3Rd Annual Stanford Drug Discovery Conference April 23-34, 2018

WINTER 2018 SPRING 2017

3rd Annual Stanford Drug Discovery Conference April 23-34, 2018

Kenneth Frazier, JD Joe Jimenez, MBA Brent Saunders, JD, MBA Bob Bradway, MBA Patrick Soon-Shiong, MD George Scangos, PhD CEO, Merck Former CEO, Novartis CEO, Allergan CEO, Amgen CEO, NantWorks CEO, Vir

Roy Vagelos, MD Janet Woodcock, MD Maria Millan, MD Gary Gibbons, MD Marc Tessier-Lavigne, PhD Brian Kobilka, MD Former CEO, Merck Director, FDA Center President, CIRM Director, NHLBI President Nobel Prize in for Drug Evaluation Stanford University Chemistry, 2012 and Research (CDER) Paul Yock Wins National Academy Faculty of Engineering’s Gordon Prize Recruitment

Paul Yock, MD, professor of medicine and of bioengineering at Stan- The Cardiovascular Institute and the De- ford University, will receive the National Academy of Engineering’s partment of Medicine at Stanford Univer- 2018 Bernard M. Gordon Prize for Innovation in Engineering and Tech- sity are recruiting a full-time academic nology Education. faculty with expertise in any of the areas of drug/gene delivery, polymer chemistry/ The academy said Yock was chosen for “the development and global nanotechnology, bioengineering/bioma- dissemination of Biodesign, a biomedical technology training pro- terial sciences, biomedical formulation, Paul Yock, MD gram that creates leaders and innovations that benefit patients.” The clinical medicinal chemistry, medical phar- prize is the academy’s top honor for teaching and carries a $500,000 award. macology/molecular pharmacology, toxicol-

Yock, who holds the Martha Meier Weiland Professorship and was the founding co-chair of ogy, bioinformatics, applied proteomics and Stanford’s Department of Bioengineering, is known for his work inventing and testing new pharmacogenomics at the rank of Assistant medical devices in the field of interventional cardiology. Motivated to help other aspiring or Associate Professor in the Non-Tenured innovators succeed in developing devices to improve health care, he founded Stanford Bio- Line-Research (NTL-R). Contact: Mark Mercola design in 2001. Biodesign is part of Bio-X, Stanford’s interdisciplinary biosciences institute. [email protected] https://medicine.stanford.edu/content/dam/ https://news.stanford.edu/thedish/2018/01/08/paul-yock-wins-national-academy-of-engineer- sm/medicine/images/faculty/openpositions/ ings-gordon-prize/ CVI-Med-PCCM-Ad-2017.pdf cvi.stanford.edu | 1 50th Anniversary Celebration of Dr. Norman E. Shumway’s First Heart Transplant Event

Dr. Norman E. Shumway performed the first adult heart transplant in the United States here at Stanford on January 6, 1968. To commemo- rate this epic event in history, on January 22, 2018, the Department of Cardiothoracic Surgery hosted a celebration of the 50th anniversary. A full day symposium was held at the Li Ka Shing Center for Learning and Knowledge at Stanford University with 350 guests in attendance.

We invited a host of speakers from around the country to detail pioneering achievements and contributions as well as provide a glimpse of the future of heart transplantation and technical circulatory support. Dr. Sara Shumway, heart transplant surgeon and daughter of Dr. Norman Shumway, and Dr. Edward Stinson, who assisted Dr. Shumway with the first adult heart transplant were among the luminaries.

Guests in attendance were also able to hear a few words from patient Linda Karr, who received a new heart from the rare procedure “dom- ino” transplant performed here at Stanford on January 30, 2016 by Dr. Joseph Woo and Dr. Jack Boyd. She was extremely thankful for the doctors here at Stanford and provided a unique, heartwarming perspective during this historic celebration.

About the Stanford Cardiovascular Institute The Institute currently consists of over 241 faculty members representing physicians, surgeons, engineers, basic scientists and clinical researchers. The mission of the Institute is to integrate fundamental research across disciplines and apply technology to prevent and treat cardiovascular disease.

To support cardiovascular research and education at CVI, please contact: Joseph Wu, CVI Director, at joewu@ stanford.edu, or Cathy Hutton, Senior Associate Director, Medical Center Development at cathy.hutton@stan- Cathy Hutton, MBA ford.edu

For more information: http://med.stanford.edu/cvi/support-our-research.html and http://cvi.stanford.edu

cvi.stanford.edu | 2 ANNIVERSARY CELEBRATION

Dr. Norman E. Shumway’s First Heart Transplant

cvi.stanford.edu | 3 Gerald Reaven, Scientist Who Coined ‘Syndrome X,’ Dies at 89 By Tracie White, Office of Communication & Public Affairs

Gerald “Jerry” Reaven, MD, who gained inter- later became known as metabolic syndrome and has become a use- national recognition for coining the term Syn- ful indicator of increased risk for heart disease, stroke and diabetes. drome X — now known as metabolic syndrome “I visited him at his house just before the Super Bowl in February, — died Feb. 12 at his home on the Stanford Uni- when I knew he was sick,” said Joshua Knowles, MD, an assistant pro- versity campus. He was 89. fessor of cardiovascular medicine. “He was very sad he couldn’t be at An endocrinologist and professor emeritus of work. I brought a paper on the effects of insulin resistance on differ- medicine at the Stanford School of Medicine, ent race ethnicities. He wanted to see the data. Science was his life.” Reaven was one of the first researchers to argue for the existence of Reaven was a Midwesterner and a baseball fan. He was born in insulin resistance, a diminished response to the hormone insulin. Gary, Indiana, on July 28, 1928, but grew up in Cleveland, which It was a controversial concept that met with huge opposition. But accounts for his lifelong “affection and frustration” with the Cleve- Reaven proved the naysayers wrong. In 1988, he also introduced land Indians baseball team, said his son, Peter Reaven, MD, an en- the novel idea of a link between insulin resistance and a cluster of docrinologist and director of the diabetes research program at the other metabolic abnormalities that together greatly increased the Phoenix Veterans Affairs Health Care System in Arizona. risk for cardiovascular disease, which he called Syndrome X. “Both my dad and my mom were academics,” he said. His moth- “Jerry Reaven was a true Stanford pioneer,” said Lloyd Minor, MD, er, Eve Reaven, PhD, is a retired electron microscopist who lives in dean of the School of Medicine. “He was the consummate scientist the Stanford home where she and Jerry raised their three children. whose rigorous scholarship was a model for researchers at Stan- “Often dinner conversations were about academics and science. ford and around the world. He will be missed.” Somehow that became comfortable.” Reaven broke ground when he argued for the existence of insulin Reaven earned his undergraduate and medical school degrees at resistance as an early and critical link in the development of Type the University of Chicago and completed his residency training at 2 diabetes and conducted numerous studies over many decades the University of Michigan. He joined the Stanford faculty in 1960. proving the existence of insulin resistance and its many implica- He worked at the School of Medicine first in the endocrinology divi- tions for metabolic diseases and cardiovascular diseases. sion and then, after semi-retirement, in the cardiovascular division. “Jerry Reaven was a giant in the Department of Medicine,” said Reaven won numerous awards, including the William S. Middleton Robert Harrington, MD, professor and chair of medicine at Stan- Award for outstanding achievement in medical research from the ford. “His scientific contribution in describing and then further Veterans Affairs Administration, the Banting Medal for Scientific defining insulin resistance is one of the great achievements in met- Achievement from the American Diabetes Association, the Banting abolic disease over the last 50 years.” Memorial Lecture from the British Diabetes Association, the Fred Conrad Koch Award from the Endocrine Society, the Distinction In the 1950s, when Reaven started out as a researcher, it was be- in Clinical Endocrinology Award from the American Association of lieved that there was only one type of diabetes and that it was Clinical Endocrinologists, and the National Lipid Association Hon- caused by a lack of insulin. orary Lifetime Member Award. “In the late ’70s early ’80s, there was a lot of controversy about in- In addition to his wife and son, he is survived by daughters Marci Reav- sulin resistance, and Jerry was not shy about standing up and shar- en of New York and Nancy Reaven of Los Angeles and their families. ing his opinions,” said Frederic Kraemer, MD, professor and chief of endocrinology, gerontology and metabolism at Stanford. “He was In lieu of flowers, the family asks for consideration of a memorial tenacious when it came to defending his scientific observations. He donation to support the Gerald M. Reaven Memorial Research Fund didn’t like to accept opinions; he liked to accept facts — facts gener- either online or by making a check payable to “Stanford University” ated from well-controlled scientific investigations.” and sending it to Stanford University Development Services, P.O. Box 20466, Stanford, CA 94309-0466. Please note “In Memory of Dr. In 1988, during the American Diabetes Association Banting award Gerald Reaven” online or on the memo line of the check. lecture, he introduced the concept of the link between insulin resistance and other metabolic abnormalities, calling it Syndrome X. http://med.stanford.edu/news/all-news/2018/02/gerald-reaven-stanford- scientist-who-coined-syndrome-x-dies-at-89.html This constellation of conditions — increased blood pressure, high blood sugar and abnormal HDL cholesterol and triglyceride levels — cvi.stanford.edu | 4 The Secret to Building a Strong Heart Lies in

Blood Vessels By Nathan Collins, Stanford News Service

Every year, a small but not insignificant number of babies are born with hearts whose muscles are spongy and thin, although exactly what causes that condition isn’t clear. Now, Stanford biologists think they may have found a clue: spongy heart muscles could be the result of improperly developed blood vessels surrounding the heart, the researchers write January 25 in Nature Communications.

