Jonathan A. Epstein

faculty photo
William Wikoff Smith Professor of Cardiovascular Research
Affiliate Member, University of Pennsylvania Cancer Center
Associate Member, Pennsylvania Muscle Institute
Member, Institute for Medicine and Engineering
Director, Molecular Cardiology Research Center, Division of Cardiology , University of Pennsylvania
Member, Center for Research on Reproduction and Women's Health
Executive Committee, Pennsylvania Muscle Institute
Executive Committee, Institute for Regenerative Medicine
Executive Vice Dean and Chief Scientific Officer, Perelman School of Medicine
Scientific Director, Penn Cardiovascular Institute
Senior Vice President and Chief Scientific Officer , University of Pennsylvania Health System
Department: Medicine

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
Graduate Group Affiliations
A.B. (Biochemistry)
Harvard College, 1983.
M.D. (Medicine)
Harvard Medical School, 1988.
Post-Graduate Training
Postdoctoral Associate, Dr. Lewis Cantley, Supervisor (part of Research Residency Program at Brigham and Women's Hospital), Tufts University Department of Physiology, 1988-1990.
Internship in Medicine, Brigham and Women's Hospital, Boston, MA, 1988-1989.
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 Fellow in Medicine, Harvard Medical School, 1991-1994.
Research/Clinical Fellow in Medicine (Cardiology), Brigham and Women's Hospital, 1991-1994.
Associate in Research, Postdoctoral Fellowship for Physicians, Howard Hughes Medical Institute, 1992-1995.
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
Epigenetic regulation of stem cell biology, developmental biology, and cardiovascular medicine.

Key words: Nuclear architecture, Cardiac development, Neural crest, Transcription, Epigenetics, Stem cells, CAR T, Fibrosis, Hopx

Research Description
In the Epstein laboratory, we are interested in molecular mechanisms of cardiovascular development and stem cell biology, and the implications for human disease. The lab has a longstanding history in pursuing the genetic causes of congenital heart disease and mechanisms of cell fate determination.
Our research combines biochemistry, cell biology, and genomics to determine how the three-dimensional organization of chromatin in the nucleus (“nuclear architecture”) contributes to cell identity and how cell differentiation is regulated by protein complexes that tether regions of the genome to the nuclear periphery. Most recently, we have focused on epigenetics, including the role of histone deacetylases in cardiac development and adult heart function. The lab has pioneered the concept that entire gene programs, such as those defining cardiac cell types, can be regulated through interactions between the nuclear lamina and chromatin. Current studies are underway to determine the factors regulating 3D chromatin organization as the cell advances through the cell cycle and as it undergoes differentiation.
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.

Potential Projects Opportunities are available to investigate the regulation and functional organization of the genome and the impact on cell identity.
Specific research topics include:
• determine the molecular mechanisms that alter nuclear architecture in response to growth and differentiation signaling
• alter the localization of individual chromatin domains within the nucleus and determine how this impacts the biology of the cell
• define mechanisms that underlie establishment and maintenance of peripheral heterochromatin including how the cell “remembers” 3D chromatin organization during mitosis
• apply statistical and computational methods to determine how the histone code dictates nuclear architecture
Projects are tailored to students' experience and interests.

Lab Members: Haig Aghajanian; Kurt Allen Engleka; Diana Fulmer; Anna Kiseleva; Jun Li; Feiyan Liu; Andrey Poleshko; Joel Rurik; Cheryl Smith; Karen Wong

Selected Publications

Kiseleva, A.A., Troisi, E.M., Hensley, S.E., Kohli, R.M., : Epstein, J.A. SARS-CoV-2 spike protein binding selectively accelerates substrate-specific catalytic activity of ACE2. The Journal of Biochemistry March 2021.

See, K., Kiseleva, A.A., Smith, C.L., Liu, F., Li, J., Poleshko, A., Epstein, J.A. : Histone methyltransferase activity programs nuclear peripheral genome positioning. Dev Biol 466(1-2): 90-98, Oct 2020.

Jang, J., Engleka,K.A., Liu, F. Li, L., Song, G., Epstein, J.A., Li, D. : An engineered mouse to identify proliferating cells and their derivatives. Frontiers in Cell and Developmental Biology, section Cell Growth and Division. 25(8): 388, 2020.

Poleshko, A., Smith, C.L., Nguyen, S.C., Sivaramakrishnan, P., Wong, K.G., Murray, J.I., Lakademyali, M., Joyce, E.F., Jain, R., Epstein, J.A. : H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis. ELife e49278, Oct 2019.

Aghajanian, H., Kimura, T., Rurik, J. G., Hancock, A. S., Leibowitz, M. S., Li, L., Scholler, J., Monslow, J., Lo, A., Han, W., Wang, T., Bedi, K., Morley, M. P., Linares Saldana, R., Bolar, N., McDaid, K., Assenmacher, C., Smith, C. L., Wirth, D., June, C. H., Margulies, K. B., Jain, R., Pure, E., Albelda, S. M., and Epstein, J. A.: Targeting cardiac fibrosis with engineered T cells. Nature Sept 2019.

Aghajanian, H., Kimura, T., Rurik, J.G., Hancock, A.S., Leibowitz, M.S., Li Li, Scholler, J. Monslow, J., Lo, A., Han, W., Wang, T., Bedi, K., Morley, M.P. Linares Saldana, R.A., Bolar, N.A., McDaid K., Assenmacher C. H., Smith, C.L., Wirth, D., June, C.H., Margulies K.B., Jain, R., Pure, E., Albelda, S.M., Epstein, J.A. : Targeting Cardiac Fibrosis with Engineered T cells. Nature 573(7774): 430-433, Sept 2019.

Sandireddy, R., Cibi, D.M., Gupta, P., Singh, A., Tee, N., Uemura, A., Epstein, J.A., Singh, M.K. : Semaphorin 3E/PlexidD1 signaling is required for cardiac ventricular compaction. JCI Insight 4(16), Aug 2019.

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.

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Last updated: 05/27/2021
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