUVZHUHIRXQGLQWKH3'/SURPRWHU %X௺DOR-DFREV6FKRRORI0HGLFLQHDQG%LRPHGLFDO6FLHQFHV region. Because our lab has previously shown that Myc and YAP %X௺DOR86$ DUH GRZQVWUHDP HႇHFWRUV RI (SK$ ZH SXUVXHG WKHVH 7)V IRU validation studies, which are ongoing. In contrast to human epithelial The order NLQHWRSODVWHD contains multiple human pathogens, FHOOV PXULQH FRXQWHUSDUWV GR QRW H[SUHVV 3'/ HYHQ DIWHU ,)1Ȗ including 7U\SDQRVRPDEUXFHLthe causative agent of Human African VWLPXODWLRQ :KLOH WKH (SK$RYHUH[SUHVVLQJ PXULQH 16&/& FHOO Trypanosomiasis, 7U\SDQRVRPD FUX]L of Chaga’s disease, and line did not display proliferative advantage over control cells LQYLWUR, /HLVKPDQLD speciesresponsible for various forms of leishmaniasis. they developed larger tumors and had worse survival in both tumor 8ULGLQHLQVHUWLRQGHOHWLRQ51$HGLWLQJLVDQHVVHQWLDODQGFRPSOH[ PRGHOV$QDO\VLVRIOXQJWXPRULPPXQHLQ¿OWUDWHUHYHDOHGGHFUHDVHG SURFHVV LQ NLQHWRSODVWLGV ZKHUHE\ PLWRFKRQGULDO P51$V DUH 1.DQG7FHOOVLQWKH(SK$RYHUH[SUHVVLQJWXPRUV PRGL¿HGE\VSHFL¿FLQVHUWLRQDQGGHOHWLRQRIXULGLQHVWKURXJKRXWWKH length of the transcript. Editing generates functional open reading 2XUVWXGLHVVXJJHVW(SK$XSUHJXODWHV3'/LQFDQFHUFHOOVDQG frames that encode mitochondrial respiratory proteins. The unique LQKLELWV WXPRU LQ¿OWUDWLRQ RI NH\ O\PSKRF\WLF SRSXODWLRQV 2QJRLQJ and essential nature of this process to the parasite makes the investigations are determining the mechanisms behind these PLWRFKRQGULDO51$HGLWLQJV\VWHPDQH[FHOOHQWSRWHQWLDOGUXJWDUJHW ¿QGLQJV'HVSLWH3'/¶VNQRZQUROHLQLPPXQHWROHUDQFHLWVLPSDFW 1XPHURXV HQ]\PDWLF DQG QRQHQ]\PDWLF IDFWRUV DUH UHTXLUHG IRU RQ WKH WXPRU PLFURHQYLURQPHQW LV XQGHUVWXGLHG FRPSDUHG WR 3' 51$ HGLWLQJ $GGLWLRQDOO\ HGLWLQJ LV GLUHFWHG E\ VPDOO QRQFRGLQJ /7KXVHOXFLGDWLRQRI(SK$¶VUROHLQUHJXODWLQJ3'DQG3'/ JXLGH51$V J51$V ZKLFKDFWDVWHPSODWHVIRUWKHHGLWLQJSURFHVV interactions and immune recruitment will further our understanding of 0XOWLSOHJ51$VDUHUHTXLUHGIRUFRPSOHWHHGLWLQJRIWKHPDMRULW\RI 3'DQG3'/ELRORJ\DQGPHFKDQLVPVRILPPXQHHYDVLRQDVZHOO WUDQVFULSWV DQG LQWHUDFWLRQV EHWZHHQ WKH J51$V DQG WKH SUH DQG as provide additional rationale for targeting EphA2 in cancer. 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The underlying mechanisms Vanderbilt University Medical Center, USA IRU GLႇHUHQFHV REVHUYHG EHWZHHQ OLIHF\FOH VWDJHV KDYH UHPDLQHG opaque given the limitations of conventional methods to examine the %DULDWULF VXUJHU\ LV WKH PRVW HႇHFWLYH DQG GXUDEOH WUHDWPHQW LQWHUPHGLDWH SDUWLDOO\HGLWHG VHTXHQFH SRSXODWLRQV 7R RYHUFRPH for obesity as well as Type 2 diabetes, though the mechanisms this limitation, we developed a novel bioinformatic platform, the XQGHUO\LQJLWVHႇHFWLYHQHVVUHPDLQWREHIXOO\HOXFLGDWHG5RX[HQ 7U\SDQRVRPH51$(GLWLQJ$OLJQPHQW7RRO 75($7 ZKLFKDOORZVXV < *DVWULF %\SDVV 5<*% LV WKH PRVW HႇHFWLYH DQG PRVW ZLGHO\ to examine whole populations of partially edited sequences using

116 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

KLJKWKURXJKSXWVHTXHQFLQJ +76 8VLQJ+7675($7ZHH[DPLQH 276 Degradable and non-degradable polymeric WUDQVFULSWV NQRZQ WR EH GLႇHUHQWLDOO\ PRGL¿HG EHWZHHQ OLIHF\FOH chloroquine: altering the pharmacokinetics of chloroquine stages in both the procyclic and bloodstream forms of 7EUXFHLWe for translational improvements in the treatment of cancer LQWHUURJDWHGLႇHUHQFHVLQWKHRUGHURIHGLWLQJPRGL¿FDWLRQVDQGWKH and Inflammatory bowel disease mechanisms by which editing progresses between the two lifecycle 5LFKDUG6OHLJKWKROP stages to uncover common and distinct mechanisms responsible for University of Nebraska Medical Center, Omaha, USA UHJXODWLQJ51$HGLWLQJLQ7EUXFHL %DFNJURXQG+\GUR[\FKORURTXLQH +&4 KDVEHHQXVHGIRUQHDUO\ 275 GATA2 in normal endometrium and GATA6 in \HDUVIRUWKHWUHDWPHQWDQGSUHYHQWLRQRIPDODULDDVZHOODVLQWKH endometriosis are associated with genome-wide H3K27ac management of autoimmune diseases like rheumatoid arthritis and KLVWRQH PRGL¿FDWLRQ DQG DFWLYH WUDQVFULSWLRQ RI JHQHV LQÀDPPDWRU\ERZHOGLVHDVH ,%' +RZHYHUFKURQLFDGPLQLVWUDWLRQ essential for tissue phenotypes FDQ OHDG WR WR[LFLWLHV OLNH UHWLQRSDWK\ 5HFHQWO\ +&4 KDV EHHQ &KULVWLD$QJHOD06LVRQ investigated as a sensitizing agent in cancer with radiation and/or Northwestern University Feinberg School of Medicine, chemotherapy. 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www.jointmeeting.org 117 POSTER ABSTRACTS

277 $QLPDO0RGHORI+XPDQ$QN\ULQ%6\QGURPH([KLELWV DQG /HQLQJUDG VWUDLQ /$,9V ZH FDQ JHQHUDWH /$,9V ZLWK D UDQJH $GUHQHUJLF0HGLDWHG$UUK\WKPLDV of replication phenotypes that could potentially expand the range of Ellen Lubbers DJHVLQZKLFK/$,9VFDQEHVDIHO\XVHG The Ohio State University, Columbus, USA 279 Weakly and semi-supervised deep learning for $QN\ULQ% $QN% LV D VSHFWULQDVVRFLDWHG F\WRVNHOHWDO SURWHLQ WKDW immunohistochemistry feature representation in tissue SOD\V D FULWLFDO UROH LQ DQFKRULQJ WKH 1D&D H[FKDQJHU 1&; microarrays with generative adversarial networks WKH 1D.$73DVH DQG WKH LQRVLWRO WULVSKRVSKDWH UHFHSWRU DW WKH $QGUHZ06RKQ transverse tubules and sarcoplasmic reticulum in cardiomyocytes. Perelman School of Medicine, University of Pennsylvania, USA $GGLWLRQDOO\ ORVVRIIXQFWLRQ PXWDWLRQV LQ $QN% FDXVH YDULRXV Histopathology is still considered to be the gold standard in the DUUK\WKPLDSKHQRW\SHVLQFOXGLQJORQJ47 /476 VLQXVEUDG\FDUGLD diagnoses of many cancers. Recently, there have been two major YHQWULFXODU ¿EULOODWLRQ FDWHFKRODPLQHUJLF SRO\PRUSKLF YHQWULFXODU developments that are poised to change the face of pathology at the WDFK\FDUGLDDQGDWULDO¿EULOODWLRQ3DVWZRUNKDVLGHQWL¿HGDQ$QN% center of clinical diagnosis: (1) digital pathology, and (2) molecular variant L1622I, which has been associated with human arrhythmia. SUR¿OLQJWHFKQRORJLHV7KHHPHUJHQFHRIGLJLWDOSDWKRORJ\DOORZVIRU 3DWLHQWV KDUERULQJ WKLV YDULDQW SUHVHQW ZLWK D ORQJ 47 LQWHUYDO the introduction of automated image analysis to pathology, which can YHQWULFXODU WDFK\FDUGLD DQG YHQWULFXODU ¿EULOODWLRQ ,Q WKLV VWXG\ ZH JUHDWO\DLGDSDWKRORJLVW¶VZRUNÀRZDQGRႇHUQHZTXDQWLWDWLYHWRROV LQYHVWLJDWHG WKH FHOOXODU SKHQRW\SHV RI D NQRFNLQ PRXVH PRGHO that are otherwise laboriously prohibitive. Molecular technologies carrying the L1662I AnkB variant. To determine the role of the L1622I RႇHU FRPSOHPHQWDU\ LQIRUPDWLRQ SUREHG DW D UHVROXWLRQ WKDW LV QRW variant in AnkB, cardiomyocytes were isolated from adult L1622I accessible by tissue morphology and phenotype analyses. While we mice. Previous studied have shown prolongation of the late phase DUHSUHVHQWO\LQWKHHUDRIµRPLFV¶KLVWRORJLFDOLPDJHVVWLOOSURYLGH RIWKHDFWLRQSRWHQWLDODQGIUHTXHQWHDUO\DIWHUGHSRODUL]DWLRQV ($'V LPSRUWDQWIHDWXUHVWKDWDUHXQDYDLODEOHIURPPROHFXODUSUR¿OLQJRPLFV and spontaneous activity when treated with 1uM isoproterenol data, such as the spatial context of the tumor microenvironment. ,62 :HK\SRWKHVL]HGWKDWWKHVHDUUK\WKPRJHQLFVXEVWUDWHVZHUH due an exacerbation of calcium overload caused by loss of proper 7KHIRRWYLHZRIRXUZRUNLVDQDWWHPSWWRH[WUDFWSKHQRW\SLF ORFDOL]DWLRQ RI 1&; +RZHYHU LPPXQRÀXRUHVFHQFH VWDLQLQJ RI features from tissue microarrays (TMAs) and correlate with genetic isolated cardiomyocytes showed reduced, but correctly localized features. To extract phenotypic features, we use techniques from 1&;LQ/,PLFH:KLOHVPDOOWKLVUHGXFWLRQPD\EHVXႈFLHQW VHPLVXSHUYLVHG GHHS OHDUQLQJ DQG PRUH VSHFL¿FDOO\ JHQHUDWLYH WR SURGXFH DUUK\WKPLD DV WHOHPHWHUHG (&* UHFRUGLQJV UHYHDOHG DGYHUVDULDO QHWZRUNV *$1V 9HU\ EULHÀ\ *$1V DUH D FODVV RI arrhythmia in mice dosed with epinephrine (2mg/kg). In conclusion, generative models (as opposed to discriminative models) that can UHGXFHG1&;GLVSOD\HGLQ/,PLFHSURYLGHDSRWHQWLDOEDVLVIRU perform representation learning on unlabeled data by imitating a real the stress induced arrhythmias of patients harboring this AnkB variant. data distribution via transforming noise variables into synthetic data ZLWKLQWDUJHWGRPDLQ8VLQJ*$1VZHSHUIRUPGDWDDXJPHQWDWLRQ 278 &RPELQLQJ.H\5HVLGXHVRIWKH5XVVLDQDQG86/LYH DQG LPDJHWRLPDJH WUDQVODWLRQLPDJH VW\OH WUDQVIHU DPRQJ ,+& $WWHQXDWHG,QÀXHQ]D9LUXV¶IRUD0RUH$WWHQXDWHG9DFFLQH stains) as proxies for representation learning as well as disentangled Andrew Smith representation learning. Once a robust deep learning model has University of Rochester, Rochester, USA been trained, we will search for a common feature space for the 6HDVRQDO LQÀXHQ]D LQIHFWV PLOOLRQ SHRSOH HYHU\ \HDU LQ WKH phenotypic and genetic features, followed by clustering analyses to 8QLWHG 6WDWHV OHDGLQJ WR WKH KRVSLWDOL]DWLRQ RI EHWZHHQ observe whether any phenotypic and genetic features correlate with DQGDQGWKHGHDWKRIEHWZHHQDQGSHRSOH one another. D\HDU:KLOHIRUPHUO\HႈFDFLRXVDVDYDFFLQHWKH/LYH$WWHQXDWHG We perform our analyses on a dataset of BRCA1 and BRCA2 ,QÀXHQ]D9LUXV /$,9 EDVHGRQWKHFROGSDVVDJHG$$QQ$UERU JHUPOLQH PXWDWLRQDVVRFLDWHG EUHDVW DQG RYDULDQ WXPRUV 7KH VWUDLQ WKDW ZDV OLFHQVHG IRU XVH LQ WKH 8QLWHG 6WDWHV LV QR ORQJHU GDWDVHWFRQVLVWVRI70$VZLWKWZHQW\GLႇHUHQWLPPXQRKLVWRFKHPLVWU\ UHFRPPHQGHGIRUXVHGXHWRDVXGGHQGHFOLQHLQVXEW\SHVSHFL¿F VWDLQV VWURPDO DQG LPPXQH DQG JHQHWLF SUR¿OHV JHQHUDWHG IURP HႈFDF\ZKLFKLVFXUUHQWO\QRWZHOOXQGHUVWRRG+RZHYHUWKH/$,9 exome sequencing. This dataset has been generated and compiled EDVHGRQWKHFROGSDVVDJHG$/HQLQJUDGLVVWLOOLQXVHDV IURPSDWLHQWVVHHQDWWKH+RVSLWDORIWKH8QLYHUVLW\RI3HQQV\OYDQLD a seasonal vaccine in multiple countries around the world. When SUHYLRXVO\LQXVHWKH86/$,9ZDVIRXQGGXULQJPXOWLSOHVHTXHQWLDO 280 CaCO3 nanoparticles modulate the tumor LQÀXHQ]DVHDVRQVWRKDYHVXSHULRUHႈFDF\LQFKLOGUHQDVFRPSDUHG microenvironment pH and subsequently inhibit growth and WRWKHLQDFWLYDWHGLQÀXHQ]DYDFFLQH'XULQJLWVXVHLQWKH86/$,9 metastasis was not recommended for children under two years of age due to Avik Som ZKHH]LQJ7KLVZKHH]LQJLVGXHWR/$,9UHSOLFDWLQJDWKLJKHQRXJK Washington University in St. Louis, Houston, USA levels in young children to be mildly pathogenic. Investigations into 0RGHOV RQ WXPRU H[WUDFHOOXODU S+ S+H GHPRQVWUDWH D VLJQL¿FDQW DOWHUDWLRQV RI DWWHQXDWLRQ DQG VDIHW\ RI /$,9 LQ D PRXVH PRGHO relationship between tumor invasiveness, chemotherapy resistance were previously impossible due to the limited replication of both and the increased production of acid in the extracellular environment /$,9VLQPLFH7RVROYHWKLVSUREOHPRXUODEGHYHORSHGDPRXVH PRVWWXPRUV9HU\IHZJURXSVKDYHDWWHPSWHGWRPRGXODWHWKLVS+ model virus that permits investigations of alterations in attenuation microenvironment for therapeutic purposes via nanoparticles. The DQGVDIHW\RI/$,9VLQPLFHLQDGGLWLRQWRHႈFDF\E\PDNLQJWKH therapeutic potential of modulating the pH has been realized recently DPLQRDFLG VXEVWLWXWLRQV UHVSRQVLEOH IRU WKH WHPSHUDWXUH VHQVLWLYH through the demonstration of metastasis inhibition from the systemic WV DQGDWWHQXDWHG DWW SKHQRW\SHVRI/$,9LQWKHPRXVHDGDSWHG administration of oral sodium bicarbonate, but is not practical. A YLUXV$3XHUWR5LFR,QWKLVVWXG\ZHXVHWKLVPRGHOYLUXV nanoparticle delivery of this base may allow similar therapeutic WRVKRZWKDWXVLQJYDULRXVFRPELQDWLRQVRIWKHSUHYLRXVO\LGHQWL¿HG UHVXOWVZLWKVLJQL¿FDQWO\ORZHUGRVHVDQGWKHUHE\VLJQL¿FDQWO\ORZHU residues responsible for the ts and att phenotypes of both Ann Arbor degrees of toxicity. We have been able to demonstrate the synthesis

118 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

DQGVWDELOL]DWLRQRIQDQR&D&23 particles in water via the use of an DQGJO\FHUROWUDQVSRUWHUDTXDSRULQ $43 )URPSRVWIHGS\WKRQ albumin based solution. In addition, we demonstrate the particle’s SODVPDWKH\LGHQWL¿HGDFRPELQDWLRQRIWKUHHIDWW\DFLGV )$V WKDW ability for modulating pH in vivo and the subsequent inhibition of replicated cardiac hypertrophy when administered subcutaneously growth and metastasis. to pythons and mice and when applied to cultured neonatal rat YHQWULFXODU P\RF\WHV 1590V 7KH )$V ZHUH P0 P\ULVWLF 281 A systematic approach to identify proteins that interact & P0SDOPLWLF & DQGP0SDOPLWROHLF & with the aryl hydrocarbon receptor in vivo In this study, we evaluated the capacity for the FAs to prevent or Jaclyn Souder reduce negative cardiac changes due to pathologic stimuli. This University of Alabama at Birmingham, Houston, USA K\SRWKHVLVZDV¿UVWWHVWHGXVLQJ)$VGLVVROYHGLQGLPHWK\OVXOIR[LGH 7KH DU\O K\GURFDUERQ UHFHSWRU $+5 LV D OLJDQGGHSHQGHQW '062 DQG 1590V $GPLQLVWHULQJ )$V WR 1590V SULRU WR WKH transcription factor that is involved in multiple developmental pathologic hypertrophic stimulus, phenylephrine (PE), blunted the processes including hematopoiesis and cardiac development. One K\SHUWURSKLFHႇHFWRI3(FRPSDUHGWR'062FRQWUROVDIWHUKRXUV K\SRWKHVLV LV WKDW$+5 UHFUXLWV FRIDFWRUV LQ D OLJDQG DQG WLVVXH RIWRWDOWUHDWPHQW:HDOVRDSSOLHG)$VWR1590VIROORZLQJ3(IRU VSHFL¿F PDQQHU WR HOLFLW ELRORJLFDO HႇHFWV \HW WKLV KDV QRW EHHQ KRXUV DQG VWLOO VDZ D VLJQL¿FDQW LQFUHDVH LQ$43 H[SUHVVLRQ FRQ¿UPHG LQ YLYR. This hypothesis could be tested by analyzing UHODWLYHWR'062FRQWUROV7KLVLQGXFWLRQRI$43DQGWKHUHGXFWLRQ $+5FRIDFWRUUHFUXLWPHQWLQVSHFL¿FWLVVXHVIROORZLQJWUHDWPHQWZLWK of pathologic hypertrophy in the presence of a pathologic stimulus $+5OLJDQGV=HEUD¿VKHPEU\RVSURYLGHDQDWWUDFWLYHPRGHOWRWHVW VXJJHVWV WKDW WKH )$V FDQ H[HUW D GRPLQDQW HႇHFW 7KHVH LQYLWUR this hypothesis due to the ease of chemical exposure and genetic ¿QGLQJVOHGXVWRLQYHVWLJDWHLQYLYR'XHWRYDULDELOLW\VHHQ XVLQJ PDQLSXODWLRQDQGFRQVHUYDWLRQRI$+5VLJQDOLQJ:HXVHG&5,635 '062)$VPLQLSXPSVZHLQYHVWLJDWHGRUDOJDYDJHDVDQDOWHUQDWH &DVWRJHQHUDWHNQRFNLQ]HEUD¿VKOLQHVZLWKHSLWRSHWDJJHG$+5 URXWHRIDGPLQLVWUDWLRQ6HYHUDOUHFHQWSDSHUVKDYHVKRZQHႈFDF\ WKH ]HEUD¿VK SDUDORJXH RI$+5 WR UHOLDEO\ DQG HႈFLHQWO\ LVRODWH of FAs via oral gavage for other purposes. The FAs were suspended AHR2 and its bound proteins LQ YLYR. In addition, we generated a in corn oil and administered to two cohorts of mice for four weeks. ORVVRIIXQFWLRQ $+5 PXWDQW OLQH $+5 WKDW GHPRQVWUDWHV The groups were either six or ten weeks of age at the beginning UDJJHG¿Q DQG SURWUXGLQJ MDZ SKHQRW\SHV LQ DGXOWKRRG DOORZLQJ of the experiment. We did not see cardiac hypertrophy in either XVWRGHWHUPLQHLIRXUNQRFNLQOLQHVUHWDLQQRUPDO$+5IXQFWLRQ JURXSEXWWKHVL[ZHHNJURXSGLGVKRZVLJQL¿FDQWXSUHJXODWLRQRI ,Q SDUDOOHO ZH FUHDWHG D VLQJOH HSLWRSH $+59 OLQH ZLWK D D0\+&ZKLFKLVDQLQGLFDWLRQRIDSK\VLRORJLFHႇHFW$OWKRXJKRUDO SHSWLGH 9 WDJ LQVHUWHG LQ WKH ahr2 gene, 2) a double epitope gavage does not cause a robust enough response to be utilized for $+56$9 OLQH ZLWK D PRGL¿HG VWUHSWDYLGLQ 6WUHS ,, 6$ 9 IXWXUHH[SHULPHQWVWKLV¿QGLQJLQGLFDWHVWKHUHZDVVRPHHႇHFW:H LQVHUWLRQDQG DWULSOHHSLWRSH$+5)69OLQHZLWKD)/$*6$ UHFHQWO\ FRQMXJDWHG WKH )$V WR ERYLQH VHUXP DOEXPLQ %6$ 2XU 9 LQVHUWLRQ %HJLQQLQJ ZLWK WKH$+59 OLQH ZH ¿UVW GHULYHG QH[WVWHSLVWRWHVW%6$)$VRQ1590VWRHQVXUHWKH\LQGXFHWKH KRPR]\JRXV$+59 HPEU\RV WKHQ FRQ¿UPHG HSLWRSH XWLOLW\ E\ K\SHUWURSK\ ZH KDYH VHHQ ZLWK '062)$V ,I VXFFHVVIXO ZH ZLOO LPPXQRSUHFLSLWDWLRQRIWKH$+59SURWHLQLQSRROHGHPEU\RVYLD SHUIRUP PLQLSXPS H[SHULPHQWV LQ PLFH 2XU XOWLPDWH JRDO LV WR ERWKZHVWHUQEORWDQGPDVVVSHFWURPHWU\:HQH[WFRQ¿UPHGWKDW DGPLQLVWHU)$VLQYLYRSULRUWRRUIROORZLQJDSDWKRORJLFVWLPXOXVVXFK HSLWRSHLQVHUWLRQGLGQRWDႇHFWQRUPDOSURWHLQIXQFWLRQLQHPEU\RV DV3(RUWUDQVDRUWLFFRQVWULFWLRQ DQG DGXOWV E\ WUHDWLQJ KRPR]\JRXV HPEU\RV ZLWK 7&'' ZKLFK FDXVHV$+5GHSHQGHQWFDUGLRWR[LFLW\LQHPEU\RV, and comparing 283 The role of neural stem cell-derived extracellular $+59DGXOWVZLWK$+5PXWDQWDGXOWV$+5HPEU\RVGRQRW vesicles as a therapeutic in a porcine middle cerebral artery UHVSRQGWR7&''WUHDWPHQWZKLOH$+59HPEU\RVGHPRQVWUDWH occlusion model of stroke. FDUGLRWR[LFLW\ HTXLYDOHQW WR ZLOGW\SH HPEU\RV FRQ¿UPLQJ QRUPDO Samantha E. Spellicy SURWHLQIXQFWLRQLQ$+59HPEU\RV)XUWKHU$+59KRPR]\JRWH Medical College of Georgia and the University of Georgia, DGXOWV DUH SKHQRW\SLFDOO\ QRUPDO LQ FRQWUDVW WR $+5 DGXOWV Athens, USA FRQ¿UPLQJQRUPDOSURWHLQIXQFWLRQLQ$+59DGXOWV)XWXUHVWXGLHV 6WURNHDQQXDOO\FODLPVRYHUPLOOLRQOLYHVZRUOGZLGHDQGLVWKHUG ZLOOXWLOL]H$+59HPEU\RVLQDPDVVVSHFWURPHWU\EDVHGDVVD\ OHDGLQJ FDXVH RI GHDWK IRU DGXOWV LQ WKH 8QLWHG 6WDWHV &XUUHQWO\ WR LGHQWLI\ WLVVXH RU OLJDQGVSHFL¿F FRIDFWRU UHFUXLWPHQW E\$+5 WKHUHLVRQO\RQH)'$DSSURYHGVPDOOPROHFXOHWKHUDS\IRULVFKHPLF and potentially discover novel interacting proteins of AHR2. We will stroke, tissue plasminogen activator (tPA). Extracellular vesicles DOVRFRQ¿UPWKHIXQFWLRQDOXWLOLW\RIRXURWKHUNQRFNLQOLQHVXVLQJWKLV (9V RUFHOOGHULYHGQDQRSDUWLFOHVKDYHEHHQVKRZQWREHLQYROYHG systematic approach. in a range of normal physiological processes as well as tissue repair, 282 Evaluation and prevention of heart disease using three stem cell maintenance, and immune surveillance. We propose to fatty acids from postprandial pythons XVHQHXUDOVWHPFHOOGHULYHGH[WUDFHOOXODUYHVLFOHV 16&(9V DVD potential novel neuroprotective therapeutic to limit gait and behavioral .HOVH\06SDXU impairments following middle cerebral artery occlusion (MCAO) in a University of Colorado School of Medicine, USA porcine stroke model. Extreme environments drive species to develop novel adaptations, (9VZHUH¿UVWLVRODWHGE\XOWUD¿OWUDWLRQIURPWKHVSHQWPHGLDRIQHXUDO ZKLFKKDYHEHHQDVRXUFHRIVFLHQWL¿FLQQRYDWLRQIRU\HDUV)RUWKH stem cells. We then performed various LQYLWUR assays, such as mass Burmese python, its environmental pressure is infrequent feeding. VSHFWURVFRS\DQG6SDWLDO/LJKW,QWHUIHUHQFH0LFURVFRS\ 6/,0 IRU Following a meal weighing up to its body weight, multiple organs WKH FKDUDFWHUL]DWLRQ DQG YLVXDOL]DWLRQ RI WKHVH 16&(9V )RU WKLV XQGHUJR VLJQL¿FDQW JURZWK WR DFFRPPRGDWH D IROG LQFUHDVH LQ study, we used 16 castrated male landrace pigs which were divided metabolic rate. Regarding the heart, the Leinwand lab showed that LQWR HLWKHU 16&(9 RU VKDP WUHDWPHQW JURXSV )ROORZLQJ 0&$2 this hypertrophy is physiologic rather than pathologic by several SLJV ZHUH ,9DGPLQLVWHUHG 16&(9V RU 3%6 VROXWLRQ UHVSHFWLYHO\ criteria including a signature of gene expression changes that were DWDQGKRXUV/RQJLWXGLQDOJDLWDQGEHKDYLRUDOWHVWVZHUH distinct from those of pathological hypertrophic growth. Most notable FRQGXFWHGRYHUGD\VSRVW0&$2WRHYDOXDWHIXQFWLRQDOUHFRYHU\ RIWKHJHQHVDFWLYDWHGE\VHUXPIURPSRVWIHGS\WKRQVZDVWKHZDWHU

