OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Muredach P. Reilly eRA COMMONS USER NAME (credential, e.g., agency login): REILLYMP POSITION TITLE: Herbert and Florence Irving Professor of Medicine, Columbia University EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) DEGREE Completion (if Date FIELD OF STUDY INSTITUTION AND LOCATION applicable) MM/YYYY

University College Dublin, Ireland MB BCh 1988 Medicine University College Dublin, Ireland BSc Pharm 1990 Pharmacology University of Pennsylvania, PA USA MSCE 2003 Epidemiology

1. A. Personal Statement

I am a cardiologist and Professor of Medicine at Columbia University, relocated from the University of Pennsylvania. I have expertise in clinical cardiovascular medicine, human genetics and functional genomics, clinical pharmacology, epidemiology and mechanistic translational research. In 2016, I relocated to Columbia from University of Pennsylvania. My Cardiometabolic Research Program is dedicated to translational and genomic studies and focuses on (1) novel mechanisms of human atherosclerosis underlying recent GWAS discoveries in human, (2) the role on innate immunity in promoting cardio-metabolic disease, (3) the functions of adipose tissue inflammation in insulin resistance and atherosclerotic risk, and (4) genomic and transcriptomic discovery in human cardio-metabolic disorders. My group employs a translational and genomic approach including human functional genomics, human induced pluripotent stem cell (hiPSC) technology and gene editing, animal based mechanistic studies, patient-oriented interrogation as well as large scale epidemiological studies. I have a track record in mentoring, collaborating, assembling and overseeing multidisciplinary teams for execution of translational, genomic and laboratory heart disease research. At Columbia, as Director-designate of the Irving Institute for Clinical and Translational Research, home of Columbia Clinical and Translational Science Award (CTSA), I will also build and extend programs in clinical and translational research as well as in genomics and precision medicine while continuing my research program in cardio-metabolic diseases.

B. Positions and Honors

Employment 1988-1989 Internship, St Vincent’s Hospital, University College Dublin, Ireland 1989-1990 Instructor in Pharmacology, University College Dublin, Ireland 1990-1992 Medical Residency, Mater Hospital, University College Dublin, Ireland 1992-1994 Fellow Cardiovascular Medicine, Mater Hospital, University College Dublin, Ireland 1994-1995 Medical Residency, Hospital of the University of Pennsylvania, Philadelphia 1995-1997 Fellow, Cardiology, Hospital of the University of Pennsylvania, Philadelphia 1997-1998 Medical Residency, Hospital of the University of Pennsylvania, Philadelphia 1998-2000 Fellow, Cardiology, Hospital of the University of Pennsylvania, Philadelphia 2000-2002 Instructor in Cardiovascular Medicine, University of Pennsylvania 2002-2010 Assistant Professor of Medicine and Pharmacology, University of Pennsylvania 2006-2006 Associate Director of the General Clinical Research Center, University of Pennsylvania 2006-2011 Director of the Translational Core Laboratories (CTSA), University of Pennsylvania 2008-2011 Director of the Biomarker Core Laboratory, (DERC), University of Pennsylvania 2010-2014 Associate Professor of Medicine and Pharmacology, University of Pennsylvania 2014-2016 Professor of Medicine, University of Pennsylvania 2016-Present Adjunct Professor of Medicine, University of Pennsylvania 2016-Present Professor of Medicine, Columbia University 2016-Present Director-designate, Irving Institute for Clinical and Translational Research, Columbia University

Other Experience and Professional Memberships 2001-2004 American Heart Association (ATVB Fall Meeting Program Committee) 2003 Ad-hoc reviewer, NLHBI RFA (HL-03-008) Role of Sleep and Sleep-Disordered Breathing in the Metabolic Syndrome 2004-2008 Reviewer NIH, Clinical & Integrative Cardiovascular Sciences (CICS) Study Section 2005-2008 Reviewer, American Heart Association (National), Lipoproteins, Lipid Metabolism and Nutrition, Study Section 2012-Present Reviewer, American Heart Association (National), Genomics and Translational Biology - Clinical Science Study Section 2006-Present American Heart Association, Leadership Committee, Council on Arteriosclerosis, Thrombosis and Vascular Biology: 2008-2010; Chair, Early Career Committee, Council on Arteriosclerosis, Thrombosis and Vascular Biology 2008-2010The NHLBI Candidate-gene Association Resource (CARe) Study, Publication Committee 2009-Present Executive Committee, Coronary Artery Disease Genome Wide Replication and Meta-analysis (CARDIoGRAM): 2011-Present; Steering Committee, CARDIoGRAM_Plus_C4D Consortium. 2012-2013 Ad-hoc reviewer, NIH NHLBI PPG Review Committee; NIH ZRG1 GGG-R (51)S; NIH, Atherosclerosis & Inflammation of the Cardiovascular System Study Section 2014-Present Member, Atherosclerosis & Inflammation of the Cardiovascular System Study Section 2013-2015 Chair, American Heart Association ATVB Spring Conference Program Committee 2015-Present National Institute of Health (NHLBI, Board of Scientific Counselors (BSC), Division of Intramural Research, Reviewer) Honors 1992-1994 Postdoctoral Research Fellow, the Health Research Board, Ireland 1992-1994 Postdoctoral Research Fellow, the Irish Heart Foundation, Ireland 1997 American College of Cardiology, Fellows Award 1999 University of Pennsylvania, Cardiovascular Fellow Research Award 2000 Merck, Young Investigator Award in Atherosclerosis 2003 American Federation for Medical Research, GSK Award 2005 American Federation for Medical Research, Young Investigator Award 2005 Gill Heart Institute, Young Physician Scientist Award 2006 The University of Pennsylvania Donald B Martin Teaching Service Award. 2010 Election to American Society for Clinical Investigation 2010 Fellow, Royal College of Physicians, Ireland 2010 Special Recognition Award for Arteriosclerosis, American Heart Association 2013 The University of Pennsylvania William Osler Award in Patient Oriented Research

