Dr. Jitka Virag, Ph.D.
| ||Assistant Professor |
Department of Physiology
Phone: (252) 744-2777
Fax: (252) 744-3460
Brody School of Medicine
Physiology Department, LSB 239
600 Moye Blvd.
Greenville, NC 27834
Brody School of Medicine
East Carolina State University, Greenville, NC
Research focus: Repair of the infarcted heart
Research Scientist (September 2004 - October 2005)
Universities Space Research Association, Division of Space Life Sciences, Center for Advanced Space Studies
Cardiovascular Laboratory, Johnson Space Center, NASA, Houston, TX
Research focus: The Effects of Microgravity on the Heart
Senior Fellow (1999-2004)
University of Washington, Seattle, WA
Advisor: Dr. Charles E. Murry, M.D., Ph.D.
Post-doctoral research project: Murine Myocardial Infarct Repair.
Doctor of Philosophy, Physiology (1994 –1999)
Louisiana State University Medical Center (LSUMC), New Orleans, LA
Advisor: Dr. Kathleen H. McDonough, Ph.D.
Dissertation title: Mechanisms of Sepsis-Induced Dysfunction and Protection from Ischemia/Reperfusion Injury
Bachelor of Science with Honors, Biology (1989 -1993)
Queen's University, Kingston, Ontario, Canada
Advisor: David Layzell, Ph.D.
Research project: Nitrogenase Activity in Soybean Root Nodules
Heart failure is a significant public health problem. Since the heart lacks sufficient regenerative potential to recover from an ischemic event, efforts are being made to prevent excessive damage and alleviate subsequent remodeling and heart failure through the use of gene or protein therapy alone or in conjunction with cell/tissue grafting. We employ the murine model of myocardial infarction, to study acute ischemia/reperfusion injury as well as chronic remodeling in non-reperfused myocardial infarction. This is a very valuable tool that can be used to investigate factors that mediate injury, determinants of the extent of remodeling, and interventions that can impede or even halt these processes once they have begun.
We are currently studying two lines of research: the influence of circadian rhythm genes and the ephrinA/EphA family of receptors tyrosine kinases on modulation of infarct size. There are clear variations in circadian rhythms in the incidence of cardiovascular disease and the risk of cardiovascular events increases when rhythms are disrupted. The genes that govern diurnal rhythms have recently been shown to exist in myocardial tissue and are involved in metabolism and contractile function. Specifically, we are exploring the mechanism by which functional deletion of the mPer2 gene reduces infarct size. This information will hopefully be useful in reducing the incidence of heart disease in susceptible populations (e.g. shift workers, jet lag).
The Eph receptors (Eph = erythropoietin-producing hepatocellular) and, their cognate ligands the ephrins (contraction of "Eph receptor interacting proteins" and after the Greek word "ephoros" meaning overseer or controller), the largest family of receptor tyrosine kinases, have been shown to contribute to differentiation, proliferation, and migration of various cell types during development. In particular, ephrinA1/EphA receptor tyrosine kinase signaling is essential to vascular growth in development as well as in adult tumor angiogenesis. The expression pattern of EphrinA1 and the eight EphA receptors is completely unknown in the adult heart, as well as in response to myocardial injury. Investigating the involvement of ephrinA1/EphA receptors in inflammation, cell kinetics, angiogenesis, and scar formation in post-MI myocardium will provide the framework from which to extrapolate the potential capacity of selectively modulating ephrinA1 and EphA receptors to improve myocardial infarct healing.
We examine the heart from the level of cardiac function using echocardiography and pressure-volume loops, to the gross level histologically, to the protein and gene level using immunohistochemistry, proteomic analyses, and RT-PCR. We also perform cell culture and molecular assays to resolve mechanistic questions. Those interested may inquire about possible openings in the laboratory.
Crystal structure of ephrinA1 created by Cameron Schmidt
(using pymol and I-TASSER software).
Brody School of Medicine Internal Seed/Bridge Grant Program. Project: Isolation and Culture of Adult Murine Cardiomyocytes to Investigate the Mechanistic Underpinnings of Cardiovascular Disease. PI: Jitka Virag, Co-I: Mark Mannie. Award: $25,000; Mar15-Dec 31, 2014
North Carolina Biotechnology Center Biotechnology Research Grant. Project: Intramyocardial EphrinA1-Fc Reduces Myocardial Infarct Injury. PI: Jitka Virag, Award Amount: $75,000; Sept 2012 - Mar 2015
ECU news: http://www.ecu.edu/cs-admin/news/virag.cfm
Local news: http://www.reflector.com/node/1238717
Past (3 years)
Office of Technology Transfer Ignition Funds, East Carolina University. Project:EphrinA1-Fc Attenuates Ischemic Injury. PI: Jitka Virag, Award Amount: $7,300; Dec 2011-Dec 2012
Intramural East Carolina Diabetes and Obesity Institute funds, East Carolina University. Project:Myocardial EphrinA/EphA in Diabetes and Infarction. PI: Jitka Virag, Award Amount: $18,500; Nov 2010-May 2012
US Patent #8580739 issued 11/12/13. Methods of Reducing Myocardial Injury Following Myocardial Infarction (for the use of EphrinA1).
