Dr John O'Sullivan

MD, PhD, MSc, FAHA, FRCPI, Cert. Biostatistics (Harvard)
“Our mission is to discover better diagnostic markers, predictors, and therapies for cardiometabolic disease.”

John received his medical degree from the National University of Ireland, Galway. After internal medicine training, he was accepted on the Cardiology Specialist Training Scheme of the Royal College of Physicians of Ireland, receiving his CSCST in Cardiology in 2017. During this time, he received a Molecular Medicine Ireland Fellowship to undertake a PhD at University College Cork, completed in 2012. He was awarded an overseas training fellowship by the Irish Cardiac Society in 2012 to train at Massachusetts General Hospital (MGH) and Harvard Medical School. From 2012-2016 he was also a postdoctoral fellow at MGH, studying functional genomics and metabolomics, and worked with the Framingham Heart Study and Broad Institute of Harvard and MIT. He joined Heart Research Institute in 2016.

Current Appointments

Cardiometabolic Disease Group Leader

Heart Research Institute and Charles Perkins Centre, The University of Sydney

Senior Lecturer

The University of Sydney.

Cardiologist

Royal Prince Alfred Hospital

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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Uncovering Novel Cardiovascular Disease Pathways

We are utilising robustly-phenotyped patient cohorts in concert with genomic, transcriptomic, and metabolomic profiling to shed new light on gene-environment interaction in cardiovascular disease. In addition to providing new markers and predictors of disease, this approach can uncover new targets for therapy. Furthermore, it is becoming increasingly evident that a ‘one-size-fits-all’ approach to cardiovascular prevention and treatment is sub-optimal. We believe re-stratifying risk and targeting disease based on a patient’s unique profile is a far more effective strategy. We have previously identified novel markers and predictors of cardiometabolic disease, in addition to a new disease pathway linking fatty liver disease with diabetes.

Probing a New Metabolic Disease Pathway

While working with Professor Robert Gerszten at Harvard Medical School, we recently discovered a new pathway linking fatty liver disease and diabetes. Integrating non-targeted metabolomic profiling (which captures thousands of metabolites) with genome-wide association (GWAS), we elucidated the chemical identity of a new marker of fatty liver disease. After synthesis and purification, we developed a new assay that we used to show this same marker independently predicted diabetes over a decade in advance in the Malmo Diet and Cancer Study (a Caucasian cohort) and the Jackson Heart Study (an African-American cohort). We are now focusing on functionally interrogating this pathway in model systems, including genetically-modified mouse models.

Discovery Profiling

Truly novel small molecule biomarker discovery is extremely rare, and non-targeted metabolomic profiling offers this potential. However, success stories using this approach are extremely rare. We have previously identified novel disease metabolites using this approach, both in a clinical cohort and in a cell-model system. We are extending our capability and streamlining our discovery pipeline. We have unique expertise with the latest-generation mass spectrometers, chemometric software, and integrative ‘omics’. Furthermore, we are recruiting bioinformaticians to develop novel algorithm, machine learning, and network analysis approaches that harness vast open-access online databases to inform our own data.

Research Grants
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2015  Harvard Tosteson Award; Fund for Medical Discovery
2013  Postdoctoral Fellowship: NIH Fund for Medical Discovery
2012  Overseas Training Fellowship, Irish Cardiac Society
2012  Clinical Research Project Grant, Mater Foundation
2008  Molecular Medicine Ireland Clinician-Scientist Fellowship 
Recent Publications
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Original Research Articles: 

1. DMGV is Marker of Liver Fat and Predicts Future Diabetes. John F O’Sullivan, Jordan E Morningstar, Baohui Zheng, Sarah Jeanfavre, Justin Scot, Qiong Yang, Celine Fernandez, Ramachandran S. Vasan, Michelle T. Long, Olle Melander, Thomas J. Wang, Caroline Fox, Randall T. Peterson, Clary Clish, Kathleen Corey, Robert E. Gerszten. J Clin Invest. 2017. PMID: 29083323. 

2. Increasing proportion of ST elevation myocardial infarction patients with coronary atherosclerosis poorly explained by standard modifiable risk factors. Stephen T Vernon, Sean Coffey, Ravinay Bhindi, Soon Yeng Soo Hoo, Gregory I Nelson, Michael R Ward, Peter S Hansen, Kaleab N Asrress, Clara K Chow, David Celermajer, John F. O’Sullivan, and Gemma A Figtree. European Journal of Preventive Cardiology, 2017 Jan 1:2047487317720287. PMID: 28703626. 

