Signaling Effectors Required for G Protein-Coupled Estrogen Receptor-, GPER, Induced Events Associated with Breast Cancer Progression by Hilary Thompson Magruder B.A. Wheaton College, 2009 A dissertation submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in the Division of Biology and Medicine at Brown University. May, 2014 © Copyright 2014 by Hilary Thompson Magruder This presentation by Hilary Thompson Magruder is accepted in its present form by the Division of Biology and Medicine as satisfying the dissertation requirements for the degree of Doctor of Philosophy Date__________ ________________________________ Edward J. Filardo, Ph.D., Director Recommended to the Graduate Council Date__________ ________________________________ Richard Freiman, Ph.D., Reader Date__________ ________________________________ Jonathan Reichner, Ph.D., Reader Date__________ ________________________________ Wentian Yang, Ph.D., Reader Date__________ ________________________________ Eric Prossnitz, Ph.D., Outside Reader Approved by the Graduate Council Date_________ ________________________________ Peter M. Weber, Ph.D. Dean of the Graduate School iii Hilary T. Magruder 29 High Hawk Road Portsmouth, RI 02871 (401) 662-9588 [email protected] Education Brown University (Providence, Rhode Island) Anticipated 2014 Ph.D. Candidate in Pathobiology under the Division of Biology and Medicine Thesis: “Signaling Effectors Required for G Protein-Coupled Estrogen Receptor-, GPER, Induced Events Associated with Breast Cancer Progression” in Dr. Edward Filardo’s laboratory Mentored Brown University undergraduate students in Dr. Jonathan Reichner’s laboratory Teaching Assistant for a virology course Nominated for the June Rockwell Levy Predoctoral Fellowship in the Fall of 2009 Brown University (Providence, Rhode Island) Anticipated 2014 M.A. in Pathobiology under the Division of Biology and Medicine Wheaton College (Norton, Massachusetts) 2005 – 2009 B.A. in Biochemistry & Psychology (Double Major) Cumulative GPA- 3.75; Biochemistry GPA- 3.77 Honors: The Villar’s Prize in Science, Julia R. Lange Fellowship, Phi Beta Kappa Honors Society, Psi Chi Honors Society, Tri Beta Biological Honors Society, Biochemistry Departmental Honors, Dean’s List, National Scholars Honors Society Biochemistry Honors Thesis on GPR30 in ovarian cancer under the supervision of Dr. Edward Filardo from Rhode Island Hospital/Brown University and Dr. Elita Pastra-Landis from Wheaton College Publications, Citations, and Abstracts Magruder H, Quinn JA, Schwartzbauer JE, Reichner J, Huang A, Filardo EJ. The G-protein- coupled estrogen receptor, GPER-1, promotes fibrillogenesis via a Shc-dependent pathway resulting in anchorage-independent growth. Hormones and Cancer (in preparation). iv Magruder H, Reichner J, Huang A, Filardo EJ. PTPN12 inhibits estrogen action via the G- protein-coupled receptor, GPR30/GPER-1. (in preparation). Magruder H, Filardo EJ. Epidermal growth factor receptor transactivation and fibronectin matrix assembly by the G-protein coupled receptor, GPER, requires a transmembrane signaling complex consisting of PTPN12, integrin α5β1, and MMP-3. Abstract presented at the Experimental Biology Annual Meeting; April 2012, San Diego, California. Dewan S, Magruder H. Re-treatment of vestibular schwannomas with gamma knife radiosurgery. Abstract Presented at The 14th International Meeting of the Leksell Gamma Knife Society; May 2008, Quebec, Canada. McCormack E, Magruder H, Steinhoff MM, Gass J, Legare ED, Wiggins DL, Tejada-Berges T, Sikov W, Strenger R, Dizon DS. Clinicopathic analysis of tubular carcinoma of the breast: the experience from Women & Infants’ Hospital of Rhode Island. American Journal of Clinical Oncology, 2007; 30: 454-455. Bonzagni A, Magruder H, Benoit JM. Mercury uptake from fish fertilizer by spinach plants. Eighth Annual Northeast Student Chemistry Research Conference (NSCRC) 2006; Cambridge, MA. Work Experience and Internships Wheaton College 2013 - Present Laboratory Instructor of a general chemistry course and an organic chemistry course 2008 – 2009 Instructed a general and inorganic chemistry weekly review and graded papers under the supervision of Professor Matthew Evans 2007 Attempted to create an environmentally friendly stereoisomer of an amino acid through hydrogenation reactions under the supervision of Professor Christopher Kalberg 2006 – 2007 Teaching fellow in general and inorganic chemistry under the supervision of Professor Jani Benoit that included tutoring students and grading examinations 2006 – 2007 Kollett Center tutor for general and inorganic chemistry students Memorial Hospital of Rhode Island 2008-2009 v Conducted a clinical research project on patient satisfaction in labor and