www.jointmeeting.org 119 POSTER ABSTRACTS

0DJQHWLFUHVRQDQFHLPDJLQJ 05, ZDVFRQGXFWHGDWDQGGD\V sham surgery as a negative control. SRVW0&$2 8FHOODQG+53(VKRZHGVLPLODUH[SUHVVLRQRI53(VSHFL¿FJHQHV &KDUDFWHUL]DWLRQ RI 16&(9V WKURXJK PDVV VSHFWURVFRS\ UHYHDOHG including visual cycle genes (RPE65, CRLBP), RPE membrane WKH\FRQWDLQHGRIWKHPRVWFRPPRQO\UHSRUWHG(9PDUNHUV FKDQQHODQGWUDQVSRUWHUJHQHV %(67 DQGSLJPHQWDQGPHODQLQ 6/,0 LPDJLQJ VWXGLHV UHYHDOHG HႈFLHQW DQG UREXVW XSWDNH DQG ELRV\QWKHVLV JHQHV 7<53 W\URVLQDVH DQG 0,7) 7KH 3PHO LQWHUQDOL]DWLRQRI16&(9VE\PHVHQFK\PDOVWHPFHOOV 06&V 05, JHQH ZDV H[SUHVVHG LQ RI 8 FRQGXFWHGRQ'D\SRVW0&$2GHPRQVWUDWHGWKDW16&(9WUHDWPHQW RI 8 DQG RI +53( 7KHUH ZDV QR VLJQL¿FDQW eliminated intracranial hemorrhage (ICH) following ischemic lesion GLႇHUHQFHEHWZHHQ8DQG853( 0DQQ:KLWQH\WHVWWZRWDLOHG 16&(9 WUHDWHG YV VKDP JURXS ,Q DGGLWLRQ 16&(9 S RU8DQG+53( 0DQQ:KLWQH\WHVWWZRWDLOHGS WUHDWPHQW UHVXOWHG LQ GHFUHDVHG PLGOLQH VKLIW DV ZHOO D VLJQL¿FDQW 3PHOH[SUHVVLRQ8FHOO53(PRUSKRORJ\DQGSKDJRF\WRVLVDELOLW\ (p<0.01) decrease in cerebral infarct volume and edema when ZHUHDOVRVLPLODUWRWKRVHRI+53( FRPSDUHGWRVKDPSLJV7KURXJKIXQFWLRQDOWHVWLQJDWZHHNSRVW 2XU UHVXOWV LQ YLWUR VKRZ WKDW 8FHOO53( LV VLPLODU LQ IRUP DQG 0&$216&(9WUHDWHGSLJVVKRZHGOLPLWHGFKDQJHVLQPHDVXUHG IXQFWLRQWR+53( LQYLYRUHVXOWVSHQGLQJ 53(IURP8FHOOVLVD RSHQ¿HOGDQGJDLWSDUDPHWHUVZKLOHFRQWUROSLJVKDGDVWDWLVWLFDOO\ QRYHODSSURDFKWRE\SDVVLPPXQHPHGLDWHGJUDIWUHMHFWLRQZLWKRXW VLJQL¿FDQW S GHFUHDVHLQYHORFLW\DQGGLVWDQFHWUDYHOHGGXULQJ XVLQJLPPXQRVXSSUHVVLRQ8VLQJ8FHOOVDVSURJHQLWRUVPD\EHDOVR RSHQ¿HOGWHVWLQJDVZHOODVLQFDGHQFHVWULGHOHQJWKDQGUHODWLYH be applicable to transplantation of other cell types. SUHVVXUH PHDVXUHG GXULQJ JDLW WHVWLQJ $W ZHHNV SRVW0&$2 16&(9WUHDWHG SLJV KDG VLJQL¿FDQW S! LQFUHDVHV LQ YHORFLW\ 285 Exploring substrate promiscuity toward a novel DQGGLVWDQFHWUDYHOHGIURPWKHLUSUH0&$2RSHQ¿HOGWHVWLQJZKLOH method of sortase-mediated bioorthogonal protein labeling sham pigs did not. (ULFD06WRUP ,Q WKLV VWXG\ ZH GHPRQVWUDWHG IRU WKH ¿UVW WLPH WKDW LQWUDYHQRXV Stanford University School of Medicine, USA WUHDWPHQWRI16&(9VLQDSRUFLQHODUJHDQLPDOLVFKHPLFVWURNHPRGHO 6RUWDVHV DUH EDFWHULDO WUDQVSHSWLGDVHV ZLWK ZLGH DSSOLFDWLRQV IRU can robustly prevent critical structural changes in the brain, limiting SRVWWUDQVODWLRQDO FRYDOHQW PRGL¿FDWLRQ RI SURWHLQV 6RUWDVH $ LV IXQFWLRQDOJDLWDQGEHKDYLRUDOGH¿FLWVDQGSURPRWLQJUHFRYHU\ KLJKO\ VSHFL¿F IRU LWV /3;7* SHSWLGH UHFRJQLWLRQ PRWLI ZKLFK LW incorporates to any substrate with a terminal oligoglycine moiety. 284 HLA-E-expressing “universal” pluripotent stem cells Recent engineering of sortase A has improved its catalytic activity, as a source of retinal pigment epithelium to treat age-related but its utility for in vivo labeling remains limited by the lack of cell 䯠 macular degeneration permeable and commercial available oligoglycine peptide probes. 0DUWD6WHYDQRYLF Thus, there remains a need for a versatile biorthogonal method of University of Southern California, USA VLWHVSHFL¿FSURWHLQODEHOLQJLQOLYLQJFHOOV Identifying a suitable stem cell source for retinal pigmented epithelium :HSUHVHQWDWZRVWHSVRUWDVHEDVHGDSSURDFKWRLQYLYRSURWHLQ 53( KDV EHHQ D FKDOOHQJH LQ WUHDWLQJ GU\ DJHUHODWHG PDFXODU labeling using an intermediate azide tag. First, we demonstrated that GHJHQHUDWLRQ $0' 8VLQJ KXPDQ HPEU\RQLF VWHP FHOOV K(6& DQHQJLQHHUHGVRUWDVH$YDULDQW WHUPHG0 H[KLELWVSURPLVFXRXV which express polymorphic human leukocyte antigens (HLA), may DFWLYLW\ ZLWK DQ DUUD\ RI SULPDU\ DPLQHV LQFOXGLQJ D]LGR cause immune rejection. Creating induced pluripotent stem cells propanamine (Azp) and propargylglycine, with incorporation rates of IURPDSDWLHQW¶VRZQWLVVXHLVFRVWO\DQGWLPHFRQVXPLQJ$VROXWLRQ XSWR%\XVLQJVRUWDVH$0WRHQ]\PDWLFDOO\ODEHOSURWHLQV PD\EHWRXVH³XQLYHUVDOVWHPFHOOV´ 8FHOOV ZKLFKGRQRWH[SUHVV ZLWK$]SZHVKRZHGWKDWÀXRUHVFHQWSUREHVFRXOGWKHQEHDGGHG SRO\PRUSKLF +/$ SURWHLQV :H GLႇHUHQWLDWHG 8FHOOV LQWR 53( DQG through click chemistry via the azide tag. We have demonstrated this WHVWHGWKHSKHQRW\SHDQGIXQFWLRQRI53(GHULYHGIURP8 ODFN+/$ strategy both in vitro and in vivo using an Escherichia coli expression FODVV,H[SUHVVLRQ 8 ODFN+/$FODVV,DQG,,H[SUHVVLRQ DQGWKH system. Application of 25 mM Azp to E. coli cultures coexpressing FRQWUROV8DQG+LQYLWUR:HZLOOLQMHFW88DQG853(FHOO䯠 VRUWDVH $ 0 DQG DQ /37(*WDJJHG *)3 YDULDQW IROORZHG E\ VXVSHQVLRQVLQWRWKHVXEUHWLQDOVSDFHRISLJPHQWHGDWK\PLFQXGH LQFXEDWLRQ ZLWK D &\GLEHQ]RF\FORRFW\QH '%&2 PRGL¿HG G\H 5&6 UDWV ZLWK 53( G\VIXQFWLRQ WR WHVW WKH DELOLW\ RI 8FHOO53( WR yielded complete conversion to the labeled protein conjugates. rescue photoreceptor function in vivo. To demonstrate the versatility of our sortase bioconjugation system, 4XDQWLWDWLYH 3&5 43&5 ZDV XVHG WR DQDO\]H 53( JHQH we sought to optimize the sortase labeling reaction in mammalian expression and test for genes of contaminating cell types. Morphology FHOOV 6RUWDVH $ 0 ZDV VXFFHVVIXOO\ H[SUHVVHG DW ORZ OHYHOV LQ and epithelial polarity were assessed using light microscopy and DGKHUHQW +(. FHOOV EXW QRW LQ VXVSHQVLRQ +(. FXOWXUHV LPPXQRKLVWRFKHPLVWU\ 'LႇHUHQWLDWLRQ HႈFLHQF\ ZDV H[DPLQHG E\ &RQYHUVHO\ VXVSHQVLRQ +(. FXOWXUHV GLVSOD\HG IROG ORZHU ÀRZF\WRPHWU\XVLQJWKH3PHODQWLERG\ZKLFKODEHOVSLJPHQWHG sensitivity to Azp concentrations than adherent HEK cells. Thus, FHOOV /RVV RI 2FW D SOXULSRWHQF\ PDUNHU ZDV DOVR GHWHUPLQHG engineering of sortase A for selective Azp activity is essential not only E\ÀRZF\WRPHWU\8FHOO53(IXQFWLRQZDVDQDO\]HGE\PHDVXULQJ to expand the toolbox of sortase variants but to reduce concentrations VHFUHWLRQRIWKHJURZWKIDFWRU3(')XVLQJ(/,6$DVVD\VDQGDOVR of Azp substrate to sustainable levels for mammalian culture. E\PHDVXULQJWKHDELOLW\RI8FHOO53(WRFDUU\RXWSKDJRF\WRVLVRI ERYLQHSKRWRUHFHSWRURXWHUVHJPHQWV)RUDOOLQYLWURVWXGLHVK(6& 7RZDUGVWKLVHQGD\HDVWGLVSOD\OLEUDU\RIVRUWDVH$0 GHULYHG + 53( ZDV D SRVLWLYH FRQWURO )RU WKH LQ YLYR VWXG\ variants was generated through saturation mutagenesis of four immunocytochemistry of retinal tissue will be performed 1 and 3 residues within the predicted oligoglycine pocket of sortase A. In order months after injections. Photoreceptor nuclei in the outer nuclear WR TXDQWLI\ WKH ELRFRQMXJDWLRQ UHDFWLRQ RI \HDVWGLVSOD\HG VRUWDVH OD\HU ZLOO EH TXDQWL¿HG DQG URGFRQH UDWLRV ZLOO EH GHWHUPLQHG YDULDQWVZHGHYHORSHGDVLPSOL¿HGGXDOSURWHLQH[SUHVVLRQYHFWRU 3KDJRF\WLFFDSDELOLW\RIWKH8FHOO53(ZLOOEHH[DPLQHGE\VWDLQLQJ WHUPHG S&/ 2XU FRQVWUXFW XWLOL]HV ERWK WHUPLQL RI WKH DDJJOXWLQLQ tissue sections for rhodopsin and quantifying phagosomes. For all mating protein (Aga2p) subunit to facilitate internal conjugation of LQYLYRH[SHULPHQWV853(ZLOOEHXVHGDVDSRVLWLYHFRQWURODQG WKH/3(7*UHFRJQLWLRQPRWLIE\FRGLVSOD\HGVRUWDVH$,QGXFWLRQRI

120 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

WKHS&/\HDVWOLEUDU\LQWKHSUHVHQFHRI$]SZDVIROORZHGE\FRSSHU 287 Decreased expression of TCF12 transcription IUHH FOLFN UHDFWLRQ ZLWK ELRWLQ'%&2 DQG FRQMXJDWLRQ GHWHFWHG E\ factor in glioblastoma stem-like cells results in an increased VWDLQLQJZLWK3(ODEHOHGDYLGLQ)OXRUHVFHQFHDFWLYDWHGFHOOVRUWLQJ mesenchymal subtype signature )$&6 ZLOOEHXVHGWRVHOHFWHQ]\PHYDULDQWVIRUVHTXHQFLQJDQG 5XND\DW07DLZR additional kinetic characterization. Identifying sortase variants with Washington University School of Medicine, USA improved Azp functionality will further demonstrate the versatility RI RXU S&/ GLVSOD\ V\VWHP DQG IDFLOLWDWH ELRUWKRJRQDO VLWHVSHFL¿F 7KH EDVLF KHOL[ORRSKHOL[ E+/+ WUDQVFULSWLRQ IDFWRU 7&) KDV protein labeling in mammalian cells. been implicated in precursor cell proliferation during embryogenic neurogenesis and continues to be expressed postnatally in 286 Krüppel-like factor 2 regulates an extracellular matrix mitotically active regions of the brain. TCF12 has been shown to remodeling transcriptional network in macrophages EHSUHIHUHQWLDOO\H[SUHVVHGLQJOLREODVWRPDVWHPOLNHFHOOV *6&V 'DYLG56ZHHW a key subpopulation of cancer cells thought to underlie tumor Case Western Reserve University and University Hospitals therapy resistance and recurrence. But the exact role of TCF12 Cleveland Medical Center, Cleveland, USA in gliomagenesis has remained unclear since it has been shown WREHERWKDSURWRRQFRJHQHDQGWXPRUVXSSUHVVRUGHSHQGLQJRQ )LEURVLVWKHUHVXOWRIXQUHVWUDLQHGZRXQGKHDOLQJSURFHVVHVDႇHFWV the cellular context. We therefore investigated the potential role of QHDUO\HYHU\RUJDQV\VWHPDQGVLJQL¿FDQWO\FRQWULEXWHVWRPRUWDOLW\LQ 7&)LQUHJXODWLQJWKHELRORJ\RI*6&V8VLQJPLFURDUUD\DQDO\VLV WKH8QLWHG6WDWHV:LWKDGYDQFLQJDJHFKURQLFQR[LRXVLQVXOWVUHVXOWLQ RISDWLHQWGHULYHG*6&VZH¿QGWKDW7&)LVKLJKO\H[SUHVVHG cellular damage with compensatory tissue remodeling. Macrophages LQ SURQHXUDO *6&V UHODWLYH WR QRUPDO KXPDQ DVWURF\WHV DQG are central orchestrators of physiological and pathological tissue GLႇHUHQWLDWLRQRISURQHXUDO*6&VLQFXOWXUHPDUNHGO\GRZQUHJXODWHG remodeling, secreting a multitude of proteases, growth factors, and 7&)P51$7RWHVWWKHUROHRI7&)LQ*6&VORVVRIIXQFWLRQ chemokines that result in cellular proliferation, matrix deposition, DSSURDFKHV XVLQJ ERWK 51$ LQWHUIHUHQFH DQG &5,635&DV and angiogenesis. Modulating the macrophage response to tissue PHGLDWHGNQRFNRXWGHPRQVWUDWHGUHGXFHGVHOIUHQHZDOFDSDFLW\D damage, therefore, represents a potential therapeutic avenue for NH\ PHDVXUH RI VWHPOLNH FHOO LGHQWLW\ UHODWLYH WR FRQWURO LQIHFWLRQ diseases of aberrant ECM remodeling. Previous work in our group &RQYHUVHO\ RYHUH[SUHVVLRQ RI 7&) XVLQJ D OHQWLYLUDO DSSURDFK KDV LGHQWL¿HG .USSHOOLNH IDFWRU ./) DV D WRQLF UHSUHVVRURI LQFUHDVHG*6&VHOIUHQHZDOFDSDFLW\0HFKDQLVWLFDOO\DPLQLVFUHHQ macrophage activation, serving as a “transcriptional brake” that RI FDQGLGDWHV NQRZQ WR UHJXODWH *6& VHOIUHQHZDO UHYHDOHG WKDW UHVLVWVLQÀDPPDWLRQ:KLOHWKHORVVRIP\HORLG./)UHVXOWVLQUREXVW NQRFNGRZQ RI 7&) OHG WR D GHFUHDVH LQ WKH H[SUHVVLRQ RI WKH LQÀDPPDWRU\DFWLYDWLRQDQGLQÀDPPDWRU\GLVHDVHLQYLYRWKHHႇHFWV E+/+ WUDQVFULSWLRQ IDFWRU 2/,* KHOL[ORRSKHOL[ SURWHLQ ,' %\ of sustained overexpression of myeloid KLF2 are unknown. High FRQWUDVWRYHUH[SUHVVLRQRI7&)OHGWRLQFUHDVHGH[SUHVVLRQRI WKURXJKSXW51$VHTXHQFLQJDQDO\VLVRQPDFURSKDJHVGH¿FLHQWLQ these markers. Furthermore, bioinformatic analysis of the genomic KLF2 indicates substantial downregulation of genes critical to ECM UHJLRQVXSVWUHDPRI2/,*DQG,',WUDQVFULSWLRQVWDUWVLWHVUHYHDOHG remodeling, providing the basis of our hypothesis that KLF2 governs the presence of evolutionarily conserved TCF12 binding sites, macrophage ability to remodel matrix during physiological and LPSOLFDWLQJ WKHVH VWHPLGHQWLW\ JHQHV DV SRWHQWLDO WUDQVFULSWLRQDO pathological processes. To determine if KLF2 expression is critical WDUJHWVRI7&)7DNHQWRJHWKHUWKHVH¿QGLQJVVXJJHVWWKDW7&) in acute ECM remodeling, we performed a cutaneous wound healing FRQWUROV WKH VWHPOLNH LGHQWLW\ RI SURQHXUDO *6&V E\ VWLPXODWLQJ DVVD\LQPLFHZLWKP\HORLGVSHFL¿FGHOHWLRQ ..2 RURYHUH[SUHVVLRQ H[SUHVVLRQRIWUDQVFULSWLRQDOUHJXODWRUV2/,*DQG,')LQDOO\XVLQJ (K2Tg) of KLF2. We observed substantial impairment in wound 2/,*DQG&'DVPDUNHUVRISURQHXUDODQGPHVHQFK\PDOLGHQWLW\ healing in K2KO mice while K2Tg mice healed faster than control UHVSHFWIXOO\NQRFNGRZQRI7&)GHPRQVWUDWHGGHFUHDVHG2/,* PLFH VXJJHVWLQJ WKDW ./) SURPRWHV EHQH¿FLDO (&0 G\QDPLFV H[SUHVVLRQZLWKDFRQFRPLWDQWLQFUHDVHLQ&'H[SUHVVLRQ7KHVH DQG UHJHQHUDWLRQ *LYHQ WKDW DJH LV D ULVN IDFWRU IRU PDQ\ ¿EURWLF ¿QGLQJVVXJJHVWWKDW7&)LVQHFHVVDU\IRUWKHPDLQWHQDQFHRID diseases, we sought to explore whether myeloid KLF2 fostered proneural stem identity and loss of TCF12 may lead to a switch from pathological ECM remodeling as well. Indeed, aged K2Tg mice proneural to mesenchymal subtype. GHPRQVWUDWHG HQKDQFHG VSRQWDQHRXV ¿EURVLV RI PXOWLSOH RUJDQV LQFOXGLQJNLGQH\OXQJDQGKHDUW,QDGGLWLRQWKH¿EURWLFFKDQJHVHHQ 288 &.į%5' SDWKZD\ DV QRYHO WKHUDSHXWLF WDUJHW IRU in K2Tg hearts contributed to systolic dysfunction as evidenced by SHH subtype of medulloblastoma echocardiocraphic features. Mechanistically, macrophages isolated Sze Kiat Tan from K2Tg mice exhibit increased transcription of genes associated University of Miami Miller School of Medicine, Miami, USA ZLWK(&0UHPRGHOLQJLQFOXGLQJ¿EUREODVWVWLPXODWLQJJURZWKIDFWRUV Background: Medulloblastoma is the most common malignant (HJ)JI)JI+JI,JI), matrix metalloproteinases (HJ0PS pediatric brain tumor with variable prognosis due to its clinical 0PS0PS), angiogenic factors (HJ9HJID9HJIE9HJIG DQG DQG JHQRPLF KHWHURJHQHLW\ 'HVSLWH GHFDGHV RI WUHDWPHQW PDUNHUVRIµSUR¿EURWLF¶SRODUL]DWLRQ HJ$UJ

www.jointmeeting.org 121 POSTER ABSTRACTS

Methods: *UDQXOHFHOOSURJHQLWRUV *&3V PHGXOOREODVWRPDPtch- DFFXPXODWLRQ RI &'+/$'5hi&' cells, indicating an /-3-/- mouse cells and SUFU-/-PRXVHHPEU\RQLF¿EUREODVWVZHUH LQYROYHPHQWRIJXWGHULYHGPLFURELDOSURGXFWVLQOLYHULQÀDPPDWLRQ LQFXEDWHGZLWKWKH&.įLQKLELWRU65DQGWKHSKRVSKRU\ODWLRQ 7KHUHZHUHVLJQL¿FDQWSRVLWLYHFRUUHODWLRQVEHWZHHQEDFWHULDOSURGXFW OHYHOVRI%5'ZHUHGHWHUPLQHGE\:%DQGLWVELQGLQJWRFKURPDWLQ WUDQVORFDWLRQ VHUXP *0&6) FRQFHQWUDWLRQ DQG WKH LQWUDKHSDWLF by ChIP. ,QYLWURSKRVSKRU\ODWLRQVWXGLHVZLWKKXPDQ%5'SXUL¿HG IUHTXHQF\ RI &'+/$'5hi&' cells. We demonstrated that from (FROL were performed. In addition, we tested whether genetic EDFWHULDO SURGXFWV /36 LQFUHDVHG WKH H[SUHVVLRQ RI &' DQG GLVUXSWLRQ RI &.į DOVR UHGXFHG %5' SKRVSKRU\ODWLRQ :H SURLQÀDPPDWRU\ F\WRNLQH VHFUHWLRQ E\ &' myeloid cells in a FRPELQHG%5'DQG&.įLQKLELWRUV -4DQG65UHVSHFWLYHO\ *0&6)GHSHQGHQWPDQQHUDQGZDVDEROLVKHGZLWKDQWL*0&6) DQGDQDO\VHG*OLP51$H[SUHVVLRQDQG(G8LQFRUSRUDWLRQWR QHXWUDOLVLQJ DQWLERGLHV VXJJHVWLQJ D SUHYLRXVO\ XQGH¿QHG UROH IRU GHWHUPLQHV\QHUJLVWLFHႇHFWV:HGHOHWHG&.įLQ*&3VLQPtch-/- *0&6) LQ FKURQLF OLYHU LQÀDPPDWLRQ 7KHVH ¿QGLQJV KLJKOLJKW ;3-/- mouse models of medulloblastoma by breeding these mice WKH LPSRUWDQFH RI WKH JXWOLYHU D[LV LQ FKURQLF YLUDOUHODWHG OLYHU with a Tg $WRK&UH &.įÀÀ strain. Furthermore, we intracranially LQÀDPPDWLRQ DQG VXSSRUW WKH XVH RI JXW PLFURELRPHPRGLI\LQJ WUDQVSODQWHGKXPDQ6++PHGXOOREODVWRPD7%FHOOV VSHFL¿F &' PDFURSKDJHGHSOHWLQJ RU *0&6)QHXWUDOLVLQJ expressing luciferase in mice, to validate the combination therapy. therapies for the management of these patients. 5HVXOWV&.įLQKLELWRUWUHDWPHQWDQG&.įNQRFNRXWUHGXFHG%5' 290 The role of cerebellum in Huntington’s disease SKRVSKRU\ODWLRQVXJJHVWLQJWKDW&.įSKRVSKRU\ODWHV%5'DQGLV Alexander V. Tereshchenko UHTXLUHGIRU%5'UHFUXLWPHQWWRFKURPDWLQ,QYLWURSKRVSKRU\ODWLRQ University of Iowa, Iowa City, USA VWXGLHV ZLWK SXUL¿HG KXPDQ %5' DQG &.į FRQ¿UPHG &.į PHGLDWHG %5' SKRVSKRU\ODWLRQ DQG &.į LV UHTXLUHG IRU %5' +XQWLQJWRQ¶V GLVHDVH +' LV D IDWDO QHXURGHJHQHUDWLYH GLVRUGHU SKRVSKRU\ODWLRQDWVHULQHDQGLQYLYR8VLQJORVVRIIXQFWLRQ FDXVHG E\ D &$* WULQXFOHRWLGH H[SDQVLRQ LQ WKH KXQWLQJWLQ HTT) VWXGLHV LQ *&3V ERWK &.į DQG %(7 LQKLELWLRQ UHGXFHG %5' gene. The characteristic neuropathological change associated with DVVRFLDWLRQZLWK*OLSURPRWHUWKHUHE\UHGXFLQJ*OLP51$OHYHOV +' LV VWULDWDO DWURSK\ :KLOH 05, VWXGLHV KDYH VKRZQ WKDW VWULDWDO )XUWKHUPRUH 65 VXSSUHVVHG 6++ VLJQDOLQJ GRZQVWUHDP RI volume decreases up to 20 years before the disease onset, patients 68)8RIPHGXOOREODVWRPDFHOOVLQYLWUR and LQYLYR. We also found have no detectable motor symptoms. This suggests that another synergy by combining these compounds LQ YLWUR and in reducing brain region compensates for failing striatal function. Previous tumor burden in the LQYLYR model with intracranial allografts. animal tracing studies established that bidirectional connections exist between cerebellum and striatum. The purpose of our study &RQFOXVLRQ7RJHWKHURXUVWXGLHVYDOLGDWHWKH&.į%5'SDWKZD\ ZDVWRDVVHVVFHUHEHOORVWULDWDOFRQQHFWLYLW\SDWWHUQVLQDVDPSOHRI DVDQRYHOWDUJHWLQPHGXOOREODVWRPD7KHVLJQL¿FDQFHRIRXUZRUN SUHV\PSWRPDWLF+'VXEMHFWV LV XQGHUVFRUHG E\ WKH SRVVLELOLW\ WKDW VLPXOWDQHRXV &.į%5' LQKLELWLRQ FRXOG RYHUFRPH WKH UHVLVWDQFH REVHUYHG ZLWK %5' 7KH 8QLYHUVLW\ RI ,RZD .LGV+' SURJUDP HQUROOV SDUWLFLSDQWV LQKLELWRUVDQGZHDUHWKH¿UVWJURXSWRGHPRQVWUDWHWKDW&.įDFWV \HDUVRIDJHZKRKDYHDIDPLO\KLVWRU\RI+'7KHVXEMHFWVZHUH GRZQVWUHDPRI6++VLJQDOOLQJLQ6++GULYHQPHGXOOREODVWRPD6LQFH tested for HTT gene expansion. All genetic information is used for &.įLQKLELWLRQFRXOGGHFUHDVH%5'SKRVSKRU\ODWLRQDQGVLJQDOLQJ UHVHDUFK SXUSRVHV RQO\ 6XEMHFWV ZLWK &$* ! DUH FDOOHG JHQH YLDWKH:17SDWKZD\LWLVIHDVLEOHWKDWFRPELQDWRULDOWKHUDS\PD\ H[SDQGHG *( ±WKH\DUHFXUUHQWO\SUHV\PSWRPDWLFEXWZLOOGHYHORS UHGXFH%(7UHVLVWDQFHDQGHQKDQFHWKHUDSHXWLFEHQH¿WVWRSDWLHQWV +'DVDQDGXOW$WRWDORI*(FKLOGUHQZHUHVWXGLHG PHDQ&$* *(VXEMHFWVZHUHFRPSDUHGWRDODUJHFRPELQHGFRQWURO && 289 Intrahepatic CD206+ macrophages contribute to group composed of subjects who did not inherit a gene expansion LQÀDPPDWLRQLQDGYDQFHGYLUDOUHODWHGOLYHUGLVHDVH SOXVWKHVXEMHFWVIURPIDPLOLHVZLWKQR+' Q PHDQ&$* Alfonso Tan Garcia 20). Each participant undergoes an MRI scan, including resting state Duke-NUS Medical School, singapore, Singapore I05,6HHGWRVHHGFRQQHFWLYLW\LQWKHFHUHEHOORVWULDWDOQHWZRUNZDV HYDOXDWHGEHWZHHQJURXSV S! /LYHU LQÀDPPDWLRQ LV FHQWUDO WR WKH SURJUHVVLRQ RI FKURQLF YLUDO hepatitis to cirrhosis and hepatocellular carcinoma. Monocytes and *( VXEMHFWV KDG VXEVWDQWLDOO\ LQFUHDVHG UHVWLQJ VWDWH IXQFWLRQDO PDFURSKDJHV &' myeloid cells) are increasingly recognised connectivity between anterior cerebellar lobe and dentate nucleus DV SURWDJRQLVWV RI FKURQLF YLUDOUHODWHG OLYHU LQÀDPPDWLRQ EXW WKHLU (p 1RWDEO\ZH REVHUYHG QR VWDWLVWLFDOO\ VLJQL¿FDQW FKDQJHV IXQFWLRQDOFKDUDFWHULVDWLRQDQGUHODWLRQWRLQÀDPPDWLRQLQKXPDQOLYHUV LQ WKH EDVDO JDQJOLD FRQQHFWLYLW\ RI WKH *( FRKRUW GRUVDO FDXGDO LVVWLOOSRRUO\XQGHUVWRRG:HDLPWREHWWHUGH¿QHWKHPHFKDQLVPV putamen to globus pallidus externus to subthalamic nucleus). Finally, E\ ZKLFK LQWUDKHSDWLF &' myeloid cells contribute to chronic KLJKHUQXPEHURI&$*UHSHDWVZLWKLQ*(JURXSZDVDVVRFLDWHGZLWK YLUDOUHODWHGOLYHULQÀDPPDWLRQ'HWDLOHGSKHQRW\SLFPROHFXODUDQG stronger connectivity between cerebellar seeds. IXQFWLRQDOFKDUDFWHULVDWLRQRILQWUDKHSDWLF&' myeloid cells from 7KHSULPDU\SDWKRORJ\RI+'H[WHQGVEH\RQGWKHVWULDWDOFKDQJHV KHDOWK\ GRQRUV DQG SDWLHQWV ZLWK YLUDOUHODWHG OLYHU FLUUKRVLV +%9 Mutant HTT may alter not only striatal development, but also the +%9+'9RU+&9 ZDVSHUIRUPHG8QVXSHUYLVHGDQDO\VLVRIPXOWL FHUHEHOORVWULDWDO FRQQHFWLYLW\ &HUHEHOORVWULDWDO QHWZRUN GLUHFWO\ SDUDPHWULFGDWDUHYHDOHGWKDWFKURQLFYLUDOUHODWHGOLYHULQÀDPPDWLRQ integrates with indirect pathway in the basal ganglia, which is ZDVDVVRFLDWHGZLWKWKHH[SDQVLRQRIDFWLYDWHG&' myeloid cells responsible for suppressing excess movements. Increased cerebellar hi ZLWKLQ WKH OLYHU SULPDULO\ SURLQÀDPPDWRU\ &' +/$'5 &' activity stimulates indirect pathway, inhibiting involuntary movement FHOOV ZKLFK VSRQWDQHRXVO\ SURGXFHG 71)Į DQG *0&6) 7KHVH LQSUHV\PSWRPDWLF+'DGXOWV:KHQFHUHEHOODUFRPSHQVDWLRQIDLOV FHOOVZHUHUHIUDFWRU\WRHQGRWR[LQLQGXFHGWROHUDQFHDQGGLVSOD\HG symptoms of chorea emerge. Further study is needed to assess how UREXVWSURLQÀDPPDWRU\UHVSRQVHVWREDFWHULDO7/5DJRQLVWV8VLQJ FHUHEHOODUIXQFWLRQLQ+'FKDQJHVDFURVVWKHHQWLUHGLVHDVHVSDQ DKXPDQLVHGPRXVHPRGHORI+%9LQGXFHGOLYHULQÀDPPDWLRQZH REVHUYHGDVLPLODUDFFXPXODWLRQRI&'+/$'5hi&' cells in +%9LQIHFWHG PLFH ZKLFK RFFXUUHG LQ D WHPSRUDO DQG OLYHUVSHFL¿F manner. Treatment with oral antibiotics abrogated this intrahepatic