Apart from a deeper understanding of congenital heart disease, the results could shed light on how heart muscle forms in the first place, said the study’s two senior authors, Ashby Morrison and Kristy Red-Horse, assistant profes- Kristy Red-Horse, sors of biology. PhD

Morrison, Red-Horse and their colleagues did not set out to understand congenital heart disease. Instead, they attribute the project to something altogether more random: their offices are right next to each other. Their physical proximity got them talking, and among the topics of conversation was a particular molecule that Morrison had been looking at, called Ino80. Without it, yeast get sick and die off – but in other organisms, “we didn’t know what to expect,” Morrison said.

To find out, Red-Horse and her lab started the process of genetically modifying mice to lack Ino80, either throughout their bodies or in specific areas of the body or specific cell types. The most intriguing results came from mice which didn’t produce Ino80 in endothelial cells – the progenitors of blood vessels that feed the muscles of the heart. Without Ino80, the network doesn’t develop properly, and as a result, cardiac muscles couldn’t develop properly either – instead remaining spongy and weak. It was at this point that the team noticed the similarity between their mice and a form of heart disease called left ventricular non-compaction, the third most common disease of the heart muscle.

What they’ve found should change how both doctors and biologists think about how the heart forms. Farther down the road, the research could also have implications for regenerative medicine specialists working to grow hearts and other organs in the lab, Red-Horse and Morrison said. https://news.stanford.edu/2018/01/25/secret-building-strong-heart-blood-vessels/ Stanford Medicine to Collaborate on Apple Heart Study Stanford Medicine re- Each year in the United States, atrial fibrillation causes 130,000 searchers are working with deaths and 750,000 hospitalizations. It can lead to blood clots Apple on a research study and is a leading cause of stroke, but many don’t experience to determine whether the symptoms, so it often goes undiagnosed. Apple Watch’s heart-rate The sensor in the Apple Watch uses LED lights to measure heart sensor can identify irregu- rate. The technology can also monitor the pattern of the heart- lar heart rhythms associat- beat. The app uses this technology combined with software al- ed with a condition known gorithms to identify an irregular heart rhythm. as atrial fibrillation. “Through the Apple Heart Study, Stanford Medicine faculty will The Apple Heart Study app explore how technology like Apple Watch’s heart-rate sensor can was launched November help usher in a new era of proactive health care central to our 30. As part of the study, if precision health approach,” said Lloyd Minor, MD, dean of the an irregular heart rhythm School of Medicine. is observed, participants will receive a notification Drs. Mintu Turakhia and Marco Perez are the co-PIs of the Apple on their Apple Watch and iPhone, a free consultation with a Heart Study. SCCR, CDH, QSU, IRT and others are partnering to study doctor and an electrocardiograph patch for additional make this project a success. monitoring. http://med.stanford.edu/news/all-news/2017/11/stanford-medicine-to-collaborate-on-apple-heart-study.html cvi.stanford.edu | 5 Creating a Platform to Help Transplanted Stem Cells Survive After a Heart Attack Kevin Mccormack, The Stem Cellar, CIRM

Repairing, even reversing, the damage caused by a heart attack is the Holy Grail of stem cell researchers. For years the Grail seemed out of reach because the cells that researchers transplanted into heart attack patients didn’t stick around long enough to do much good. Now researchers at Stanford may have found a way around that problem.

In a study published in the journal Nature Biomedical Engineering, a team at Stanford – led by Drs. Patricia Nguyen, Jayakumar Rajadas, and Joseph Wu – believe they have managed to create a new way of delivering these cells, one that combines them with a slow-release delivery mechanism to increase their chances of success. The team began by Patricia Nguyen, working with a subset of bone marrow cells that had been shown in previous studies to have what are called “pro-sur- MD vival factors.” Step two involved creating a matrix that would enable the researchers to link the peptides and combine them with a delivery system they hoped would produce a slow release of pro-survival factors.

The team focused on cardiac progenitor cells (CPCs) which have shown potential to help repair damaged hearts, but which also have a low survival rate when transplanted into hearts that have experienced a heart attack. The team de- livered CPCs to the hearts of mice and found the cells without the pro-survival matrix didn’t last long. In contrast, the cells on the peptide-infused matrix were found in large numbers up to eight weeks after injection. And the cells didn’t just survive, they also engrafted and activated the heart’s own survival pathways. Jayakumar Rajadas, PhD The team then tested to see if the treatment was helping improve heart function and found that mice treated with the matrix combination had statistically improved left ventricular function.

https://blog.cirm.ca.gov/2018/02/06/creating-a-platform-to-help-transplanted-stem-cells-survive-after-a-heart-attack/

Weight Flux Alters Molecular Profile Hanae Armitage, Office of Communication & Public Affairs The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

As people pack on pounds or shed excess weight, they exhibit no- table changes in their microbiome, cardiovascular system, immune system and levels of gene expression, the study found.

A paper describing the work was published online January 17 in Cell Systems. Senior authorship is shared by Michael Snyder, PhD, professor of genetics at Stanford; Tracey McLaughlin, MD, professor of medicine at Stanford; and George Weinstock, PhD, professor and director of microbial genomics at the Jackson Laboratory, an independent, nonprofit biomedical research institution. ciated with heart disease activated. But that’s not the end of the “The goal here was to characterize what happens during weight story. When study participants lost the weight, most of the rest of gain and loss at a level that no one has ever done before,” Snyder the body’s systems recalibrated back to their original states, the said. “We also really wanted to learn how prediabetic folks might study found. differ in terms of their personal omics profiles and their molecular responses to weight fluctuation.” The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the Snyder and his colleagues found that even with modest weight healthy and precisely diagnose and treat disease in the ill. gain—about 6 pounds—the human body changed in dramatic fash- ion at the molecular level. Bacterial populations morphed, immune http://med.stanford.edu/news/all-news/2018/01/weight-flux-alters-molecular-profile.html responses and inflammation flared, and molecular pathways asso-

cvi.stanford.edu | 6 Higher Blood Sugar in Early Pregnancy Raises Baby’s

Heart-defect Risk By Erin Digitale, Office of Communication & Public Affairs Higher blood sugar early in pregnancy raises the heart disease by looking at their glucose values during the first tri- baby’s risk of a congenital heart defect, even mester of pregnancy.” among mothers who do not have diabetes, ac- The research team studied medical records from mothers and their cording to a study led by researchers at the Stan- babies born between 2009 and 2015. The scientists analyzed blood ford University School of Medicine published glucose levels collected from the mothers between four weeks online December 15 in The Journal of Pediatrics. prior to the estimated date of conception and the end of the 14th James Priest, MD For many years, physicians have known that gestational week, just after the completion of the first trimester of women with diabetes face an increased risk of giving birth to ba- pregnancy. After excluding women who had diabetes before preg- bies with heart defects. Some studies have also suggested a link nancy or who developed it during pregnancy, the results showed between nondiabetic mothers’ blood sugar levels and babies’ that the risk of giving birth to a child with a congenital heart defect heart defect risk. However, the new study is the first to examine was elevated by 8 percent for every increase of 10 milligrams per this question in the earliest part of pregnancy, when the fetal heart deciliter in blood glucose levels in the early stages of pregnancy. is forming. The next step is to conduct a prospective study that follows a large “Most women who have a child with congenital heart disease are group of women through pregnancy to see if the results are con- not diabetic,” said the study’s senior author, James Priest, MD, as- firmed, Priest said. If researchers see the same relationship, it may sistant professor of pediatric cardiology. “We found that in women be helpful to measure blood glucose early in pregnancy in all preg- who don’t already have diabetes or develop diabetes during pregnant women to help determine which individuals are at greater risk nancy, we can still measure risk for having a child with congenital for having a baby with a heart defect. http://med.stanford.edu/news/all-news/2017/12/higher-blood-sugar-in-early-pregnancy-raises-babys-heart-risk.html Paul Yock, MD New Toolkit Will Help Doctors Spot Heart Disease Linked to Pregnancy By Erin Digitale, Scope A new set of guidelines will help doctors spot hidden heart disease in pregnant women and new mothers. The guidelines, part of a recently released toolkit from the Stanford-based California Maternal Quality Care Collaborative, are intended to improve diagnosis and treatment of women whose new or existing heart conditions interact with pregnancy. Heart problems are the leading cause of death in pregnant women and new moms.

