Corazon-Paciente-Kenya

Kovacic, Jason C

jason-c-kovacic
Jason Ciril Kovacic, MD

ASSISTANT PROFESSOR | Medicine, Cardiology
Icahn School of Medicine at Mount Sinai
Specialty: Cardiology
URL: http://icahn.mssm.edu/profiles/jason-c-kovacic

Current research support:

K08HL111330-01 PI: Kovacic Award Period: 12/12/2011 – 11/30/2016
“Cellular and molecular mechanisms of endothelial repair and atherosclerosis”
Awarding Body: NIH/NHLBI
Using murine Cre-lox lineage tracing systems, this proposal will define the functional contribution of endothelial cells to arterial homeostasis, arterial repair and atherosclerosis, and also investigate the ability of endothelial cells to change their phenotype to become smooth muscle cells, fibroblasts or other cells that drive atherosclerosis.

ISSCRES0141 PI: Kovacic Award Period: 04/29/2013 – 11/20/2014
“YELLOW II Study – Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering”
Awarding Body: AstraZeneca
This investigator initiated clinical study will assess the in vivo regression of atherosclerotic yellow plaque content and changes in plaque morphology after high-dose statin therapy by utilizing diffuse reflectance near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT) in diseased coronary arteries of ischemic heart disease patients presenting for coronary angiography. Concurrently, lipid trafficking, reverse cholesterol transport and the inflammatory macrophage phenotype will be assessed in response to changes in patient lipid profiles. High-dose statin therapy (rosuvastatin 40mg daily) will be administered to all subjects (n = 80), with baseline measurements being compared to those at final follow-up after 8-12 weeks of therapy for each subject.
LEDUCQ Transatlantic Network of Excellence“Cellular and molecular targets to promote therapeutic cardiac regeneration”
PI: Jason Kovacic Award Period: 1/1/2014 – 1/1/2019
Awarding body: Foundation LEDUCQ (Transatlantic Networks of Excellence Programme)
The rationale for this network lies in the acute need for defining the mechanisms regulating and ultimately limiting regenerative responses of the adult heart. Unraveling the complex and poorly understood processes mediating the age-dependent decline in cardiovascular stem cell efficacy and regenerative capacity is a core objective of this network. A suite of mechanistic studies will lead to the identification of targets that can be modulated to boost the endogenous regenerative potential of the adult mammalian heart, including the use of small molecules that stimulate the mobilization of endogenous CSCs or transiently activate de-differentiation.

Mount Sinai Heart Fibromuscular Dysplasia Research Program (PIs: Olin & Kovacic) Award Period: 3/31/2013 – 3/30/2016
Awarding Body: Anonymous Philanthropic Donor
Title: DEFINE FMD Study
Fibromuscular Dysplasia (FMD) is a non-inflammatory vascular disease of unknown etiology. This program will undertake an extensive molecular/genetic (PI: Kovacic) and clinical (PI: Olin) characterization of this disease. Using skin biopsies to generate patient-specific cell lines, we will establish the cellular and genetic profile of fibroblasts and other vascular cells from FMD patients and matched healthy controls. Our aim is to identify activated pathways and genes, and to ultimately elucidate the underlying cause of this condition.

Biography

I am a practicing interventional cardiologist, with extensive experience in diagnosing and treating cardiovascular diseases. As an established investigator at the Icahn School of Medicine at Mount Sinai, I run a vascular cell-focused lab with a strong interest in the cellular, molecular and genetic mechanisms underlying atherosclerosis, inflammation, cardiovascular disease and aging. I have over 20 years’ experience in this line of research, and also more recently in the investigation of vascular inflammation and its interplay with cardiovascular risk. Major achievements include successful investigator-initiated clinical studies of vascular progenitor cell therapy, characterization of embryonic stem cell-derived vascular progenitor cells, profiling inflammatory pathways regulating vascular injury and elucidating mechanisms of vascular calcification. The long-term goal of my research program is to make meaningful inroads into the prevention and treatment of cardiovascular disease.