122 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

291 %UHDVW FDQFHU DQWLHVWURJHQ UHVLVWDQFH %&$5 292 +\DOXURQLF $FLG$VWURF\WH ([WUDFHOOXODU 0DWUL[ regulates epithelial homeostasis, cell migration, and tumor Hydrogels Improve Histological Outcomes following Spinal growth in colorectal cancer Cord Injury and Support V2a Interneuron Transplantation Joshua Thompson 5XVVHOO(7KRPSVRQ Vanderbilt University, Nashville, USA Washington University in St Louis, St Louis, USA %ORRG YHVVHO HSLFDUGLDO VXEVWDQFH %9(6 LV D WLJKW MXQFWLRQ %DFNJURXQG(YHU\\HDU$PHULFDQVVXႇHUDWUDXPDWLFVSLQDO DVVRFLDWHG SURWHLQ WKDW UHJXODWHV HSLWKHOLDOWRPHVHQFK\PDO FRUG LQMXU\ 6&, WKDW OHDGV WR D VLJQL¿FDQW OLIHORQJ KHDOWKFDUH transition (EMT) and functions as a tumor suppressor in colorectal burden due to the limited of regenerative capacity of the adult FDQFHU &5& 7KURXJKD\HDVWWZRK\EULGVFUHHQ%9(6ZDVVKRZQ mammalian spinal cord. This lack of regeneration is due, in part, to WRLQWHUDFWZLWKEUHDVWFDQFHUDQWLHVWURJHQUHVLVWDQFH %&$5 a highly organized, predominantly astrocytic glial scar that forms to %&$5 ZDV RULJLQDOO\ LGHQWL¿HG YLD LWV XSUHJXODWLRQ LQ WDPR[LIHQ limit the spread of secondary injury, but also represents a chemical resistant breast cancer cell lines and functions as an adapter protein, and physical barrier to neuronal growth. Interestingly, it has been recruiting p130Cas to focal adhesions, and regulating cellular observed that astrocytes are also present where axons are able to DGKHVLRQPLJUDWLRQDQGSUROLIHUDWLRQ:HVRXJKWWRGH¿QHWKHUROH cross the injury site. This suggests that astrocytes are involved in both of BCAR3 in colorectal cancer (CRC) and determined which cellular the formation of the glial scar and the creation of bridges across the SKHQRW\SHVZHUHGHSHQGHQWRQWKH%&$5SLQWHUDFWLRQ VFDUDQGOHVLRQHQYLURQPHQWV9DLQWHUQHXURQVDUHJOXWDPDWHUJLF :H EHJDQ E\ DQDO\]LQJ WKH FRPELQHG 0RႈWW &DQFHU &HQWHU ipsilaterally projecting cells that have been found to be important for 9DQGHUELOW8QLYHUVLW\0HGLFDO&HQWHU&5&H[SUHVVLRQDUUD\GDWDVHW ORFDOUHZLULQJIROORZLQJ6&,SDUWLFXODUO\LQWKHSKUHQLFFLUFXLW,QWKLV consisting of normal, adenomatous, and 250 tumor samples ZRUNZHSUHVHQWDQRYHOK\DOXURQLFDFLG +$ DVWURF\WHH[WUDFHOOXODU organized by tumor stage. BCAR3 was downregulated in adenomas matrix (ECM) hydrogel and demonstrate that this hydrogel can be S DQGIXUWKHUGHFUHDVHGDWDOO&5&VWDJHV S H XVHGWRGHOLYHU9DLQWHUQHXURQVLQWRWKHLQMXUHGVSLQDOFRUG $QDO\VLV RI 7&*$ 51$6HT GDWD FRQ¿UPHG UHGXFWLRQV DW DOO 0HWKRGV 3URWRSODVPLF DVWURF\WHV ZHUH GHULYHG IURP 5: PRXVH VWDJHV S H ,QDSDQHORISDLUHGQRUPDODQGWXPRUVDPSOHV HPEU\RQLFVWHPFHOOV P(6&V DQGWKHFXOWXUHSODWHVGHFHOOXODUL]HG BCAR3 expression was reduced in seven out of eleven samples 3URWRSODVPLF H[WUDFHOOXODU PDWUL[ 3(&0 ZDV WKHQ VFUDSHG IURP EXWZDVVLJQL¿FDQWO\HOHYDWHGLQDVXEVHW Q RIWXPRUVVK51$ WKH SODWH DQG O\RSKLOL]HG 9D LQWHUQHXURQV ZHUH GHULYHG IURP NQRFNGRZQ RI %&$5 DQG &ULVSU&DV PHGLDWHG NQRFNRXW RI &K[3$&&$*7G7RPDWRP(6&VDQGDJJUHJDWHGIRUWUDQVSODQW BCAR3 in HCT116 cells impaired transwell migration. Conversely, in 7KLVFHOOOLQHSURGXFHVFXOWXUHVFRQWDLQLQJ&K[FHOOV 9D WKHORZ%&$5H[SUHVVLQJ0&FHOOVVWDEOHOHQWLYLUDOH[SUHVVLRQ Interneurons) following puromycin selection.ECM was reconstituted of mouse BCAR3 (mBCAR3) increased transwell migration and LQ +$PHWK\OIXUDQ SULRU WR DGGLWLRQ RI 3(*ELVPDOHLPLGH LQYDVLRQWKURXJK0DWULJHOFRDWHGLQVHUWV YV FURVVOLQNHU N' DQG 9D DJJUHJDWHV 7KH UHVXOWLQJ VKHDU S DQGYVPLJUDWHGFHOOVSHU[¿HOG WKLQQLQJJHOVZHUHWKHQLQMHFWHGLQWR/RQJ(YDQVUDWVZHHNVDIWHU S 0HWDVWDVLVPRGHOLQJYLDVSOHQLFLQMHFWLRQRI0&FHOOV D7GRUVDOKHPLVHFWLRQ6&,)ROORZLQJLPSODQWDWLRQDQLPDOVZHUH demonstrated increased micrometastasis in the mBCAR3 expressing LPPXQHVXSSUHVVHGZLWKF\FORVSRULQH$+LVWRORJLFDOUHFRYHU\ZDV OLQH YVVXUIDFHPLFURPHWDVWDVLVLQOHIWODWHUDO DVVHVVHG ZHHNV DIWHU LPSODQWDWLRQ ZLWK VWDLQLQJ IRU7XM *)$3 OLYHUOREHS LPSOLFDWLQJ%&$5LQFRORUHFWDOPLJUDWLRQDQG &6 DQG (' 7KH SKHQRW\SH RI WKH WUDQVSODQWHG 9DV ZDV metastasis. Mechanistically, BCAR3 mediated transwell migration is GHWHUPLQHGZLWKWKH7G7RPDWR9JOX7DQG1HX1 GHSHQGHQWRQWKH%&$5S&DVLQWHUDFWLRQDV%&$5DGGEDFN 5HVXOWV:HIRXQGWKDWHLWKHU3(&0RU9DLQWHUQHXURQSUHVHQFH ZLWK D %&$5S XQFRXSOLQJ PXWDQW DEURJDWHV PLJUDWRU\ LQFUHDVHGKRVWD[RQDOJURZWKLQWRD6&,OHVLRQ3(&0LQFRUSRUDWLRQ SKHQRW\SHVLQERWK+&7DQG0&FHOOV ZDV DOVR IRXQG WR UHGXFH DVWURF\WH UHDFWLYLW\ VXUURXQGLQJ WKH 6&, ,QWHUHVWLQJO\ DOWHULQJ %&$5 H[SUHVVLRQ KDV PLQLPDO HႇHFW RQ OHVLRQ DQG UHGXFH PDFURSKDJH LQ¿OWUDWLRQ LQWR WKH OHVLRQ DQG proliferation LQ YLWUR EXW VXEFXWDQHRXV DOORJUDIWV RI 0& FHOOV LQ surrounding tissue compared to HA alone. The HA hydrogel itself V\QJHQHLF&%/PLFHGHPRQVWUDWHGDIROGLQFUHDVHLQWXPRU was found to reduce staining for inhibitory proteoglycans in the YROXPHGD\VSRVWLQMHFWLRQ YVPP3S glial scar compared to a sham implant. By quantifying TdTomato F'1$UHVFXHXVLQJDJXLGH51$UHVLVWDQW%&$5FRQVWUXFW H[SUHVVLRQ ZH IRXQG WKDW WKH WUDQVSODQWHG 9D LQWHUQHXURQV in HCT116 Crispr KO lines similarly promotes tumor growth. This VXUYLYHG LQ ERWK +$ DQG +$ (&0 JHOV )XUWKHUPRUH EDVHG RQ discordance between LQ YLYR and LQ YLWUR tumor growth may be FRORFDOL]DWLRQRI7G7RPDWRZLWKȕWXEXOLQWUDQVSODQWHGLQWHUQHXURQV attributable to circulating growth factors as BCAR3 is known to aid H[WHQGSURFHVVHVERWKZLWKLQWKH6&,OHVLRQDQGLQWRWKHKRVWVSLQDO in integrating receptor tyrosine kinase mediated signaling cascades. cord. This work shows that astrocyte ECM maintains bioactivity and $FFRUGLQJO\ZHVKRZIRUWKH¿UVWWLPHKHUHWKDW%&$5LQWHUDFWVZLWK LPSURYHVKLVWRORJLFDORXWFRPHVIROORZLQJ6&,)XWXUHZRUNZLOOIRFXV WKHKHSDWRF\WHJURZWKIDFWRU +*) UHFHSWRUF0(7DQGFDQDOWHU on determining if transplantation of these HA:ECM hydrogels and/ cMET phosphorylation. Together, these results implicate BCAR3 in RU WKH 9D LQWHUQHXURQV UHVXOWV LQ DQ\ EHKDYLRUDO LPSURYHPHQWV cell migration, tumor growth, and receptor tyrosine kinase signaling IROORZLQJ6&, in CRC.

www.jointmeeting.org 123 POSTER ABSTRACTS

293 0RGHOLQJ LQÀDPPDWLRQ LQ KHWHURWRSLF RVVL¿FDWLRQ FDQFHUFHOOVVHUYHGDVFRQWUROV$IWHUDQGGD\VFRQVWUXFWV using human induced-pluripotent stem cells ZHUH¿[HGWKHQLPPXQRKLVWRFKHPLFDOO\VWDLQHGZLWK+RHVFKWQXFOHDU Amy N. Ton VWDLQ DQG &\WRNHUDWLQ /LSLG WUDQVIHU DQG EUHDVW FDQFHU FHOO University of California, San Francisco, USA invasion into the collagen bulk were analyzed using laser scanning confocal microscopy and images were processed with Imaris. +HWHURWRSLF RVVL¿FDWLRQ +2 LV D GHELOLWDWLQJ SURFHVV ZKHUH ERQH forms abnormally in soft tissue. This can occur in response to trauma 7KH ' FROODJHQ FXOWXUH SODWIRUP GHPRQVWUDWHG %2',3<VWDLQHG RU LQMXU\ DQG FRPSOLFDWHV RYHU RI KLS UHSODFHPHQW VXUJHULHV mature adipocytes neighbored by stromal cells, akin to the native However, what factors predispose HO formation are largely architecture in human breast tissue. At the interface of the cancer XQNQRZQ 7R DGGUHVV WKLV ZH HVWDEOLVKHG DQ L36 FHOO PRGHO RI cells with the biomimetic stroma, lipid transfer was observed— ¿EURG\VSODVLDRVVL¿FDQVSURJUHVVLYD )23 DFRQJHQLWDOGLVHDVHRI EUHDVWFDQFHUFHOOVZKLFKZHUHFORVHLQSUR[LPLW\WRWKHOLSLG¿OOHG +2FDXVHGE\DJDLQRIIXQFWLRQPXWDWLRQLQWKH$&95UHFHSWRURI DGLSRF\WHV GHPRQVWUDWHG VPDOO JUHHQ ÀXRUHVFHQW OLSLG GURSOHWV LQ WKH%03SDWKZD\*LYHQWKDW)23SDWLHQWVGHYHORS+2LQUHVSRQVH the cytoplasm. Breast cancer cell invasion into the collagen bulk was to trauma, sepsis, or immunizations, we sought to understand how assessed via confocal Z stacks on Imaris. WKHFODVVLFDO$&955+PXWDWLRQPD\DႇHFWDFXWHLQÀDPPDWLRQ :HKDYHHVWDEOLVKHGDQRYHO'WLVVXHHQJLQHHUHGSODWIRUPWRVWXG\ Macrophages and endothelial cells are found in nascent HO lesions breast cancer microenvironment, including metabolic interactions DQGERWKFHOOW\SHVSOD\FULWLFDOUROHVLQLQÀDPPDWLRQRIQXPHURXV between primary human breast adipocytes and breast cancer cells. tissues. Our prior clinical studies showed that FOP patients are 7UDQVIHU RI ÀXRUHVFHQWO\ODEHOHG OLSLGV GLUHFWO\ IURP DGLSRF\WHV WR LQ D SURLQÀDPPDWRU\ VWDWH ZLWK LQFUHDVHG SRSXODWLRQV RI SUR breast cancer cells may induce aberrant metabolism to fuel malignant LQÀDPPDWRU\ PRQRF\WHV DQG HOHYDWHG FLUFXODWLQJ LQÀDPPDWRU\ growth and adaptive survival which may have implications in breast F\WRNLQHV,QDGGLWLRQ)23L36FHOOGHULYHGHQGRWKHOLDOFHOOV L(& FDQFHUSURJQRVLVLQSDWLHQWVRIGLႇHUHQWREHVLWLHVDVZHOODVLQWKH FDQ VHFUHWH LQFUHDVHG LQÀDPPDWRU\ IDFWRUV ZKHQ FRFXOWXUHG setting of autologous fat transfer after oncologic resection. ZLWK PHVHQFK\PDO VWHP FHOOV 6LQFH +2 OHVLRQV VKRZ D PDVVLYH LQ¿OWUDWLRQ RI LPPXQH FHOOV E\ KLVWRORJ\ ZH K\SRWKHVL]HG WKDW WKH 295 19-gene risk score predicts poor survival in FOP endothelial cells induce increased chemotaxis of monocytes hepatocellular carcinoma patients in response to injury. Because primary tissue specimens are not Lynn Tran possible to obtain from FOP patients due to the risk of inducing Medical College of Georgia at Augusta University, Augusta, PRUH+2ZHJHQHUDWHGPDFURSKDJHVIURPRXUL36FHOOOLQHV L0DF USA XVLQJDQHZKLJKO\HႈFLHQWDQGUHSURGXFLEOHGLႇHUHQWLDWLRQSURWRFRO +HSDWRFHOOXODUFDUFLQRPDLVWKHWKOHDGLQJFDXVHRIFDQFHUUHODWHG L0DFVH[SUHVVPDFURSKDJHOLQHDJHPDUNHUVRI&'DQG&'E GHDWKV DQG SDWLHQWV KDYH PHGLDQ VXUYLYDO WLPHV RI PRQWKV ZLWK )23 L0DFV KDYLQJ ODUJHU SRSXODWLRQV RI &'H[SUHVVLQJ 'HVSLWHWKLVSRRUSURJQRVLVWKHUHDUHQRFOLQLFDOO\DYDLODEOHSURJQRVWLF FHOOV WKDQ WKDW RI &' :H DUH FXUUHQWO\ FRFXOWXULQJ RXU L0DFV biomarkers to identify patients with particularly poor survival. We aim with iECs in a transwell model to assess macrophage migration WRLGHQWLI\SXWDWLYHSRRUVXUYLYDOJHQHVXVLQJ7KH&DQFHU*HQRPH DQGFKHPRWD[LV7KHVHGDWDVXJJHVWWKDW)23L0DFVKDYHGLႇHUHQW $WODV¶V KHSDWRFHOOXODU FDUFLQRPD JHQH H[SUHVVLRQ GDWD %ULHÀ\ immune responses caused by abnormal BMP signaling that may univariate Cox proportional hazard models were constructed for DႇHFWFHOOFHOOLQWHUDFWLRQV7KLVLPPXQHDFWLYDWLRQPD\SUHGLVSRVH 20,530 genes based on individual genes’ expression values and FOP patients to the development of HO, and may also be a key RYHUDOOVXUYLYDOVWDWXV*HQHVZLWKWKHKLJKHVWKD]DUGUDWLR +5 DQG UHJXODWRURIERQHIRUPDWLRQLQQRQJHQHWLFIRUPVRI+2 VLJQL¿FDQW SYDOXHV DIWHU DSSOLFDWLRQ RI D JHQRPHZLGH %RQIHUURQL FRUUHFWLRQZHUHUHGXFHGWRDULVNVFRUHFRQVLVWLQJRIJHQHVXVLQJ Biomimicry of the breast cancer microenvironment in 294 a supervised generalized linear model (least absolute shrinkage and a 3D, patient-derived, tissue engineered model VHOHFWLRQRSHUDWRUUHJUHVVLRQ QHWZRUNDOJRULWKP8VLQJWKLVJHQH Yoshiko Toyoda risk score as a univariate survival prediction model, the hazard ratio Weill Cornell Medical College, USA LV ZLWK D SYDOXH RI [ GHPRQVWUDWLQJ D VLJQL¿FDQW Obesity is a known risk factor for the development and prognosis separation of good survival (low risk score) and poor survival (high of breast cancer. Obesity is associated with less response to breast ULVNVFRUH SDWLHQWV2QHJURXSRIJHQHVZHLGHQWL¿HGLVDVVRFLDWHG cancer therapy and more aggressive disease. Adipocytes have been with mitosis, cell division, and cell cycle regulation; these genes may LGHQWL¿HGDVDVRXUFHRIH[RJHQRXVOLSLGVLQPDQ\FDQFHUFHOOW\SHV play important roles in tumor progression and resistance. We plan including breast, and provide energy to fuel malignant survival and WR YDOLGDWH WKLV JHQH ULVN VFRUH LQ D VLQJOHFHQWHU UHWURVSHFWLYH growth in breast cancer. Autologous fat transfer is an increasingly DQDO\VLV RI DUFKLYHG SDWLHQW IRUPDOLQ¿[HG SDUDႈQHPEHGGHG ubiquitous procedure for breast reconstruction after mastectomy, but (FFPE) tissues. the oncologic safety is largely unknown. There is a compelling need WR EHWWHU XQGHUVWDQG WKH ELRORJ\ EHKLQG WKH REHVLW\EUHDVW FDQFHU 296 Discovery of a Proliferative Gene Signature Predictive OLQN :H KDYH GHYHORSHG D ' SDWLHQWGHULYHG WLVVXH HQJLQHHUHG of Cancer Patient Survival platform to directly assess the metabolic interactions among cells of Paul Tran the breast cancer tumor microenvironment. Augusta University, Augusta, USA Breast tissue was enzymatically digested to retrieve adipocytes. :H KHUHLQ DQDO\]H GDWD IURP 7KH &DQFHU *HQRPH$WODV 7&*$ 3RO\GLPHWK\OVLOR[DQH ZHOOV ZHUH ¿OOHG ZLWK W\SH , FROODJHQ GDWDEDVH WR LGHQWLI\ SDWLHQW JURXSV ZLWK GLႇHUHQWLDO VXUYLYDO encapsulated with stromal cells and adipocytes labeled with the characteristics using gene expression data. Our goal is to use ÀXRUHVFHQW OLSLG G\H ERURQGLS\UURPHWKHQH %2',3< molecular data to help stratify patients in terms of survival prognosis DQG5)3ODEHOHG0'$0%EUHDVWFDQFHUFHOOVRQWKHVXUIDFH DQGFDQFHUWKHUDS\VHOHFWLRQ:HGRZQORDGHG7&*$JHQHH[SUHVVLRQ &XOWXUHV RI 0'$0% LQ QRQDGLSRF\WH FRQWDLQLQJ FROODJHQ 51$6HTGDWDDQGFOLQLFDOGDWDIURPWKH8QLYHUVLW\RI&DOLIRUQLD6DQWD matrices as well as adipocyte containing constructs without breast &UX] 8&6& ;HQD3XEOLF'DWD+XE:HDSSOLHGDXQLYDULDWH&R[