“Most pregnancies occur in young, healthy women and there is an overlap between signs and symptoms women may experience in a normal pregnancy and those they may experience due to cardiac disease, specifically shortness of breath, fatigue and swelling,” the toolkit authors write. As a result, doctors can mistake warning signs of peripartum cardiomyopathy for harmless pregnancy side effects. A 2016 study found that about half of these cardiac patients were initially misdiagnosed, while a statewide survey of maternal deaths that oc- curred in California between 2002 and 2006 found that most women who died of heart problems did not have a known cardiac condition before pregnancy.

The toolkit identifies “red flag” symptoms of pregnancy-related heart disease. The guidelines also describe diagnostic tests to order if a woman shows signs of heart disease. Stanford cardiologist Abha Khandelwal, MD, and nurse-researcher Julie Arafeh wrote the guidelines for women with adult congenital heart disease, and Stanford research sociologist Christine Morton, PhD, is a co-author of the section describing cardiovascular health disparities in African-American women.

Importantly, the toolkit also encourages all pregnant women to receive screening for cardiovascular disease, and provides a detailed algorithm to help doctors decide what combinations of symptoms, vital-sign abnormalities, cardiac risk factors and warning signs on a physical exam should prompt them to refer a patient for follow-up with a cardiologist. http://scopeblog.stanford.edu/2018/01/16/new-toolkit-will-help-doctors-spot-heart-disease-linked-to-pregnancy/ cvi.stanford.edu | 7 Induced Pluripotent Stem Cells Could Serve as Cancer Vaccine By Krista Conger, Office of Communication & Public Affairs

Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or disease. Now, a study in mice from the Stanford University School of Medicine suggests another use for iPS cells: training the immune system to attack or even prevent tumors.

“We’ve learned that iPS cells are very similar on their surface to tumor cells,” said Joseph Wu, MD, PhD, director of Stanford’s Cardiovascular Institute and professor of cardio- Nigel Kooreman, vascular medicine and of radiology. “When we immunized an MD animal with genetically matching iPS cells, the immune system could be primed to reject the development of tumors in the future. Pending replication in humans, our findings indicate these cells may one day serve as a true patient-specific cancer vaccine.”

Wu is the senior author of the study, which was published online February 15 in Cell Stem Cell. Former postdoctoral scholar Nigel Kooreman, MD, is the lead author. “These cells, as a component of our proposed vaccine, have strong immunogen- ic properties that provoke a systemwide, cancer-specific immune response,” said Kooreman, who is now a surgery resident in the Netherlands. “We believe this approach has exciting clinical potential.”

“Although much research remains to be done, the concept itself is pretty simple,” Wu said. “We would take your blood, make iPS cells and then inject the cells to prevent future cancers. I’m very excited about the future possibilities.” http://med.stanford.edu/news/all-news/2018/02/induced-pluripotent-stem-cells-could-serve-as-cancer-vaccine.html http://www.latimes.com/science/sciencenow/la-sci-sn-stem-cells-cancer-vaccine-20180215-story.html https://gizmodo.com/scientists-successfully-test-a-vaccine-in-mice-that-cou-1823034669

4th International Symposium From Precision Biology to Precision Medicine in Pulmonary Hypertension: Revolutionizing Healthcare through Revolutionary Science.

Friday, May 18, 2018 Sheraton Palo Alto Hotel

Dan Bernstein, MD Helen Blau, PhD Mark Mercola, PhD Named Associate Dean for Curriculum and AIMBE | Elected Fellow CIRM | DISC2 Award: Multipotent Student Scholarship Cardiovascular Progenitor Regeneration of the Myocardium after MI

Latha Palaniappan, MD Joseph Wu, MD, PhD Michael Kapiloff, MD, PhD India Community Center AIMBE | Elected Fellow Tobacco Related Disease Health Leadership Award Research Program High Impact Research Project Award “SRF Phosphorylation and the Progression to Heart Failure”

Travel Award Winners Three times a year the CVI grants awards to trainees to support their travel to national conferences to present their work. Congratulations to the recent winners!

Aldo Cordova Palomera, PhD Nadia Ouazani, MD David Paik, PhD Mentor: James Priest, MD Mentor: Jeffrey Teuteberg, MD Mentor: Joseph Wu, MD, PhD Genome-Wide Association Study Estimation of Pulmonary Capillary Human iPSC-Derived Endothelial of Congenital Heart Disease Wedge Pressure by Transthoracic Cells Predict Predilection in the UK Biobank Echocardiography in Mechanically to Atherogenesis by Endothelial American Society of Human Genetics Ventilated Patients: Comparison Proinflammatory Activation (ASHG) Conference 2017 Tissue Doppler Imaging with Color AHA Scientific Sessions Orlando, Florida M-mode Doppler Propagation Flow Anaheim, California October 17-21, 2017 Acute Cardiovascular Care November 11-15, 2017 Milan, Italy March 3-5, 2018

cvi.stanford.edu | 9 Faculty Funding Opportunities

Stanford Neurosciences Institute Clinical Trial Stage Projects Center for Health Policy (CHP)/ Center Big Ideas in Neuroscience: Transformative CLN 1: Partnering Opportunity for Late for Primary Care and Outcomes Research Research Initiatives in the Brain Sciences Stage Preclinical Projects (PCOR) Call for Letters of Intent (Round 2, Phase 1) CLN 2: Partnering Opportunity for Clinical VA Fellowship in Health Services Research The Institute is dedicated to stimulating Stage Projects and Development and supporting interdisciplinary efforts CLN 3: Partnering Opportunity for Deadline: Applications accepted anytime that advance neuroscience research and Supplemental Accelerating Activities CHP education. Deadline: CIRM is establishing an open call Letter of intent (required) deadline: for proposals and will accept applications Center for Health Policy (CHP)/ Center March 12, 2018 on a monthly basis for Primary Care and Outcomes Research Full proposal (by invitation only) deadline: CIRM Clinical Trial Stage Projects (PCOR ) July 11, 2018 VA Medical Informatics Fellowship SNI Children’s Cardiomyopathy Foundation Combine Formal Training in Medical Research Grant Program Informatics with Research Applying Burroughs Wellcome Fund Amount of funding: $25-50K for 1 year Medical Informatics to Areas of Relevance Quantitative and Statistical Thinking Deadline: June 14, 2018 to the VA Health Care System. in the Life Sciences CCF Deadline: Applications accepted anytime Deadline: March 14, 2018 CHP BWFund Stanford Bio-X Interdisciplinary Initiatives Seed Grant Program-Round 9 Marfan Foundation The Stanford Institute for Immunity, High-risk, high-reward collaborative Clinical Research Program Transplantation and Infection (ITI) proposals Faculty Grant Program NIH Cooperative Centers for Translational Letter of intent deadline: March 19, 2018 Deadline: April 20, 2018 Research in Human Immunology (CCHI) Biox Marfan Foundation Pilot Project Grants Deadline: March 16, 2018 Intermountain-Stanford Collaboration Breakthrough Prizes ITI Grants Topics: Life Sciences, Physics, Research to advance healthcare Mathematics National Institutes of Health transformation, ideally through the scale Deadline: April 30, 2018 Improving Outcomes in Cancer and spread of proven or promising clinical Breakthrough Prize Treatment-Related Cardiotoxicty (R21) improvements. Deadline: Mar 16, 2018 Deadline: March 2018 Breakthrough Prizes – Early career PA-18-013 Intermtn-SU researchers Topics: Fundamental Physics and Improving Outcomes in Cancer Stanford Nano Shared Facilities (SNSF) Mathematics Treatment-Related Cardiotoxicity (R01) Bio/Medical Mini Seed Grants Deadline: April 30, 2018 Deadline: June 5, 2018 Deadline: Proposals are accepted on an Breakthrough Prize PA-18-003 ongoing basis as funds permit. SNSF Stanford Cardiovascular Institute California Institute for Regenerative 2018 Seed Grants Medicine (CIRM) Deadline: August 1, 2018 Discovery Stage Research Projects DISC 2: CVI Seed Grants The Quest Awards Deadline: March 15, 2018 CIRM Discovery Stage Research Awards

cvi.stanford.edu | 10 Med 223: Cardiovascular Research & Medicine Winter 2018 The focus of MED223 is to fine tune critical thinking skills by analyzing original publications and understand the current complexities of the cardiovascular system.