2. C. Contribution to Science (names of pre- and post-doctoral trainees mentored by Dr. Reilly are underlined) 1. Tissue-specific genomics in cardiometabolic disease: Many discovered loci for complex human diseases, including heart diseases, may act via regulatory molecular processes (e.g., non coding RNA, alternative splicing, posttranslational protein modifications) and in cell and tissue specific manners that are not necessarily conserved in lower species. Understanding such processes and translation toward clinical applications requires human tissue-specific focus and human-relevant functional models. With my MPI collaborator, Dr. Mingyao Li, my group has focused on these questions. We have (a) used RNA-seq to identify novel cell and tissue specific non-coding RNA in humans, (b) contributed to bioinformatics and statistical approaches that have advanced the field, and (c) led novel studies developing and applying protocols for generation of a renewable source of macrophages using human induced pluripotent stem cells (hiPSC) for functional genomics. This work provides researchers with important human datasets and tools for functional investigation of disease causing genes, and cell-specific targets in cardiometabolic disease. a) Liu Y, Ferguson JF, Xue C, Silverman IM, Gregory BS, Reilly MP*, Li M*. (2013) Evaluating the impact of sequencing depth on transcriptome profiling of human adipose. PLoS One 8(6): e66883, PMC ID 3691247. b) Liu Y*, Ferguson JF*, Xue C, Ballantyne RL, Silverman IM, Gosai S, Serfecz J, Morley MP, Gregory BD, Li M*, Reilly MP*. (2014) Tissue-specific RNA-Seq in human evoked inflammation identifies blood and adipose lincRNA signatures of cardiometabolic disease. Arterioscl Thromb Vasc Biol. 34(4):902-12. PMC ID 3966947. c) Zhang H, Xue C, Shah R, Bermingham K, Hinkle CC, Li W, Rodrigues A, Tabita-Martinez J, Millar JS, Cuchel M, Pashos E, Liu Y, Yan R, Yang W, Gosai SJ, VanDorn D, Chou S, Gregory BD, Morrisey E, Li M, Rader DJ, Reilly MP. Functional Analysis and Transcriptomic Profiling of iPSC-Derived Macrophages and Their Application in Modeling Mendelian Disease. Circ Res Jun 19;117(1):17-28. PMC ID 4565503 d) Ballantyne RL*, Zhang X*, Nuñez S, Xue C, Zhao W, Reed E, Salaheen D, Foulkes AS, Li M, Reilly MP. (2016) Genome-wide interrogation reveals hundreds of long intergenic noncoding RNAs that associate with cardiometabolic traits. Hum Mol Genet. 2016 Jun 10. [Epub ahead of print] PMID: 27288454 (PMC ID in progress) 2. Evoked human inflammation in pathophysiological and genetic discoveries: For over a decade, I have directed novel experimental studies in humans using an evoked model of inflammation (experimental endotoxemia) to understand the impact of activation of innate immunity on cardiometabolic responses and the underlying genomic basis of these responses and related diseases. For example, my group was the first to show that activation of innate immunity in human induces lipoprotein changes with HDL particle dysfunction and adipose inflammation with insulin resistance. Recently, we have uncovered novel genetic regulation of fever, plasma cytokine inflammatory responses and inflammatory macrophage phenotypes. Such studies provide new insights into causal dynamic processes underlying the complex association of inflammation with acute and chronic human diseases, including heart disease. They have also defined for the field a refined model for physiological studies, genetic discovery and therapeutic testing in complex and dynamic human inflammatory and cardiometabolic disorders. a) Meyer NJ, Ferguson JF, Feng R, Wang F, Patel PN, Li M, Xue C, Qu L, Liu Y, Boyd JH, Russell JA, Christie JD, Walley KR, Reilly MP. (2014) A Functional Synonymous Coding Variant in the IL1RN Gene Is Associated with Survival in Septic Shock. Am J Respir Crit Care Med; 190(6):656-64. PMC ID 4214110. b) Ferguson JF, Meyer NJ, Qu L, Xue C, Liu Y, DerOhannessian SL, Rushefski M, Paschos GK, Tang S, Schadt EE, Li M, Christie JD, Reilly MP. (2015) Integrative genomics identifies 7p11.2 as a novel locus for fever and clinical stress response in humans. Human Molecular Genetics; 24(6):1801-12. PMC ID 4351381. c) Patel PN, Shah RY, Ferguson JF, Reilly MP. (2015) Human experimental endotoxemia in modeling the pathophysiology, genomics, and therapeutics of innate immunity in complex cardiometabolic diseases (Review). Arterioscler Thromb Vasc Biol 35(3):525-34. PMC ID: 4344396. d) Lin J, Hu Y, Nunez S, Foulkes AS, Cieply B, Xue C, Gerelus M, Li W, Zhang H, Rader DJ, Musunuru K, Li M, Reilly MP. (2016) Transcriptome-Wide Analysis Reveals