124 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

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Turnbull score are more likely to have worse survival prognosis compared to University of Michigan, USA tumors with a lower gene expression score, demonstrated through 6WDWLQV LQKLELW K\GUR[\PHWK\OJOXWDU\O&R$ UHGXFWDVH DQ HQ]\PH .DSODQ0HLHU VXUYLYDO DQDO\VLV DQG XQLYDULDWH DQG PXOWLYDULDWH in the cholesterol synthesis pathway, and are widely prescribed &R[SURSRUWLRQDOKD]DUGPRGHOV7KLVVXJJHVWVZHKDYHLGHQWL¿HG for cardiovascular risk reduction. In addition to lowering plasma D FRUHJXODWHG JHQH H[SUHVVLRQ QHWZRUN DVVRFLDWHG ZLWK FHOOXODU cholesterol levels, statins have also been proposed to further reduce SUROLIHUDWLRQ ZKLFK SUHGLFWV RYHUDOO DQG UHFXUUHQFHIUHH VXUYLYDO LQ FDUGLRYDVFXODUULVNYLDRWKHUSOHLRWURSLFDQWLLQÀDPPDWRU\DQG SUR PDQ\RIWKHFDQFHUVLQWKH7&*$GDWDVHW:HSODQWRYDOLGDWHWKHVH DQJLRJHQLF HႇHFWV SRWHQWLDOO\ PHGLDWHG WKURXJK WKH HQGRWKHOLXP ¿QGLQJV LQ D VLQJOH FHQWHU UHWURVSHFWLYH DQDO\VLV RI FDQFHU SDWLHQW though the underlying molecular mechanisms are still largely IRUPDOLQ¿[HGSDUDႈQHPEHGGHG ))3( WLVVXHEORFNV unknown. Analysis of endothelial cells (ECs) in vivo has been limited due to their extensive heterogeneity across vascular beds as well 7KHUDSHXWLF 5ROH RI ,QWUDSDUWXP 3'( ,QKLELWLRQ RQ 297 as their interspersed anatomical distribution. In addition, isolation of %ORRG3UHVVXUHDQG5HQDO,QMXU\LQ2IIVSULQJRI3UHHFODPSWLF ECs from complex tissues and/or expansion in vitro results in rapid 5DWV phenotypic drift and changes in gene expression programs. +DQQDK57XUEHYLOOH University of Mississippi Medical Center, Brandon, USA To characterize changes in the EC transcriptome induced by statin WUHDWPHQWZHDSSOLHGWKH7UDQVODWLQJ5LERVRPH$ႈQLW\3XUL¿FDWLRQ 8SWRRISUHJQDQFLHVDUHFRPSOLFDWHGE\SUHHFODPSVLD$VD (TRAP) technique, tagging the ribosomal protein RPL22 with UHVXOWXSWRPLOOLRQ86FLWL]HQVWRGD\DUHRႇVSULQJRISUHHFODPSWLF hemagglutinin (HA) in all ECs in the mouse in vivo by crossing a SUHJQDQFLHV2ႇVSULQJRISUHHFODPSWLFSUHJQDQFLHVKDYHLQFUHDVHG FRQGLWLRQDO5SO+$DOOHOHZLWKD7HN&UHUHFRPELQDVHWUDQVJHQH blood pressure (BP) during childhood, and preeclamptic pregnancy 0LFH DUH SHUIXVHG ZLWK F\FORKH[LPLGH DW WKH WLPH RI VDFUL¿FH can result in small for gestational age babies that are at a heightened IUHH]LQJ DFWLYHO\ WUDQVODWLQJ P51$ ZLWKLQ WKH ULERVRPDO FRPSOH[ risk for chronic kidney disease later in life. The Barker hypothesis EC ribosomes are then selectively isolated from tissue lysates by proposes that the adverse intrauterine environment created by LPPXQRVHOHFWLRQIRUWKH+$WDJDQGWKHDVVRFLDWHGP51$LVWKHQ preeclampsia programs fetal tissues and organs to develop high SXUL¿HGIURPWKLVFRPSOH[0XOWLSOHWLVVXHV EUDLQKHDUWNLGQH\OLYHU BP from early childhood. Clinical and experimental studies have OXQJDQGVNHOHWDOPXVFOH ZHUHVXEMHFWHGWRKLJKWKURXJKSXW51$ demonstrated the ability of various therapies that target the nitric sHTXHQFLQJ 51$6HT DQG(&HQULFKHGWUDQVFULSWVZHUHLGHQWL¿HG R[LGH 12 F*03VLJQDOLQJSDWKZD\VXFKDV12GRQRUVWRDWWHQXDWH E\FRPSDULVRQRIWKH+$VHOHFWHGP51$WRWRWDOWLVVXHP51$7R K\SHUWHQVLRQ 6LOGHQD¿O FLWUDWH D SKRVSKRGLHVWHUDVH 3'( VWXG\WKHHႇHFWVRIVWDWLQWUHDWPHQWRQWKHHQGRWKHOLXPPDOHPLFH LQKLELWRU SURORQJV WKH 12F*03 VLJQDOLQJ FDVFDGH DQG LPSURYHV were treated orally with 1mg/kg body weight atorvastatin daily for one the maternal syndrome of preeclampsia; however, determination week, and 3 untreated males were used as controls. RI RSWLPDO WLPLQJ HႇHFWLYHQHVV DQG VDIHW\ GXULQJ SHULQDWDO XVH have yet to be reported. This project tests the hypothesis that use 51$6HT DQDO\VLV RI FRQWURO WLVVXHV LGHQWL¿HG D VHW RI SDQ(& RI D 3'( LQKLELWRU GXULQJ SUHHFODPSWLF SUHJQDQF\ LPSURYHV WKH enriched genes in all tissues evaluated, including the known EC ORQJWHUP%3DQGUHQDOLQMXU\LQWKHRႇVSULQJ)HPDOH'DKO6UDWV PDUNHUV 7HN &GK )OW DQG 1RV $GGLWLRQDOO\ HDFK WLVVXH RQDVDOWGLHWDSUHYLRXVO\FKDUDFWHUL]HGVSRQWDQHRXVPRGHO H[KLELWHGDVHWRIYDVFXODUEHGVSHFL¿F(&WUDQVFULSWVZKLFKZDV of superimposed preeclampsia, were mated and treated orally PRVW SURPLQHQW LQ EUDLQ *HQH RQWRORJ\ DQDO\VLV RI LGHQWL¿HG (& ZLWKVLOGHQD¿O PJNJGD\ ODEHWDORO FXUUHQWO\XVHGWRPDQDJH PDUNHUVVKRZHGHQULFKPHQWIRUYDVFXODUUHODWHGELRORJLFSURFHVVHV hypertension in preeclamptic patients, 10 mg/kg/day), or vehicle from LQFOXGLQJ µYDVFXODU GHYHORSPHQW¶ µEORRG YHVVHO PRUSKRJHQHVLV¶ JHVWDWLRQDOGD\WRGHOLYHU\$OOGDPVZHUHUHWXUQHGWRFRQWURO DQG µDQJLRJHQHVLV¶7KRXJK DQDO\VLV RI WKH VWDWLQ WUHDWHG VDPSOHV is still in progress, preliminary unsupervised hierarchical clustering VDOWGLHWDWGHOLYHU\XSWKURXJKZHDQLQJRIRႇVSULQJDWIRXUZHHNVRI analysis of the brain samples showed high similarities between DJH$WVHYHQZHHNVRIDJHPDOHDQGIHPDOHRႇVSULQJ Q SHU WUDQVFULSWLRQDOSUR¿OHVIRUWKHVWDWLQWUHDWHGDQGFRQWUROJURXSV:H JURXS ZHUHDFFOLPDWHGWRUHVWUDLQWVIRUIRXUGD\VEHIRUHWDLOFXႇ%3 DUHFXUUHQWO\YDOLGDWLQJWKHVH¿QGLQJVLQRWKHUWLVVXHVDVZHOODVYLD PHDVXUHPHQWRQGD\¿YH%3ZDVPHDVXUHGDJDLQDWZHHNVRI VLQJOHPROHFXOHLQVLWXK\EULGL]DWLRQDVVD\V DJHIRUDQDO\VLVRIWKHWLPHGHSHQGHQWFKDQJHLQV\VWROLF%36\VWROLF %3LQFUHDVHGLQ'DKO6UDWVRIXQWUHDWHGPRWKHUVDVH[SHFWHGIURP ,QFRQFOXVLRQZHDUHDEOHWRLVRODWHHQGRWKHOLDOVSHFL¿FP51$LQ ZHHN WR KRZHYHU WKH ULVH LQ %3 ZDV DEROLVKHG LQ RႇVSULQJ YLYRDQGREVHUYHGGLVWLQFWKHWHURJHQHLW\EHWZHHQH[SUHVVLRQSUR¿OHV IURPVLOGHQD¿OWUHDWHGGDPV 9(+PP+J6/'PP+J RIGLႇHUHQWYDVFXODUEHGVDVZHOODVLQUHVSRQVHWRWUHDWPHQWZLWK S 7KLVSURWHFWLYHHႇHFWZDVQRWHOLFLWHGE\WUHDWPHQWZLWK atorvastatin. 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www.jointmeeting.org 125 POSTER ABSTRACTS

299 0RGHOEDVHG DGDSWDWLRQ RI DUWL¿FLDO SDQFUHDV JDLQV LQFUHDVHG 2*1 DQG H[KLELW VHYHUH V\VWROLF G\VIXQFWLRQ OHIW using physiologic noise adjustment calculations YHQWULFXODUHMHFWLRQIUDFWLRQ /9() YHUVXV:7DWZHHNV Nichole S. Tyler S DQGLQFUHDVHGPRUWDOLW\FRPSDUHGWR:7 PHGLDQVXUYLYDO Oregon Health and Science University, Portland, USA 7J2*7ZHHNV WUDQVJHQLF2*$ 7J2*$ PLFHH[KLELWQRUPDO FRQWUDFWLOLW\ /9() FRPSDUHG WR :7 DQG QR VLJQL¿FDQW (YROXWLRQV LQ WKH WUHDWPHQW RI7\SH 'LDEHWHV 7' KDYH OHG WR PRUWDOLW\ 7J 2*7 DQG 7J 2*$ LQWHUEUHG PLFH RYHUH[SUHVVLQJ DXWRPDWHGLQVXOLQGHOLYHU\RUDUWL¿FLDOSDQFUHDV $3 WHFKQRORJLHV ERWK2*7DQG2*$LQP\RFDUGLXPKDGORZHUOHYHOVRI2*1DQG +RZHYHU ODFNLQJ ZLWKLQ WKLV WUHDWPHQW IUDPHZRUN LV D PRGHO demonstrated marked improvement of systolic function when based approach that provides adaptive adjustments to basal and FRPSDUHGWR7J2*7PLFH 7J2*72*$/9()YHUVXV bolus dosing recommendations. Here, we propose new strategies 7J2*7/9()DQG:7/9()DOOS of adaptive dosing adjustments to determine precise treatment UHFRPPHQGDWLRQV IRU 7' E\ PRGHOLQJ WKH SK\VLRORJLF YDULDWLRQV 2XUQHZSUHOLPLQDU\GDWDVKRZWKDWFKURQLFP\RFDUGLDO2*7RYHU surrounding meals and exercise on blood glucose measures. H[SUHVVLRQ LV PDODGDSWLYH DQG VXႈFLHQW WR FDXVH +)HYHQ LQ WKH DEVHQFH RI K\SHUJO\FHPLD RU LQMXU\ ,QFUHDVHG 2*$ H[SUHVVLRQ &RQWLQXRXV *OXFRVH 0RQLWRU &*0 GDWD ZDV REWDLQHG IURP is well tolerated, and has the ability to prevent cardiomyopathy VXEMHFWVZLWK7'GXULQJDZHHNORQJ$3VWXG\0HDOVDQGH[HUFLVH LQGXFHGE\H[FHVVLYH2*12XUGDWDLGHQWLI\H[FHVVLYH2*1DVDQ events were controlled and repeated on day one and day four of LQGHSHQGHQW+)PHFKDQLVPDQGVXJJHVW2*1PD\FRQWULEXWHWR WKH VWXG\ 7KH 6LPSOH 2UDO *OXFRVH 0LQLPDO 0RGHO 62*00 RI diverse types of HF associated with diabetes and common forms of insulin and glucose kinetics served as the basis of our adaptive myocardial injury. DSSURDFK)LUVWZHXVHG&*0WUDFHVIURPVWXG\GD\RQHWRLGHQWLI\ DUHDVRISRRUJOXFRVHFRQWURODQGWKHQDQDO\WLFDOO\VROYHGIRUVXEMHFW 301 &KDJDV 'LVHDVH 8QGHUVWDQGLQJ ([SRVXUH 5LVN VSHFL¿FSK\VLRORJLFDOHUURUVVXUURXQGLQJPHDODQGH[HUFLVHHYHQWV Across a Land Use Gradient in Panama XVLQJWKHEHVWXQELDVHGOLQHDUHVWLPDWRU %/8( PHWKRG6HFRQG Erin Allmann Updyke WKURXJK VLPXODWLRQ ZH LGHQWL¿HG RSWLPDO $3 JDLQ DGMXVWPHQWV WR University of Illinois Urbana-Champaign, Urbana, USA prevent hypoglycemia on day one data. We then applied these gain adjustments and analytic physiologic noise to day four data and &KDJDV GLVHDVH D QHJOHFWHG WURSLFDO GLVHDVH DႇHFWLQJ PLOOLRQV RI simulated the blood glucose response. Our adaptive gain adjustments people throughout the world, is transmitted by multiple species of UHVXOWHGLQDGHFUHDVHLQWLPHVSHQWLQK\SRJO\FHPLDZLWKD triatomine “kissing bug” (Hemiptera: Reduviidae). In Panama, species FRUUHVSRQGLQJGHFUHDVHLQHXJO\FHPLD WKDW WUDQVPLW WKH GLVHDVH DUH V\OYDWLF LH ZLOGOLYLQJ DQG WKH ULVN factors that govern human transmission are not well characterized. 7KLVXVHRIFOLQLFDOGDWDUHSUHVHQWVDQRYHOSODWIRUPIRUPRGHOEDVHG This study investigates the factors potentially contributing to Chagas $3SDUDPHWHUDGDSWDWLRQIRUWKHWUHDWPHQWRI7\SH'LDEHWHV)XWXUH GLVHDVHH[SRVXUHULVNDFURVVDKXPDQODQGXVHJUDGLHQWLQFHQWUDO GLUHFWLRQVLQFOXGHXVHRI%/8(WRVROYHIRUDQDO\WLFLQVXOLQGRVHVWR 3DQDPD (SLGHPLRORJLFDO VXUYH\V DQG VL[WHHQ PRQWKV RI LQKRPH SUHFLVHO\LQIRUPWLPHYDU\LQJJDLQDGMXVWPHQWVDQGLPSOHPHQWDWLRQ kissing bug collection were performed in nine communities across RIPRGHOEDVHGDGDSWLYHVWUDWHJLHVLQVLPXODWHGSDWLHQWSRSXODWLRQV WKUHHXUEDQWRUXUDOODQGXVHJUDGLHQWV+RXVHKROGVXUYH\VH[SORUHG 300 Genetic elevation of beta-linked N-acetylglucosamine social and behavioral factors, such as living conditions, education in cardiomyocytes causes heart failure level, socioeconomic status, and knowledge of both kissing bugs and Priya Umapathi Chagas disease. Reported presence of domestic and wild animals Johns Hopkins Medical Institutions, Hunt Valley, USA around the home was positively correlated with having seen kissing bugs around the home and with greater average kissing bug capture 7KH SDWKRORJLF HႇHFW RI K\SHUJO\FHPLD RQ FDUGLRP\RF\WHV PD\ GXULQJ WKH VWXG\ (QWRPRORJLFDO VXUYH\V FDSWXUHG ¿YH FRPPRQ LQYROYHWKHH[FHVVLYHSRVWWUDQVODWLRQDOSURWHLQPRGL¿FDWLRQNQRZQDV species of kissing bug across the gradients, with a greater diversity 2*OF1$F\ODWLRQ 2*1 ,QWULJXLQJO\LQFUHDVHG2*1LVDIHDWXUHRI RINLVVLQJEXJVSHFLHVLQPRUHUXUDODUHDV*HQHUDOL]HGOLQHDUPRGHOV myocardial infarction (MI) and heart failure (HF), even in the absence SHUIRUPHGLQ5ZLWKWKHOPHSDFNDJH XVLQJD3RLVVRQGLVWULEXWLRQ RI K\SHUJO\FHPLD 2*1 LV GHSHQGHQW RQ PHWDEROLVP WKURXJK WKH UHYHDOHG VLJQL¿FDQWO\ PRUH NLVVLQJ EXJV FDSWXUHG LQ VHPLXUEDQ hexosamine biosynthesis pathway, which incorporates glucose, (p<0.001) and rural areas (p<0.001) as compared to urban areas. DPLQRDQGIDWW\DFLGVLQWRSURGXFWLRQRIDUDWHOLPLWLQJVXEVWUDWH8'3 Additionally, the number of domestic animals, including dogs and *OF1$&8OWLPDWHO\2*1OHYHOVDUHGHWHUPLQHGE\WKHQHWDFWLYLW\RI FKLFNHQV WKDW KRXVHKROGV NHSW ZDV VLJQL¿FDQWO\ DVVRFLDWHG ZLWK WZRHQ]\PHV2*7 2*OF1$FWUDQVIHUDVH DGGV2*1IURP8'3 the kissing bug capture rate (p<0.02 and 0.006, respectively). *OF1$&DQG2*$ 2*OF1$FDVH UHPRYHV2*12*1LVDKLJKO\ PCR and qPCR testing has indicated presence of Trypanosoma FRQVHUYHG VWUHVV UHVSRQVH DQG FRQVWLWXWLYH P\RFDUGLDOUHVWULFWHG FUX]LFDXVDWLYHDJHQWRI&KDJDVGLVHDVHLQRINLVVLQJEXJV 2*7NQRFNRXWLVHPEU\RQLFOHWKDOZKLOHLQGXFLEOHP\RFDUGLDO2*7 ZLWKGLႇHUHQFHVDFURVVWKHODQGXVHJUDGLHQW,QUXUDODUHDV NQRFNRXWFRQWULEXWHVWR+)VXJJHVWLQJVRPH2*1LVUHTXLUHGIRU of kissing bugs were infected with 7FUX]LZKLOHLQVHPLXUEDQDQG myocardial development, and normal heart function. However, it is XUEDQDUHDVZHUHLQIHFWHGUHVSHFWLYHO\7KLVKDVLPSRUWDQW XQNQRZQLIH[FHVVLYH2*1FRQWULEXWHVGLUHFWO\WRP\RFDUGLDOGLVHDVH potential implications for the distribution of risk of Chagas disease DQG+)8SXQWLOQRZWKHODFNRIJHQHWLFWRROVWRLQFUHDVH2*1LQ transmission across a land use gradient and according to household vivo, independent of glucose or pathological stress, has prevented a factors, and a better understanding of these risk factors is integral to FOHDUGHWHUPLQDWLRQRIWKHSDWKRORJLFDOSRWHQWLDORI2*1 VXFFHVVIXOFRQWUROHႇRUWV %DVHG RQ LQFUHDVHG 2*1 DIWHU 0, DQG LQ +) ZH K\SRWKHVL]HG WKDWH[FHVVLYH2*1FDQSURPRWH+):HFUHDWHGWUDQVJHQLFPLFH RYHUH[SUHVVLQJ2*7RU2*$H[FOXVLYHO\LQP\RFDUGLXPLQRUGHUWR GLUHFWO\WHVWLI2*1FDQFDXVH+)LQGHSHQGHQWO\RIK\SHUJO\FHPLD RU SDWKRORJLFDO VWUHVV 2XU WUDQVJHQLF 2*7 7J 2*7 PLFH KDYH

126 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

302 ,GHQWLW\RQWKH:HVW6LGHRI*UDQG5DSLGV$+LVWRU\RI ,QYLWURZHVKRZWKDWDIWHUFRFXOWXUHZLWKRUH[SRVXUHWRFDQFHU Westown conditioned medium, developing or mature white adipocytes have Kenny Urena-Gonzalez VLJQL¿FDQWO\ VPDOOHU OLSLG GURSOHWV +RZHYHU QR DFFRPSDQ\LQJ Grand Valley State University, Wyoming, USA LQFUHDVHVLQ8&3SURWHLQH[SUHVVLRQRUP51$H[SUHVVLRQRIUcp1 and other thermogenic markers such as 3JFĮ and &LGHD were This paper traces the history of what it means to be a “Westsider,” observed. Our data indicate that breast cancer promotes localized LQ *UDQG 5DSLGV 0LFKLJDQ :HVWRZQ LV D QHLJKERUKRRG ZLWK D ZKLWHDGLSRVHWLVVXHEURZQLQJQRWGULYHQE\GLUHFWFDQFHUVHFUHWHG KLVWRU\DQGLGHQWLW\GLVWLQFWIURPRWKHUDUHDVRIWKHFLW\'UDZLQJRQ mediators. Instead, the data support the alternative hypothesis that LQWHUYLHZDQGDUFKLYDOGDWDDVZHOODVSDUWLFLSDQWREVHUYDWLRQWKH the tumor microenvironment, not the tumor directly, is responsible paper suggests that Westown identity is rooted in the neighborhood’s IRU :$7 EURZQLQJ DW WKH WXPRUDGLSRVH WLVVXH LQWHUIDFH )XWXUH KLVWRU\RILPPLJUDWLRQLWVZRUNLQJFODVVFKDUDFWHUDQGWKHLPSDFWV experiments are underway to determine whether the critical cells are of construction projects in the past that served to physically separate stromal or immunologic in nature, to elucidate the signaling pathways Westown from other parts of the city. With this, the paper explores by which these changes occur, and to project the impact of this local WKHKLVWRU\RIPHGLFLQHLQWKLVDUHDDVZHOODVFXUUHQW¿QGLQJVRILW WAT browning on clinical endpoints including tumor progression, being medically underserved and trends on disease/health disparity HQHUJ\H[SHQGLWXUHDQGFDQFHUDVVRFLDWHGFDFKH[LD RIWKHDUHD,QFRQFOXVLRQWKH:HVWRZQRI*UDQG5DSLGVKDVEHHQ culturally diverse in the past, but recent demographic data suggests 304 Breast milk fed infant derived Propionibacterium WKDWWKHUHKDVEHHQDJHQWUL¿FDWLRQRISRRU&DXFDVLDQVLQWRWKHDUHD VWUDLQ8)PLWLJDWHVLQWHVWLQDOLQÀDPPDWLRQLQPLFHV\QWKHWLF as the majority group with the introduction of a new group, university biology approaches students. History shows that the area has been unrepresented in 0D[9DQ%HONXP *UDQG 5DSLGV LQ PRVW DUHDV LQFOXGLQJ PHGLFLQH DQG LQWHJUDWLRQ University of Florida, Destin, USA of medical programs/clinics. Currently there are no clinics in the 3XUSRVH 'HWHUPLQH ZKHWKHU KXPDQ EUHDVW PLON SURELRWLF Westown and is still underserved medically, with many residents 3URSLRQLEDFWHULXP IUHXGHQUHLFKLL VWUDLQ 8QLYHUVLW\ RI )ORULGD showing health concerns and stating a need for medical assistance. 38) KDV SRWHQWLDO DV D WKHUDSHXWLF IRU KXPDQ LQWHVWLQDO 303 Local white adipose tissue browning in breast cancer GLVHDVHVVXFKDVQHFURWL]LQJHQWHURFROLWLV 1(& 0HFKDQLVWLFDOO\ is not mediated by direct tumor-adipocyte interactions H[SODLQWKHSURIRXQGSURWHFWLYHHႇHFWRI38)RQPXULQHGLVHDVH Janina A. Vaitkus models of human intestinal diseases. Virginia Commonwealth University School of Medicine, 0HWKRGV 38) QDPHG E\ RXU ODE DIWHU WKH LQVWLWXWLRQ LW ZDV Midlothian, USA GLVFRYHUHGLQZDVLGHQWL¿HGYLDVU'1$IURPWKHIHFHVRIKXPDQ The role of adipose tissue in the context of cancer is multifaceted. infants fed human breast milk, but could not be found in those fed µ%URZQLQJ¶RUµEHLJLQJ¶RIZKLWHDGLSRVHWLVVXH :$7 WRWKHUPRJHQLF exclusively infant formula. We then created a series of experiments µEHLJH¶ RU EURZQLQZKLWH µEULWH¶ DGLSRVH WLVVXH KDV EHHQ LQYROYLQJ JURXSV RI PLFH JDYDJHG ZLWK 38) RU JHQHWLFDOO\ demonstrated in several cancer models; however, the mechanisms HQJLQHHUHGYDULDQWV RUZLWK3KRVSKDWH%XႇHUHG6DOLQHDVDFRQWURO underlying this process, and its implications relative to tumor :H XVHG ÀRZ F\WRPHWU\ WR DQDO\]H WKH LPPXQH IXQFWLRQ RI PLFH SURJUHVVLRQ DQG ZKROHERG\ HQHUJ\ H[SHQGLWXUH LQ WKH FRQWH[W RI in both groups in steady state and in a variety of disease states cancer, are not fully understood. Breast cancer is contiguous to LQFOXGLQJOLVWHULDPRQRF\WRJHQHV¨DFW$ (mutation to prevent escape adipose tissue, and therefore represents an ideal experimental IURPLQWHVWLQH 1(&ZDVWHVWHGZLWKSUHWHUPPLFHLQVWHDGRIDGXOW model to assess the interactions between tumor microenvironment PLFHUHÀHFWLQJWKHGHPRJUDSKLFRIKXPDQVPRVWDႇHFWHGE\1(& and adipose tissue. Our objectives were to characterize the extent Results: Flow cytometry of murine tissues showed gavage of of WAT browning in breast cancer and to investigate whether or not 38) WR KDYH DQWLLQÀDPPDWRU\ HႇHFWV LQ VWHDG\ VWDWH /LVWHULD LWLVPHGLDWHGE\GLUHFWWXPRUDGLSRF\WHLQWHUDFWLRQV:HHPSOR\HG PRQRF\WRJHQHV¨DFW$ (variant localized to intestine), and, in preterm immunohistochemistry for key thermogenic and immunologic PLFH 1(& 7KHVH DQWLLQÀDPPDWRU\ HႇHFWV LQFOXGHG PDUNHGO\ PDUNHUV LQ D PRXVH WUDQVJHQLF PDPPDU\ WXPRU PRGHO %)9% PLWLJDWHG LQÀDPPDWLRQ E\ GHFUHDVHG LQÀDPPDWRU\ ,/ LQFUHDVHG 7J 00793\97 0XO/HOO- DVZHOODVLQVHYHUDOKXPDQVDPSOHV DQWLLQÀDPPDWRU\,/7*)ȕ7UHJVDQG,/F\WRNLQHLQFUHDVHG of breast ductal carcinoma. We performed a series of LQ YLWUR 7+ GLႇHUHQWLDWLRQ GHFUHDVHG LQÀDPPDWRU\ 7K GLႇHUHQWLDWLRQ experiments using primary and immortalized mouse preadipocytes DQGGUDVWLFDOO\LQFUHDVLQJVXUYLYDOGXULQJ1(&LQQHRQDWDOPLFH:H as well as primary human preadipocytes. Cells were exposed to both used guanidine hydrochloride to isolate the surface layer protein of FRFXOWXUHDQGFDQFHUFRQGLWLRQHGPHGLXPIURPHLWKHU(0&) RXU EDFWHULXP DQG GLVFRYHUHG LW KDG D KLJK DႈQLW\ IRU 0+& FODVV RU0'$0%EUHDVWFDQFHUFHOOOLQHVIRUYDULRXVWLPHIUDPHV ,,'HOHWLRQRIWKHJHQHdlaT, responsible for producing the surface both during and after maturation to white adipocytes. Analyses were OD\HUSURWHLQYLDKRPRORJRXVUHFRPELQDWLRQUHVXOWHGLQDORVVRIDQWL carried out for lipid droplet sizes using microscopy, thermogenic LQÀDPPDWRU\HႇHFWUHODWLYHWRFRQWUROLQGLVHDVHPRGHOVDQGVWHDG\ JHQH SUR¿OHV XVLQJ UHDOWLPH T3&5 DQG SURWHLQ H[SUHVVLRQ XVLQJ VWDWH 7UDQVJHQLF PLFH ODFNLQJ WKH GHQGULWLF FHOO 6,*15 UHFHSWRU western blot. Immunohistochemistry experiments demonstrate that DOVR GLG QRW VKRZ WKH DQWLLQÀDPPDWRU\ UHVXOWV RI 38) JDYDJH XQFRXSOLQJSURWHLQ 8&3 WKHKDOOPDUNRIIXQFWLRQDOWKHUPRJHQLF ZKLFKZHSUHGLFWHGE\VKRZLQJWKDWWKH38)VXUIDFHOD\HUSURWHLQ DGLSRVH WLVVXH LV RYHUH[SUHVVHG DW WKH WXPRUDGLSRVH LQWHUIDFH KDVDKLJKDႈQLW\IRU6,*15EXWQRWRWKHU&W\SHOHFWLQUHFHSWRUV ,QWHUHVWLQJO\ 8&3 LV H[SUHVVHG LQ D JUDGLHQWOLNH PDQQHU ZLWK +\SR[LDLQGXFHG1(&DႉLFWHGSUHWHUPPLFHEUHDVWIHGE\PRWKHUV highest expression most proximal to the tumor and rapidly decreasing WKDWKDGEHHQJDYDJHGZLWK38)VLQFHSUHJQDQF\VKRZHGD moving distally. Lipid droplet size follows a gradient as well, with VXUYLYDO UDWH DQG PDUNHG UHGXFWLRQ RI LQÀDPPDWLRQ FRPSDUHG WR smaller lipid droplets closest to tumor. We also demonstrate that FRQWUROZKLFKKDGDVXUYLYDOUDWH WKH H[SUHVVLRQ RI LQWHUOHXNLQ ,/ D F\WRNLQH LQYROYHG LQ PDQ\ 'LVFXVVLRQ 7KHVH H[SHULPHQWV VKRZ WKDW 38) LVRODWHG IURP LQÀDPPDWRU\SURFHVVHVLVLQFUHDVHGDWWKHWXPRUDGLSRVHLQWHUIDFH breastfed human infants, markedly improved the immune response