Directors: Patricia Ngyuen, MD; Themistocles L. Assimes, MD, PhD; Ioannis Karakikes, PhD; Ngan Huang, PhD http://med.stanford.edu/cvi/education/med223.html

January 11, 2018 February 22, 2018 KIRAN K. KHUSH, MD, MAS JAMES R. PRIEST, MD Associate Professor of Medicine, Cardiovascular Medicine Assistant Professor of Pediatrics, Cardiology

January 18, 2018 March 1, 2018 SIDDHARTHA JAISWAL, MD, PHD SANJIV NARAYAN, MD Assistant Professor of Pathology Professor of Medicine, Cardiovascular Medicine

January 25, 2018 March 8, 2018 OLIVER O. AALAMI, MD RONGLIH LIAO, PHD Clinical Associate Professor of Surgery, Vascular Surgery Professor of Medicine, Cardiovascular Medicine

February 1, 2018 March 15, 2018 JOSHUA W. KNOWLES, MD, PHD NICHOLAS J. LEEPER, MD Assistant Professor of Medicine, Cardiovascular Medicine Associate Professor of Surgery, Vascular Surgery and February 8, 2018 Associate Professor of Medicine, Cardiovascular Medicine ALEXANDER DUNN, PHD Associate Professor of Chemical Engineering

February 15, 2018 MICHAEL SNYDER, PHD Stanford W. Ascherman, MD, FACS, Professor in Genetics Chair, Department of Genetics

Postdoctoral Funding Opportunities

France-Stanford Center for Thrasher Research Fund Mechanisms and Innovations in Interdisciplinary Studies (FSCIS) Early Career Awards Cardiovascular Disease T32 Training Grant 2018-2019 Visiting Junior Scholar Deadline: March 13, 2018 July 1, 2018 (two slots) apply by May 25 Fellowship (Concept submission) Oct. 1, 2018 (two slots) apply by Aug. 26 Deadline: March 1, 2018 Thrasher Early Career Awards Dec. 1, 2018 (one slot) apply by Oct. 28 France-Stanford Stanford Career Development Program in Stanford Child Health Research Institute ‘Omics’ of Lung Disease (K12) Multidisciplinary Training Program in (CHRI) Deadline: accepted on an ongoing basis Cardiovascular Imaging T32 Training Postdoctoral Support Program "Omics" of Lung Disease Fellowship Grant Deadline: March 1, 2018 Deadline (rolling): Next start date: Nov. 1, CHRI Stanford Systems Biology Seed Grants 2018 (one slot) apply by Sept. 23 Deadline: June 8, 2018 Department of Pediatrics-Division of Systems Biology Seed Grants Pediatric Hematology/Oncology Pediatric Nonmalignant Hematology National Institutes of Health and Stem Cell Biology Training Grant Ruth L. Kirschstein National Research Program Service Awards (NRSA) for Individual NIH/NHLBI T32 Training Program Postdoctoral Fellows Deadline: March 1, 2018 Deadline: August 8, 2018 PHO NRSA

cvi.stanford.edu | 11 http://cvi.stanford.edu

Frontiers in Cardiovascular Science 2017-2018

Tuesdays 12:30 - 1:20 p.m. (unless otherwise noted), Li Ka Shing Center, LK130

January 9, 2018 February 20, 2018 May 1, 2018 JENNIFER VAN EYK, PHD KAJIMURA SHINGO, PHD GEOFFREY PITT, MD, PHD Director, Advanced Clinical Biosystems Associate Professor, Department of Cell Director of the Cardiovascular Research Institute in the Department of Biomedical and Tissue BiologyUCSF Institute; The Ida and Theo Rossi Sciences; Director, Basic Science Distinguished Professor of Medicine, Weill Research in the Women’s Heart Center; March 6, 2018 Cornell Medical College Erika J. Glazer Chair in Women’s Heart The Steven M Gootter Foundation HealthCedars Sinai Lecture May 8, 2018 MARK E. ANDERSON, MD, PHD ROBERT J. GROPLER, MD January 16, 2018 William Osler Professor of Medicine; Chair, Professor of Radiology, Medicine and ERIK INGELSSON, MD Department of Medicine, Johns Hopkins Biomedical Engineering Professor of Medicine (Cardiovascular University Senior Vice-Chair and Division Director Medicine) and, by courtesy, of Health Radiological Sciences & Research and Policy (Epidemiology) March 13, 2018 Chief, Cardiovascular Imaging Laboratory Stanford KAM W. LEONG, PHD Washington University School of Medicine Samuel Y. Sheng Professor; EiC, January 23, 2018 Biomaterials; Department of Biomedical May 15, 2018 JAMES F. MARTIN, MD, PHD Engineering, Columbia University BRADFORD C. BERK, MD, PHD Professor, Vivian L. Smith Chair in Distinguished University Professor in Regenerative Medicine March 20, 2018 Medicine, Baylor College of Medicine RICHARD SCHELLER, PHD Neurology, Pathology, and Pharmacology Chief Science Officer & Physiology January 30, 2018 & Head of Therapeutics, 23andme Director, University of Rochester ALISON L. MARSDEN, PHD Neurorestoration Institute University of Rochester Medical Center Associate Professor of Pediatrics March 27, 2018 (Cardiology) and of Bioengineering SARAH C. HEILSHORN, PHD and, by courtesy, of Mechanical Associate Professor, Materials Science & May 22, 2018 PETER LIBBY, MD EngineeringStanford Engineering, StanfordAssociate Editor, Mallinckrodt Professor of Medicine, Science Advances, AAAS February 6, 2018 Harvard Medical School Senior Physician, Brigham and Women’s (1:30 p.m., Munzer Auditorium) April 10, 2018 BRIAN BLACK, PHD THOMAS M. VONDRISKA, PHD Hospital Professor, Cardiovascular Research Professor of Anesthesiology, Medicine and Institute, Department of Biochemistry and Physiology, UCLA June 5, 2018 CHRISTINE MUMMERY, PHD Biophysics, UCSF Professor of Developmental Biology, Chair April 17, 2018 Dept. of Anatomy & Embryology, Leiden February 13, 2018 PEIPEI PING, PHD University Medical Center WALTER J. KOCH, PHD Professor, Physiology; Professor, Medicine/ William Wikoff Smith Endowed Chair in Cardiology, and Bioinformatics, UCLA; Cardiovascular Medicine; Professor and Director, NIH BD2K Center of Excellence Chair, Pharmacology, Temple University at UCLA; Director, NIH BD2K Centers- Coordination Center at UCLA

cvi.stanford.edu | 12 National and Global Cardiovascular Conferences

MARCH 2018 MAY 2018 22nd Annual Hypertension, Diabetes and

American College of Cardiology AHA ATVB|PVD (formerly: Dsylipidemia Conference June 22-24, 2018 Scientific Session & Expo Arteriosclerosis, Thrombosis and Charleston, South Carolina March 10-12, 2018 Vascular Biology | Peripheral Vascular HDD Orlando, Fl Disease) Scientific Session May 10–12, 2018 Vascular Annual Meeting San Francisco, Calif. June 21-23, 2018 Epidemiology and Prevention; Lifestyle AHA Boston, MA and Cardiometabolic Health SVS March 20-23, 2018 Heart Rhythm Scientific Sessions New Orleans, LA May 9-12, 2018 JULY 2018 EPI LIFESTYLE 2018 Boston HR Sessions Basic Cardiovascular Sciences Scientific APRIL 2018 Sessions July 30-Aug 2, 2018 AHA QCOR (Quality of Care and Big Data in Biomedicine Conference May 23-24, 2018 San Antonio, TX Outcomes Research) April 6–7, 2018 Stanford, CA BCVS Arlington, Va. Big Data 10 Day Seminar on the Epidemiology and AHA European Society of Cardiology – Heart Prevention of Cardiovascular Disease

Mayo Clinic School of Continuous Failure and Stroke May 26-29, 2018 July 22-Aug 3, 2018 Professional Development: Vienna, Austria Tahoe City, CA Extracorporeal Membrane Oxygenation Heart Failure 10 Day Seminar (ECMO) Symposium 2018 April 10-18, 2018 JUNE 2018 International Academy of Cardiology – Scottsdale, AZ Stanford’s 4th Annual Mechanical 23rd World Congress on Heat Disease Mayo Clinic July 27-29, 2018 Circulatory Support: Optimal Boston, MA Stanford Pulmonary Artery Management and New Frontiers IAC Reconstruction and Right Ventricle Li Ka Shing Center for Learning and Knowledge, Stanford, CA Rehabilitation Symposium AUGUST 2018 Li Ka Shing Center for Learning and June 9, 2018 Knowledge, Stanford, CA SMCSOMNF European Society of Cardiology – April 14-15, 2018 Congress 2017 SPARRVRS International Society for Stem Cell Aug 25-29, 2018 Research Munich, Germany 2018 Drug Discovery Conference June 20-23 ESC Congress April 23-24, 2018 Melbourne, Australia Li Ka Shing Center for Learning ISSCR and Knowledge, Stanford, CA CVI CARDIA 2018: Cardiac Arrhythmia, Sudden Death, Inherited Cardiovascular Society for Cardiovascular Angiography Disease, Athletes and Interventions June 21-22, 2018 April 25-28, 2018 Paul Brest Hall San Diego, CA Stanford, CA SCAI 2018 CARDIA

