Cell & Developmental Biology
faculty photo

Jonathan A. Epstein, M.D.

William Wikoff Smith Professor of Cardiovascular Research
Department: Medicine
Graduate Group Affiliations

Contact information
Executive Vice Dean and Chief Scientific Officer
602 PCAM South Expansion
3400 Civic Center Blvd.
Philadelphia, PA 19104
Office: (215) 898-8731
Fax: (215) 573-2030
Education:
A.B. (Biochemistry)
Harvard College, 1983.
M.D. (Medicine)
Harvard Medical School, 1988.
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Description of Research Expertise

Research Interests
Epigenetic regulation of stem cell biology, developmental biology, and cardiovascular medicine.

Key words: Cardiac development, Neural crest, Transcription, Epigenetics, Stem cells, Nuclear architecture, Hopx.

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. The lab has a longstanding history in the genetic causes of congenital heart disease and transcriptional regulation of cell fate determination. Most recently, the lab has focused on epigenetics, including the role of histone deacetylases in cardiac development and adult heart function. Active projects involve the understanding of the packaging of DNA and chromatin in the nucleus in three dimensions (“nuclear architecture”) and the regulation of cell differentiation by protein complexes that tether regions of the genome to the nuclear periphery. The lab has pioneered the concept that entire gene programs that define cardiac cell types can be regulated through interactions between the nuclear lamina and the chromatin. The Epstein lab discovered the tumor suppressor and stem cell gene Hopx and continues to study its role in the heart and in numerous tissue-specific adult resident stem cells including those in the central nervous system, the intestine and the skin. Finally, the lab is using novel methods of engineering immune cells to develop proof-of-principle approaches for treating common cardiovascular disorders.

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
Nikhita Bolar
Kurt Allen Engleka
Aidan Hancock
Deqiang Li
Jun Li
Feiyan Liu
Andrey Poleshko
Kelvin See
Cheryl Smith
Qiaohong Wang




Selected Publications

Ramjee, V., Li, D., Manderfield, L.J., Liu, F., Engleka, K.A., Aghajanian, H., Rodell, C.B., Lu, W., Ho, V., Wang, T., Li, L., Singh, A., Cibi, D.M., Burdick, J.A., Singh, M.K., Jain, R., Epstein, J.A.: Epicardial YAP/TAZ orchestrate an immunosuppressive response following myocardial infarction. J Clin Invest 127(3): 899-911, Mar 2017.

Loh, K.M., Chen, A., Koh, P.W., Deng, T.Z., Sinha, R., Tsai, J.M., Barkal, A.A., Shen, K.Y., Jain, R., Morganti, R.M., Shyh-Chang, N., Fernhoff, N.B., George, B.M., Wernig, G., Salomon, R.E., Chen, Z., Vogel, H., Epstein, J.A., Kundaje, A., Talbot, W.S., Beachy, P.A., Ang, L.T., Weissman, I.L.: Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types. Cell 166(2): 451-67, July 2016.

Aghajanian, H., Cho, Y.K., Manderfieldm L.J., Herling, M.R., Gupta, M., Ho, V.C., Li, L., Degenhardt, K., Aharonov, A., Tzahor, E., Epstein, J.A.: Coronary vasculature patterning requires a novel endothelial ErbB2 holoreceptor. Nat Commun 7: 12038, June 2016.

Singh, A., Ramesh, S., Cibi1, D.M., Yun, L.S., Li, J. Li, L., J. Manderfield, L., Olson, E.N., Epstein, J.A. and Singh, M.K.: Hippo signaling mediators Yap and Taz are required in the epicardium for coronary vasculature development. Cell Reports 17(15): 1384-93, May 2016.

He, S., Mansour, M.R., Zimmerman, M.W., Ki, D.H., Layden, H.M., Akahane, K., Gjini, E., DeGroh, E.D., Perez-Atayde, A.R., Zhu, S., Epstein, J.A., Look, A.T.: Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain eLife 5:e14713, 2016.

Yzaguirre, A.D., Padmanabhan,A., de Groh, E.D., Engleka, K.A., Li, J., Speck, N.A., Epstein, J.A.: Loss of neurofibromin Ras-GAP activity enhances the formation of cardiac blood islands in murine embryos. eLife 4, Oct 2015.

Li, D., Takeda, N., Jain, R., Manderfield, L.J., Liu, F., Li, L., Anderson, S.A., Epstein, J.A.: Hopx distinguishes hippocampal from lateral ventricle neural stem cells. Stem Cell Res 15(3): 522-529, Oct 2015.

Manderfield, L.J., Aghajanian, H., Engleka, K.A., Lim, L.Y., Liu, F., Jain, R., Li, L., Olson, E.N., Epstein, J.A. : Hippo signaling is required for Notch-dependent smooth muscle differentiation of neural crest. Development 142(17): 2962-71, Sep 2015.

Jones, A., Opejin, A., Henderson, J.G., Gross, C., Jain, R., Epstein. J.A., Flavell, R.A., Hawiger, D.: Peripherally Induced Tolerance Depends on Peripheral Regulatory T Cells That Require Hopx To Inhibit Intrinsic IL-2 Expression. J Immunol 195(4): 1489-97, Aug 2015.

Han, S., Zhang, R., Jain, R., Shi, H., Zhang, L., Zhou, G., Sangwung, P., Tugal, D., Atkins, G.B., Prosdocimo, D.A., Lu, Y., Han, X., Tso, P., Liao, X., Epstein, J.A., Jain, M.K.: Corrigendum: Circadian control of bile acid synthesis by a KLF15-Fgf15 axis. Nat Commun 6: 8270, Aug 2015.

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Last updated: 11/17/2017
The Trustees of the University of Pennsylvania
 

Department of Cell and Developmental Biology
1150 BRB II
421 Currie Boulevard
Philadelphia, PA 19104
Tel: (215) 573-9306
Fax: (215) 898-9871