www.jointmeeting.org 127 POSTER ABSTRACTS

LQ GLVHDVH VWDWHV E\ IDFLOLWDWLQJ DQWLLQÀDPPDWRU\ DQG UHJXODWRU\ and plays a role in RSPO2-overexpressing liver cancers. We then FRQGLWLRQV LQ PLFH :H PHFKDQLVWLFDOO\ OLQNHG WKH SURELRWLF HႇHFW H[SUHVVHGDQVK51$WDUJHWLQJPRXVHretinoblastoma protein (Rb), one of the main oncogenic 'XULQJHPEU\RQLFGHYHORSPHQWDWELUWKDQGDWSRVWQDWDOGD\ 3 PHFKDQLVPVLQ0&&&RQVHTXHQWO\H[SUHVVLRQRIWKHµ:('¶HSLWRSH Zfp503 was expressed in the retinal pigment epithelium (RPE) and is required for tumor growth and persistence, and sequence analysis in the inner neuroblastic layer of the retina. In the adult mouse, indicates that this region is highly conserved among MCC tumors. =IS ZDV H[SUHVVHG LQ WKH 53( WKH LQQHU QXFOHDU OD\HU ,1/ $GGLWLRQDOO\ZHVKRZWKDWµ:('¶VSHFL¿F&'7FHOOVDUHFDSDEOHRI DQG WKH JDQJOLRQ FHOO OD\HU *&/ 7R HVWDEOLVK ZKDW FHOO W\SHV KRPLQJWRDQGLQ¿OWUDWLQJ0&&WXPRUVDQGH[KLELWVWULNLQJO\GLYHUVH7 H[SUHVV=ISZHSHUIRUPHGDVHULHVRIFRORFDOL]DWLRQVWXGLHVE\ FHOOUHFHSWRUUHSHUWRLUHV7DNHQWRJHWKHUZHKDYHLGHQWL¿HGDKLJKO\ LPPXQRÀXRUHVFHQFH LQ DGXOW PLFH XVLQJ NQRZQ PDUNHUV RI UHWLQDO FRQVHUYHG DQG SRSXODWLRQSUHYDOHQW &' HSLWRSH ZLWKLQ 0&3\9 FHOOW\SHVUHVLGLQJLQWKH,1/DQG*&/7KHSUHVHQFHRI=ISLQ 7KHVH GDWD SURYLGH D UREXVW IRXQGDWLRQ WR GHYHORS &'EDVHG DVPDOOQXPEHURI%UQDSRVLWLYHFHOOVLQWKH*&/VXJJHVWHGWKDW cellular therapies and/or a therapeutic cancer vaccine against this Zfp503 is expressed in a subpopulation of retinal ganglion cells. deadly skin cancer. ,Q DGGLWLRQ FHOOV GRXEOHSRVLWLYH IRU =IS DQG ,VO LQ WKH *&/ established Zfp503 expression in a subset of displaced amacrine &RQÀLFW RI ,QWHUHVW 7KH DXWKRUV GHFODUH QR SRWHQWLDO FRQÀLFWV RI FHOOV6LPLODUO\ZHREVHUYHGIHZFHOOVSRVLWLYHIRUERWK=ISDQG interest. FDOUHWLQLQLQWKH*&/DQG,1/ZKLFKIXUWKHUVXSSRUWHGORFDOL]DWLRQRI 306 RSPO2 overexpression in the mouse liver induces Zfp503 in amacrine cells. Cells positive for both Zfp503 and Lhx2 (a tumor formation and progression via the Wnt and Hippo/Yap PDUNHURI0OOHUJOLDDQGDVXEVHWRIDPDFULQHFHOOV ZHUHLGHQWL¿HG pathways LQWKH,1/+RZHYHU=ISGLGQRWFRORFDOL]HZLWKFDOELQGLQDQG ChAT, which label horizontal cells and cholinergic amacrine cells, *HUPDQ/9HOH]5H\HV UHVSHFWLYHO\:HWKXVFRQFOXGHGWKDW=ISSRVLWLYHFHOOVOLNHO\IRUP University of Minnesota, Minneapolis, USA part of distinct subsets of amacrine cells and retinal ganglion cells. 5HFHQWO\ZHLGHQWL¿HGRSPO2 as an oncogene in a subset of human :H¿QDOO\LQYHVWLJDWHGWKHKLVWRORJ\RIWKHUDUH=ISNRPLFHWKDW EUHDVW FRORUHFWDO SHULSKHUDO QHUYH DQG OLYHU FDQFHUV 5632 we could identify at P0 before death ensued. In these mice, failure of LV D PHPEHU RI WKH 5VSRQGLQ SURWHLQ IDPLO\ ZKLFK RQFRJHQLF WKHRSWLF¿VVXUHWRIXVHFDXVHGWKHDSSURDFKLQJUHWLQDOOLSVWRH[WHQG DFWLYLW\ DULVHV YLD WKH :QWȕFDWHQLQ SDWKZD\ LPSRUWDQW IRU RUJDQ and overlap. In addition, the usually monolayered RPE appeared development and regeneration of the liver. We hypothesized PXOWLOD\HUHG DQG UHWLQDOLNH JLYLQJ WKH DSSHDUDQFH RI WZR GLVWLQFW that the Hippo/YAP pathway is activated in the liver upon RSPO2 OD\HUVRIUHWLQD:HSRVLWWKDW=ISPD\SOD\YHU\VSHFL¿FIXQFWLRQV overexpression given its role in organ development and the Wnt LQVXEW\SHVRIDPDFULQHDQGUHWLQDOJDQJOLRQFHOOVEHVLGHVLWVUROHLQ -/- pathway. We overexpressed RSPO2 in the Fah mouse liver and RSWLF¿VVXUHFORVXUH IRXQGLQFUHDVHGQXFOHDUORFDOL]DWLRQRQ

128 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

308 Inhibition of V-type ATPase in Small Airways Increases Moreover, the process served as professional development for Airway Surface Liquid pH program students who will likely participate in similar reviews during 5DXO9LOODFUHVHV the careers. Together, our approach demonstrated the value of University of Iowa - Department of Internal Medicine, Iowa City, partnering with student leaders in program evaluation and yielded a USA survey tool that easily could be adapted to other institutions. Cystic Fibrosis (CF) is a genetic disorder caused by mutations in the 310 Pancreatic islets in short-duration type 2 diabetes have F\VWLF¿EURVLVWUDQVPHPEUDQHFRQGXFWDQFHUHJXODWRU &)75 JHQH secretory dysfunction, variable amyloid accumulation, and CFTR encodes an anion channel permeable to both chloride and altered islet-enriched transcription factor expression ELFDUERQDWH,QODUJH&)DLUZD\VORVVRI&)75PHGLDWHGELFDUERQDWH John T. Walker VHFUHWLRQ DQG XQRSSRVHG SURWRQ VHFUHWLRQ DFLGL¿HV WKH DLUZD\ Vanderbilt University, Nashville, USA VXUIDFHOLTXLG $6/ DQGLPSDLUVDLUZD\KRVWGHIHQVHVWKHVHFUHWLRQ 7\SH GLDEHWHV 7' LV FKDUDFWHUL]HG E\ ERWK SHULSKHUDO LQVXOLQ of H LVPHGLDWHGE\WKHQRQJDVWULF+ /K ATPase (ATP12A). CF resistance and pancreatic islet dysfunction, but islet dysfunction is a disease that starts in the small airways. Therefore, we asked XQGHUOLHV WKH SURJUHVVLYH QDWXUH RI 7' LQ SDWLHQWV 'LVVHFWLQJ what type of proton pump mediates proton secretion in pigs small PHFKDQLVPV RI 7' SURJUHVVLRQ LQ KXPDQV LV FKDOOHQJLQJ GXH WR airways? and, whether inhibition of proton secretion in the small FOLQLFDOGLVHDVHKHWHURJHQHLW\DQGWKHGLႈFXOW\RIREWDLQLQJUHOHYDQW DLUZD\VZLOOLQFUHDVH$6/S+HQKDQFHEDFWHULDONLOOLQJDQGGHFUHDVH pancreatic samples. Our group is addressing these limitations $6/YLVFRVLW\" by using an integrated approach to functionally and molecularly We investigated the location of ATP12A by immunocytochemistry study the native pancreas and isolated islets from the same in small and large airways from pigs, and we compared the human cadaveric donors linked with donor clinical information. To H[SUHVVLRQSUR¿OHXVLQJ$ႇ\PHWUL[*HQH&KLSZLWKHPSKDVLVRQ LGHQWLI\ HDUO\ SDWKRORJLF PHFKDQLVPV ZH KDYH IRFXVHG RQ 7' the expression of proton pumps. ATP12A was expressed in large GRQRUV ZLWK VKRUW GLVHDVH GXUDWLRQ Q DJH \HDUV airway epithelia and submucosal glands but not in small airways. years duration, oral medications) and age matched controls. We Moreover, we found a higher expression (50x) of the vacuolar type GHWHUPLQHG WKDW7' LVOHWV KDG UHGXFHG EDVHOLQH LQVXOLQ VHFUHWLRQ H$73DVH 9$73DVH 9GVXEXQLWLVRIRUP $739' LQVPDOO DQG EOXQWHG UHVSRQVH WR KLJK JOXFRVH F$03HYRNHG VWLPXODWLRQ DLUZD\VHSLWKHOLDFRPSDUHGWRODUJHDLUZD\V7KHUHZDVQRVLJQL¿FDQW DQG.&OPHGLDWHGGHSRODUL]DWLRQLQLVOHWSHULIXVLRQDVVD\VGHVSLWHQR GLႇHUHQFHLQRWKHU9W\SH$73DVHVXEXQLWV GLႇHUHQFHLQLQVXOLQFRQWHQWFRPSDUHGWRFRQWUROLVOHWV&RQYHUVHO\ 7'LVOHWVKDGLQFUHDVHGEDVHOLQHDQGVWLPXODWHGJOXFDJRQVHFUHWLRQ 7RLQYHVWLJDWHWKHHႇHFWRI9$73DVHRQ$6/S+UHJXODWLRQLQVPDOO LQUHVSRQVHWRVWLPXODWLRQE\F$03HSLQHSKULQHDQG.&O*OXFDJRQ DLUZD\VZHVWXGLHGWKHHႇHFWRIED¿ORP\FLQ 9$73DVHLQKLELWRU RQ FRQWHQW RI 7' LVOHWV ZDV YDULDEOH EXW QRW GLႇHUHQW WKDQ FRQWURO $6/S+XVLQJZLWK61$5)S+LQGLFDWRU7KH$6/S+EHFDPHPRUH LVOHWV3DQFUHDWLFVHFWLRQVVKRZHGQRGLႇHUHQFHLQLVOHWPRUSKRORJ\ DONDOLQH6PDOODLUZD\VVWXGLHGZLWKRXW+&2IDLOHGWREHFRPHPRUH RUFHOOXODUFRPSRVLWLRQ 7'YVFRQWUROȕĮDQGį acidic when stimulated with cAMP agonist suggesting the ATP12A is FHOOVYVȕĮDQGįFHOOV ,QWHUHVWLQJO\7'SDQFUHDWD DEVHQWDQGWKH9$73DVHLVQRWUHJXODWHGE\F$03 KDG VLJQL¿FDQW YDULDELOLW\ LQ SURSRUWLRQ RI LVOHWV FRQWDLQLQJ DP\ORLG ,QKLELWLRQRIWKH9$73DVH+LQFUHDVHVWKH$6/S+LQWKHSUHVHQFH ZLWKIRXU7'GRQRUVKDYLQJDP\ORLGDFFXPXODWLRQLQ!RILVOHWV of HCO3 containing media and HCO3 free media in the basolateral ZKLOH RWKHU7' GRQRU LVOHWV KDG OLWWOH DP\ORLG GHSRVLWLRQ RI side in cell cultures in basal and cAMP stimulated conditions. This LVOHWV 51$VHTXHQFLQJDQDO\VLVIURP)$&6SXUL¿HGĮDQGȕFHOOV GDWDVXJJHVWVWKDWWKH9$73DVHPLJKWSOD\DQLPSRUWDQWUROHLQWKH VKRZHGUHGXFWLRQVLQ7'GRQRUVFRPSDUHGWRFRQWUROVLQVHYHUDO $6/S+UHJXODWLRQLQVPDOODLUZD\V LVOHWHQULFKHG WUDQVFULSWLRQ IDFWRUV NQRZQ WR SOD\ FUXFLDO UROHV LQ PDLQWHQDQFHRILVOHWFHOOLGHQWLW\DQGIXQFWLRQLQFOXGLQJ1.;DQG 309 7KH0673WUDLQLQJJUDQWUHQHZDOLVDQRSSRUWXQLW\IRU 3$;7RJHWKHUWKLVGDWDVXJJHVWVWKDWLQWULQVLFGHIHFWVLQ7'ĮDQG student-directed program evaluation. ȕFHOOVFRQWULEXWHWRLVOHWG\VIXQFWLRQHDUO\LQWKHFRXUVHRI7'DQG Anil Wadhwani that amyloid accumulation is not a driver of the disease. Northwestern University (Feinberg), Chicago, USA 311 Toward a single-neuronal basis of social reciprocity 0HGLFDO6FLHQWLVW7UDLQLQJ3URJUDPV 0673 IXQGHGE\WKH1DWLRQDO within the macaque anterior cingulate cortex Institutes of Health undergo periodic training grant renewal for Amy J. Wang FRQWLQXHGRUHQKDQFHGVXSSRUWRIWHQWULJJHULQJWRSGRZQUHYLHZRI Massachusetts General Hospital, USA SURJUDPSROLFLHVPLOHVWRQHVDQGJRDOV'LUHFWVWXGHQWLQSXWGXULQJ the renewal is commonly only gathered by external evaluators 6RFLDOG\VIXQFWLRQLVDFRUHFRPSRQHQWRIPDQ\SV\FKLDWULFGLVRUGHUV GXULQJDVLWHYLVLW8QOLNHRWKHUKLJKVWDNHVH[WHUQDOHYDOXDWLRQVLQ EXW LWV VLQJOHQHXURQDO DQG FDXVDO XQGHUSLQQLQJV UHPDLQ ODUJHO\ medical education, such as reaccreditation, there is no established unknown. Reciprocity, a central feature of social interaction, allows mechanism for systematically collecting and evaluating student individuals in a group to forge alliances towards augmenting individual perceptions of their training, program leadership, and learning DQGPXWXDO¿WQHVV+HUHZHVWXGLHGWKHQHXURQDOFRUUHODWHVRIJURXS environment. In our program, student leaders leveraged the training LQWHUDFWLRQE\REWDLQLQJPXOWLSOHQHXURQDOUHFRUGLQJVLQWKHDQWHULRU JUDQW UHQHZDO DQG VLWH YLVLW WR LQLWLDWH D PXOWLIDFHWHG UHYLHZRI cingulate cortex (ACC) of rhesus macaques as they performed a our program, including periodic open forums, collaboration with structured social task. leadership during a mock review, and a comprehensive survey of :H GHYLVHG D WKUHHDJHQW VRFLDO WDVN LQ ZKLFK WKUHH PDFDTXHV VWXGHQW SHUFHSWLRQV ,QGHSHQGHQW VWXGHQW DQDO\VLV LGHQWL¿HG ERWK interacted with each other over multiple rounds. The task required areas of strength that leadership was able to incorporate into the grant the monkeys to sit around a rotary table apparatus; in each trial, renewal application and areas of weakness that were addressed prior RQH LQGLYLGXDO ZRXOG RႇHU D IRRG UHZDUG WR RQH RI WKH RWKHU WZR to initiation of external review. The survey was deployed for a second Throughout sessions, individuals could reciprocate past rewards that \HDUDQGDOORZLQJXVWRPHDVXUHWKHHႇHFWVRIOHDGHUVKLSGHFLVLRQV had been delivered to them. Based on this design, we could dissociate

www.jointmeeting.org 129 POSTER ABSTRACTS

core computations associated with interactive behavior: the animal’s RI PLFURVWUXFWXUDO GLVUXSWLRQ DQG LURQ DFFXPXODWLRQ GLႇHU DPRQJ own decisions, the decisions of others, their social identities, and WKHP 7KH QDWXUH RI WKH GLႇHUHQFHV DQG FRUUHODWLRQV UHTXLUH SDVW LQWHUDFWLRQV 'XULQJ WDVN SHUIRUPDQFH ZH UHFRUGHG QHXURQDO further investigation, particularly where changes and correlations DFWLYLW\IURPWKHLU$&&XVLQJPLFURHOHFWURGHDUUD\V RYHUODS2IQRWHDUHWKHFRQWUDVWLQJ83'56,DQG)$FRUUHODWLRQV The monkeys showed strategic preferences for other individuals, and DPRQJV\QGURPHV$V'7,DQG5 DUHQRWFDSDEOHRIGHVFULELQJ preferred to reward those who reciprocated. Engaging in this social exact microstructural changes, association of measurements with strategy increased the amount of reward received by a given animal, KLVWRSDWKRORJLFDO¿QGLQJVLQIXWXUHVWXGLHVPD\KHOSGH¿QHFKDQJHV HQKDQFLQJ LQGLYLGXDO ¿WQHVV 0DLQWDLQLQJ D PHQWDO UHSUHVHQWDWLRQ VSHFL¿F WR GLVHDVH 1HYHUWKHOHVV GLVWLQFW GLႇHUHQFHV LQ OLPELF RI VSHFL¿F SUHIHUUHG LQGLYLGXDOV LV D SUHUHTXLVLWH IRU DFWLQJ RXW VWUXFWXUHVDVFDSWXUHGE\'7,DQG5 PD\KDYHFHUWDLQGLDJQRVWLF VWUDWHJLF VRFLDO SUHIHUHQFHV :H GLVFRYHUHG D VXESRSXODWLRQ RI YDOXHLQGLႇHUHQWLDWLQJEHWZHHQSDUNLQVRQLDQV\QGURPHV neurons encoding such a signal: these neurons tracked the reward 314 +\SR[LDLQGXFHGWUDQVODWLRQDOSUR¿OHVRIHPEU\RQLFDQG UHFHLYHGE\RWKHUJURXSPHPEHUVDQGGLVSOD\HGGLႇHUHQWLDODFWLYLW\ adult-derived macrophages: implications in cardiac injury and LQUHVSRQVHWRGLႇHUHQWLQGLYLGXDOV repair responses to ischemia 7KHVH ¿QGLQJV GHPRQVWUDWH D QRYHO VXESRSXODWLRQ RI QHXURQV LQ Nicholas S. Wilcox the primate ACC that encode information about particular individuals, Yale University School of Medicine, USA forming the necessary basis for social reciprocity. These results lay Myocardial infarction (MI) remains one of the leading causes WKH JURXQGZRUN IRU LGHQWLI\LQJ VSHFL¿F QHXURELRORJLFDOO\JXLGHG of mortality. Healing after MI depends on tight regulation of the targets for treatment of social behavioral disorders. LQÀDPPDWRU\ UHVSRQVH EHFDXVH FDUGLRP\RF\WHV KDYH D OLPLWHG 312 '7,DQG5 UHYHDOGLVWLQFWOLPELFVWUXFWXUHFKDQJHVLQ ability to regenerate following injury and consequent cell loss. parkinsonian syndromes Macrophages are important in both injury and repair responses to MI Ernest W. Wang because they clear necrotic cardiomyocytes, promote angiogenesis Penn State College of Medicine, Hummelstown, USA and produce cytokines, chemokines and growth factors. The mammalian heart contains at least 2 macrophage subsets. Yolk Previous studies of clinically similar parkinsonian syndromes have VDFGHULYHG PDFURSKDJHV <6'0V HVWDEOLVK WKHPVHOYHV GXULQJ XVHG PXOWLPRGDO 05, WR H[DPLQH GLႇHUHQFHV LQ PRWRUUHODWHG HPEU\RQLF GHYHORSPHQW DQG XQGHUJR VHOIUHQHZDO ,Q FRQWUDVW structures. However, limbic structure changes have yet to be ERQH PDUURZGHULYHG PDFURSKDJHV %0'0V SULPDULO\ RULJLQDWH compared despite neuropsychiatric and histologic evidence of limbic from circulating monocytes recruited to the heart following an acute network involvement. The present study investigated limbic structure perturbation. 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To test this, we are employing translating ribosome +DPLOWRQ 'HSUHVVLRQ 5DWLQJ 6FDOH +$0' 05, PHDVXUHPHQWV DႈQLW\SXUL¿FDWLRQ 75$3 DQRYHOWUDQVODWLRQDOSUR¿OLQJDSSURDFK were compared among controls and parkinsonian syndromes, and which when coupled with a transgenic murine model enables the correlated to clinical scores. LVRODWLRQRIFHOOVSHFL¿FSRO\VRPDOP51$ $FFRXQWLQJIRUERWKDJHDQGJHQGHU0'ZDVKLJKHULQ363WKDQLQ We have determined, by quantitative polymerase chain reaction FRQWUROV DQG 06$ LQ ERWK WKH DP\JGDOD DQG KLSSRFDPSXV ,Q WKH (qPCR), the optimal duration (16 to 20 hours) of hypoxic incubation of KLSSRFDPSXV0'ZDVDOVRKLJKHULQ363WKDQLQ3')$YDOXHVLQ PXULQH%0'0VIROORZLQJVHYHQGD\FXOWXUHIRULQGXFWLRQRIDQP51$ WKHKLSSRFDPSXVZHUHORZHULQ363WKDQLQFRQWUROV5 ZDVKLJKHU VXEVHW7KLVLQFOXGHVYDVFXODUHQGRWKHOLDOJURZWKIDFWRU 9HJI PDWUL[ LQWKHDP\JGDODLQ3'WKDQLQFRQWUROVKLJKHULQWKHKLSSRFDPSXV PHWDOORSURWHLQDVH 0PS DQGJOXFRVHWUDQVSRUWHU *OXW *HQH LQ06$WKDQLQ3'DQG363DQGKLJKHULQWKHQXFOHXVDFFXPEHQV RQWRORJ\ DQDO\VLV LGHQWL¿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ÀDPPDWLRQ T3&5 DQDO\VLV RI SRO\VRPDO 51$ IURP %0'0V QXFOHXVDFFXPEHQVLQ363,QWKHKLSSRFDPSXV+$0$QHJDWLYHO\ showed enrichment of select transcripts following hypoxia, including FRUUHODWHGZLWK)$LQFRQWUROVZKLOH+$0'QHJDWLYHO\FRUUHODWHGZLWK +VSE9HJIDQG0PS)LQDOO\0PSZDVHQULFKHGLQSRO\VRPDO )$LQ3'$OOZHUHVLJQL¿FDQWDIWHUDGMXVWLQJIRUPXOWLSOHFRPSDULVRQV 51$UHODWLYHWRQRQSRO\VRPDO51$DIWHUK\SR[LD and correlations. :H KDYH HPSOR\HG 75$3 WR LVRODWH VXႈFLHQW \LHOGV RI SRO\VRPDO 7KH UHVXOWV VXJJHVW WKDW '7, DQG 5 FDQ FDSWXUH GLVWLQFW OLPELF 51$IURPPXULQH%0'0VGHULYHGIURP+X5ZLOGW\SHRUNQRFNRXW structure changes in parkinsonian syndromes, and that patterns PLFH DIWHU K\SR[LD RU QRUPR[LD IRU 51$VHT DQDO\VLV :H KDYH