Stanford Cardiovascular Health Leadership in heart and vascular care, research, and education have made Stanford Cardio- vascular Health a destination for patient referrals from around the country and around the world. Each year, we receive more than 80,000 visits from patients who come to us for state- of-the-art cardiovascular care. Our experts collaborate to deliver the personalized approach integral to optimizing each patient’s heart and vascular health. Learn more about our clinical and research program https://issuu.com/stanfordhospital/docs/cardio_telescop- ing_br_v9_ppt?e=10554343/57900660cvi.stanford.edu . | 13 CVI Cores Stanford CVI Human iPSC Biobank Service Normal and patient-derived reprogrammed cardiomyocytes are a tremendous resource for researchers and physicians here at Stanford and around the country. Un- derstanding the disease process directly at the popula- tion level and observing these cells as surrogates under a Cardiovascular Pharma- myriad conditions has the potential to be a game-chang- er for cardiovascular medical research. cology (BioADD)

To facilitate research in a dish that allows screening of new compounds or characterization of The Cardiovascular Pharmacology/Bioma- human disease phenotypes using cardiomyocytes, the Institute created a service by which terials and Advanced Drug Delivery (Bio- de-identified peripheral blood mononuclear cell (PBMC) samples from selected patients ADD) Laboratory is a cutting edge research can be sent to Stanford CVI for reprogramming free of cost. facility that specializes in the creation of biomaterials and drug delivery agents. SCVI biobank is supported in part by National Heart, Lung and Blood Institute (NHLBI) and the The lab lends its expertise toward design- Stanford Cardiovascular Institute (CVI). ing and analyzing biomaterials, developing drug delivery devices and formulations, Stanford iPSC Biobank was recently mentioned in Nature Methods news: nature.com/nmeth/ pharmacokinetic and pharmacodynamic journal/v12/n2/full/nmeth.3263.html. studies, and developing smart materials for Contact: Joseph Wu, MD, PhD / [email protected] biomedical applications. The CVI Cardio- or Biobank manager, Yan Zhuge / [email protected] with any questions. vascular Pharmacology also offers trainings and lectures.

Clinical Biomarker & Phenotyping Core Lab (BPCL) Contact: Jayakumar Rajadas, PhD [email protected] BPCL provides quantitative assessment of clinical cardiovascular phenotypes for translational research and clinical trials. These cardiovascular phenotypes include evaluating cardiac structure and function, measuring carotid intimal thickness and arterial stiffness, and testing endothelial function and cardiopulmonary exercise testing.

In collaboration with the Human Immune Monitoring Center at Stanford and members of the Cardiovascular Institute, we also offer central blood processing and banking capabilities. In addition, we develop new biomarker platforms and imaging modalities.

Contact: Francois Haddad, MD / [email protected] 3DQ Imaging Laboratory

Stanford’s 3DQ Imaging Laboratory de- CVI Clinical Trials Core velops new approaches to exploration, analysis and quantitative assessments of The CVI Clinical Trials Core provides full spectrum of support to CVI members and their clinical tri- diagnostic images that result in new and/ als. The coordinators has extensive clinical research experience in both industry and academia. or more cost-effective diagnostic approach- The team provides services and support to principal investigators and sponsors, including: es, and new techniques for the design and monitoring of therapy. The lab processes • Consultation • Data management over 1,200 clinical cases to deliver relevant • Study start-up management, including • Regulatory compliance and documen- visualization and analysis of medical imag- IRB applications, budget development tation ing data at Stanford. • Subject recruitment, site visits, and • Closeout follow-ups (AE reporting and queries) The lab is co-directed by Dominik Fleis- chmann, MD, Roland Bammer, PhD and , Clinical Trials Manager or , Clinical Research Coordinator at Contact: Ed Finn Hoa Ly Sandy Napel, PhD. (650) 498-6279 Contact: Dominik Fleischmann, MD [email protected] cvi.stanford.edu | 14 Member Publications

Communication is at the heart of scientific advancement and innovation. This quarter, the Stanford Cardiovascular Institute members published over 350 original manuscripts and reviews, further contributing to our understanding of cardiovascular biology and disease. Here, we highlight selected manuscripts by our members.

JANUARY Anticoagulant and antiplatelet therapy choices for patients with atrial fibrillation one year after coronary stenting or acute coronary syndrome. Olivier CB, Geometric Deformations of the Thoracic Aorta and Supra-Aortic Arch Branch Turakhia MP, Mahaffey KW. Expert Opin Drug Saf. 2018 Jan 24:1-8

Vessels Following Thoracic Endovascular Aortic Repair. Ullery BW, Suh GY, Hi- Altmetric Scores, Citations, and Publication of Studies Posted as Preprints. Ser- rotsu K, Zhu D, , , , Cheng CP. Vasc Endovascular Lee JT Dake MD Fleischmann D ghiou S, Ioannidis JPA. JAMA. 2018 Jan 23;319(4):402-404 Surg. 2018 Jan 1:1538574417753452 Integrative Personal Omics Profiles during Periods of Weight Gain and Loss. Pi- Comparison of Non-human Primate versus Human Induced Pluripotent Stem ening BD, Zhou W, Contrepois K, Röst H, Gu Urban GJ, Mishra T, Hanson BM, Cell-Derived Cardiomyocytes for Treatment of Myocardial Infarction. Zhao X, Bautista EJ, Leopold S, Yeh CY, Spakowicz D, Banerjee I, Chen C, Kukurba K, Chen H, Xiao D, Yang H, Itzhaki I, Qin X, Chour T, Aguirre A, Lehmann K, Kim Y, Perelman D, Craig C, Colbert E, Salins D, Rego S, Lee S, Zhang C, Wheeler J, Sail- Shukla P, Holmström A, Zhang JZ, Zhuge Y, Ndoye BC, Zhao M, Neofytou E, Zim- ani MR, Liang L, Abbott C, Gerstein M, Mardinoglu A, Smith U, Rubin DL, Pitteri S, mermann WH, Jain M, . Stem Cell Reports. 2018 Jan 26. Wu JC Sodergren E, McLaughlin TL, Weinstock GM, Snyder MP. Cell Syst. 2018 Jan 16.

Inhibition of Methyltransferase Setd7 Allows the In Vitro Expansion of Myogenic Growth and remodeling play opposing roles during postnatal human heart valve Stem Cells with Improved Therapeutic Potential. Judson RN, Quarta M, Oudhoff development. Oomen PJA, Holland MA, Bouten CVC, Kuhl E, Loerakker S. Sci MJ, Soliman H, Yi L, Chang CK, Loi G, Vander Werff R, Cait A, Hamer M, Blonigan J, Rep. 2018 Jan 19;8(1):1235 Paine P, Doan LTN, Groppa E, He W, Su L, Zhang RH, Xu P, Eisner C, Low M, Barta I, Lewis CB, Zaph C, Karimi MM, Rando TA, Rossi FM. Cell Stem Cell. 2018 Feb Dose-Dependent Cardioprotection of Moderate (32°C) Versus Mild (35°C) Thera- 1;22(2):177-190.e7 peutic Hypothermia in Porcine Acute Myocardial Infarction. Dash R, Mitsutake Y, Pyun WB, Dawoud F, Lyons J, Tachibana A, Yahagi K, Matsuura Y, Kolodgie FD, Cancer therapy-induced cardiomyopathy: can human induced pluripotent stem Virmani R, McConnell MV, Illindala U, Ikeno F, Yeung A. JACC Cardiovasc Interv. cell modelling help prevent it? Stack JP, Moslehi J, Sayed N, Wu JC. Eur Heart 2018 Jan 22;11(2):195-205 J. 2018 Jan 25 ReprDB and panDB: minimalist databases with maximal microbial representa- Independent mapping methods reveal rotational activation near pulmonary tion. Zhou W, Gay N, Oh J. Microbiome. 2018 Jan 18;6(1):15 veins where atrial fibrillation terminates before pulmonary vein isolation. Na- vara R, Leef G, Shenasa F, Kowalewski C, Rogers AJ, Meckler G, Zaman JAB, Pathway Analysis of Gene Expression of E14 Versus E18 Fetal Fibroblasts. Hu MS, Baykaner T, Park S, Turakhia M, Zei P, Viswanathan M, Wang PJ, Narayan SM. J Borrelli MR, Januszyk M, Luan A, Malhotra S, Walmsley GG, Hong WX, Tevlin R, Cardiovasc Electrophysiol. 2018 Jan 29. Gurtner GC, Longaker MT, Lorenz HP. Adv Wound Care (New Rochelle). 2018 Jan 1;7(1):1-10 Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes congenital heart disease. Rhee S, Chung JI, King DA, D’amato G, Paik DT, Duan A, Inhibition of Drp1/Fis1 interaction slows progression of amyotrophic lateral Chang A, Nagelberg D, Sharma B, Jeong Y, Diehn M, Wu JC, Morrison AJ, Red- sclerosis. Joshi AU, Saw NL, Vogel H, Cunnigham AD, Shamloo M, Mochly-Rosen Horse K. Nat Commun. 2018 Jan 25;9(1):368 D. EMBO Mol Med. 2018 Jan 15.

