Dr John O'Sullivan

MD, PhD, FAHA, FRCPI
Our mission is to discover better diagnostic markers, predictors, and therapies for cardiometabolic disease.

Dr John O’Sullivan joined the HRI in 2016 as Cardiometabolic Disease Group Leader. John joins the HRI from Harvard Medical School and Massachusetts General Hospital where he was a Postdoctoral Fellow and Clinical Observer. John received his medical degree from the National University of Ireland, Galway, and his PhD from University College Cork, in Ireland. He undertook internal medicine and cardiology training in Ireland. John’s research focusses on the cardiovascular effects of obesity-driven metabolic diseases, which together are the greatest health challenges in the modern era. Combining genomic and metabolomic profiling in carefully-phenotyped patient cohorts, he has discovered several novel markers, effectors, and predictors of disease. Using animal and cellular models of disease, he has revealed the functional roles of these metabolites.

Current Appointments

Cardiometabolic Disease Group Leader

Heart Research Institute

Fellow

Royal College of Physicians of Ireland (FRCPI)

Fellow

American Heart Association

Dr John O'Sullivan leads group:
Research covers areas of:
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More about Dr John O'Sullivan

Research Project Opportunities
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A new therapy for fatty liver and diabetes

We recently discovered a new pathway that links liver fat to type 2 diabetes and independently predicted future diabetes 12 years ahead of diagnosis in two separate human cohorts. However, it is unknown if this new pathway can be used to treat fatty liver disease and/or diabetes. We have organised the necessary expertise, transgenic models, and human cohorts to probe this pathway more thoroughly to assess its therapeutic potential.

Novel disease pathways in coronary artery disease

Up to 30 per cent of patients who present with myocardial infarction do not have traditional risk factors. Mirroring this observation, two-thirds of the genomic loci associated with coronary artery disease are not associated with traditional risk factors. Using a novel lipidomic profiling platform, we have recently identified two novel non-lipoprotein lipids associated with coronary artery disease in patients without risk factors. One of these is inversely associated, possibly protective, and the other positively associated, likely damaging. We are currently undertaking the necessary steps to identify these novel lipids that may reveal alternative therapeutic strategies in coronary artery disease.

Discovering new disease pathways in young people at risk of cardiometabolic disease

We will use whole genome scanning and non-targeted metabolomic profiling for novel discovery in young people with a high-risk factor burden but without overt cardiometabolic disease. Whole genome scanning is now affordable and tractable. Non-targeted metabolomic profiling (thousands of metabolites) captures a far greater portion of the human genome than targeted metabolomic profiling (hundreds of metabolites). Dr O'Sullivan has previously successfully used this strategy, one of the few worldwide to do so, and will now apply this approach to younger people at risk of cardiometabolic disease. This has enormous clinical utility: if we can successfully capture new disease markers at a much earlier age, we can truly alter the course of disease, thereby preventing disease onset.

Recent Publications
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Induced Pluripotent Stem Cell Differentiation Enables Functional Validation of GWAS Variants in Metabolic Disease.  Curtis R. Warren, John F. O’Sullivan, Max Friesen, Caroline E. Becker, Xiaoling Zhang, Yoshi Wakabayashi, Jordan E. Morningstar, Xu Shi, Jihoon Choi, Fang Xia, Mary H. C. Florido, Jennifer Shay, Derek T. Peters, Kiran Musunuru, Sekar Kathiresan, Laurence Daheron, Jun Zhu, Robert E. Gerszten, Rahul Deo, Vasan Ramachandran, Christopher J. O’Donnell, and Chad A. Cowan. Cell Stem Cell 2017 Apr 6;20(4):547-557. (IF 23.6).

Metabolite Profiling Identifies Anandamide as a Biomarker of Nonalcoholic Steatohepatitis. W. Taylor Kimberly, John O’Sullivan, Anjali Nath, Michelle Keyes, Qiong Yang, Martin G. Larson, Vasan Ramachandran, Randall T. Peterson, Thomas J. Wang, Kathleen Corey, and Robert E. Gerszten. J Clin Invest. Insight 2017 May 4;2(9). PMID: 28469090

HELZ2 is an IFN Effector Mediating Suppression of Dengue Virus. Dahlene Fusco, Henry Pratt, Wenyu Lin, D.  Alex Cronkite, Kate Jeffrey, Joshua Pondick, Alan Mullen, Anthony Anselmo, Ruslan Sadreyev, John O’Sullivan, Robert Gerszten, Tetsurou Satoh, Raymond T. Chung. Frontiers in Microbiology Front Microbiol. 2017 Feb 20;8:240. PMID: 28265266.

Aptamer-based proteomic profiling reveals novel candidate biomarkers of cardiovascular disease. Debby Ngo, Sumita Sinha, Dongxiao Shen, Eric Kuhn, Michelle Keyes, Xu Shi, Mark Benson, John F O’ Sullivan, Hasmik Keshishian, Laurie Farrell, Michael A. Fifer, Ramachandran S. Vasan, Marc Sabatine, Martin G. Larson , Steven A. Carr, Thomas J. Wang, Robert E. Gerszten. Circulation 2016; 134:270-285. (IF 14.4). PMID: 27444932.

miR-93-5p and other miRNAs as Predictors of Stable Coronary Artery Disease and STEMI. JF O’Sullivan, A Neylon, C McGorrian, G Blake. International Journal of Cardiology Dec 2016, Vol 24, 310-316. (IF 4.0). PMID: 27665403.