130 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

GHPRQVWUDWHGHႈFLHQW+X5GHOHWLRQLQ%0'0VIURPNQRFNRXWPLFH and has a role in stem cell maintenance of multiple epithelial tissues. E\ÀRZF\WRPHWU\DQGZHVWHUQEORW51$VHTZLOOHQDEOHXQELDVHG Cancer may originate from transformed adult stem cells, due to GHWHFWLRQRIQRYHORUOHVVDEXQGDQWWUDQVFULSWVDQGHOXFLGDWH+X5 VLPLODULWLHV LQ VLJQDOLQJ SDWKZD\V DQG VHOIUHQHZDO DELOLWLHV S¶V PHGLDWHG VWDELOL]DWLRQ RI SRO\VRPDO 51$ IRU WDUJHWV RI LQWHUHVW UROH KDV EHHQ GLႈFXOW WR FKDUDFWHUL]H DV LW KDV WZR LVRIRUPV ZLWK 6LPLODUH[SHULPHQWVZLOOHVWDEOLVKDFRPSDUDWLYHWUDQVODWLRQDOSUR¿OH GLVWLQFWIXQFWLRQV7$SDQGǻ1SSLVH[SUHVVHGLQWKHEDVDO IRU <6'0V 5HVXOWV ZRXOG SURYLGH D PROHFXODU EDVLV WR H[SODLQ stem cells of the lung, which is thought to be the cell of origin for WKH QRQRYHUODSSLQJ SURSHUWLHV RI WKHVH PDFURSKDJH VXEVHWV DQG lung squamous cell carcinoma however, the physiological roles of identify novel therapeutic targets. individual p63 isoforms have not been characterized. 316 Clinical, onychoscopic and histopathological features of To understand the roles of individual p63 isoforms, we utilized ¿QJHUQDLODQGWRHQDLORQ\FKRSDSLOORPD 7$S and ¨1S conditional knock out mice generated by our lab. Vivian Wong 7RVSHFL¿FDOO\ WDUJHW WKH WUDFKHD DQG OXQJV IRU UHFRPELQDWLRQ ZH Brown University, Providence, USA used an intubation technique that involves administering adenoviral Cre Recombinase directly into the mouse trachea to induce Background: Onychopapilloma is a benign tumor of the distal nail recombination in the trachea and lungs, with characterization at matrix and proximal nail bed with heterogenous clinical presentations. WLPHSRLQWVWRDVVHVVWKHHႇHFWRQGLႇHUHQWVWHPFHOOSRSXODWLRQVE\ It poses a diagnostic challenge since it could mimic subungual staining with lung stem cell markers. PDOLJQDQFLHV DQG LQÀDPPDWRU\ FRQGLWLRQV &OLQLFDO RQ\FKRVFRSLF and histopathological clues play critical roles in diagnosis. :H IRXQG WKDW '1S QRW 7$S LV WKH SULPDU\ LVRIRUP WKDW Objective: We aim to expand our knowledge on onychopapilloma by UHJXODWHVWKHPDLQWHQDQFHDQGGLႇHUHQWLDWLRQRIWUDFKHDOEDVDOVWHP DGGLQJFDVHVRI¿QJHUDQGWRHQDLORQ\FKRSDSLOORPDWRWKHOLWHUDWXUH cells in the mouse, through regulation of cell identity genes. Mice with NQRFNRXWRIǻ1SH[KLELWHGLQLWLDOK\SHUSUROLIHUDWLRQDQGDSRSWRVLV Methods: We performed a retrospective chart review of RI.UWEDVDOFHOOVLQWKHWUDFKHDOHSLWKHOLXPIROORZHGE\HSLWKHOLDO onychopapilloma cases collected over ten years, and characterized hypoplasia with loss of the basal cell population at a later time point, WKH FOLQLFDO RQ\FKRVFRSLF DQG KLVWRSDWKRORJLFDO IHDWXUHV RI ¿QJHU suggesting ¨1S plays a role in maintenance of this progenitor and toenail onychopapilloma at an academic institution. cell population. By isolating the basal cells LQ YLWUR, we observed 5HVXOWV :H REWDLQHG WKLUW\WKUHH ELRSV\FRQ¿UPHG FDVHV RI WKDWORVVRIǻ1SOHGWRLPSDLUPHQWRIEDVDOFHOOVSKHUHIRUPDWLRQ RQ\FKRSDSLOORPD RI ZKLFK KLVWRSDWKRORJLFDO VOLGHV ZHUH DQGWHUPLQDOGLႇHUHQWLDWLRQLQ'FXOWXUH7KURXJKDFRPELQDWLRQRI DYDLODEOH IRU UHYLHZ 2Q\FKRSDSLOORPD SUHGRPLQDQWO\ DႇHFWV 51$VHTDQG&K,3VHTDQDO\VLVRIZLOGW\SHDQGǻ1SNQRFNRXW adults, with a median age of 52 at the time of diagnosis. There is WUDFKHDOEDVDOFHOOVZHLGHQWL¿HGDWUDQVFULSWLRQDOQHWZRUNRIJHQHV DIHPDOHJHQGHUSUHGLOHFWLRQZLWKDIHPDOHWRPDOHUDWLRRI UHJXODWHGE\ǻ1SLQFOXGLQJHSLWKHOLDOGHYHORSPHQWSUROLIHUDWLRQ 7KH OHIW VLGH LV PRUH FRPPRQO\ LQYROYHG OHIW ULJKW UDWLR DQGPHWDEROLVP2XU&K,3VHTDQDO\VLVGHPRQVWUDWHGDVLJQL¿FDQW 7KH ¿QJHUV HVSHFLDOO\ WKH OHIW WKXPE RI DOO FDVHV DUH SHUFHQWDJH RI ǻ1S UHJXODWHG JHQHV ZHUH VXSHUHQKDQFHUV favored. Two cases of toenail onychopapilloma were found, VXJJHVWLQJDPHFKDQLVPIRUǻ1SPHGLDWHGHSLJHQHWLFUHJXODWLRQ both involving the halluces. Onychopapilloma could manifest as RI FHOO LGHQWLW\ JHQHV ,QWHUHVWLQJO\ǻ1S LV KLJKO\ DPSOL¿HGDQG longitudinal erythronychia, longitudinal leukonychia, chromonychia, RYHUH[SUHVVHGLQOXQJVTXDPRXVFHOOFDUFLQRPDDQGRXUǻ1SJHQH and longitudinal melanonychia. Long longitudinal or short splinter VLJQDWXUHZDVVLPLODUO\XSUHJXODWHGLQWKH7&*$OXQJVTXDPRXVFHOO KHPRUUKDJHVPD\EHSUHVHQW'LVWDO¿VVXULQJZLWK9VKDSHGQRWFK FDUFLQRPDFRKRUW2XUUHVHDUFKSURYLGHVQHZLQVLJKWVWRWKHXQGHU as well as onycholysis, are other discernable features. The presence characterized p63 gene in lung cancer while investigating a novel of a subungual keratotic mass is an additional distinctive diagnostic regulatory process for progenitor cells of the lung. clue. Onychoscopy could help pinpoint these aforementioned clinical features. Histopathological features include papillomatosis 318 8VLQJ DUWL¿FLDO DQWLJHQSUHVHQWLQJ FHOOV WR HQKDQFH acanthosis of the distal nail bed, premature keratinization, antigen presentation in the treatment of glioblastoma hyperkeratosis and splinter hemorrhages. Yuanxuan Xia Limitations: This is a retrospective, single institution study involving Johns Hopkins University School of Medicine, USA Caucasian patients only. Immunotherapy has become a promising tool in the oncologist’s Conclusions: Onychopapilloma has polymorphic clinical and DUPDPHQWDULXPIRUWUHDWLQJFDQFHU*OLREODVWRPD *%0 KRZHYHU morphological features. Onychoscopic and histopathological studies exhibits an extremely immunosuppressive tumor microenvironment are important to help exclude malignant mimickers. Consider through multiple mechanisms, including upregulation of checkpoint RQ\FKRSDSLOORPD LQ WKH GLႇHUHQWLDO GLDJQRVHV RI D PRQRGDFW\ORXV PROHFXOHVOLNH3'LWVOLJDQG3'/DQGWKHSUHVHQFHRIVXSSUHVVLYH tumor of the nail, especially on the left thumb of an adult female. P\HORLGFHOOVVXFKDVPLFURJOLDPDFURSKDJHVDQGP\HORLGGHULYHG suppressor cells. To counteract the immunosuppressive milieu in 317 ǻ1S LV HVVHQWLDO IRU PDLQWHQDQFH RI WUDFKHDO EDVDO *%0 ZH KDYH GHYHORSHG D ELRGHJUDGDEOH PLFURSDUWLFOHEDVHG cells through modulation of super-enhancers. V\VWHP RI DUWL¿FLDO DQWLJHQ SUHVHQWLQJ FHOOV D$3&V WKDW FDQ EH Sarah Wu SODFHG ORFDOO\ ZLWKLQ D WXPRU $V DUWL¿FLDO FRQVWUXFWV D$3&V FDQ MD Anderson Cancer Center, Houston, USA SHUIRUP WKH GXWLHV RI QDWLYH $3&V ZLWKRXW H[SHULHQFLQJ WXPRU The transcription factor p53 is a well characterized tumor suppressor LQGXFHG LPPXQRVXSSUHVVLRQ 7KURXJK D PL[WXUH RI SRO\ EHWD and is commonly mutated gene in many cancers, including lung DPLQR HVWHU 3%$( DQG SRO\ ODFWLFFRJO\FROLF DFLG 3/*$ ZH FDQFHU $ S IDPLO\ PHPEHU S ZDV LGHQWL¿HG E\ WKH &DQFHU generated biodegradable microparticle cores that can be loaded with *HQRPH$WODVDVKLJKO\DPSOL¿HGEXWQRWPXWDWHGLQOXQJVTXDPRXV DQ\FRPELQDWLRQRILPPXQRVWLPXODWRU\PROHFXOHV1RUPDOO\$3&V cell carcinoma, suggesting p63 and its target genes may be excellent DFWLYDWHWKHLPPXQHV\VWHPE\SUHVHQWLQJDVSHFL¿FSHSWLGH 6LJQDO candidates for treating cancers with mutant or deleted p53. DQGDYDULHW\RIFRVWLPXODWRU\PROHFXOHV 6LJQDO WRDFWLYDWH7 SLVDPDVWHUUHJXODWRURIHSLWKHOLDOGHYHORSPHQWDQGGLႇHUHQWLDWLRQ cells and drive an adaptive immune response against the peptide of

www.jointmeeting.org 131 POSTER ABSTRACTS

LQWHUHVW8VLQJWKHZHOOFKDUDFWHUL]HG2729$V\VWHPZHORDGHG 320 The effect of vitamin D on Th17-hyperresponsive 0+& , GLPHU H[SUHVVLQJ 29$ FKLFNHQ SHSWLGH 6LJQDO DQG FR systemic lupus erythematosus VWLPXODWRU\DQWL&'DQWL2;DQGDQWL%%PROHFXOHV 6LJQDO Erin A. Yamamoto 2) onto our microparticle surface. To identify what combination of Case Western Reserve University, USA 6LJQDO PROHFXOHV EHVW VWLPXODWHV D F\WRWR[LF LPPXQH UHVSRQVH ZHSHUIRUPHGFRFXOWXUHDVVD\VZLWK27&'7FHOOVDQGD$3&V 5HFHQWO\ DSSUR[LPDWHO\ RI 6\VWHPLF /XSXV (U\WKHPDWRVXV ZLWK HDFK SHUPXWDWLRQ RI FRVWLPXODWRU\ PROHFXOHV 6XUSULVLQJO\ patients of European decent were found to harbor a mutation in ACT1 D$3&VORDGHGZLWKMXVW0+&29$JHQHUDWHGDVJUHDWDSUROLIHUDWLRQ UV ZKLFKOHDGVWRDQRQIXQFWLRQDO$&7SURWHLQYDULDQW UHVSRQVH DV WKRVH D$3&V ORDGHG ZLWK ERWK 0+&29$ DQG FR $&7'1 $&7LVWKHNH\GRZQVWUHDPVLJQDOLQJPROHFXOHIRU VWLPXODWRU\ PROHFXOHV 7KLV VXJJHVWV WKDW 29$ V\VWHP D$3&V ,/ D FKDUDFWHULVWLF F\WRNLQH IRU 7K FHOOV 7KH$FW PRXVH EHDULQJRQO\6LJQDODUHVXႈFLHQWWRVWLPXODWHDVWURQJUHVSRQVHLQ GLVSOD\V D OXSXVOLNH SKHQRW\SH WKDW LV LQLWLDWHG E\ EDFWHULDO JXW YLWUR1H[WWRWUDQVODWHWKLV29$D$3&V\VWHPLQWRLQYLYRH[SHULPHQWV FRORQL]DWLRQDQGGULYHQE\7KFHOOVDQGFRUUHVSRQGLQJF\WRNLQHV IRU*%0WKHUDS\ZHWHVWHGWKHHႈFDF\RIDGRSWLYHWUDQVIHURI27 6LQFHYLWDPLQ'LVDNQRZQVXSSUHVVRURI7KGLႇHUHQWLDWLRQDQG 7FHOOVLQWRPLFHLPSODQWHGZLWK29$H[SUHVVLQJ*/WXPRUV7R YLWDPLQ'GH¿FLHQF\LVVXVSHFWHGWRFRQWULEXWHWROXSXVSDWKRORJ\ WHVWZKHWKHUWUDQVIHURI277FHOOVDORQHHUDGLFDWHV*/WXPRUV ZHK\SRWKHVL]HWKDWYLWDPLQ'VXSSOHPHQWDWLRQZLOODPHOLRUDWHWKH ZHWUHDWHGPLFHZLWKHVFDODWLQJGRVHVRI277FHOOV,QWHUHVWLQJO\ $FW SKHQRW\SH$GGLWLRQDOO\ ZH SURSRVH WKDW SDWLHQWV ZLWK WKH QRGRVHRI277FHOOVVLJQL¿FDQWO\LPSURYHGVXUYLYDOFRPSDUHGWR $&7'1YDULDQWZLOOGLVSOD\D7KK\SHUUHVSRQVLYHOXSXVVLPLODU FRQWUROV&XUUHQWO\ZHDUHWHVWLQJWKHLQYLYRHႈFDF\RID$3&VLQ WKDWRIWKH$FWPRXVH FRPELQDWLRQZLWK3'EORFNDGHLQPLFHKDUERULQJ29$H[SUHVVLQJ $FW7KFHOOSRSXODWLRQVDQGGLVHDVHSDWKRORJ\ZHUHDVVHVVHG */WXPRUV DIWHUZHHNVRIHLWKHUDYLWDPLQ'ORZ ,8J QRUPDO ,8J RU KLJK ,8J GLHW&RPSDUHGWRPLFHRQDQRUPDOYLWDPLQ'GLHW 319 ,QWHUOHXNLQPHGLDWHVLQQDWHOLNHUHOHDVHRILQWHUIHURQȖ WKH VSOHHQ ZHLJKWV RI PLFH LQ WKH ORZ DQG KLJK YLWDPLQ ' JURXSV IURPFRVWLPXODWHG&'7FHOOVWKURXJKLQWHJUDWLRQRIP725DQG ZHUH DSSUR[LPDWHO\ WLPHV JUHDWHU DQG WLPHV UHGXFHG STAT pathways UHVSHFWLYHO\ 'LႇHUHQFHV LQ VHUXP YLWDPLQ ' OHYHOV ZHUH DSSDUHQW 0DULD0;X as early as 3 weeks. There was a negative correlation between UConn Health, New Britain, USA YLWDPLQ'DQG7K7UHJUDWLRLQVSOHQRF\WHVDQGSHULSKHUDOEORRG ,QWHUOHXNLQ ,/ Į ȕ DQG Ȗ DUH QHZ DGGLWLRQV WR WKH mononuclear cells at the last time point available for each mouse. 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132 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

321 Investigation of molecular mechanisms mediating SURWRFROWRGLႇHUHQWLDWHKXPDQLQGXFHGSOXULSRWHQWVWHPFHOOV L36&V 0$3IXQFWLRQLQD[RQEUDQFKLQJ to endometrial stromal cells (our unpublished observations). In this Benjamin Yang GD\SURWRFROGD\FHOOVFRUUHVSRQGHGWRWKH0XOOHULDQGXFW 0' 7KRPDV-H௺HUVRQ8QLYHUVLW\3KLODGHOSKLD86$ VLQFHWKH\H[SUHVVHGKLJKHUOHYHOVRIWKHPDUNHUVIRU0'VXFKDV SDLUHGER[JHQH 3$; FRPSDUHGZLWKL36&V&RPSDULVRQRIJHQH Axon branching is a fundamental process of the developing nervous H[SUHVVLRQE\51$6HTXHQFLQJ 51$6HT DVZHOODVTXDQWLWDWLYH system, and disruptions are implicated in a variety of pathological 573&5 T3&5 RYHUWKHFRXUVHRIGLႇHUHQWLDWLRQUHYHDOHGLQFUHDVHG conditions including epilepsy and autism. Branching has also been H[SUHVVLRQRI¿EUREODVWJURZWKIDFWRUUHFHSWRU )*)5 JHQHDW shown to occur after nerve injury. Previous work has shown that 1) GD\IROORZHGE\GRZQUHJXODWLRQLQGD\FHOOVWKDWFRUUHVSRQGWR microtubules (MT) in the axon are reorganized during branching, mature endometrial stromal cells. Another stem cell surface marker DQG WKDW WKLV UHRUJDQL]DWLRQ LV QHFHVVDU\ IRU EUDQFKLQJ 6LQFH $73ELQGLQJ FDVVHWWH VXEIDPLO\ * PHPEHU $%&* ZKLFK LV MT organization is regulated by microtubule associated proteins expressed in side populations, has been previously demonstrated 0$3V ,DPLQWHUHVWHGLQWKHIXQFWLRQRI0$3ZKLFKZDVUHFHQWO\ in endometrial stem cells. Our gene expression analyses showed LGHQWL¿HG LQ WKH GHYHORSPHQWDO UHJXODWLRQ RI EUDQFKLQJ RI VHQVRU\ LQFUHDVHGH[SUHVVLRQRI$%&*GXULQJHDUO\VWDJHVRIGLႇHUHQWLDWLRQ QHXURQVLQWKHGRUVDOURRWJDQJOLRQ '5* 0$3KDVVHYHUDOXQLTXH ZLWKDUREXVWGHFOLQHRQGD\'XHWRLWVVLPLODUH[SUHVVLRQSDWWHUQ IHDWXUHV ,WLVFDSDEOHRIGLUHFWO\UHFUXLWLQJNLQHVLQPRWRUSURWHLQV ZLWK$%&*ZHK\SRWKHVL]HGWKDW)*)5FRXOGEHDQRYHOWLVVXH WR07VYLDLWV&GRPDLQ ,WSRVVHVVHVPXOWLSOH07ELQGLQJGRPDLQV stem cell marker for endometrial stromal stem cells. Endometrial DVZHKDYHGHPRQVWUDWHGWKDWWKH3GRPDLQFDQGLUHFWO\ELQG07V stromal cells were dispersed from a hysterectomy specimen after 6WUXFWXUHIXQFWLRQ DQDO\VLV RI 0$3 LQ QHXURQV UHYHDOV WKDW WKH PHFKDQLFDODQGHQ]\PDWLFGLJHVWLRQDQG)*)5 DQG)*)5 3GRPDLQ LV UHTXLUHG IRU EUDQFK IRUPDWLRQ DQG JURZWK ZKLOH WKH FHOOVZHUHLVRODWHGIURPHQGRPHWULDOVWURPDOFHOOVXVLQJÀXRUHVFHQFH &GRPDLQLVUHTXLUHGIRUEUDQFKJURZWK,Q&26FHOOVH[SUHVVLRQRI DFWLYDWHG FHOO VRUWLQJ )*)5 FHOOV FRPSULVH RI WKH 0$3UHVXOWVLQWKHUHRUJDQL]DWLRQRI07VLQWREXQGOHVLQDQDFWLYLW\ SUROLIHUDWLYHVWURPDOFHOOSRSXODWLRQ)*)5 FHOOVZKHQFRPSDUHG WKDW UHTXLUHV WKH 3GRPDLQ 7KH PRUSKRORJ\ RI WKHVH QRUPDOO\ ZLWK)*)5 FHOOVKDYHKLJKHUP51$OHYHOVRI(65 HVWURJHQ VWDWLFEXQGOHVFDQEHDOWHUHGE\FRH[SUHVVLRQZLWKNLQHVLQ7KLV UHFHSWRUȕ 1$12* WKH SOXULSRWHQF\ PDUNHU DQG 3$; WKH 0' FRXOG UHÀHFW HQKDQFHG 07RQ07 VOLGLQJ DV NLQHVLQ LV UHFUXLWHG marker. Immunohistochemistry staining of whole endometrial tissue WR07E\0$3DVLWFDQERWKZDONDORQJDQGWUDQVSRUW07V$V07 GHPRQVWUDWHG)*)5H[SUHVVLRQLQWKHSHULYDVFXODUDUHDERWKLQWKH sliding is thought to be required for axon outgrowth this is a potential functionalis and basalis layers. Other previously detected putative PHFKDQLVPE\ZKLFK0$3FRXOGUHJXODWHEUDQFKLQJ VWHP FHOO PDUNHUV VXFK DV $%&* DQG VXVKL GRPDLQ FRQWDLQLQJ 7R GLUHFWO\ WHVW WKH UROH RI 0$3 RQ ERWK 07 UHRUJDQL]DWLRQ DQG 686' ZHUH DOVR VKRZQ WR KDYH D SHULYDVFXODU ORFDWLRQ :H sliding, we have developed in vitro assays for bundle formation VSHFXODWH WKDW VRPDWLF VWHP FHOOV DUH RQH RI WKH ¿UVW FHOO W\SHV and sliding. These assays utilize taxol stabilized MT in conjunction that come in contact with circulating estrogen, which stimulates ZLWK FHOO H[WUDFWV FRQWDLQLQJ 0$3 DQG NLQHVLQ 7KLV DSSURDFK LV proliferation through direct or paracrine mechanisms. Altogether, advantageous as it allows for rigorous titration of MTs, MAPs, and RXU SUHOLPLQDU\ ¿QGLQJV VXJJHVW WKDW )*)5 LV D SRWHQWLDO QRYHO motors as well as examination of MT interactions which are not easily marker for isolation of endometrial stromal stem cells based on gene UHVROYHG LQ QHXURQV 2XU UHVXOWV VKRZ WKDW 0$3 HQKDQFHV 07 H[SUHVVLRQ DQDO\VHV GXULQJ WKH GLႇHUHQWLDWLRQ VWDJHV RI L36&V WR bundling and increases the number and velocity of MT sliding events endometrial stromal cells. in a dose dependent manner. These results support a model in which + 0$3HQKDQFHVERWKWKHQXPEHUDQGOHQJWKRID[RQEUDQFKHVYLD 324 Exosome-mediated systemic deliver of NAD its ability to reorganize MT and enhance MT sliding. In future studies, biosynthetic enzyme extends lifespan and delay aging ZHZLOODOVRXVHWKHVHDVVD\VWRDVVHVVWKHSRODULW\RI0$307 0LWVXNXQL

www.jointmeeting.org 133 POSTER ABSTRACTS

325 Phyllanthusmins induce apoptosis and reduce tumor scale and the AOT (and three AOT subscales), 2) age (in years) and burden in high grade serous ovarian cancer by late-stage the AOT (and two subscales), and 3) socially desirable responding autophagy inhibition and two AOT subscales. Regression analyses showed the AOT Alexandria Young FRXOGSUHGLFWSHUFHSWLRQVRIPHGLFDOSURIHVVLRQDOLVP U S Univeristy of Illinois at Chicago, Chicago, USA with certain subscales and items having greater positive correlations. +LJKJUDGHVHURXVRYDULDQFDQFHU +*62& LVDOHWKDOJ\QHFRORJLFDO 'LVFXVVLRQ 7KH UHVXOWV VKRZ SV\FKRPHWULF WHVWLQJ WKH$27 FDQ malignancy with a need for new therapeutics. Many of the most widely be informative regarding medical professionalism after controlling used chemotherapeutic drugs are derived from natural products or IRUVRFLDOO\GHVLUDEOHUHVSRQGLQJ7KLVVWXG\LGHQWL¿HGVSHFL¿F$27 WKHLU VHPLV\QWKHWLF GHULYDWLYHV :H GHYHORSHG SRWHQW V\QWKHWLF items that demonstrate strong positive correlations with perceptions analogues of a class of compounds known as the phyllanthusmins, of professionalism. Through the sensemaking approach, further inspired by natural products isolated from 3K\OODQWKXV SRLODQHL research could identify additional items to incorporate in a new scale %HLOOH7KHPRVWSRWHQWDQDORJXH3+<KDGWKHKLJKHVWSRWHQF\ WR HYDOXDWH VWXGHQWV¶ SURSHQVLW\ IRU UHÀHFWLRQ ZKLFK FRXOG UHGXFH LQ+*62&FHOOOLQHVLQYLWUR and displayed cytotoxic activity through problems inherent in the predominant rationalist approach. DFWLYDWLRQRIDSRSWRVLV3+<H[HUWVLWVHႇHFWVE\LQLWLDOO\LQKLELWLQJ 327 EptB pseudogene accumulation contributes to autophagy at a late stage in the pathway, involving the disruption enhanced systemic dissemination and stealth of typhoidal of lysosomal function. The autophagy activator, rapamycin, Salmonella serovars FRPELQHG ZLWK 3+< HOLPLQDWHG DSRSWRVLV VXJJHVWLQJ WKDW Lillian F. Zhang DXWRSKDJ\LQKLELWLRQZDVUHTXLUHGIRUDSRSWRVLV3+<ZDVUHDGLO\ University of California, Davis, Davis, USA bioavailable through intraperitoneal administration LQ YLYR where it VLJQL¿FDQWO\LQKLELWHGWKHJURZWKRIFDQFHUFHOOOLQHVLQKROORZ¿EHUV 6DOPRQHOOD HQWHULFD LV D KLJKO\ GLYHUVH VSHFLHV RI *UDPQHJDWLYH as well as reduced ovarian tumor burden in a xenograft model. We EDFWHULD WKDW FDQ EH JURXSHG LQWR W\SKRLGDO DQG QRQW\SKRLGDO GHPRQVWUDWH WKDW 3+< DFWV DV D ODWHVWDJH DXWRSKDJ\ LQKLELWRU VHURYDUV 1RQW\SKRLGDO VHURYDUV VXFK DV S. Typhimurium, cause ZLWK QDQRPRODU SRWHQF\ DQG VLJQL¿FDQW DQWLWXPRU HႈFDF\ DV D JDVWURHQWHULWLV DQG LQÀDPPDWRU\ GLDUUKHD ZKHUHDV W\SKRLGDO VLQJOHDJHQWDJDLQVW+*62&LQYLYR. This class of compounds holds serovars, such as S. Typhi, cause systemic disease with a promise as a potential, novel chemotherapeutic and demonstrates FRPSDUDWLYHO\GHFUHDVHGLQÀDPPDWRU\UHVSRQVH$VPDOOSHUFHQWDJH WKH HႇHFWLYHQHVV RI WDUJHWLQJ WKH DXWRSKDJLF SDWKZD\ DV D YLDEOH of patients infected with S. Typhi may become asymptomatic chronic strategy for combating the disease. carriers of disease. These individuals serve as reservoirs to transmit LQIHFWLRQWRRWKHUVDQGSRVHDVLJQL¿FDQWFKDOOHQJHIRUHUDGLFDWLRQ 326 Applying Psychometric Testing to Evaluation of of typhoid fever. Although S. Typhi and S. Typhimurium are very 3URIHVVLRQDOLVPLQ0HGLFDO(GXFDWLRQ closely related organisms, the properties that distinguish the two and Tyler Zahrli contribute to the S. Typhi carrier state remain poorly understood. Saint Louis University, Saint Louis, USA Previously, comparative analysis of 6DOPRQHOOD genomes revealed Introduction: There are two main approaches to medical that typhoidal serovars contain a higher number of pseudogenes professionalism: the rationalist approach and the sensemaking RU GLVUXSWHG QRQIXQFWLRQDO JHQHV WKDQ QRQW\SKRLGDO VHURYDUV approach. Although predominant, the rationalist approach is VXJJHVWLQJWKDWGLႇHUHQFHVLQSVHXGRJHQHQXPEHUFRXOGSOD\DUROH fraught with practical limitations: vague terminology, competing LQWKHGLႇHUHQWLDOSDWKRJHQHVLV2QHVXFKSVHXGRJHQHLQS. Typhi is models, faulty scales, and poor clinical application. The result of HSW% which codes for a phosphoethanolamine transferase that can WKLV DSSURDFK LV FRPPRQO\ UHIHUHQFHG GH¿QLWLRQV JXLGHOLQHV DQG VSHFL¿FDOO\PRGLI\WKHRXWHUNHWRGHR[\RFWXORVRQDWH .'2 UHVLGXH checklists. The sensemaking approach encourages physicians RI OLSRSRO\VDFFKDULGH /36 S. 7\SKL SRVVHVVHV D QRQIXQFWLRQDO DQG UHVHDUFKHUV WR FULWLFDOO\ UHÀHFW RQ WKH G\QDPLF HQYLURQPHQW copy of eptB, whereas S. Typhimurium possesses a functional LQZKLFKWKH\ZRUN6HQVHPDNLQJLVVXSSRUWHGLQWKHOLWHUDWXUHIRU copy of HSW%Here, we show that loss of HSW% function in typhoidal mitigating unprofessional behavior among medical researchers. serovars may serve as a virulence mechanism that allows S. Typhi Philosophers, psychologists, and bioethicists have also argued for to evade detection by the immune system, leading to a diminished WKHLPSRUWDQFHRIUHÀHFWLRQLQSURIHVVLRQDOGHYHORSPHQW$FFHSWLQJ KRVW LQÀDPPDWRU\ UHVSRQVH DQG WKH GHYHORSPHQW RI WKH FKURQLF the sensemaking approach, this study aims to determine the utility FDUULHUVWDWH+XPDQLQWHOHFWLQLVNQRZQWRELQGWRDQGUHFRJQL]H of psychometric testing in medical professionalism training and PXOWLSOHPLFURELDOJO\FDQHSLWRSHVLQFOXGLQJWKH.'2RI/36DQG HGXFDWLRQE\PHDVXULQJVHOIUHÀHFWLRQ PD\IXQFWLRQLQGHWR[L¿FDWLRQRI/362XUUHVXOWVGHPRQVWUDWHWKDW /36LVRODWHGIURPS.7\SKLZKLFKSRVVHVVHVDQRQIXQFWLRQDOHSW% Methods: The questionnaire developed consisted of four validated pseudogene, is bound by intelectin, whereas S.7\SKLPXULXP/36 and reliable measures: 1) Perceptions of Medical Professionalism is not bound by intelectin. Furthermore, loss of EptB function in S. LWHPV ¿YHVXEVFDOHVIURPWKH$FWLYHO\2SHQPLQGHG7KLQNLQJ Typhimurium allows binding of intelectin to S. 7\SKLPXULXP /36 $27 6FDOHPHDVXULQJSURSHQVLW\IRUUHÀHFWLRQ LWHPV WKH Mice infected with an HSW%mutant demonstrate increased bacteria &RJQLWLYH 5HÀHFWLRQ7HVWPHDVXULQJ DELOLW\ IRU UHÀHFWLRQ LWHPV load in the Peyer’s patches than mice infected with a wild type S. DQG WKH 0DUORZH&URZQH 6KRUW )RUP & WR FRQWURO IRU VRFLDOO\ Typhimurium. Additionally, mice infected with the HSW% mutant GHVLUDEOHUHVSRQGLQJ LWHPV 'HPRJUDSKLFLWHPVZHUHLQFOXGHG S. 7\SKLPXULXP H[KLELW GHFUHDVHG H[SUHVVLRQ RI LQÀDPPDWRU\ as indicated in the literature. With IRB approval, the questionnaire cytokines in the spleen compared to mice infected with the wild ZDV GLVWULEXWHG WR WKLUG DQG IRXUWK\HDU FOLQLFDO PHGLFDO type S. Typhimurium, suggesting that loss of HSW% function allows VWXGHQWVYLDHPDLOWKURXJK4XDOWULFV DQRQW\SKRLGDO6DOPRQHOOD serovar to mimic the stealth phenotype 5HVXOWVTXHVWLRQQDLUHVZHUHFRPSOHWHG\LHOGLQJDUHVSRQVHUDWH of typhoidal serovars. Together, these results suggest that loss of RI7KHUHZHUHPDQ\VLJQL¿FDQWSRVLWLYHVFRUUHODWLRQVWKHPRVW HSW% function allows intelectin to bind to and detoxify 6DOPRQHOOD important being between 1) the Perceptions of Medical Professional /36OHDGLQJWRGHFUHDVHGV\VWHPLFLQÀDPPDWLRQGXULQJLQIHFWLRQ