O'Neal, WT, Griffin, WF, Kent, SD, Faiz, F, Hodges, J, Vuncannon, J, and Virag, JAI. Deletion of the EphA2 receptor exacerbates myocardial injury and the progression of ischemic cardiomyopathy. Frontiers in Physiology, Integrative Physiology 2014 Mar 17, 5: 132. doi:10.3389/fphys.2014.00132 (in press).
Johnson, Tracy, Tulis, DA, Keeler, BE, Virag, JAI, Lust, RM, and Clemens, S. The dopamine D3 receptor knockout mouse mimics aging- related changes in autonomic function and cardiac fibrosis. PLoS One. 2013 Aug 30 8(8) doi:10.1371/journal.pone.0074116
Jitka A. I. Virag, Ethan J. Anderson, Susan D. Kent, Harrison D. Blanton, Tracy L. Johnson, Fatiha Moukdar, Jonathan H. DeAntonio, Kathleen Thayne, Jian M. Ding, and Robert M. Lust. Cardioprotection via Preserved Mitochondrial Structure and Function in the mPer2-mutant Mouse Myocardium. Am J Physiol Heart and Circ. 2013 Jun 14 (epub).
Wesley T. O'Neal MD; Jessica L. Dries PhD; Susan D. Kent BS; Jin Chen MD, PhD, Monte S. Willis MD, PhD, Jitka A. I. Virag PhD. Ephrin-Eph Signaling as a Potential Therapeutic Target for the Treatment of Myocardial Infarction. Medical Hypotheses 80(6): 738-744, 2013. (Epub April 4, 2013)
Wesley T. O'Neal, MD, William F. Griffin MS, Susan D. Kent BS, Jitka A. I. Virag PhD. Cellular Pathways of Death and Survival in Acute Myocardial Infarction. J Clin Exp Cardiol 2012. Invited submission for special issue: "Coronary Heart Disease". http://dx.doi.org/10.4172/2155-9880.S6-003.
Virag, J. A., Lust, R. M., Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction J Vis Exp. (2011) Jun 7;(52). pii: 2581. doi: 10.3791/2581 (http://www.jove.com/details.stp?id=2581)
Dries JL, Kent SD, Virag JA. Intramyocardial Administration of EphrinA1-Fc Promotes Tissue Salvage Following Myocardial Infarction in Mice. J of Physiol Apr 1; 589(Pt7):1725-40 (Epub Jan 31, 2011)
Virag JA, Dries JL, Easton PR, Friesland AM, DeAntonio JH, Chintalgattu V, Cozzi E, Lehmann BD, Ding JM, Lust RM. Attenuation of myocardial injury in mice with functional deletion of the circadian rhythm gene mPer2. Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H1088-95. Epub 2010 Jan 8.
Virag JA, Rolle ML, Reece J, Hardouin S, Feigl EO, Murry CE. Fibroblast growth factor-2 regulates myocardial infarct repair: effects on cell proliferation, scar contraction, and ventricular function. Am J Pathol. 2007 Nov;171(5):1431-40. Epub 2007 Sep 14.
Nussbaum J, Minami E, Laflamme MA, Virag JA, Ware CB, Masino A, Muskheli V, Pabon L, Reinecke H, Murry CE. Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. FASEB J. 2007 May;21(7):1345-57. Epub 2007 Feb 6.
Stevens KR, Rolle MW, Minami E, Ueno S, Nourse MB, Virag JI, Reinecke H, Murry CE. Chemical dimerization of fibroblast growth factor receptor-1 induces myoblast proliferation, increases intracardiac graft size, and reduces ventricular dilation in infarcted hearts. Hum Gene Ther. 2007 May;18(5):401-12.
McDonough KH, Virag JI. Sepsis-induced myocardial dysfunction and myocardial protection from ischemia/reperfusion injury. Front Biosci. 2006 Jan 1;11:23-32. Review.
Reinecke H, Minami E, Virag JI, Murry CE. Gene transfer of connexin43 into skeletal muscle. Hum Gene Ther. 2004 Jul;15(7):627-36.
Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004 Apr 8;428(6983):664-8. Epub 2004 Mar 21.
Virag JI, Murry CE. Myofibroblast and endothelial cell proliferation during murine myocardial infarct repair. Am J Pathol. 2003 Dec;163(6):2433-40.
Ismail JA, Poppa V, Kemper LE, Scatena M, Giachelli CM, Coffin JD, Murry CE. Immunohistologic labeling of murine endothelium. Cardiovasc Pathol. 2003 Mar-Apr;12(2):82-90.
Ismail JA, McDonough KH. The role of K+ATP channels in the control of pre- and post-ischemic left ventricular developed pressure in septic rat hearts. Can J Physiol Pharmacol. 2001 Mar;79(3):213-9.
Ismail JA, McDonough KH. The role of coronary flow and adenosine in postischemic recovery of septic rat hearts. Am J Physiol. 1998 Jul;275(1 Pt 2):H8-14.