Penn Cardiovascular Institute

Heart and Vascular Faculty

faculty photo

Jonathan A. Epstein, M.D.

William Wikoff Smith Professor of Cardiovascular Research
Department: Medicine

Contact information
Chairman of Cell and Developmental Biology
9-105 Smilow Center for Translational Research
3400 Civic Center Blvd.
Philadelphia, PA 19104
Office: (215) 898-8731
Fax: (215) 898-9871
Graduate Group Affiliations
Education:
A.B. (Biochemistry)
Harvard College, 1983.
M.D. (Medicine)
Harvard Medical School, 1988.
Post-Graduate Training
Internship in Medicine, Brigham and Women's Hospital, Boston, MA, 1988-1989.
Postdoctoral Associate, Dr. Lewis Cantley, Supervisor (part of Research Residency Program at Brigham and Women's Hospital), Tufts University Department of Physiology, 1988-1990.
Clinical Fellow in Medicine, Harvard Medical School, 1988-1991.
Residency in Medicine, Research Residency Program, Brigham and Women's Hospital, Boston, MA, 1989-1991.
Chief Medical Resident, Brockton-West Roxbury VA Medical Center, 1990-1990.
Research/Clinical Fellow in Medicine (Cardiology), Brigham and Women's Hospital, 1991-1994.
Research Fellow in Medicine, Harvard Medical School, 1991-1994.
Associate in Research, Postdoctoral Fellowship for Physicians, Howard Hughes Medical Institute, 1992-1995.
Certifications
National Board Examinations in Medicine, Part I, 1986.
National Board Examinations in Medicine, Part II, 1988.
National Board Examinations in Medicine, Part III, 1989.
Board Certified in Internal Medicine by ABIM, 1991.
Board Certified in Cardiovascular Medicine by ABIM, 1995.
Board Certified in Cardiovascular Medicine by ABIM, 2006.
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Description of Research Expertise

Research Interests
Transcriptional regulation of cardiac development and function using mouse models

Key words: Cardiac development, Neural crest, Transcription, Hypertrophy, Pax, Neurofibromatosis

Research Description
The Epstein laboratory is interested in molecular mechanisms of cardiovascular development and stem cell biology, and the implications of these mechanisms for understanding human disease. Transgenic and knockout mouse models are used. One area of interest is the developmental biology of neural crest. Neural crest cells are multipotent progenitors that give rise to nerve, bone, muscle, melanocytes and other cell types. Hence, they are an attractive model for studying stem cell biology. Neural crest defects are associated with congenital heart disease. Using Cre-lox approaches, we have demonstrated that neural crest cells in mammals give rise to the smooth muscle of the great vessels and portions of the outflow tract of the heart. Semaphorins, molecules that mediate repulsive axon guidance in the central nervous system, also mediate proper neural crest patterning and we have identified novel semaphorin pathways functional in the vasculature. Neural crest patterning is affected in mouse models of DiGeorge syndrome, a common human congenital condition associated with congenital heart disease. We have studied mouse models of DiGeorge syndrome including those with deletions or mutations in the Tbx1 transcription factor gene. Another human disorder associated with neural crest defects is Type I Neurofibromatosis. We have demonstrated that heart defects in Nf1 mutant mice are related to a function for this gene in endothelial cells which is distinct from its role in neural crest. Our lab is also interested in transcriptional regulation of cardiac muscle development and function. We have discovered an unusual homeobox gene that affects heart growth and function. Knockouts in mice and zebrafish have poorly formed hearts, and over-expression in adults causes adult cardiac hypertrophy and heart failure. Chromatin remodeling of cardiac-specific genes is affected. More recent work focuses on the role of chromatin remodeling, histone deacetylation (HDACs) and a small homeodomain protein called Hopx that is expressed in adult stem cells. We have developed several outstanding core facilities for histology, transgenics and mouse physiology to aid students and postdocs in accomplishing research goals and in accelerating productivity.

Rotation Projects
Opportunities are available to analyze transgenic and knockout mice that serve as models of congenital and adult heart disease. Analysis is at the whole animal level and at the molecular level. Specific projects involve the investigation of Pax3, Hopx, Tbx1 and Nf1 function in cardiovascular and neural crest tissues. Assays involving protein-protein interactions, transcriptional regulation and chromatin modification are commonly used. Projects are tailored to students' experience and interests.

Lab Members
Haig Aghajanian
Kurt Engleka
Mudit Gupta
Vivienne Ho
Rajan Jain
Deqiang Li
Jun Li
Feiyan Liu
Lauren Manderfield
Qiaohong Wang



Description of Clinical Expertise

Cardiovascular Medicine

Selected Publications

Degenhardt, K., Singh, M.K., Aghajanian, H., Massera, D., Wang, Q., Li, J., Li, L., Choi, C., Yzaguirre, A.D., Francey, L.J., Gallant, E., Krantz, I.D., Gruber, P.J., Epstein, J.A. : Semaphorin 3d signaling defects are associated with anomalous pulmonary venous connections. Nature Medicine 19(6): 760-5, Jun 2013.

Takeda, N., Jain, R., LeBoeuf, M.R., Padmanabhan, A., Wang, Q., Li, L, Lu, M.M., Millar, S., and Epstein, J.A. : Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells. Development March 2013.

de la Pompa, J.L., Epstein, J.A. : Coordinating tissue interactions: notch signaling in cardiac development and disease. Dev Cell. 2012 Feb 14;22(2):244-54. 22(2): 244-54, Feb 2012.

de la Pompa José Luis, Epstein Jonathan A: Coordinating tissue interactions: Notch signaling in cardiac development and disease. Developmental cell 22(2): 244-54, Feb 2012.

Engleka Kurt A, Manderfield Lauren J, Brust Rachael D, Li Li, Cohen Ashley, Dymecki Susan M, Epstein Jonathan A: Islet1 derivatives in the heart are of both neural crest and second heart field origin. Circulation research 110(7): 922-6, Mar 2012.

Manderfield Lauren J, High Frances A, Engleka Kurt A, Liu Feiyan, Li Li, Rentschler Stacey, Epstein Jonathan A: Notch activation of Jagged1 contributes to the assembly of the arterial wall. Circulation 125(2): 314-23, Jan 2012.

Shin, J., Padmanabhan, A., de Groh, E.D., Lee, J.S., Haidar, S., Dahlberg, S., Guo, F., He, S., Wolman, M.A., Granato, M., Lawson, N.D., Wolfe, S.A., Kim, S.H., Solnica-Krezel, L., Kanki, J.P., Ligon, K.L., Epstein, J.A., Look, A.T. : Zebrafish neurofibromatosis type 1 genes have redundant functions in tumorigenesis and embryonic development. Dis Model Mech Aug 2012.

Loscalzo, J., Libby, P., Epstein, J. : Basic Biology of the Cardiovascular System.New York, USA: Harrison’s Texbook of Medicine. D.L. Longo, H.T. Randolf, (eds.). The McGraw Hill Companies, Inc. 18th ed.,: 1798-1811, 2011.

Rentschler Stacey, Harris Brett S, Kuznekoff Laura, Jain Rajan, Manderfield Lauren, Lu Min Min, Morley Gregory E, Patel Vickas V, Epstein Jonathan A: Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways. J Clin Invest 121(2): 525-33, Feb 2011.

Takeda Norifumi, Jain Rajan, LeBoeuf Matthew R, Wang Qiaohong, Lu Min Min, Epstein Jonathan A: Interconversion between intestinal stem cell populations in distinct niches. Science (New York, N.Y.) 334(6061): 1420-4, Dec 2011.

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Last updated: 08/15/2014
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