Jonathan A. Epstein, M.D.

faculty photo
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
Jun Li
Feiyan Liu
Andrey Poleshko
Kelvin See
Cheryl Smith



Selected Publications

Berg, D.A., Su, Y., Jimenez-Cyrus, D., Patel, A., Huang, N., Morizet, D., Lee, S., Shah, R., Ringeling, F.R., Jain, R. Epstein, J.A., We, Q.F., Canzar, S., Ming, G.L., Song, H., Bond, A.M.: A Common Embryonic Origin of Stem Cells Drives Developmental and Adult Neurogenesis. Cell 177(3): 654-668, April 2019.

See, K., Lan, Y., Rhoades, J., Jain, R., Smith, C.L., Epstein, J.A.: Lineage-specific reorganization of nuclear peripheral heterochromatin and H3K9me2 domains. Development 146(3), Feb 2019.

Artap, S., Manderfield, L.J., Smith, C.L., Poleshko, A., Aghajanian, H., See, K., Li, L., Jain, R., Epstein, J.A. : Endocardial Hippo signaling regulates myocardial growth and cardiogenesis. Dev Biol 440(1): 22-30, Aug 2018.

Jain, R., Poleshko, A., Epstein, J.A. : Beating the odds: programming proliferation in the mammalian heart. Genome Med 10(1): 36, May 2018.

Lin, W., Li, D., Cheng, L., Li, L., Liu, F., Hand, N.J., Epstein, J.A., Rader, D.J.: Zinc transporter Slc39a8 is essential for cardiac ventricular compaction. J Clin Invest 128(2): 826-833, Feb 2018.

Pauerstein PT, Tellez K, Willmarth KB, Park KM, Hsueh B, Arda HE, Gu X, Aghajanian H, Deisseroth K, Epstein JA, Kim SK.: A radial axis defined by Semaphorin to Neuropilin signaling controls pancreatic islet morphogenesis. Development 144(20): 3744-3754, Oct 2017.

Pleshko, A., Shah, P.P., Gupta, M., Babu, A., Moreley, M., Manderfield, L.J., Ifkovits, J.L., Dubois, N., Morrisey, E.E., Lazar, M.A., Smith, C.L., Epstein, J.A., Jain, R.: Geome–nuclear lamina interactions regulate progenitor cell lineage restriction during cardiogenesis. Cell 171(3): 573-587, Oct 2017.

Palpant, N.J., Wang, Y., Hadland, B., Zaunbrecher, R.J., Redd, M., Jones, D., Pabon, L., Jain, R., Epstein, J.A., Ruzzo, W.L., Zheng, Y., Bernstein, I., Margolin, A., Murry, C.E.: Chromatin and Transcriptional Analysisof Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis. Cell Reports 20: 597-608, Aug 2017.

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.

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Last updated: 06/06/2019
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