3. 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. (Impact Factor 23.6). PMID: 28388431. 

4. 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. 

5. 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. 

6. 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. (Impact Factor 14.4). PMID: 27444932. 

7. 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. (Impact Factor 4.0). PMID: 27665403. 

8. 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. (Impact Factor 7.9). 

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. (Impact Factor 18.7). PMID: 26214132. 

10. 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. (Impact Factor 3.2). PMID: 24932507. 

11. 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. (Impact Factor 17.6). PMID: 24411942. 

12. 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. (Impact Factor 7.8). PMID: 25969127. 

13. 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. (Impact Factor 12.6). PMID: 24091325. 

14. 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. (Impact Factor 17.8). PMID: 23177294. 

15. Association of Bicuspid Aortic Valve with an Abnormally Elongated Rudimentary Chordae Tendinae Protruding into the Levt Ventricular Outflow Tract Abid Hussaini, John F O’Sullivan, Nazima Hussaini, Brendan Meany. Int J Cardiol 01/2012; 159(3):45-6. (Impact Factor 4.0). PMID: 22217483. 

16. Potent Long-term Cardioprotective Effects of Single Low Dose Insulin-like Growth Factor-1 (LD-IGF-1) Treatment Post Myocardial Infarction. John F O’Sullivan, Anne-Laure Leblond, Geraldine Kelly, Arun HS Kumar, Pat    Metharom, Ivalina Hristova, Niki Alizadeh-Vikali, Brian G Hynes, Rosemary O’Connor, Noel M Caplice. Circulation: Cardiovascular Interventions 2011;4:327-335. (Impact Factor 7.0). PMID: 21712526 

17. Potent EPC conditioned media induced anti-apoptotic, cardiotrophic and proangiogenic effects post myocardial infarction are mediated by IGF1. Brian Hynes, Arun HS Kumar, John O’Sullivan, Anne-Laure Leblond, Sharon Weiss, Jeffrey Schmeckpeper, Kenneth Martin, Noel M Caplice. Eur Heart J 2011 Dec 15. (Impact Factor 15.2). PMID: 22173909 

18. Thrombin Stimulates Smooth Muscle Cell Differentiation From Peripheral Blood Mononuclear Cells via Protease-Activated Receptor-1, RhoA, and Myocardin. Kenneth Martin, Sharon Weiss, Pat Metharom, Jeffrey S Schmeckpeper, Brian G Hynes, John F O’Sullivan, Noel M Caplice. Circulation Research 2009;105:214-218. (Impact Factor 11.0). PMID: 19574550 

19. Enhancing Back-up Support During Difficult Coronary Stent Delivery: Single Center Case Series of Experience with the Heartrail II Catheter. Brian Hynes, Grainne Murphy, James Dollard, John O’Sullivan, Nicholas Ruggerio, Ronan Margey, Thomas J. Kiernan, Eugene McFadden. J Invasive Cardiol 2011; 23(3):E43-6. (Impact Factor 1.1). PMID: 21364247 

20. Bone marrow mononuclear stem cells: potential in the treatment of myocardial infarction. Anne-Laure Leblond, John O’Sullivan, Noel Caplice. Stem Cells and Cloning: Advances and Applications, December 2009, Volume 2009:2 Pages 11 – 19. (Impact Factor 2.7). PMID: 24198506. 

21. Ostial left main stenosis in a frequent flyer. O’Sullivan JF, McFadden E. Int J Cardiol 2008 Mar 28. (Impact Factor 4.0). PMID: 18378023. 

22. Soft tissue neoplasm invading the heart with associated thrombus in a 74 year old man. John O'Sullivan, David Kerins, Peter McEneaney, Carl Vaughan. Eur J Echocardiogr. 2007 Jul 30. (Impact Factor 4.3). PMID: 17669689. 

23. Massive thrombus in the aortic arch: A 59-year-old lady with an unknown familial predisposition to vascular thrombosis. O’Sullivan J, Kerins D, Vaughan C. Eur J Echocardiogr. 2007 Sep 19. (Impact Factor 4.3). PMID: 17888744.  