CRISPR/Cas9 genome editing in human hematopoietic stem cells. Bak RO, Dever Improving immune-vascular crosstalk for cancer immunotherapy. Huang Y, Kim DP, Porteus MH. Nat Protoc. 2018 Feb;13(2):358-376 BYS, Chan CK, Hahn SM, Weissman IL, Jiang W. Nat Rev Immunol. 2018 Jan 15

Circulating plasmablasts are elevated and produce pathogenic anti-endothelial A New Approach to Rare Diseases of Children: The Undiagnosed Diseases Net- cell autoantibodies in idiopathic pulmonary arterial hypertension. Blum LK, Cao work. Reuter CM, Brimble E, DeFilippo C, Dries AM; Undiagnosed Diseases Net- RRL, Sweatt AJ, Bill M, Lahey LJ, Hsi AC, Lee CS, Kongpachith S, Ju CH, Mao R, work, Enns GM, Ashley EA, Bernstein JA, Fisher PG, Wheeler MT. J Pediatr. 2018 Wong HH, Nicolls MR, Zamanian RT, Robinson WH. Eur J Immunol. 2018 Jan 25 Jan 11.

Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. Identification and Characterization of Sites Where Persistent Atrial Fibrillation Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTag- Is Terminated by Localized Ablation. Zaman JAB, Sauer WH, Alhusseini MI, gart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Baykaner T, Borne RT, Kowalewski CAB, Busch S, Zei PC, Park S, Viswanathan Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, MN, Wang PJ, Brachmann J, Krummen DE, Miller JM, Rappel WJ, Narayan SM, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG; Peters NS. Circ Arrhythm Electrophysiol. 2018 Jan;11(1):e005258 DEFUSE 3 Investigators. N Engl J Med. 2018 Jan 24 Structure and dynamics of GPCR signaling complexes. Hilger D, Masureel M, Ko- Geographic and racial representation and reported success rates of studies of bilka BK. Nat Struct Mol Biol. 2018 Jan;25(1):4-12 catheter ablation for atrial fibrillation: Findings from the smash-af meta-analy- Microtubule Polymerization and Cross-Link Dynamics Explain Axonal Stiffness sis study cohort. Leef GC, Perino AC, Cluckey A, Yunus FN, Askari M, Heidenreich and Damage. de Rooij R, Kuhl E. Biophys J. 2018 Jan 9;114(1):201-212 PA, Narayan SM, Wang PJ, Turakhia MP. J Cardiovasc Electrophysiol. 2018 Jan 24

cvi.stanford.edu | 15 Canakinumab for Atherosclerotic Disease. Harrington RA. N Engl J Med. 2018 Boothroyd DB, Barbato E, Tonino P, Jüni P, Pijls NHJ, Hlatky MA; FAME 2 Trial Jan 11;378(2):199-200 Investigators. Circulation. 2018 Jan 30;137(5):480-487 iPSC-Derived Organs In Vivo: Challenges and Promise. Suchy F, Yamaguchi T, Na- Limited root repair in acute type A aortic dissection is safe but results in in- kauchi H. Cell Stem Cell. 2018 Jan 4;22(1):21-24 creased risk of reoperation. Chiu P, Trojan J, Tsou S, Goldstone AB, Woo YJ, Fis- chbein MP. J Thorac Cardiovasc Surg. 2018 Jan;155(1):1-7.e1 Cardiac Cell Cycle Activation as a Strategy to Improve iPSC-Derived Cardiomyo- cyte Therapy. Rhee JW, Wu JC. Circ Res. 2018 Jan 5;122(1):14-16 Cangrelor compared with clopidogrel in patients with prior myocardial infarction - Insights from the CHAMPION trials. Eisen A, Harrington RA, Stone GW, Thy1-Targeted Microbubbles for Ultrasound Molecular Imaging of Pancreatic Steg PG, Gibson CM, Hamm CW, Price MJ, Prats J, Deliargyris EN, Mahaffey KW, Ductal Adenocarcinoma. Abou-Elkacem L, Wang H, Chowdhury SM, Kimura RH, White HD, Bhatt DL; CHAMPION Investigators. Int J Cardiol. 2018 Jan 1;250:49-55 Bachawal SV, Gambhir SS, Tian L, Willmann JK. Clin Cancer Res. 2018 Jan 4. Human Induced Pluripotent Stem Cell (hiPSC)-Derived Cells to Assess Drug Car- Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrat- diotoxicity: Opportunities and Problems. Magdy T, Schuldt AJT, Wu JC, Bern- ing Lymphocytes. Gee MH, Han A, Lofgren SM, Beausang JF, Mendoza JL, Birn- stein D, Burridge PW. Annu Rev Pharmacol Toxicol. 2018 Jan 6;58:83-103 baum ME, Bethune MT, Fischer S, Yang X, Gomez-Eerland R, Bingham DB, Siben- er LV, Fernandes RA, Velasco A, Baltimore D, Schumacher TN, Khatri P, Quake SR, Changes in Geometry and Cardiac Deformation of the Thoracic Aorta after Tho- Davis MM, Garcia KC. Cell. 2018 Jan 25;172(3):549-563.e16 racic Endovascular Aortic Repair. Hirotsu K, Suh GY, Lee JT, Dake MD, Fleis- chmann D, Cheng CP. Ann Vasc Surg. 2018 Jan;46:83-89 Effect of Individualized Combined Exercise Versus Group-Based Maintenance Exercise in Patients With Heart Disease and Reduced Exercise Capacity: THE Dietary Patterns and Long-Term Survival: A Retrospective Study of Healthy DOPPELHERZ TRIAL. Christle JW, Schlumberger A, Zelger O, Haller B, Beckers Primary Care Patients. Shah NS, Leonard D, Finley CE, Rodriguez F, Sarra- P, Myers J, Halle M, Pressler A. J Cardiopulm Rehabil Prev. 2018 Jan;38(1):31-37 ju A, Barlow CE, DeFina LF, Willis BL, Haskell WL, Maron DJ. Am J Med. 2018 Jan;131(1):48-55 What This Computer Needs Is a Physician: Humanism and Artificial Intelligence. Verghese A, Shah NH, Harrington RA. JAMA. 2018 Jan 2;319(1):19-20 Acute Type B Dissection Causing Collapse of EVAR Endograft and Iliac Limb Occlusion. Itoga NK, Wu T, Dake MD, Dalman RL, Lee JT. Ann Vasc Surg. 2018 Physiological Mitochondrial Fragmentation Is a Normal Cardiac Adaptation to Jan;46:206.e1-206.e4 Increased Energy Demand. Coronado M, Fajardo G, Nguyen K, Zhao M, Kooiker K, Jung G, Hu DQ, Reddy S, Sandoval E, Stotland A, Gottlieb RA, Bernstein D. Circ Res. 2018 Jan 19;122(2):282-295 DECEMBER