delivery, and disparities in access to healthcare American Cancer Society Fuller Fellowship 2007 Studied GPER at Alpert Medical School of Brown University/Rhode Island Hospital under the supervision of Dr. Edward Filardo New England Gamma Knife Center 2007 Investigated vestibular schwannomas at Alpert Medical School of Brown University/Rhode Island Hospital under the supervision of Dr. Georg Noren Research published in the Journal of Neurosurgery NeuroHealth 2007 Explored the correlation between lack of smell and apathy in Parkinson’s patients under the supervision of Dr. Joseph Friedman and Dr. Megan Spencer Merck Scholar Internship 2006 Investigated mercury levels in human hair and in leaves around the Wheaton College Vernal Pool under the supervision of Professor Jani Benoit Women & Infants Hospital- Program in Women’s Oncology 2006 – 2007 Chaired and managed the Patient Advocate Fundraiser, which raised over $60,000 Structured and conducted a clinical research project on tubular carcinomas of the breast Published an abstract in the American Journal of Clinical Oncology Research Presentations Experimental Biology Annual Meeting 2012 in San Diego 2012 Presented Epidermal growth factor receptor transactivation and fibronectin matrix assembly by the G-protein coupled receptor, GPER, requires a transmembrane signaling complex consisting of PTPN12, integrin α5β1, and MMP-3 Pathobiology Program Retreat 2012 Presented Epidermal growth factor receptor transactivation and fibronectin matrix assembly by the G-protein coupled receptor, GPER, requires a transmembrane signaling complex consisting of PTPN12, integrin α5β1, and MMP-3 19th Annual Hospital Research Celebration at Rhode Island Hospital 2011 vi Presented Transmembrane signaling effectors that regulate GPER-mediated fibrillogeness and EGFR transactivation Department of Medicine’s 17th Annual Research Forum- Brown University 2011 Presented Transmembrane signaling effectors that regulate GPER-mediated EGFR transactivation Brown University Pathology II Course 2011 Presented Extracellular Matrix: Integrins and Matrix Metalloproteinases in Cancer Brown University Virology Course 2011 Presented Herpesviridae Pathobiology Program Retreat 2011 Presented Transmembrane signaling effectors that regulate GPER-mediated EGFR transactivation 18th Annual Hospital Research Celebration at Rhode Island Hospital 2010 Presented Role of GPR30 in breast tumor cell survival and its influence on mammary stromal fibroblast transformation Pathobiology Program Retreat 2010 Presented Role of GPR30 in breast tumor cell survival and its influence on mammary stromal fibroblast transformation Fuller and Stone Fellowship Reception 2007 Presented Expression of GPR30, a novel membrane estrogen receptor, in human breast and ovarian cancer Wheaton College Academic Festival XVI 2007 Nominated and accepted to present Mercury Deposition to the Wheaton College Vernal Pool via Leaf Litter Fall Wheaton College Research Symposium 2007 Presented Mercury Deposition to the Wheaton College Vernal Pool via Leaf Litter Fall Achievements and Honors June Rockwell Levy Predoctoral Fellowship Nominee 2009 The Villar’s Prize in Science 2009 vii Julia R. Lange Fellowship 2009 Academic Festival XVIII Nominee and Participant at Wheaton College 2009 Outstanding Service as a Partner in Philanthropy Awarded by the 2007 Association of Fundraising Professionals American Cancer Society Fuller Fellow 2007 Academic Festival XVI Nominee and Participant at Wheaton College 2007 Merck Scholar 2006 Wheaton Fellows Scholarship 2006 – 2007 Dean’s List Fall 2005 – 2009 Memberships American Society for Pharmacology and Experimental Therapeutics 2011 - Present Phi Beta Kappa Honors Society 2008 - Present Psi Chi Honors Society in Psychology 2008 - Present Pre-Health Society - President 2008 – 2009 Tri-Beta Biological Honors Society, Chi Nu – Vice President 2008 – 2009 American Cancer Society’s Fuller Fellow 2007 – 2008 National Scholars Honors Society 2007 - Present Wheaton Fellow 2006 – 2007 Patient Advocate Fundraising Committee - Chair, Project Manager 2006 – 2007 Public Vaccination Council 2006 Pre-Health Society - Secretary and Events Coordinator 2006 – 2008 Biomedical Science Careers Program at Harvard 2006 - Present viii Program in Women’s Oncology Chemotherapy Committee 2006 Society of Surgical Oncology Application Committee 2006 Breast Fellowship Committee 2006 Certifications NIH Clinical Research Training Course Certificate 2013 NIH Office of Clinical Research Training and Medical Education Sheridan Teaching Certificate I 2010 Sheridan Center at Brown University Training in Responsible Conduct in Research Certificate 2009 Brown University Initiative to Maximize Student Development Certificate