24. Distinct Effects of High-Glucose Conditions on Endothelial Cells of Macrovascular and Microvascular Origins. A. Duffy, A. Liew, J. O’Sullivan, G. Avalos, A. Samali, T. O’ Brien Endothelium. 2006 Jan-Feb;13(1):9-16. (Impact Factor 5.5). PMID: 16885062.  

25. Survival of ruptured abdominal aortic aneurysms in the west of Ireland; do prognostic indicators of outcome exist? Sultan S, Maneshka R, O’ Sullivan J, Hynes N, Quill D, Courtney D. Vasc Endovasc Surg, 2004, Jan-Feb; 38(1):43-9. (Impact Factor 0.9). PMID: 14760476.  

26. Aortic Surgery: Do preoperative Cardio-selective β-blockers improve clinical outcome? Sultan S, O’Sullivan J, Manecksha R, Ishak L, Sharman A, Quill D, Courtney D. Irish Journal of Medical Science 01/2002; 171(3):S2:20. (Impact Factor 1.12). 

27. Ruptured abdominal aortic aneurysms: prognostic indicators for outcome. Sultan S, Manecksha R, O’Sullivan J, Ishak L, Sharman A, Quill D, Courtney D. Irish Journal of Medical Science 01/2002; 171(3):S2:22. (Impact Factor 1.12). 

Reviews: 

1. Microribonucleic acids for Prevention of Plaque Rupture and Instent Restenosis: “A Finger in the Dam”. John F O’Sullivan, Kenneth Martin, Noel M Caplice. State of the Art Paper. J Am Coll Cardiol 2011 Jan 25;57(4):383-9. (Impact Factor 17.8). PMID: 21251577 

2. New Therapeutic Potential of MicroRNA Treatment to Target Vulnerable Atherosclerotic Lesions and Plaque Rupture. Kenneth Martin, John F O’Sullivan, Noel M Caplice. Current Opinion in Cardiology 2011 Sep 13. (Impact Factor 2.7). PMID: 21918434 

3. MicroRNA Expression in Coronary Artery Disease. John F O’Sullivan, Antoinette Neylon, Catherine McGorrian, Gavin J Blake. MicroRNA Volume 2, Issue 3, 2013. (Impact Factor 3.8). PMID: 25069444. 

Invited Reviews: 

1. Metabolite Profiles and the Risk of Cardiometabolic Disease. O’Sullivan J, Gerszten RE. Eur Heart J 2014; 35; 2197–2204. (Impact Factor 15.2). DOI: 10.1093/eurheartj/ehu270. 

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
Prizes and Awards
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2011  1st Place, Young Investigator Award, American College of Cardiology. 
2011  1st Place, Young Investigator Award, Irish Cardiac Society. 
2011  Finalist, Young Investigator Award, American Heart Association (Melvin Judkins Award). 
2011  Fellowship of the American Heart Association (FAHA). 
2011  “Top 30 Outstanding Young People in the World” (Medical Innovation), JCI. 
2011  Prof Raymond Shanahan Prize in Cardiovascular Research, University College Cork, Cork, Ireland. 
2011  Prof Brian McGovern (Irish Cardiac Society) Overseas Training Fellowship to Massachusetts General Hospital. 
2011  European Society of Cardiology “First Contact Initiative Award”. 
2014  Poster of Distinction Award, 67th Annual Mass Gen Hospital SAC. 
2014  1st Place Poster, MGH CVRC at the American Academy of Sciences. 
2011  NSW Ministerial Award for Rising Stars in Cardiovascular Research Excellence.  
2016  Young Investigator Award, American Heart Association (AHA) Functional Genomics and Translational Biology. 
2017    Sydney Medical School Foundation Chapman Fellowship
Collaborations
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Prof Walter Wahli, Imperial College, London; Lee Kong Chian School of Medicine, Singapore. 
Prof Robert Gerszten, Beth Israel Deaconess and Harvard Medical School. 
Dr Roman Rodionov, Dresden University, Germany. 
Prof David James, Charles Perkins Centre, The University of Sydney. 
Prof Stephen Simpson, Charles Perkins Centre, The University of Sydney. 
Prof Mark Febbraio, Garvan Institute, Sydney. 
Dr Dorit Samocha-Bonet, Garvan Institute, Sydney. 
Media Appearances
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Channel 7 News: “New Biomarker of Liver Fat and Predictor of Diabetes.