Association of insurance type with receipt of oral anticoagulation in insured Non-coding RNAs: key regulators of smooth muscle cell fate in vascular disease. patients with atrial fibrillation: A report from the American College of Cardiol- Leeper NJ, Maegdefessel L. Cardiovasc Res. 2017 Dec 29. ogy NCDR PINNACLE registry. Yong CM, Liu Y, Apruzzese P, Doros G, Cannon CP, Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrat- Maddox TM, Gehi A, Hsu JC, Lubitz SA, Virani S, Turakhia MP; ACC PINNACLE ing Lymphocytes. Gee MH, Han A, Lofgren SM, Beausang JF, Mendoza JL, Birn- Investigators. Am Heart J. 2018 Jan;195:50-59 baum ME, Bethune MT, Fischer S, Yang X, Gomez-Eerland R, Bingham DB, Siben- Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses mac- er LV, Fernandes RA, Velasco A, Baltimore D, Schumacher TN, Khatri P, Quake SR, rophages and is a target of cancer immunotherapy. Barkal AA, Weiskopf K, Kao Davis MM, Garcia KC. Cell. 2017 Dec 20. KS, Gordon SR, Rosental B, Yiu YY, George BM, Markovic M, Ring NG, Tsai JM, Prevalence, Characteristics, and Outcomes of Valvular Heart Disease in Patients McKenna KM, Ho PY, Cheng RZ, Chen JY, Barkal LJ, Ring AM, Weissman IL, Maute With Atrial Fibrillation: Insights From the ORBIT-AF (Outcomes Registry for Better RL. Nat Immunol. 2018 Jan;19(1):76-84 Informed Treatment for Atrial Fibrillation). Thomas KL, Jackson LR 2nd, Shrader Prochemerin cleavage by factor XIa links coagulation and inflammation. Ge X, P, Ansell J, Fonarow GC, Gersh B, Kowey PR, Mahaffey KW, Singer DE, Thomas L, Yamaguchi Y, Zhao L, Bury L, Gresele P, Berube C, Leung LL, Morser J. Blood. Piccini JP, Peterson ED. J Am Heart Assoc. 2017 Dec 22;6(12). 2018 Jan 18;131(3):353-364 Inhibition of JAK-STAT Signaling Suppresses Pathogenic Immune Responses in Thermal Stimulation Alters Cervical Spinal Cord Functional Connectivity in Hu- Medium and Large Vessel Vasculitis. Zhang H, Watanabe R, Berry GJ, Tian L, mans. Weber KA 2nd, Sentis AI, Bernadel-Huey ON, Chen Y, Wang X, Parrish TB, Goronzy JJ, Weyand C. Circulation. 2017 Dec 18. Mackey S. Neuroscience. 2018 Jan 15;369:40-50 First Trimester Plasma Glucose Values in Women without Diabetes are Asso- Randomized study of continuous high-dose lenalidomide, sequential azaciti- ciated with Risk for Congenital Heart Disease in Offspring. Helle EIT, Biegley dine and lenalidomide, or azacitidine in persons 65 years and over with new- P, Knowles JW, Leader JB, Pendergrass S, Yang W, Reaven GR, Shaw GM, Ritchie ly-diagnosed acute myeloid leukemia. Medeiros BC, McCaul K, Kambhampati M, Priest JR. J Pediatr. 2017 Dec 13. S, Pollyea DA, Kumar R, Silverman LR, Kew A, Saini L, Beach CL, Vij R, Wang X, Hypoxia-inducible factor 1 in clinical and experimental aortic aneurysm disease. Zhong J, Gale RP. Haematologica. 2018 Jan;103(1):101-106 Wang W, Xu B, Xuan H, Ge Y, Wang Y, Wang L, Huang J, Fu W, Michie SA, Dalman Clinical Outcomes and Cost-Effectiveness of Fractional Flow Reserve-Guided RL. J Vasc Surg. 2017 Dec 11. Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Spatiotemporal Progression of Early Human Ventricular Fibrillation. Vidmar D, Disease: Three-Year Follow-Up of the FAME 2 Trial (Fractional Flow Reserve Ver- Krummen DE, Hayase J, Narayan SM, Ho G, Rappel WJ. JACC Clin Electrophysiol. sus Angiography for Multivessel Evaluation). Fearon WF, Nishi T, De Bruyne B, 2017 Dec 11;3(12):1437-1446. cvi.stanford.edu | 16 Nativity Status and Cardiovascular Disease Mortality Among Hispanic Adults. Organoids lead the cancer attack. Smith AR, Kuo CJ. Nat Med. 2017 Dec Rodriguez F, Hastings KG, Hu J, Lopez L, Cullen M, Harrington RA, Palaniappan 7;23(12):1399-1400. LP. J Am Heart Assoc. 2017 Dec 13;6(12). Interpreting Activation Mapping of Atrial Fibrillation: A Hybrid Computational/ Association of Antibodies to Citrullinated Protein Antigens with Blood Pressure Physiological Study. Sahli Costabal F, Zaman JAB, Kuhl E, Narayan SM. Ann in First-Degree Relatives of Rheumatoid Arthritis Patients: The Studies of the Eti- Biomed Eng. 2017 Dec 6. ology of Rheumatoid Arthritis. Hughes-Austin JM, Gan RW, Deane KD, Weisman Thrombus Burden of Deep Vein Thrombosis and Its Association with Throm- MH, Demoruelle MK, Sokolove J, Robinson WH, Holers VM, Norris JM, Ix JH. Am boprophylaxis and D-Dimer Measurement: Insights from the APEX Trial. Chi G, J Nephrol. 2017 Dec 13;46(6):481-487. Goldhaber SZ, Hull RD, Hernandez AF, Kerneis M, Al Khalfan F, Cohen AT, Har- Practices surrounding pulmonary hypertension and bronchopulmonary dys- rington RA, Gibson CM. Thromb Haemost. 2017 Dec;117(12):2389-2395. plasia amongst neonatologists caring for premature infants. Altit G, Lee HC, The TIME Trial - Effect of Timing of Stem Cell Delivery Following ST-Elevation Hintz S, Tacy TA, Feinstein JA, Bhombal S. J Perinatol. 2017 Dec 12. Myocardial Infarction on the Recovery of Global and Regional Left Ventricular CRISPR/Cas9 microinjection in oocytes disables pancreas development in Function: Final 2-Year Analysis. Traverse JH, Henry TD, Pepine CJ, Willerson JT, sheep. Vilarino M, Rashid ST, Suchy FP, McNabb BR, van der Meulen T, Fine EJ, Chugh AR, Yang PC, Zhao D, Ellis SG, Forder JR, Perin EC, Penn MS, Hatzopoulos Ahsan S, Mursaliyev N, Sebastiano V, Diab SS, Huising MO, Nakauchi H, Ross PJ. AK, Chambers JW, Baran K, Raveendran G, Gee AP, Taylor DA, Moyé L, Ebert RF, Sci Rep. 2017 Dec 12;7(1):17472. Simari RD. Circ Res. 2017 Dec 5.

Physiologic Mitochondrial Fragmentation Is a Normal Cardiac Adaptation to In- Molecular and functional resemblance of differentiated cells derived from creased Energy Demand. Coronado M, Fajardo G, Nguyen K, Zhao M, Kooiker KB, isogenic human iPSCs and SCNT-derived ESCs. Zhao MT, Chen H, Liu Q, Shao Jung G, Hu DQ, Reddy S, Sandoval E, Stotland A, Gottlieb RA, Bernstein D. Circ NY, Sayed N, Wo HT, Zhang JZ, Ong SG, Liu C, Kim Y, Yang H, Chour T, Ma H, Guti- Res. 2017 Dec 12. errez NM, Karakikes I, Mitalipov S, Snyder MP, Wu JC. Proc Natl Acad Sci USA. 2017 Dec 26;114(52):E11111-E11120. Exercise testing in heart failure: a contemporary discussion in an era of novel diagnostic techniques and biomarkers. Moneghetti KJ, Christle JW, Myers Relationship between several surrogate estimates of insulin resistance and a J, Haddad F. Curr Opin Cardiol. 2017 Dec 8. direct measure of insulin-mediated glucose disposal: Comparison of fasting versus post-glucose load measurements. Abbasi F, Silvers A, Viren J, Reaven GM. GDF-15 (Growth Differentiation Factor 15) Is Associated With Lack of Ventricu- Diabetes Res Clin Pract. 2017 Dec 2;136:108-115. lar Recovery and Mortality After Transcatheter Aortic Valve Replacement. Kim JB, Kobayashi Y, Moneghetti KJ, Brenner DA, O’Malley R, Schnittger I, Wu A Comparative Assessment of Implant Site Viability in Humans and Rats. Chen JC, Murtagh G, Beshiri A, Fischbein M, Miller DC, Liang D, Yeung AC, Haddad CH, Pei X, Tulu US, Aghvami M, Chen CT, Gaudillière D, Arioka M, Maghazeh F, Fearon WF. Circ Cardiovasc Interv. 2017 Dec;10(12). Moghim M, Bahat O, Kolinski M, Crosby TR, Felderhoff A, Brunski JB, Helms JA. J Dent Res. 2017 Dec 1:742631. mTORC1 Activation during Repeated Regeneration Impairs Somatic Stem Cell Maintenance. Haller S, Kapuria S, Riley RR, O’Leary MN, Schreiber KH, Andersen Adapting to insulin resistance in obesity: role of insulin secretion and clearance. JK, Melov S, Que J, Rando TA, Rock J, Kennedy BK, Rodgers JT, Jasper H. Cell Jung SH, Jung CH, Reaven GM, Kim SH. Diabetologia. 2017 Dec 1. Stem Cell. 2017 Dec 7;21(6):806-818.e5. Computational simulation of postoperative pulmonary flow distribution in Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche. Alagille patients with peripheral pulmonary artery stenosis. Yang W, Hanley FL, Madl CM, Heilshorn SC. Annu Rev Biomed Eng. 2017 Dec 8. Chan FP, Marsden AL, Vignon-Clementel IE, Feinstein JA. Congenit Heart Dis. 2017 Dec 1. Challenges and recommendations for epigenomics in precision health. Car- ter AC, Chang HY, Church G, Dombkowski A, Ecker JR, Gil E, Giresi PG, Greely Incremental Value of Deformation Imaging and Hemodynamics Following Heart H, Greenleaf WJ, Hacohen N, He C, Hill D, Ko J, Kohane I, Kundaje A, Palmer Transplantation: Insights From Graft Function Profiling. Kobayashi Y, Sudini NL, M, Snyder MP, Tung J, Urban A, Vidal M, Wong W. Nat Biotechnol. 2017 Dec Rhee JW, Aymami M, Moneghetti KJ, Bouajila S, Kobayashi Y, Kim JB, Schnitt- 8;35(12):1128-1132. ger I, Teuteberg JJ, Khush KK, Fearon WF, Haddad F. JACC Heart Fail. 2017 Dec;5(12):930-939. Computed Tomography Features associated With the Eighth Edition TNM Stage Classification for Thymic Epithelial Tumors. Padda SK, Terrone D, Tian L, Khu- Conquering the first hurdles in cardiac transplantation: In the footprints of gi- ong A, Neal JW, Riess JW, Berry MF, Hoang CD, Burt BM, Leung AN, Schwartz ants. Hess ML, Hunt S. J Heart Lung Transplant. 2017 Dec;36(12):1276-1278. EJ, Shrager JB, Wakelee HA. J Thorac Imaging. 2017 Dec 6. Risky Business: Meeting the Structural Needs of Transdisciplinary Science. Wise Transapical Transcatheter Aortic Valve Replacement Is Associated With In- PH, Shaw GM, Druzin ML, Darmstadt GL, Quaintance C, Mäkinen E, Relman creased Cardiac Mortality in Patients With Left Ventricular Dysfunction: Insights DA, Quake SR, Butte AJ, Angst MS, Muglia LJ, Macones G, Driscoll D, Ober C, From the PARTNER I Trial. Elmariah S, Fearon WF, Inglessis I, Vlahakes GJ, Lind- Simpson JL, Katz M, Howse J, Stevenson DK. J Pediatr. 2017 Dec;191:255-258. man BR, Alu MC, Crowley A, Kodali S, Leon MB, Svensson L, Pibarot P, Hahn RT, Moderate to High Levels of Cardiorespiratory Fitness Attenuate the Effects of Tri- Thourani VH, Palacios IF, Miller DC, Douglas PS, Passeri JJ; PARTNER Trial In- glyceride to High-Density Lipoprotein Cholesterol Ratio on Coronary Heart Dis- vestigators and PARTNER Publications Office. JACC Cardiovasc Interv. 2017 Dec ease Mortality in Men. Farrell SW, Finley CE, Barlow CE, Willis BL, DeFina LF, Has- 11;10(23):2414-2422. kell WL, Vega GL. Mayo Clin Proc. 2017 Dec;92(12):1763-1771.

