Dr. Jitka Virag, Ph.D.
Heart failure is a significant public health problem. The heart lacks sufficient regenerative potential to recover from an ischemic event. Investigative efforts aim 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.
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, autophagy, 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, MALDI-IMS, 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.
- 2017-present: Associate Professor, Department of Physiology, Brody School of Medicine, East Carolina University
- 2015-2016: Interim Chief Diversity Officer, Office of Academic Affairs, Brody School of Medicine, East Carolina State University
- 2009-2017: Assistant Professor, Department of Physiology, Brody School of Medicine, East Carolina University
- 2006-2009: Research Assistant Professor, Department of Physiology, Brody School of Medicine, East Carolina University
- 2004-2005: Research Scientist, Universities Space Research Association, Division of Space Life Sciences, Center for Advanced Space Studies, Cardiovascular Laboratory, Johnson Space Center, NASA
- 1999-2004: Senior Fellow, University of Washington, Seattle: Advisor: Dr. Charles E. Murry, M.D., Ph.D.
- 1994-1999: Doctor of Philosophy, Physiology, Louisiana State University Medical Center; Advisor: Dr. Kathleen H. McDonough, Ph.D.
- 1989-1993: Bachelor of Science with Honors, Biology, Queen’s University, Kingston, Ontario, Canada; Advisor: Dr. David Layzell, PhD
- US Patent #10,448,631 issued 10/22/19. Cryopreservation Using Sucralose
- US Patent #9974831 issued 5/22/18. Methods of Reducing Myocardial Injury Following Myocardial Infarction (for the use of EphrinA1)
- US Patent #8580739 issued 11/12/13. Methods of Reducing Myocardial Injury Following Myocardial Infarction (for the use of EphrinA1)
Current Research Support
Funding Agency: North Carolina Biotechnology Center Biotechnology, Translational Research Grant.
Project: Preservation of Refrigerated Blood Products. Award Amount: $100,000
Role: co-PI; Award requested: $100,000; Award Notification: 12/2019
Past Research Support
Funding Agency: National Institutes of Health, NHLBI, R15, 1RH15HL124483-01A1
Project: Salvaging the Ischemic Myocardium: The Role of EphrinA1/EphA Bidirectional Signaling
Role: PI; Award Amount: $300,000; Duration of Award: 3 years (07/01/2015 – 06/30/2018)
Funding Agency: North Carolina Biotechnology Center, Institutional Development Grant.
Project: Automated Slide Scanning to Enhance Research Infrastructure and Throughput at East Carolina University. Requested Amount: $178,026
Role: PI; Award Notification: 3/23/16
- Mohammad R. Islam; Jitka Virag; Michelle L. Oyen. Micromechanical poroelastic and viscoelastic properties of ex-vivo soft tissues. Journal of Biomechanics. October 27, 2020, DOI: 10.1016/j.jbiomech.2020.110090
- Whitehurst, K.S.; Chan, V.A.; Estes, H.K.; Valsaraj, S.; Kent, S.; Sharma, U.M.; Chase, R.C.; Bhuiyan, M.; Virag, J.A.I. EphrinA1-Fc Attenuates Ventricular Remodeling and Dysfunction in Chronically Nonreperfused WT but not EphA2-R-M mice. Int. J. Mol. Sci. 2020, 21, 5811
- Hughes, R.M.; Virag, J.A. Harnessing the Power of Eph/ephrin Biosemiotics for Theranostic Applications. Pharmaceuticals 2020, 13, 112
- Maria J. Torres, Kelsey McLaughlin, Randall Renegar, Smrithi Valsaraj, K’Shylah Whitehurst, Omar Sharaf, Uma Sharma, Julie L. Horton, Brinda Sarathy, Justin Parks, Jeffrey J. Brault, Kelsey H. Fisher-Wellman, P. Darrell Neufer, and Jitka A. I. Virag. Intra-cardiac administration of EphrinA1-Fc preserves mitochondrial bioenergetics during acute ischemia reperfusion injury. Life Sciences 2019, 13 Nov:117053
- Julie Horton and Jitka Virag. Use of Multifactorial Treatments to Address the Challenge of Translating Experimental Myocardial Infarct Reduction Strategies. Int J Mol Sci *special issue*: Novel Molecular Targets for Cardioprotection. 2019. Invited contribution. Mar 22, 20(6), 1449
- Stephan Lefcoski, Kimberly Kew, Shaun Reece, Maria J. Torres, Justin Parks, Sky Reece, Lisandra E. de Castro Brás, and Jitka A. I. Virag. Anatomical-Molecular Distribution of EphrinA1 in Infarcted Mouse Heart Using MALDI Mass Spectrometry Imaging. J Am Soc Mass Spec 2018 Jan 5
- Merry L. Lindsey, Zamaneh Kassiri, Jitka Amira Ismail Virag, Lisandra E. de Castro Brás, and Marielle Scherrer-Crosbie. Guidelines for Measuring Cardiac Physiology in Mice. Am J Physiol 2018 Jan 5
Podcast with Merry Lindsey, Marielle Scherrer-Crosbie, Jitka Virag, and Dave Kass
- Augustin DuSablon, Justin Parks, K’Shylah Whitehurst, Heather Estes, Robert Chase, Eleftherios Vlahos, Uma Sharma, David Wert, and Jitka Virag. EphrinA1-Fc Attenuates Ischemia/Reperfusion Injury in Mice. PLOS ONE 2017 Dec 13
- Anh Thi Van Bui, Truc Le Buu Pham, Jitka Virag. Improving stem cell engraftment to enhance function efficacy in cardiovascular disease: where are we now? Biomedical Research & Therapy 4(1): 1082-1097, Jan 17, 2017
- Jitka Virag. Healing the Broken Heart. International Innovation 2015, June 12
- Lalage A. Katunga, Preeti Gudimella, Jimmy T. Efird, Scott Abernathy, Taylor A. Mattox, Cherese Beatty, Timothy M. Darden, Kathleen A. Thayne, Hazaim Alwair, Alan P. Kypson, Jitka A. Virag, Ethan J. Anderson. Obesity in a model of gpx4 haploinsufficiency uncovers a causal role for lipid-derived aldehydes in human metabolic disease and cardiomyopathy. Molecular Metabolism 2015, Apr 21
- Jitka A.I. Virag. Circadian Rhythm Complexities in Cardiovascular Dynamics. Sleep Medicine, Editorial 2015, January 26
- Jitka A.I. Virag and Robert M. Lust. Circadian Influences on Myocardial Infarction. Frontiers in Physiology, Integrative Physiology. Special topics issue “Mechanistic Underpinnings of Circadian Physiology in Heart Disease”, October 30, 2014
- Augustin DuSablon, Susan Kent, Anita Coburn, and Jitka Virag. EphA2-Receptor Deficiency Exacerbates Myocardial Infarction and Reduces Survival in Hyperglycemic Mice. Cardiovascular Diabetology 2014, August 13:114
- 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
- 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)
- 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”
- 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
- 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.