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Education
University of Melbourne, Melbourne, Australia
University of Melbourne, Melbourne, Australia
Prince of Wales Hospital, Sydney, Australia
St Vincent’s Hospital, Sydney, Australia
University of New South Wales, Sydney, Aust.
National Institutes of Health, Bethesda, MD

Additional Information

Research and/or Professional Experience

Employment
01/1996 – 12/1998 Intern and Resident, Prince of Wales Hospital, Sydney, Australia
01/1999 – 12/2000 Internal Medicine Fellow, St Vincent’s Hospital, Sydney, Australia
01/2001 – 12/2003 Cardiology Fellow, St Vincent’s Hospital, Sydney, Australia
01/2004 – 06/2007 Doctoral Student, The Victor Chang Cardiac Research Institute and St Vincent’s Hospital, Sydney, Australia
07/2007 – 06/2009 Postdoctoral Fellow, Translational Medicine Branch, Intramural Program, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD
07/2009 – 06/2010 Interventional Cardiology Fellow, Mount Sinai Hospital, New York, NY
07/2010 – 06/2011 Associate (Cardiology), Mount Sinai School of Medicine, New York, NY
07/2011 – pres  Assistant Professor of Medicine (Cardiology), Icahn School of Medicine at Mount Sinai, New York, NY

Honors
1986     Valedictorian, Caulfield Grammar School, Melbourne, Australia
1992     Academic Achievement Award, The Australian Institute of Sport, Canberra, Australia
1994     Honors graduate, The University of Melbourne, Melbourne, Australia
2005     Australian Delegate to Lindau Nobel Prizewinners Meeting, Lake Constance, Germany
2009     FARE award, National Institutes of Health
2010     Dedication and Achievement Award in Interventional Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai Medical Center
2011     Doris Duke Charitable Foundation Clinical Scientist  Development Award Finalist
2013     “Emerging Leader”, Society for Cardiovascular Angiography and Interventions, and American College of Cardiology.

Professional Societies and Public Advisory Committees
2003 – pres       Fellow, Royal Australasian College of Physicians
2004 – 2007       International Associate Member, American College of Cardiology
2008 – pres       Fellow, American College of Cardiology
2004 – pres       Member, Cardiac Society of Australia and New Zealand
2005 – pres       Member, American Heart Association
2010 – pres       Fellow, Society for Cardiovascular Angiography and Interventions

NIH/NHLBI committees
2008 – pres      Organizing committee member, 3rd, 4th and 5th NHLBI Symposium on Cardiovascular Regenerative Medicine meeting
2011    NHLBI Program Project Grant Ad Hoc Review Committee Member
2012   NHLBI Cardiovascular Cell Therapy Research Network (CCTRN) Protocol Review Committee

Selected Peer-reviewed Publications (from a total of ~60)

(1)        Kovacic JC, Macdonald P, Feneley MP, Muller DWM, Freund J, Dodds A, Milliken S, Tao H, Itescu S, Moore J, Ma D, Graham RM. Safety and efficacy of consecutive cycles of granulocyte-colony stimulating factor, and an intracoronary CD133+ cell infusion in patients with chronic refractory ischemic heart disease: the GAIN I trial. Am Heart J. 2008; 156: 954-63. PMID: 19061712

(2)        Olive M, Mellad JA, Beltran LE, Ma M, Cimato T, Noguchi AC, San H, Childs R, Kovacic JC, Boehm M. p21Cip1 modulates arterial wound repair through the SDF-1/CXCR4 axis. J Clin Invest. 2008; 118: 2050-61. PMID: 18464929

(3)        Kovacic JC, Boehm M. Resident vascular progenitor cells: an emerging role for non-terminally differentiated vessel-resident cells in vascular biology. Stem Cell Res. 2008; 2: 2-15. PMID: 19383404

(4)        Wragg A, Mellad JA, Beltran LE, Konoplyannikov M, San H, Boozer S, Deans RJ, Mathur A, Lederman RJ, Kovacic JC, Boehm M. VEGFR1/ CXCR4 positive progenitor cells modulate local inflammation and augment tissue perfusion by a SDF-1 dependent mechanism. J Mol Med. 2008; 86:1221-32. PMID: 18690419