cvi.stanford.edu | 17 Association of Omics Features with Histopathology Patterns in Lung Adenocar- Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses mac- cinoma. Yu KH, Berry GJ, Rubin DL, Ré C, Altman RB, Snyder M. Cell Syst. 2017 rophages and is a target of cancer immunotherapy. Barkal AA, Weiskopf K, Kao Dec 27;5(6):620-627.e3. KS, Gordon SR, Rosental B, Yiu YY, George BM, Markovic M, Ring NG, Tsai JM, McKenna KM, Ho PY, Cheng RZ, Chen JY, Barkal LJ, Ring AM, Weissman IL, Maute Resuscitating Cardiovascular Drug Development. Helmy K, Harrington RA, RL. Nat Immunol. 2017 Nov 27. Kocher B. JAMA Cardiol. 2017 Dec 1;2(12):1295-1296. Insulin resistance, an unmasked culprit in depressive disorders: Promises for Maintenance of neural progenitor cell stemness in 3D hydrogels requires matrix interventions. Watson K, Nasca C, Aasly L, McEwen B, Rasgon N. Neuropharma- remodelling. Madl CM, LeSavage BL, Dewi RE, Dinh CB, Stowers RS, Khariton M, cology. 2017 Nov 24. Lampe KJ, Nguyen D, Chaudhuri O, Enejder A, Heilshorn SC. Nat Mater. 2017 Dec;16(12):1233-1242. Anatomical Road Mapping Using CT and MR Enterography for Ultrasound Molec- ular Imaging of Small Bowel Inflammation in Swine. Wang H, Felt SA, Guracar I, Selected 2016 Highlights in Congenital Cardiac Anesthesia. Resheidat A, Qui- Taviani V, Zhou J, Sigrist RMS, Zhang H, Liau J, Vilches-Moure JG, Tian L, Saenz nonez ZA, Mossad EB, Wise-Faberowski L, Mittnacht AJC. J Cardiothorac Vasc Y, Bettinger T, Hargreaves BA, Lutz AM, Willmann JK. Eur Radiol. 2017 Nov 23. Anesth. 2017 Dec;31(6):1927-1933. Disease models: Method in the madness of fibrosis. Gurtner GC, Padmanabhan Risk of cardiovascular disease among women with endometrial cancer com- J. Nat Mater. 2017 Nov 24;16(12):1176-1177. pared to cancer-free women in the Women’s Health Initiative. Felix AS, Lehman A, Foraker RE, Naughton MJ, Bower JK, Kuller L, Sarto GE, Stefanick ML, Van Ultrafast non-radiative dynamics of atomically thin MoSe2. Lin MF, Kochat V, Horn L, Jackson RD, Paskett ED. Cancer Epidemiol. 2017 Dec;51:62-67. Krishnamoorthy A, Bassman L, Weninger C, Zheng Q, Zhang X, Apte A, Tiwary CS, Shen X, Li R, Kalia R, Ajayan P, Nakano A, Vashishta P, Shimojo F, Wang X, Mechanical confinement regulates cartilage matrix formation by chondro- Fritz DM, Bergmann U. Nat Commun. 2017 Nov 23;8(1):1745 cytes. Lee HP, Gu L, Mooney DJ, Levenston ME, Chaudhuri O. Nat Mater. 2017 Dec;16(12):1243-1251. Role of epithelial to mesenchymal transition associated genes in mammary gland regeneration and breast tumorigenesis. Sikandar SS, Kuo AH, Kalisky T, A method for determining exercise oscillatory ventilation in heart failure: Prog- Cai S, Zabala M, Hsieh RW, Lobo NA, Scheeren FA, Sim S, Qian D, Dirbas FM, Som- nostic value and practical implications. Vainshelboim B, Amin A, Christle JW, lo G, Quake SR, Clarke MF. Nat Commun. 2017 Nov 21;8(1):1669. Hebbal S, Ashley EA, Myers J. Int J Cardiol. 2017 Dec 15;249:287-291. Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage an- Bronchoscopy in children with tetralogy of fallot, pulmonary atresia, and ma- titumor activity. Ring NG, Herndler-Brandstetter D, Weiskopf K, Shan L, Volkmer jor aortopulmonary collaterals. Sidell DR, Koth AM, Bauser-Heaton H, McEl- JP, George BM, Lietzenmayer M, McKenna KM, Naik TJ, McCarty A, Zheng Y, Ring hinney DB, Wise-Faberowski L, Tracy MC, Hanley FL, Asija R; Pulmonary Ar- AM, Flavell RA, Weissman IL. Proc Natl Acad Sci USA. 2017 Nov 20. tery Reconstruction Program at Stanford University. Pediatr Pulmonol. 2017 Dec;52(12):1599-1604. Prochemerin cleavage by Factor XIa links coagulation and inflammation. Ge X, Yamaguchi Y, Zhao L, Bury L, Gresele P, Berube C, Leung LL, Morser J. Blood.

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cvi.stanford.edu | 18 Accelerometer-Measured Physical Activity and Mortality in Women Aged 63 to Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in 99. LaMonte MJ, Buchner DM, Rillamas-Sun E, Di C, Evenson KR, Bellettiere J, Human Induced Pluripotent Stem Cells and Somatic Cells. Zhao MT, Shao NY, Hu Lewis CE, Lee IM, Tinker LF, Seguin R, Zaslovsky O, Eaton CB, Stefanick ML, LaC- S, Ma N, Srinivasan R, Jahanbani F, Lee J, Zhang SL, Snyder MP, Wu JC. Circ Res. roix AZ. J Am Geriatr Soc. 2017 Nov 16. 2017 Nov 10;121(11):1237-1250.

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cvi.stanford.edu | 19 Leadership

Joseph C. Wu, MD, PhD Robert A. Harrington, MD Director, Stanford Cardiovascular Institute Arthur L. Bloomfield Professor of Medicine Simon H. Stertzer Professor of Medicine Chair, Dept. of Medicine (Cardiovascular) and Radiology

Ronald L. Dalman, MD Stephen J. Roth, MD, MPH Walter C. and Elsa R. Chidester Professor and Chief, Pediatric Cardiology Professor of Surgery Director, Children’s Heart Center Chief, Division of Vascular Surgery

Dominik Fleischmann, MD Michael Snyder, PhD Professor, Dept. of Radiology Professor and Chair, Dept. of Genetics Chief, Cardiovascular Imaging Director, Stanford Center for Genomics and Personalized Medicine

Kenneth Mahaffey, MD Y. Joseph Woo, MD Professor, Dept. of Medicine Norman E. Shumway Professor Vice Chair of Medicine in Cardiothoracic Surgery for Clinical Research Chair, Dept. of Cardiothoracic Surgery

Mark Nicolls, MD Alan Yeung, MD The Stanford Professor of Pulmonary and Li Ka Shing Professor of Medicine Critical Care Medicine, Dept. of Medicine, Co-Chief (Clinical), Chief, Pulmonary and Critical Division of Cardiovascular Medicine Care Medicine

Tom Quertermous, MD Paul Yock, MD William G. Irwin Professor of Medicine Martha Meier Weiland Professor, Co-Chief (Research), Bioengineering and Medicine; Division of Cardiovascular Medicine and Professor, by courtesy, of Mechanical Engineering, Director, Byers Center for Biodesign

Marlene Rabinovitch, MD Dwight and Vera Dunlevie Professor in Pediatric Cardiology

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