134 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS

These results have broad implications for how pathogens such as FRQFHQWUDWLRQV RI 3) DQGRU RWKHU HQWU\ LQKLELWRUV DQGRU S. Typhimurium induce systemic shock during infection and may DQWLERGLHV 7KH YLUXVLQKLELWRU PL[WXUH ZDV WKHQ DGGHG WR &' also help to explain a mechanism for how S. Typhi is able to evade &&5&'&;&5RU&'&&5WDUJHWFHOOVDQGOXFLIHUDVH immune detection and enhance dissemination to systemic sites, DFWLYLW\ZDVPHDVXUHGWRKRXUVODWHU leading to the development of the asymptomatic chronic carrier state. 2IWKHIRXU3)GLDVWHUHRPHUVRQO\RQH0)LQKLELWHGWKH 329 %UHDVWFDQFHUFHOOVH[SORLWDQRUSKDQ51$WRGULYH LQIHFWLRQRI&'&&5FHOOVE\VRPH+,9VWUDLQV8QH[SHFWHGO\ metastatic progression 0)DFWLYDWHGWKHLQIHFWLRQRI&'&&5FHOOVE\VHYHUDO+,9 VWUDLQVUHVLVWDQWWRWKHFRPSRXQG¶VLQKLELWRU\HႇHFWVLQ&'&&5 Steven Zhang WDUJHW FHOOV ,Q ERWK FDVHV WKH VWUDLQ VXVFHSWLELOLW\ SUR¿OHV ZHUH University of California, San Francisco, USA XQLTXHIURPWKRVHRIRWKHUHQWU\LQKLELWRUV6HQVLWLYLW\WRRWKHUHQWU\ Cancer cells often hijack endogenous regulatory programs to achieve LQKLELWRUVLQWKHSUHVHQFHRI0)LQGLFDWHGWKDW0)DFWLYDWHG SDWKRORJLFDO JHQH H[SUHVVLRQ ODQGVFDSHV 1RWDEOH H[DPSOHV RI YLUXV HQWU\ UHTXLUHV &&5 ELQGLQJ DV ZHOO DV JS KHSWDG UHSHDW WKHVH VWUDWHJLHV LQFOXGH VRPDWLF PXWDWLRQV JHQHWLF DPSOL¿FDWLRQV IRUPDWLRQDQGH[SRVXUH:DVKRXWRI0)SULRUWRDGGLWLRQRIWKH DQG GHOHWLRQV DQG HSLJHQHWLF PRGL¿FDWLRQV $GGLWLRQDOO\ SRVW YLUXVPL[WXUHWRWDUJHWFHOOVZDVDEOHWRDEURJDWHLWVLQKLELWRU\HႇHFW transcriptional pathways have also emerged as major regulators of LQ &' &&5 WDUJHW FHOOV EXW QRW LWV DFWLYDWLQJ HႇHFW LQ &' WKLVWUDQVIRUPDWLRQLQFOXGLQJWKRVHLQYROYLQJPL51$V51$ELQGLQJ &&5WDUJHWFHOOV,QFRQWUDVWWR&'PLPHWLFFRPSRXQGV0) SURWHLQV DQG W51$V DQG W51$ IUDJPHQWV +RZHYHU D VKDUHG inhibitory and activating activity did not depend upon availability of characteristic among these strategies is that they rely on existing WKHJS3KHFDYLW\0XWDQWVZLWKDOWHUHG(QYUHDFWLYLW\RU6WDWH SDWKZD\V ZLWKLQ WKH FHOO *LYHQ WKDW FDQFHU FDQ EH YLHZHG DV DQ SUHIHUHQFH SUHYLRXVO\GHPRQVWUDWHGWREHUHVLVWDQWWR&'PLPHWLF evolutionary process, there is a distinct possibility that cancer cells FRPSRXQGV UHPDLQHGVXVFHSWLEOHWR0)&RQYHUVHO\FKDQJHV are capable of evolving or rewiring new regulatory pathways during LQ WKH JS '6/ DQG JS & UHJLRQV FRQIHUUHG UHVLVWDQFH WR disease progression. One possible source for novel pathways is 0)EXWQRW&'PLPHWLFFRPSRXQGV7KHKDOIOLYHVRIWKHRQVHW QRQFRGLQJ 51$V DV WKHVH PROHFXOHV FDQ DULVH GXH WR HFWRSLF DQGGHFD\RIWKH0)DFWLYDWHGVWDWHZHUHGLႇHUHQWIURPWKRVH DFWLYDWLRQRI51$SRO\PHUDVHVRUQXFOHDVHVZKLOHDOVRSRVVHVVLQJ RI&'PLPHWLFFRPSRXQGV)LQDOO\ZKLOH0)DQG&'PLPHWLF YHUVDWLOHUHJXODWRU\FDSDFLW\:HSRVLWHGWKDWQRQFRGLQJ51$VDULVH FRPSRXQGVERWKHQKDQFHGVXVFHSWLELOLW\RIVRPH+,9VWUDLQVWRWKH in cancer cells as a consequence of tumorigenesis and provide a EDQGEDQWLERGLHVDJDLQVWD&'LQGXFHG &'L HSLWRSHDQG SRRO RI FDQFHUVSHFL¿F PROHFXOHV ZLWK UHJXODWRU\ SRWHQWLDO ,Q WKLV WKHJS9ORRSUHVSHFWLYHO\RQO\0)HQKDQFHGVXVFHSWLELOLW\ study, we performed a systematic search for the emergence of such WRWKHHDQWLERG\DJDLQVWWKHJSPHPEUDQHSUR[LPDOH[WHUQDO QHRUHJXODWRUVRIJHQHH[SUHVVLRQLQEUHDVWFDQFHU:HSHUIRUPHGD region (MPER). V\VWHPDWLFVHDUFKIRUVXFKFDQFHUVSHFL¿F51$VSHFLHVE\FRPSDULQJ 0) DSSDUHQWO\ ELQGV D VLWH RQ WKH +,9 (QY XQLTXH IURP WKH WKH VPDOO 51$ SUR¿OHV RI HLJKW KXPDQ EUHDVW FDQFHU FHOO OLQHV WR &' ELQGLQJ VLWH DQG DFWLYDWHV D FRQIRUPDWLRQDO FDVFDGH WKDW KXPDQPDPPDU\HSLWKHOLDOFHOOV:HLGHQWL¿HGDSRRORIVPDOO51$V leads to virus entry. This pathway is parallel to but distinct from that that whose presence was further associated with breast cancer using WULJJHUHGE\&'DQG&'PLPHWLFFRPSRXQGV$QXQGHUVWDQGLQJRI GDWDREWDLQHGIURP7KH&DQFHU*HQRPH$WODV'DWDDQGWKHVPDOO WKHPHFKDQLVPVRIDFWLYLW\RI0)VKRXOGDVVLVWHႇRUWVWRRSWLPL]H 51$SUR¿OHVRISDWLHQWGHULYHG[HQRJUDIWVDPSOHV:HVXEVHTXHQWO\ its utility. GLVFRYHUHG WKDW D IXQFWLRQDO RQF51$ WHUPHG7S RULJLQDWLQJ IURP the 3’ end of TERC, acts as a broad regulator of gene expression and 331 3KRVSKRJO\FHUDWH0XWDVHLVD0HWDEROLF5HJXODWRU is a robust promoter of breast cancer metastasis. We found that T3p RI0\RJHQLF'LIIHUHQWLDWLRQ H[HUWVLWVSURPHWDVWDWLFHႇHFWVE\LQWHUDFWLQJZLWKWKH5,6&FRPSOH[ David Zhao DQGLQFUHDVLQJWKHH[SUHVVLRQRISURPHWDVWDWLFJHQHV1835DQG 8QLYHUVLW\RI&KLFDJR'HHU¿HOG86$ 3$1;2XU¿QGLQJVUDLVHWKHSRVVLELOLW\WKDWIXUWKHUH[DPLQDWLRQRI WKHFDQFHUVSHFL¿F51$ODQGVFDSHDQGLQYHVWLJDWLRQLQWRRQF51$V Myogenesis, the formation of skeletal muscle tissue, is contingent may yield novel strategies in developing diagnostic and therapeutic RQ WKH SUROLIHUDWLRQ DQG VXEVHTXHQW GLႇHUHQWLDWLRQ RI VDWHOOLWH FHOO methods across many cancer types. derived myoblasts into multinucleated myotubes, which eventually \LHOGIXQFWLRQDOO\PDWXUHPXVFOH¿EHUV7KHVKLIWIURPSUROLIHUDWLQJ 330 Strain-dependent activation and inhibition of Human P\REODVWVWRGLႇHUHQWLDWHGP\RWXEHVLVGULYHQE\GUDVWLFPRGL¿FDWLRQV ,PPXQRGH¿FLHQF\9LUXVHQWU\E\D3)GLDVWHUHRPHU to aggregate metabolic activity, but it is not precisely understood how Connie A. Zhao this important metabolic shift occurs. C2C12 is a mouse murine Dana-Farber Cancer Institute, USA myogenic cell line that undergoes rapid myoblast proliferation and myotube formation. We sought to determine the metabolic switch +XPDQ,PPXQRGH¿FLHQF\9LUXV +,9 HQWU\LQWRFHOOVLVPHGLDWHG WKDWRFFXUVGXULQJWKHVKLIWIURPSUROLIHUDWLRQWRGLႇHUHQWLDWLRQ:H E\ WKH HQYHORSH (QY WULPHU RI JS DQG JS KHWHURGLPHUV IRXQG WKDW DV && P\REODVWV GLႇHUHQWLDWH WKH\ H[KLELW D ORZHU 6HTXHQWLDO ELQGLQJ WR WKH WDUJHW FHOO UHFHSWRUV &' DQG &&5 glycolytic rate and increased mitochondrial respiration. Paradoxically, RU &;&5 WULJJHUV WKH PHWDVWDEOH (QY WR XQGHUJR HQWU\UHODWHG GHVSLWH D UHGXFWLRQ LQ JO\FRO\VLV GLႇHUHQWLDWLRQ LQGXFHV LQFUHDVHG FRQIRUPDWLRQDO FKDQJHV 3) ZDV UHFHQWO\ LGHQWL¿HG DV D expression of phosphoglycerate mutase 2 (Pgam2), a glycolytic VPDOO PROHFXOH WKDW LQKLELWV LQIHFWLRQ RI D VXEVHW RI +,9 VWUDLQV enzyme abundant in skeletal muscle that reversibly catalyzes the by interfering with an Env function other than receptor binding, with HLJKWKVWHSRIJO\FRO\VLVFRQYHUWLQJSKRVSKRJO\FHUDWH 3* LQWR UHVLVWDQFHGHWHUPLQDQWVPDSSLQJWRWKHJSGLVXO¿GHORRS '6/ SKRVSKRJO\FHUDWH 3* 3JDPLVFRQFRPLWDQWO\XSUHJXODWHGZLWK and the gp120 C5 region. We investigated the antiviral mechanism RWKHUNQRZQP\RJHQLFGLႇHUHQWLDWLRQPDUNHUVVXFKDVWUDQVFULSWLRQ RI3) factors myogenin (Myog) and myogenic determination protein 5HFRPELQDQW OXFLIHUDVHH[SUHVVLQJ +,9 SVHXGRW\SHG E\ ZLOG 0\R' P\RVLQKHDY\FKDLQ¿EHUSURWHLQVDQGFUHDWLQHNLQDVH &NP W\SH :7 RU PXWDQW +,9 (QYV ZDV LQFXEDWHG ZLWK LQFUHDVLQJ Importantly, we found that Pgam2 is required for C2C12 myogenic

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GLႇHUHQWLDWLRQ DV VL51$ NQRFNGRZQ RI 3JDP UHVXOWV LQ PDUNHG 333 Chemotherapy augments recombinant oncolytic GHFUHDVHLQWKHH[SUHVVLRQRIP\RJHQLFGLႇHUHQWLDWLRQPDUNHUV6LQFH SROLRYLUXVHI¿FDF\IRUWUHDWPHQWRIJOLREODVWRPD 3JDPFDWDO\]HVDELGLUHFWLRQDOUHDFWLRQLWSOD\VDUROHQRWRQO\LQ Justin Zhuo glycolysis but also in gluconeogenesis. We found that enzymes of Duke University Medical Center, USA gluconeogenesis, including phosphoenolpyruvate carboxykinase 1 3FN DQGJOXFRVHSKRVSKDWDVH *3& DUHXSUHJXODWHGGXULQJ *OLREODVWRPD *%0 WKH PRVW FRPPRQ SULPDU\ PDOLJQDQW EUDLQ P\RJHQLFGLႇHUHQWLDWLRQ,QVXPPDU\WKHVHUHVXOWVVXJJHVW3JDP tumor in adults, is a highly lethal cancer with nearly all patients LVUHTXLUHGIRUP\RJHQLFGLႇHUHQWLDWLRQ8SUHJXODWLRQRI3JDPDQG experiencing tumor recurrence after standard of care surgery, gluconeogenesis enzymes while glycolysis is reduced suggest that radiation, and chemotherapy. Thus, novel therapeutic strategies are Pgam2 may play a role in metabolic reprogramming during myogenic XUJHQWO\ PDQGDWHG 3965,32 LV D KLJKO\DWWHQXDWHG UHFRPELQDQW GLႇHUHQWLDWLRQ polio:rhinovirus chimera that has demonstrated promising and robust clinical and radiographic responses in phase I clinical trials 332 21& ,QKLELWV +,9 5HSOLFDWLRQ ,Q +XPDQ IRU UHFXUUHQW *%0 3965,32 FDXVHV GLUHFW WXPRU F\WRWR[LFLW\ 0DFURSKDJHV9LD)2;2$DQG71)6) YLD ELQGLQJ WR WKH &' SROLRYLUXV UHFHSWRU H[SUHVVHG LQ *%0 5XQ]H=KDR and virtually all solid neoplasms. Eliciting type I interferon signals University of Nebraska Medical School, omaha, USA in antigen presenting cells leads to robust innate and adaptive antitumor immunity. An unexpected discovery during the phase I trial Background: +,9 HQWHUV WKH &16 HDUO\ LQ WKH DFXWH VWDJHV RI was the achievement of complete and durable responses in patients LQIHFWLRQDQGUHPDLQVVKHOWHUHGLQWKH&167KHORQJOLYHGFHOOVLQ ZKRZHUHWUHDWHGZLWKVLQJOHGRVHFKHPRWKHUDS\PRQWKVDIWHUWXPRU WKH&16LQFOXGLQJSHULYDVFXODUPDFURSKDJHVDQGPLFURJOLDVXSSRUW SURJUHVVLRQIROORZLQJ3965,32LQIXVLRQ7KLVOHGWRWKHLQLWLDWLRQRI SURGXFWLYH+,9LQIHFWLRQDQGPD\FRQWULEXWHWRWKHYLUDOUHVXUJHQFH DQ RQJRLQJ SKDVH ,, WULDO FRPSDULQJ WKH HႈFDF\ RI 3965,32 DQG 'HVSLWHHႇHFWLYHF$57HUDGLFDWLRQRI+,9IURPWKHVHUHVHUYRLUFHOOV VLQJOHGRVHFKHPRWKHUDS\WR3965,32DORQH UHPDLQVHOXVLYH7UDQVFULSWLRQIDFWRU)2;2DDQG71)VXSHUIDPLO\ F\WRNLQH71)6)DUHNQRZQWRWDUJHWV+,9LQIHFWHGPDFURSKDJHV The goal of this study is to elucidate the therapeutic mechanisms IRUDSRSWRVLV21&LVDQRYHODQGSRWHQWVPDOOPROHFXOH)2;2D RI FRPELQHG 3965,32 DQG VLQJOHGRVH O\PSKRGHSOHWLYH DFWLYDWRUFDSDEOHRILQGXFLQJ71)6),WLVRUDOO\DFWLYHFDQFURVV chemotherapy using syngeneic mouse tumor models. 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Tumor PRQLWRUHG E\ +,9 UHYHUVH WUDQVFULSWDVH DFWLYLW\ S OHYHOV DQG caliper measurement data and survival analyses demonstrate that WZRVWHS$OXEDVHGQHVWHG3&5)RULQYLYRVWXGLHV+,9LQIHFWHG combination treatment decreases tumor growth and increases macrophages were intracranially injected into the basal ganglia of overall survival compared to either treatment alone. Furthermore, 12'VFLG,/5JFQXOO PLFH 0LFH ZHUH LQWUDSHULWRQHDOO\ LQMHFWHG HDUO\ÀRZF\WRPHWU\DQDO\VHVRILQWUDWXPRUDOO\PSKRF\WHSRSXODWLRQV GDLO\ZLWK21&RU'062IRUGD\VEHIRUHWKHFROOHFWLRQRIEUDLQ VXJJHVW WKDW FKHPRWKHUDS\ DGPLQLVWUDWLRQ IROORZLQJ 3965,32 WLVVXHV%UDLQ+,9SOHYHOVZHUHGHWHUPLQHGE\:HVWHUQEORWDQG WUHDWPHQWPD\LQGXFHPHPRU\7FHOODQGUHJXODWRU\7FHOOLQ¿OWUDWLRQ LPPXQRKLVWRFKHPLVWU\6ROXEOH71)6)UHFHSWRUDQGVL51$VIRU RIWKHWXPRU2QJRLQJH[SHULPHQWVXWLOL]LQJWHPR]RORPLGHUHVLVWDQW )2;2DZHUHXVHGWREORFN71)6)DQG)2;2DUHVSHFWLYHO\ cell lines will serve to better highlight the role of chemotherapy in 6WDWLVWLFDODQDO\VLVZDVSHUIRUPHGXVLQJWKHRQHZD\$129$ZLWK restoring antitumor immunity by minimizing its ability to cause direct Tukey’s multiple comparison test. P < 0.05 was considered as tumor cytotoxicity. 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136 2018 AAP / ASCI / APSA Joint Meeting ORAL PRESENTATIONS & POSTER ABSTRACTS AUTHOR INDEX

www.jointmeeting.org

www.jointmeeting.org 137 ORAL PRESENTATIONS & POSTER ABSTRACTS AUTHOR INDEX

APSA Trainee Oral Presentations Index AUTHOR PAGE ĞƌƌǇ͕<ĂǇůĂ ϭ Ϯϱ ^ŵĞƐƚĂĚ͕:ŽŚŶ Ϯ Ϯϱ

Poster Abstracts Author Index AUTHOR POSTER PAGE AUTHOR POSTER PAGE AUTHOR POSTER PAGE A ƌĞŶƚ͕:ŽŶĂƚŚĂŶ Ϯϲ ϯϰ ŚƵŶŐ͕^ŚĂŶŐͲ>ŝŶ ϱϮ ϰϯ ďĞĐĂƐƐŝƐ͕ĂĐŚĂƌǇ͘ ϭ Ϯϲ ƌŝŐŐƐ͕EĞŝŵĂ Ϯϳ ϯϰ ŽŽŵĞƌ͕ŚĂƌůĞƐ ϱϯ ϰϯ ĚĞůĂũĂ͕ĚĞǁƵŶŵŝ Ϯ Ϯϲ ƌŝŶŬůĞǇ͕'ĂƌƌĞƩ Ϯϴ ϯϰ ŽƌŬƌƵŵ͕DŝĐŚĞůůĞ ϱϰ ϰϯ ůŚĂǇďŝ͕KŵĂƌ ϯ Ϯϲ ƌŝƐĐŽĞ͕:ĞƐƐŝĐĂ͘ Ϯϵ ϯϱ ŽǀĞƐͲĂƚƐŽŶ͕ǀĞůǇŶ ϱϱ ϰϰ ůĐŽƌĞǌĂ͕KƐĐĂƌ͘ ϰ Ϯϳ ƌŽŽŬĞ͕ĞǁĞǇ ϯϬ ϯϱ ƵůůĞǇ͕DŝƌĂŶĚĂ ϱϲ ϰϰ ƵĐŚĂŶĂŶ͕<ĞůůǇ>͘ ϯϭ ϯϱ ůŝŶŐĞƌ͕:ŽƐŚƵĂ ϱ Ϯϳ D ůŵŝƌŽŶŽŶŶŝŶ͕ĂŵŝĂŶ ϲ Ϯϳ ƵŶŐĂƌƚ͕ƌŝƩĂŶŝ ϯϮ ϯϲ ĂƌĚŝĐŬ͕:ŽƐĞƉŚD͘ ϱϳ ϰϱ ůŽŝ͕:ŽƐĞƉŚ ϳ Ϯϴ C ĚĞƐ:ĂƌĚŝŶƐͲWĂƌŬ͕,ĞĂƚŚĞƌ͘ ϱϴ ϰϱ ŵĂůƌĂũ͕^ĂƌĂŚ<͘ ϴ Ϯϴ ĂƐĂŽƐ͕:ŽƐŚƵĂ ϯϯ ϯϲ ŚŝůůŽŶͲ:ŚĂƩƵ͕^ĂŶŐĞĞƚ ϱϵ ϰϲ Ameri, Amir H. 9 28 ŚĂŶĚƌĂ͕ŶŬƵƐŚ ϯϰ ϯϲ ŚŝŶŐƌĂ͕ŶƐŚƵů ϲϬ ϰϲ ŶĂŶĚĂƉƉĂ͕ŶŶĂďĞůůĞ:͘ ϭϬ Ϯϴ ŚĂŶŐ͕,ƐŝĂŶŐͲŚƵŶ ϯϱ ϯϳ ŽŶŐ͕DŝĐŚĂĞů ϲϭ ϰϲ ƌĂŽ͕ŝĂŶĐĂ ϭϭ Ϯϵ ŚĂŶŐ͕>ĞƐůŝĞ>͘ ϯϲ ϯϳ Dues, Dylan 62 46 ƌŝĂŐŶŽ͕^ǇĚŶĞǇE͘ ϭϮ Ϯϵ ŚĂƵŶǌǁĂ͕dĂĨĂĚǌǁĂ ϯϳ ϯϳ ǁĂŚ͕͘ĚŵŽŶĚ ϭϯ ϯϬ ŚĞŶ͕ǇŶƚŚŝĂ ϯϴ ϯϴ E B ŚĞŶ͕:ĂƐƉĞƌZ͘ ϯϵ ϯϴ ƌŝĐŬƐŽŶ͕,ĂŶŶĂ ϲϯ ϰϳ ƐƐĞŐŝĂŶ͕ĞƌĞŬ ϲϰ ϰϳ ĂĐŽŶ͕EŝĐŬŽůĂƐ ϭϰ ϯϬ ŚĞŶ͕Yŝ>ŝĂŶŐ ϰϬ ϯϴ ƐƐƵŵĂŶ͕<Žǁ ϲϱ ϰϳ ĂŶĞƌũĞĞ͕ďŚŝŬ ϭϱ ϯϬ ŚĞŶ͕^ƚĞůůĂy͘ ϰϭ ϯϵ ƵƐƚĂĐĞ͕EŝĐŚŽůĂƐ ϲϲ ϰϴ ĂƐƚĂ͕ŵĞĞƌ ϭϲ ϯϬ ŚĞŶŐ͕ŶŶĂD͘ ϰϮ ϯϵ ĂǇĂŶũĂƌŐĂů͕ƌŝƵŶĂĂ ϭϳ ϯϭ ŚŽ͕ĞŶŶĞƚ^͘ ϰϯ ϯϵ F ŚŽ͕:ĂŶŝĐĞ ϰϰ ϰϬ ĞƌŐĞƌ͕ǀĂŶ ϭϴ ϯϭ &ĂŶ͕ĂƌŽŶ ϲϳ ϰϴ ŚŽŬƐŝ͕zĂƐŚ ϰϱ ϰϬ ĞƌŶ͕DŝĐŚĂĞů ϭϵ ϯϭ &ĂŶ͕>ŝǇĂŶ ϲϴ ϰϴ ŚŽƵĚŚƵƌǇ͕^ŽŶŐŝƚĂ ϰϲ ϰϬ ŚĂŶƐĂůŝ͕ZĂŚƵů^͘ ϮϬ ϯϮ &ĂƌŵĞƌ͕ƌĂŶĚŽŶ ϲϵ ϰϵ ŚƌŝƐƚĞŶƐĞŶ͕WĂƵů ϰϳ ϰϭ ŝŶŶƐ͕dŚŽŵĂƐ͘ Ϯϭ ϯϮ &ĂƌƌĂƌ͕:ĂƌĞĚ ϳϬ ϰϵ ŚƵ͕^ŝŵŽŶE͘ ϰϴ ϰϭ ŝƌŽ͕ĂŶŝĞů ϮϮ ϯϮ &ĂƟŵĂ͕EŽŽƌ ϳϭ ϰϵ ŚƵŶŐ͕:ĞŶŶŝĨĞƌ ϰϵ ϰϮ ůĂǇŶĞǇ͕ůĂŶ Ϯϯ ϯϮ &ĞĚŽƌŽǀĂ͕KůŐĂ ϳϮ ϱϬ ŚƵŶŐ͕DŝĐŚĂĞů ϱϬ ϰϮ ŽůŝĐŬ͕EŝĐŽůĞ Ϯϰ ϯϯ &ŝŶĞ͕ZĞďĞĐĐĂ>͘ ϳϯ ϱϬ ŚƵŶŐ͕DŝĐŚĞůůĞ:͘ ϱϭ ϰϮ ƌĂŵĂŚͲ>ĂǁĂŶŝ͕DĂƌŝĂŵ Ϯϱ ϯϯ &ŝƐĐŚĞƌ͕ĂǀŝĚ ϳϱ ϱϭ