(5)        Kovacic JC, Gupta R, Lee AC, Ma M, Fang F, Tolbert CN, Walts AD, Beltran LE, San H, Chen G, St. Hilaire C, Boehm M. STAT3-dependent acute RANTES production in vascular smooth muscle cells modulates inflammation following arterial injury. J Clin Invest. 2010; 120: 303-14. PMID: 20038813

(6)        Ma M, Ding S, Lundqvist A, San H, Fang F, Konoplyannikov M, Berry C, Beltran LE, Chen G, Kovacic JC, Boehm M. MHC-I expression on ESC-derived vascular progenitor cells is critical for syngeneic transplant survival. Stem Cells. 2010; 28: 1465-1475. PMID: 20629173

(7)        Iwasaki H, Kovacic JC, Olive M, Beers JK, Yoshimoto T, Crook MF, Tonelli LH, Nabel EG. Disruption of protein arginine N-methyltransferase 2 regulates leptin signaling and produces leanness in vivo through loss of STAT3 methylation. Circ Res. 2010; 107: 992-1001. PMID: 20798359

(8)        Kovacic JC, Lee P, Baber U, Karajgikar R, Evrard SM, Moreno P, Mehran R, Fuster V, Dangas G, Sharma S, Kini A. Inverse relationship between body mass index and coronary artery calcification in patients with clinically significant coronary lesions. Atherosclerosis 2012; 211: 176-82. PMID: 22204865

(9)        Chih S, Macdonald PS, McCrohon JA, Ma D, Moore J, Feneley MP, Law M, Kovacic JC, Graham RM. Granulocyte-Colony Stimulating Factor in Angina Patients to Stimulate Neovascularization (GAIN II) Trial: A randomized placebo-controlled crossover study. Heart 2012; 98: 282-90. PMID: 22115984

(10)       Kini AS, Baber U, Kovacic JC, Limaye A, Ali ZA, Sweeny J, Maehara A, Mehran R, Dangas G, Mintz GS, Fuster V, Narula J, Sharma SK, Moreno PR. Changes in Plaque Lipid Content after Short-Term, Intensive versus Standard Statin Therapy: The YELLOW Trial. J Am Coll Cardiol. 2013; 62: 21-29. PMID:23644090

(11)       Kovacic JC, Mercader N, Torres T, Boehm M, Fuster V. Epithelial-to-Mesenchymal and Endothelial-to-Mesenchymal Transition: From Cardiovascular Development to Disease. Circulation 2012; 125: 1795-1808. PMID: 22492947

(12)       Wood CW, Cortese-Krott MM, Kovacic JC, Noguchi A, Liu VB, Wang X, Raghavachari N, Boehm M, Kato GJ, Kelm M, Gladwin MT. Circulating Blood eNOS Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis. Arterioscler Thromb Vasc Biol. 2013; 33: 1861-1871. PMID:23702660

(13)       Lipskaia L, Bobe R, Chen J, Turnbull IC, Lopez JJ, Merlet E, Jeong D, Karakikes I, Ross AS, Liang L, Mougenot N, Atassi F, Lompré AM, Kovacic JC, Kranias E, Hajjar RJ, Hadri L. Synergistic role of Protein Phosphatase Inhibitor 1 and SERCA2a in the acquisition of the Contractile Phenotype of Arterial Smooth Muscle Cells. Accepted for publication, Circulation, Nov, 2013. PMID: 24249716

(14)       Pereira, CF, Chang B, Qiu J, Niu X, Papatsenko D, Hendry CE, Clark NR, Nomura-Kitabayashi A, Kovacic JC, Ma’ayan A, Schaniel C, Lemischka IR, Moore K. Induction of a Hemogenic Program in Mouse Fibroblasts. Cell Stem Cell. 2013; 13: 205-218. PMID:23770078

(15)       Dangas GD, Maehara A, Evrard SM, Sartori S, Li JR, Chirumamilla AP, Kitabaysahi A, Gukathasan N, Hassanin A, Baber U, Fahy M, Fuster V, Mintz GS, Kovacic JC. Coronary artery calcification is inversely related to body morphology in patients with significant coronary artery disease: a 3-dimensional intravascular ultrasound study. Accepted for publication, Eur. Heart J.- Cardiovasc. Imaging. July 2013. PMID:23904334