Integrative analysis of iPS cell models of PRKAG2 cardiomyopathy identifies AMPK as a regulator of cardiomyocyte survival, contractility and fibrosis in microtissues. J. Travis Hinson, Anant Chopra, Calvin C. Sheng, Rajat M. Gupta, Rajarajan Kuppusamy, John F. O’Sullivan, Glenn Rowe, Joshua Gorham, Kiran Musunuru, Robert E. Gerszten, Sean M. Wu, Christopher Chen, Jonathan E. Seidman, Christine E. Seidman. Cell Reports 2016 Dec 20;17(12):3292-3304. PMID: 28009297. (IF 7.9).

Rapid and efficient generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells. Christoph Patsch, Ludivine Challet-Meylan, Eva Christina Thoma, Eduard Urich, Tobias Heckel, John F O’Sullivan, Stephanie J Grainger, Friedrich G Karpp, Lin Sun, Klaus Christensen, Yulei Xia, Marie Florido, Wei He, Wei Pan, Michael Prummer, Curtis Warren, Oliver Wernet, Roland Jakob-Roetne, Ulrich Certa, Ravi Jagasia, Per-Ola Freskgård, Isaac Adatto, Dorothee Kling, Paul Huang, Leonard I Zon, Elliot Chaikof, Robert E. Gerzsten, Martin Graf, Roberto Iacone and Chad A. Cowan. Nature Cell Biology 2015 Aug;17(8):994-1003. (IF 18.7). PMID: 26214132.

Increases in Myocardial Workload Induced by Rapid Atrial Pacing Trigger Alterations in Global Metabolism. Turer AT, Lewis GD, O'Sullivan JF, Elmariah S, Mega JL, Addo TA, Sabatine MS, de Lemos JA, Gerszten RE. PLoS One. 2014 Jun 16;9(6):e99058. (IF 3.2). PMID: 24932507.

β-Aminoisobutyric Acid Increases Browning of White Fat and Hepatic β-Oxidation and is Inversely Correlated with Cardiometabolic Risk Factors in Humans. Lee D. Roberts, Pontus Boström, John F. O'Sullivan, Robert T. Schinzel, Gregory D. Lewis, Youn-Kyoung Lee, Melinda J. Palma, Sondra Calhoun, Ming-Huei Chen, Vasan S. Ramachandran, Martin G. Larson, Claude Bouchard, Tuomo Rankinen, Amanda L. Souza, Clary B. Clish, Thomas J. Wang, Alexander A. Soukas, Chad A. Cowan, Bruce M. Spiegelman, Robert E. Gerszten. Cell Metabolism Volume 19, Issue 1, 96-108, 7 January 2014. (IF 17.6). PMID: 24411942.

Bone marrow-derived mesenchymal stem cells have innate procoagulant activity and cause microvascular obstruction following intracoronary delivery: amelioration by anti-thrombin therapy. Birgitta M Gleeson, Kenneth Martin, Arun HS Kumar DVM, Mohammed T Ali, M Gopala-Krishnan Pillai, John F O’Sullivan, Derek Whelan, Frank P Barry, Timothy O’Brien, Noel M Caplice. Stem Cells. 2015 Sep;33(9):2726-37. (IF 7.8). PMID: 25969127.

2-aminoadipic acid is a novel biomarker of diabetes risk and modulates glucose homeostasis. Wang TJ, Ngo D, Psychogios N, Dejam A, Larson MG, Vasan RS, Ghorbani A, O'Sullivan J, Cheng S, Rhee EP, Sinha S, McCabe E, Fox CS, O'Donnell CJ, Ho JE, Florez JC, Magnusson M, Pierce KA, Souza AL, Yu Y, Carter C, Light PE, Melander O, Clish CB, Gerszten RE. J Clin Invest. 2013 Oct 1;123(10):4309-4317. (IF 12.6). PMID: 24091325.

Multi Detector Computed Tomography Accurately Defines Infarct Size, but not Microvascular Obstruction After Myocardial Infarction (MI). John F O’Sullivan, MD, PhD, Anne-Laure Leblond, PhD, John O’Dea, MD, Ivalina Hristova, BS, Sujith Kumar, DMRIT, Noel M Caplice, MD, PhD. J Am Coll Cardiol. 2013;61(2):208-210. (IF 17.8).

Research Grants
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Sydney Medical School Foundation Fellowship, 2017–2020
Sydney Research Excellence Initiative 2020, Associate Investigator

2015     Cert. Biostatistics, Harvard University
2012     PhD, University College Cork, Cork, Ireland
2011     FAHA, Fellow of the American Heart Association
2011     USMLE Certification, United States Medical Licensing Certification
2006     FRCPI, Royal College of Physicians of Ireland
2006     MSc (Genetics), National University of Ireland, Galway, Ireland
2001     MD, National University of Ireland, Galway