138 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS AUTHOR INDEX

AUTHOR POSTER PAGE AUTHOR POSTER PAGE AUTHOR POSTER PAGE &ůŽƌĞƐ͕ůǇƐƐĂD͘ ϳϲ ϱϭ ,ĂƌĂƐǇŵŝǁ͕>ĂƵƌĞŶ ϭϭϭ ϲϮ :ĂǀŝĚŝͲ^ŚĂƌŝĮ͕EĂƚŚĂůŝĞ ϭϰϮ ϳϮ &ůŽƌĞƐ͕'ƵŝůůĞƌŵŽ ϳϳ ϱϭ ,ĂƌĚǇ͕>ĂƵƌĂ ϭϭϮ ϲϮ :ĞĂŶͲĂƉƟƐƚĞ͕^ĂŵƵĞů ϭϰϯ ϳϯ &ŽŶŐ͕:ĞƌƌǇ ϳϴ ϱϮ ,ĂƌǀĞǇ͕>ůŽǇĚ ϭϭϯ ϲϯ :ŽŚŶƐŽŶ͕DĂƌƟŶ ϭϰϰ ϳϯ &ƌĂŶƚǌĞƐŬĂŬŝƐ͕ůĞǆŝĂ ϳϵ ϱϮ ,ĂƐĞŶŽĞŚƌů͕ƌŝŬ ϭϭϰ ϲϯ :ŽƐŚŝ͕^ƵŶŝů ϭϰϱ ϳϯ &ƌĂŶƚǌĞƐŬĂŬŝƐ͕DĞůŝŶĂ ϴϬ ϱϮ ,Ğ͕ŚĂŽ ϭϭϱ ϲϯ :ƵďďĂů͕^ĂŶĚĞĞƉ ϭϰϲ ϳϰ &ƌŝĞĚůĂŶĚ͕^ĐŽƩ ϴϭ ϱϯ ,ĞůĨĂŶĚ͕ĞŶũĂŵŝŶ ϭϭϲ ϲϰ &ƌŝĞĚůĂŶĚĞƌ͕DŽůůŝĞ ϴϮ ϱϯ ,ĞƌƌĞƌĂ͕:ŽŶĂƚŚĂŶ ϭϭϳ ϲϰ K ,ĞƌƌŝŶŐ͕ƌĞŶĚŽŶ ϭϭϴ ϲϰ <ĂƌŐŝŶŽǀ͕dŝŵŽĨĞǇ ϭϰϳ ϳϰ G ,ĞǇŵĂŶŶ͕'ĂďƌŝĞů ϭϭϵ ϲϱ <Ăǁ͕<ĂǀĞĞƚĂ ϭϰϴ ϳϰ 'ĂŝůůĂƌĚ͕:ŽŶĂƚŚĂŶZ͘ ϴϯ ϱϯ ,ŝůů͕<ĞůůǇ ϭϮϬ ϲϱ <ĂǁĂŶŝƐŚŝ͕<ƵŶŝŽ ϭϰϵ ϳϱ 'ĂůůŽ͕DĂƌǇ ϴϰ ϱϰ ,ŝŶĞƐ͕DĂƌĐƵƐ ϭϮϭ ϲϱ <ŚĂŶŽůŬĂƌ͕ĂƌƵŶŝ ϭϱϬ ϳϱ 'ĂůůŽ͕ZǇĂŶ ϴϱ ϱϰ ,ŽĐŬĞŵĞǇĞƌ͕<ĂƚĞ ϭϮϮ ϲϱ <ŝŵ͕ůůŝƐ ϭϱϭ ϳϲ 'ĂůǀĂŶ͕ĚƌŝD͘ ϴϲ ϱϱ ,ŽĚĂƌĂ͕ŵŵĂŶƵĞůůĞ ϭϮϯ ϲϲ <ŝŵ͕hƌŝĞů ϭϱϮ ϳϲ 'ĂƌďĞƌ͕ŚĂƌŝƐĞ ϴϳ ϱϱ ,ŽŶ͕tŝŶ ϭϮϰ ϲϲ <ŝŵ͕zŽŶŐ,ŽŽŶ ϭϱϯ ϳϲ 'ĂƌĮŶŬĞů͕ŵĂŶĚĂ ϴϴ ϱϱ ,ƐŝĞŚ͕:ƵƐƟŶ ϭϮϱ ϲϲ <ŝŶĚƐĨĂƚŚĞƌ͕ƵĚƌĞǇ:͘ ϭϱϰ ϳϳ 'ĂƌŐ͕ŶƵƉĂŵ ϴϵ ϱϲ ,ƐŝĞŚ͕WĂŝƐŚŝƵŶ ϭϮϲ ϲϳ <ŝŶŐ͕>ŝĂŵ ϭϱϱ ϳϳ 'ĞǌĞƌ͕ǇƐĞŐƵů ϵϬ ϱϲ ,ƐƵ͕/ƐĂďĞů ϭϮϳ ϲϳ <ůĞŵĞŶƚ͕:ŽŚŶ ϭϱϲ ϳϳ 'ŝĂŶƟŶŝ>ĂƌƐĞŶ͕ůĞǆĂŶĚƌĂD͘ ϵϭ ϱϲ ,Ƶ͕:ĞŶŶŝĨĞƌ͘t͘ ϭϮϴ ϲϳ <ŽĐŚĂŶĞŬ͕DĂůŐŽƌǌĂƚĂ ϭϱϳ ϳϴ 'ŝů͕EĞůƐŽŶ ϵϮ ϱϳ ,ƵŶŐ͕WƵƚǌĞƌ ϭϮϵ ϲϴ <ŽǌĞŬ͕<ƌǇƐƟĂŶ ϭϱϴ ϳϴ 'ŝůůŝƐͲƵĐŬ͕ǀĂD͘ ϵϯ ϱϳ ,ƵǇŶŚ͕dŝĞŶͲWŚĂƚ ϭϯϬ ϲϴ <ŽǌĞŬ͕>ŝŶĚƐĂǇ ϭϱϵ ϳϵ 'ŽŵĞǌͲEŐƵǇĞŶ͕ĚƌŝĂŶ ϵϱ ϱϴ ,ǁĂŶŐ͕ŚĂƌůĞƐ ϭϯϭ ϲϴ <ƌĂŵĞƌ͕ĂŶŝĞů ϭϲϬ ϳϵ 'ŽƟĂŶ͕ZƵƚŚ ϵϲ ϱϴ <ƌĞƐƐ͕ĞŶũĂŵŝŶd͘ ϭϲϮ ϳϵ 'ƌĂũĂůĞƐͲZĞǇĞƐ͕:ŽƐĞ ϵϳ ϱϴ I <ƌƵĞŐĞƌ͕>ĂƵƌĂ ϭϲϯ ϴϬ 'ƌĂƐƐŵĞǇĞƌ͕:ƵƐƟŶ ϵϴ ϱϵ /ŵƉĞƌŝĂůĞ͕dŚŽŵĂƐ ϭϯϮ ϲϵ <ƵůďĞ͕:ĂĐƋƵĞůŝŶĞ ϭϲϱ ϴϬ 'ƌĞĞŶ,ĂŶĞǇ͕DĞŐŚĂŶ ϵϵ ϱϵ /ŶŶŝƐƐ͕ŽŶŽǀĂŶ ϭϯϯ ϲϵ <ǁĞŬ͕^ǁĞĞ^ĞŶ ϭϲϲ ϴϭ 'ƌŝŐŽƌŽǀĂ͕zƵůŝĂ ϭϬϬ ϱϵ /ƌŽŶƐ͕ƌŝĐ ϭϯϰ ϲϵ 'ƌŽŽƉŵĂŶ͕ŵŝůǇ ϭϬϭ ϲϬ /ƐůĂŵ͕ŝĂŶĐĂ ϭϯϱ ϳϬ L 'ƌƵŶďůĂƩ͕ůŝ ϭϬϮ ϲϬ /ƐƚǀĂŶŝĐ͕&ŝůŝƉ ϭϯϲ ϳϬ >ĂĚŚĂ͕&ĞƌŝĂ ϭϲϳ ϴϭ 'ƵĂŶ͕DĂƌǇ>͘ ϭϬϯ ϲϭ /ƚŽŚ͕ŚƌŝƐƚŽƉŚĞƌz͘ ϭϯϳ ϳϭ >Ăǁ͕ƌĂŶĚŽŶD͘ ϭϲϴ ϴϭ 'ƵƉƚĂ͕ĚŝƟ ϭϬϱ ϲϭ >ĞĞ͕^ƚĞƉŚĂŶŝĞ ϭϳϬ ϴϭ 'ƵƌƵ͕WĂƌĚĞĞƉ ϭϬϲ ϲϭ J >ĞŵŝĞƵǆ͕DĂĐŬĞŶǌŝĞ ϭϳϭ ϴϮ :ĂĐŬƐŽŶ͕ŚƌŝƐƚŽƉŚĞƌ͘ ϭϯϴ ϳϭ >ĞŽŶĂƌĚ͕ĂŶŝĞů ϭϳϮ ϴϮ H :ĂĐŬƐŽŶ͕,ƵĚŝŶE͘ ϭϯϵ ϳϭ >ĞŽŶĂƌĚŽ͕dƌĞǀŽƌ ϭϳϯ ϴϯ ,ĂďŝŵĂŶĂͲ'ƌŝĸŶ͕>ĞDŽǇŶĞ ϭϬϳ ϲϮ :ĂĐŬƐŽŶ͕:ŽƐŚƵĂ ϭϰϬ ϳϮ >ĞƌŵĂŶͲ^ŝŶŬŽī͕Žǀ ϭϳϰ ϴϯ ,ĂŐŽŽĚ͕DĂĚĞůĞŝŶĞ ϭϬϴ ϲϮ :ĂĐŽď͕ŶũĂůŝ ϭϰϭ ϳϮ >ĞǀĞƌ͕:ĞƌĞŵŝĞ ϭϳϱ ϴϯ

www.jointmeeting.org 139 POSTER ABSTRACTS AUTHOR INDEX

AUTHOR POSTER PAGE AUTHOR POSTER PAGE AUTHOR POSTER PAGE >ĞǀŝŶ͕^ŽůŽŵŽŶE͘ ϭϳϲ ϴϰ DŝƐŚƌĂ͕ŶǀŝƚĂ ϮϭϬ ϵϱ WĞƫŶĂƚŽ͕ŶƚŚŽŶǇ Ϯϰϭ ϭϬϱ >ĞǀǇ͕ZĂĐŚĞů ϭϳϳ ϴϰ DŝƩĞůƐƚĞŝŶ͕ĂǀŝĚ Ϯϭϭ ϵϲ WŚŝůůŝƉƐ͕DĂƩŚĞǁ ϮϰϮ ϭϬϲ >ŝ͕>ƵĐǇ ϭϳϴ ϴϰ DŽŶƚĞůŽŶŐŽ,ĞƌŶĂŶĚĞǌ͕ĞƐĂƌ 212 96 WŽŵĂǀŝůůĞ͕DŽŶŝĐĂD͘ Ϯϰϯ ϭϬϲ >ŝ͕^ĞůĞŶĂ^͘ ϭϳϵ ϴϱ DŽŽƌĞ͕ƵƐƟŶ͘ Ϯϭϯ ϵϲ >ŝ͕^ŽŶŐũƵŶ ϭϴϬ ϴϱ DŽƌƌŝƐƐĞǇ͕^ĂŵĂŶƚŚĂ Ϯϭϰ ϵϳ Q >ŝ͕^ƚĞƉŚĞŶ ϭϴϭ ϴϱ DŽƚǁĂŶŝ͕<ĂƌƟŬ Ϯϭϱ ϵϳ YƵƌĞƐŚŝ͕&ĂƌŚĂŶ Ϯϰϰ ϭϬϲ >ŝ͕zƵƉŝŶŐ͘ ϭϴϯ ϴϱ DƵũĂŚŝĚ͕EŝƐŵĂ Ϯϭϲ ϵϳ R >ŝĞŶŐ͕DŽŶŝĐĂ ϭϴϰ ϴϲ DƵƌƌĂǇ͕DĞŐŚĂŶ Ϯϭϳ ϵϴ ZĂŚŵĂŶ͕<ĂƌŝƐŚŵĂ Ϯϰϳ ϭϬϳ >ŝŵ͕ĂƌŽŶ ϭϴϱ ϴϲ ZĂůī͕DĂƌŝĞ Ϯϰϴ ϭϬϳ >ŝŶ͕,ƐŝŶͲWŝŶ ϭϴϲ ϴϳ N ZĂŵďĂƌĂƚ͕WĂƵůĂ<͘ Ϯϰϵ ϭϬϳ >ŝŶ͕zĞŶͲEĂŶ ϭϴϳ ϴϳ E͘DĞŶĚĞƐEĞƚŽ͕EŝůƐŽŶ Ϯϭϴ ϵϴ ZĂŶĚĂůů͕DŝĐŚĂĞůW͘ ϮϱϬ ϭϬϴ >ŝƵ͕ŽŶŶŽƌ:͘ ϭϴϴ ϴϳ EĂŌĂůŽǀŝĐŚ͕ĂŶŝĞů Ϯϭϵ ϵϵ ZĂŶŐĞůZŝǀĞƌĂ͕'ƵŝůůĞƌŵŽ Ϯϱϭ ϭϬϴ >ŝƵ͕^ŚŝŵĞŶŐ ϭϴϵ ϴϳ EĞŝůƐĞŶ͕ĞƚŚ ϮϮϬ ϵϵ ZĂǁĂƚ͕ZŝƐŚŝ ϮϱϮ ϭϬϵ >ŽĐǇ͕DŽƌŐĂŶ ϭϵϬ ϴϴ EĞǀĞƐ͕'ĂďƌŝĞů&͘ ϮϮϮ ϵϵ ZĞĂƐŽŶĞƌ͕ƌŝŶ Ϯϱϯ ϭϬϵ >ŽǁŶŝŬ͕:ŽƐĞƉŚ ϭϵϭ ϴϴ EŐƵǇĞŶ͕ŝĐŚdƌĂŵ ϮϮϯ ϵϵ ZĞĞĚ͕ŚĞůƐĞǇ Ϯϱϰ ϭϬϵ >ǇŶĐŚ͕ǀĂŶ ϭϵϮ ϴϵ EŐƵǇĞŶ͕&ƌĞĚĚǇ ϮϮϰ ϭϬϬ EŽĐŚ͕ǀĂŶ ϮϮϱ ϭϬϬ ZĞŐĞ͕EŝƐĐŚĂǇ Ϯϱϱ ϭϬϵ M EŽŐƵĐŚŝ͕<ĞŶ ϮϮϲ ϭϬϬ ZŝĐŚĂƌĚƐŽŶ͕^ƉĞŶĐĞƌD͘ Ϯϱϲ ϭϭϬ DĂĐƵĸĞ͕ŵŝůǇ͘ ϭϵϯ ϴϵ EǁĂĨŽƌ͕ŝǀŝŶĞ ϮϮϳ ϭϬϭ ZŝĐŬ͕:ŽŶĂƚŚĂŶt͘ Ϯϱϳ ϭϭϬ DĂŝĂ͕:ĞƐƐŝŬĂd͘ĚĂ^͘ ϭϵϰ ϴϵ ZŽůŶŝĐŬ͕<ĞǀŝŶ/͘ Ϯϱϴ ϭϭϬ DĂŝĚĞŶ͕DŝĐŚĂĞů ϭϵϱ ϵϬ O ZŽƐĂŶǁŽ͕dŽůƵůŽƉĞK͘ Ϯϱϵ ϭϭϭ DĂƌƌĞ͕ŵŝůǇ͘ ϭϵϲ ϵϬ KĞƚũĞŶ͕>ĂŶĚŽŶ ϮϮϴ ϭϬϭ ZŽƐĞŶ͕ƌĂŶĚŽŶ ϮϲϬ ϭϭϭ DĂƌƟŶ͕ŶŶĂZ͘ ϭϵϳ ϵϬ KŚ͕^ĂŶĚĞƌƐ ϮϮϵ ϭϬϭ ZŽǇͲK͛ZĞŝůůǇ͕DĞĂŐŚĂŶ Ϯϲϭ ϭϭϭ KƌƟǌ͕ZŽďŝŶ ϮϯϬ ϭϬϮ DĂƌƟŶŝ͕DŝĐŚĂĞů ϭϵϴ ϵϭ S DĂƐƌŝ͕DŽŚĂŵĂĚ&ĂĚŚůŝ ϭϵϵ ϵϭ KƐǁĂůĚ͕ĂƌŽŶ͘ Ϯϯϭ ϭϬϮ ^ĂĞŶǌ͕:ŽƐĞ ϮϲϮ ϭϭϮ DĂƚĂƐŝĐ͕ĂŶŝĞů ϮϬϬ ϵϭ KǌŽŐ͕^ƚŽƐŚ ϮϯϮ ϭϬϮ ^ĂŚĂ͕ŶũĂŶ Ϯϲϯ ϭϭϮ DĂƵƌĂŶŽ͕DĞŐĂŶ ϮϬϭ ϵϮ P ^ĂŚĂǇ͕^ĂŶĚĞĞƉ Ϯϲϰ ϭϭϯ DĂǇ͕:ĂƐŵŝŶĞ ϮϬϮ ϵϮ WĂůŵĞƌ͕ůůǇƐŽŶ Ϯϯϯ ϭϬϯ ^ĂŝŽŶǌ͕ůŝǌĂďĞƚŚ Ϯϲϱ ϭϭϯ DĐĂǁ͕dǇůĞƌ ϮϬϯ ϵϯ WĂƌŬ͕:ŽƐĞƉŚ^͘ Ϯϯϰ ϭϬϯ ^ĂŶĚŽǀĂů͕ĂƌŽŶ'ĂďƌŝĞů Ϯϲϲ ϭϭϯ DĐ'ĞĞ͕tĂƌƌĞŶ ϮϬϰ ϵϯ WĂƚĞů͕Ƶŵ Ϯϯϱ ϭϬϯ ^ĂƌƐŽƵƌ͕dŝĂŶĂ Ϯϲϳ ϭϭϰ DĐ<ŝŶŶŽŶ͕ŵŝůŝĞ ϮϬϱ ϵϯ WĂƚĞů͕dŝƌƚŚ Ϯϯϲ ϭϬϰ ^ĐŽƩ͕ƐŚůĞǇ Ϯϲϴ ϭϭϰ DĞŝĞƌ͕>ĞĞ ϮϬϲ ϵϰ WĂƵĚĞů͕WƌĂǀĞĞŶ Ϯϯϳ ϭϬϰ ^ĞǁĂŶĂŶ͕>ŽƌĞŶǌŽ Ϯϲϵ ϭϭϰ DĞŶƐĂŚ͕<ŽĮ ϮϬϳ ϵϰ WĞĂďŽĚǇ͕:ĂĐĞůǇŶ Ϯϯϴ ϭϬϰ ^ŚĂŚ͕,ĂƌƐŚE͘ ϮϳϬ ϭϭϱ DŝĞƚƵƐ͕ŽŶƐƚĂŶĐĞ ϮϬϴ ϵϱ WĞŶŶǇ͕DŽƌŐĂŶ Ϯϯϵ ϭϬϱ ^Śŝ͕ŝĂŶĂ͘ Ϯϳϭ ϭϭϱ DŝůĞǀĂ͕'ůŽƌŝĂ ϮϬϵ ϵϱ WĞƌĞǌͲZĂƚŚŬĞ͕ůĂŶ ϮϰϬ ϭϬϱ ^ŚŝƵĂŶ͕ŝůĞĞŶ ϮϳϮ ϭϭϲ

140 2018 AAP / ASCI / APSA Joint Meeting POSTER ABSTRACTS AUTHOR INDEX

AUTHOR POSTER PAGE AUTHOR POSTER PAGE AUTHOR POSTER PAGE ^ŝŵŽ͕KƌŶĞůůĂ͘ Ϯϳϯ ϭϭϲ dƌĂŶ͕>ǇŶŶ Ϯϵϱ ϭϮϰ tŝůĐŽǆ͕EŝĐŚŽůĂƐ^͘ ϯϭϰ ϭϯϬ ^ŝŵƉƐŽŶ͕ZĂĐŚĞů Ϯϳϰ ϭϭϲ dƌĂŶ͕WĂƵů Ϯϵϲ ϭϮϰ tŽŶŐ͕sŝǀŝĂŶ ϯϭϲ ϭϯϭ ^ŝƐŽŶ͕ŚƌŝƐƟĂŶŐĞůĂ Ϯϳϱ ϭϭϳ dƵƌďĞǀŝůůĞ͕,ĂŶŶĂŚ Ϯϵϳ ϭϮϱ tƵ͕^ĂƌĂŚ ϯϭϳ ϭϯϭ ^ůĞŝŐŚƚŚŽůŵ͕ZŝĐŚĂƌĚ Ϯϳϲ ϭϭϳ dƵƌŶďƵůů͕<ĂƚŚĞƌŝŶĞE͘ Ϯϵϴ ϭϮϱ >ƵďďĞƌƐ͕ůůĞŶ Ϯϳϳ ϭϭϴ dǇůĞƌ͕EŝĐŚŽůĞ Ϯϵϵ ϭϮϲ X ^ŵŝƚŚ͕ŶĚƌĞǁ Ϯϳϴ ϭϭϴ yŝĂ͕zƵĂŶǆƵĂŶ ϯϭϴ ϭϯϭ ^ŽŚŶ͕ŶĚƌĞǁD͘ Ϯϳϵ ϭϭϴ U yƵ͕DĂƌŝĂ ϯϭϵ ϭϯϮ hŵĂƉĂƚŚŝ͕WƌŝǇĂ ϯϬϬ ϭϮϲ ^Žŵ͕ǀŝŬ ϮϴϬ ϭϭϴ Y ^ŽƵĚĞƌ͕:ĂĐůǇŶ Ϯϴϭ ϭϭϵ Updyke, Erin 301 126 zĂŵĂŵŽƚŽ͕ƌŝŶ͘ ϯϮϬ ϭϯϮ ^ƉĂƵƌ͕<ĞůƐĞǇD͘ ϮϴϮ ϭϭϵ hƌĞŶĂͲ'ŽŶǌĂůĞǌ͕<ĞŶŶǇ ϯϬϮ ϭϮϳ zĂŶŐ͕ĞŶũĂŵŝŶ ϯϮϭ ϭϯϯ ^ƉĞůůŝĐǇ͕^ĂŵĂŶƚŚĂ Ϯϴϯ ϭϭϵ V zŝůŵĂǌ͕ĂŚĂƌ ϯϮϯ ϭϯϯ ^ƚĞǀĂŶŽǀŝĐ͕DĂƌƚĂ Ϯϴϰ ϭϮϬ sĂŝƚŬƵƐ͕:ĂŶŝŶĂ ϯϬϯ ϭϮϳ zŽƐŚŝĚĂ͕DŝƚƐƵŬƵŶŝ ϯϮϰ ϭϯϯ ^ƚŽƌŵ͕ƌŝĐĂD͘ Ϯϴϱ ϭϮϬ sĂŶĞůŬƵŵ͕DĂǆ ϯϬϰ ϭϮϳ zŽƵŶŐ͕ůĞǆĂŶĚƌŝĂ ϯϮϱ ϭϯϰ ^ǁĞĞƚ͕ĂǀŝĚ Ϯϴϲ ϭϮϭ sĂŶĚĞǀĞŶ͕EĂƚĂůŝĞ ϯϬϱ ϭϮϴ Z T sĞůĞǌZĞǇĞƐ͕'ĞƌŵĂŶ ϯϬϲ ϭϮϴ ĂŚƌůŝ͕dǇůĞƌ ϯϮϲ ϭϯϰ dĂŝǁŽ͕ZƵŬĂǇĂƚD͘ Ϯϴϳ ϭϮϭ sŝĞƚĂ&ĞƌƌĞƌ͕ŵŝůĞ ϯϬϳ ϭϮϴ ŚĂŶŐ͕>ŝůůŝĂŶ ϯϮϳ ϭϯϰ dĂŶ͕^ǌĞ<ŝĂƚ Ϯϴϴ ϭϮϭ sŝůůĂĐƌĞƐĞƐ͕ZĂƵů ϯϬϴ ϭϮϵ ŚĂŶŐ͕^ƚĞǀĞŶ ϯϮϵ ϭϯϱ dĂŶ'ĂƌĐŝĂ͕ůĨŽŶƐŽ Ϯϴϵ ϭϮϮ W ŚĂŽ͕ŽŶŶŝĞ͘ ϯϯϬ ϭϯϱ dĞƌĞƐŚĐŚĞŶŬŽ͕ůĞǆĂŶĚĞƌ ϮϵϬ ϭϮϮ tĂĚŚǁĂŶŝ͕Ŷŝů ϯϬϵ ϭϮϵ ŚĂŽ͕ĂǀŝĚ ϯϯϭ ϭϯϱ dŚŽŵƉƐŽŶ͕:ŽƐŚƵĂ Ϯϵϭ ϭϮϯ tĂůŬĞƌ͕:ŽŚŶ ϯϭϬ ϭϮϵ ŚĂŽ͕ZƵŶǌĞ ϯϯϮ ϭϯϲ dŚŽŵƉƐŽŶ͕ZƵƐƐĞůů ϮϵϮ ϭϮϯ tĂŶŐ͕ŵǇ:͘ ϯϭϭ ϭϮϵ ŚƵŽ͕:ƵƐƟŶ ϯϯϯ ϭϯϲ dŽŶ͕ŵǇE͘ Ϯϵϯ ϭϮϰ tĂŶŐ͕ƌŶĞƐƚ ϯϭϮ ϭϯϬ dŽǇŽĚĂ͕zŽƐŚŝŬŽ Ϯϵϰ ϭϮϰ

www.jointmeeting.org 141 HOTEL FLOOR PLANS

Freight Elevator Storage

Cuvee Room Rouge Front Office Foyer Telephones Front Desk

Emergency Exit

Kitchen Lobby Level Eno Wine Room Emergency Private Exit Concierge Dining Room 1st Level k es D Bell To International Ballroom Level

Escalators to Lower Levels Main Entrance

Service Elevators

Public Elevators

Aria restaurant Porte-cochère Aria Entrance

Aria bar

Emergency Exit

Crystal Kosher Kitchen Room

Telephones Pre-Function Escala

to All Levels 3rd Level tors Down Service Elevators Pantry Emergency Exit

Public Elevato

rs Regent Chancellor Room Pre-Function Diplomat Room Room

142 2018 AAP / ASCI / APSA Joint Meeting HOTEL FLOOR PLANS

Exibitors Dock Freight Elevator Emergency Exit Emergency Exit and Ballroom Service

Garage Entrance

Imperial Kitchen Pantry Ballroom Intermediate Lake Street B2 Level Cashier Storage

Auto Lobby Imperial Office Emergency Exit B2 Level Entrance Exit Service Elevators Regal Public Elevators Room Pre-Function

Imperial Parlor Royal Escalators to Concourse and Lobby Room Emergency Exit Intermediate Columbus Drive B2 Level

Emergency Freight Exit Elevator

Gold Pantry International Room Ballroom

Emergency Exit Telephones

Emergency Exit Telephones Embassy Audiovisual Emergency 2nd Level Booth Escalators to All Levels Exit Room Stairs to Lobby

Pre-Function

Pantry Service Elevators

Public Elevators

Ambassador State Pre-Function Room Room

www.jointmeeting.org 143 NOTES

144 2018 AAP / ASCI / APSA Joint Meeting JOINT MEETING SPONSORS

PLATINUM

GOLD / ACADEMIC BENEFACTOR

National Institute of General Medical Sciences

SILVER / ACADEMIC SPONSOR

ACADEMIC FRIEND

BRONZE

IdZY]W`JĪWb_ghcJĪ]gOZWfÃg>ZbZfcīgIīddcfhZfg SAVE THE DATE

The next few annual meetings have been scheduled, so be sure to mark your calendars. AAP/ASCI/APSA JOINT MEETING THE PREMIER ANNUAL MEETING FOR PHYSICIAN-SCIENTISTS

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