Modulation of Human Macrophage Inflammatory Phenotype Through Alternative Splicing. Arterioscler Thromb Vasc Biol. 36(7):1434-47 PMID: 27230130 (PMC ID in progress) 3. Genomic and functional studies of human adipose and adipocytes. Obesity is associated with increased risk of metabolic, cardiovascular and inflammatory disorders. Adipose tissue is recognized as an active endocrine and inflammatory organ secreting lipid, protein, and RNA molecules that impact cell and tissue functions locally and systemically. Yet, the mechanisms of how human obesity, adipose and adipocytes influences disease remain poorly understood. My lab has performed discovery and functional studies in human adipose tissue, adipocytes and relevant rodent models that have elaborated novel genes, pathways and functions for adipose in human pathophysiology. These lay the groundwork for translation in genetic, biomarker and therapeutic trials. a) Zhang Y, McGillicuddy FC, Hinkle CC, O'Neill S, Glick JM, Rothblat GH, Reilly MP. (2010) Adipocyte modulation of high-density lipoprotein cholesterol. Circulation 121(11):1347-55. PMC ID 2925122 b) Shah R, Hinkle C, Ferguson JF, Mehta NN, Li M, Qu L, Lu Y, Putt ME, Ahima RS, Reilly MP. (2011) Fractalkine is a novel human adipochemokine associated with type 2 diabetes. Diabetes 60(5): 1512-8. PMC ID 3292325 c) O'Neill SM, Hinkle C, Chen SJ, Sandhu A, Hovhannisyan R, Stephan S, Lagor WR, Ahima RS, Johnston JC, Reilly MP. (2014) Targeting adipose tissue via systemic gene therapy. Gene Ther; 21(7):653-61. PMC ID 4342115. d) Ferguson JF, Xue C, Hu Y, Li M, Reilly MP. (2016) Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans. J Nutr Biochem. 30:126-32. PMID: 27012629 (PMC ID in progress) 4. Genetics of heart disease: Despite knowledge of risk factors for coronary heart disease (CHD), almost one third of individuals who die prematurely from heart disease, the greatest causes of morbidity and mortality in our society, are not considered at-risk by current clinical approaches. Further, CHD is heritable but only a small portion of that heritability is defined. Over the past several years, I have made fundamental contributions through genome wide association studies (GWAS) and functional genomic follow-up to our understanding of the genetic architecture of CHD, including in high-risk settings (e.g., chronic kidney disease). In 2011, I led publication of our multi- center GWAS that identified the ADAMTS7 locus for coronary atherosclerosis and the ABO locus for myocardial infarction. Later that year, as co-chair of the executive committee of the CARDIoGRAM consortium, I co-led our discovery of over a dozen additional novel loci for CHD and I have continued this work through additional consortia GWAS and exome-wide studies (2013 to 2015). These discoveries have refocused our field and our understanding of mechanisms of human atherosclerosis while providing the basis for novel therapeutic programs, diagnostics and prognostic tools for clinic. My group has pursued functional studies of specific loci and genes for heart disease and advanced understanding toward clinical translation and utility. For example, we were the first to describe that genetic deletion of Adamts7 protects against atherosclerosis in mouse models. This mechanistic support for a pro-atherogenic role of this metalloproteinase has fueled the development of ADAMTS7 inhibitors as potential therapeutics for CHD. a) Reilly MP*, Li M*, Ferguson JF, et al. (2011) Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome wide association studies. Lancet. 377(9763): 383-92. PMC ID 3297116. b) Schunkert H*, König IR*, Kathiresan S*, Reilly MP*, et al. for the CARDIoGRAM Consortium. (2011) Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 6;43(4):333-8. PMC ID 3119261. c) Bauer RC, Tohyama J, Cui J, Cheng L, Yang J, Zhang X, Ou K, Paschos GK, Zheng XL, Parmacek MS, Rader DJ, Reilly MP. (2015) Knockout of Adamts7, a Novel CAD Locus in Humans, Reduces Atherosclerosis in Mice. Circulation. 131(13):1202-13. PMC ID 4382454. d) Golbus JR, Stitziel NO, Zhao W, Xue C, Farrall M, McPherson R, Erdmann J, Deloukas P, Watkins H, Schunkert H, Samani NJ, Saleheen D, Kathiresan S, Reilly MP. (2016) Common and Rare Genetic Variation in CCR2, CCR5, or CX3CR1 and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits; CARDIoGRAMplusC4D, Myocardial Infarction Genetics (MIGen), Exome Sequencing Project and Early-Onset Myocardial Infarction (ESP EOMI), and the Pakistan Risk of Myocardial Infarction Study (PROMIS) Consortia*. Circ Cardiovasc Genet. 9(3):250-8. PMID: 27013693 (PMC ID in progress)

Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/muredach.reilly.1/bibliography/41153966/public/? sort=date&direction=ascending

D. Research Support Ongoing Research Support 1UL1 TR001873 (Ginsberg) 7/01/2016 to 5/31/2021 NIH/NCATS Clinical and Translational Science Award—Columbia University The goal of the Irving Institute CTSA is to transform the culture of biomedical research enabling CUMC investigators to develop new treatments faster and deliver those treatments to patients more efficiently, effectively, and safely than before; to utilize medical research advances to benefit patients and the community. Role: Co-Project Lead of the Administrative Core

K24-HL107643 (PI: Reilly) 5/13/11 to 4/30/2021

NIH/NHLBI Mentored Patient Oriented Research in Cardio-metabolic Disease Goals: To augment Dr. Reilly’s scientific and mentoring skills and devote more time to mechanistic POR, and provide increased time and structure in mentoring new clinical investigator in the conduct of mechanistic POR, and pursue new innovative POR in order to generate a unique training environment and POR framework for mentoring young clinical investigator. Role: Principal Investigator

R01-HL-113147 (PI: Reilly) 4/16/12 to 3/31/17 NIH/NHLBI $462,033 Elucidation of Tissue-Specific Transcriptomic Profiles in Cardio-metabolic Disease Goals: To apply deep RNA sequencing of human tissue to identify novel transcriptomic variations and mechanisms of tissue-specific genetic dysfunction in cardio-metabolic disease. Role: Principal Investigator

R01-HL-111694 (PI: Reilly) 7/19/12 to 6/30/17 NIH/NHLBI Translational Studies of ADAMTS7 a Novel GWAS Locus for Coronary Atherosclerosis Goals: Define structure-function of ADAMTS7 interactions with target proteins, assess the effects of loss function and gain of function on mouse atherosclerosis and VSMC function, and interrogate non-synonymous variants discovered upon sequencing of ADAMTS7 in humans for potential loss and gain of function and for association with CAD. Role: Principal Investigator

R01-GM-108600 (PI: Li) 5/1/14 to 1/31/18 NIH/NIGMS Statistical Methods for Transcriptome Profiling Using RNA Sequencing Goals: To allow biologists to better disentangle complex cellular circuitry, precisely related genomic sequence to gene regulation, and facilitate the translation of basic research findings into clinical studies of cardiovascular and eye diseases. Role: Co-Investigator

R01-HL107196 (Foulkes) 02/01/11 – 01/31/17 NIH/NHLBI Methods for high-dimensional data in HIV/CVD research This project aims to develop and evaluate statistical methods for analyzing high-dimensional genetic and immunological data at the intersection of HIV and CVD research. Role: Co-investigator

Completed Research Support R01-DK-090505 (PI: Reilly) 7/19/11 to 5/31/16

NIH/NIDDK Fractalkine in Adipose Inflammation and Insulin Resistance Goals: Using mice models and human translation, to determine whether fractalkine (CX3CL1- CX3CR1) modulates adipose inflammation and its metabolic consequences and if this action is independent of CCR2.

U01-HL108636 (PI: Reilly) 8/20/11 to 6/30/15

NIH/NHLBI Glycomics of Heart and Lung Disease in the Genomic Era Goals: Using unbiased mass-spectrometry approaches, we propose to define disease (myocardial infarction and acute lung injury) and cell (platelets and endothelium) specific ABO glycoproteomes in order to develop glycopeptides markers of risk and cross-organ, mechanisms-based phenotypes in heart and lung disease.