Jonathan Epstein
William Wikoff Smith Professor of Medicine
Chair, Dept of Cell and Dev. Biology
Scientific Director, Penn Cardiovascular Institute

Developmental Biology Program

Address

1154 Biomedical Rsch Bldg (BRB) II/III
421 Curie Boulevard
Philadelphia, PA 19104-6140

Office tel.: 215-898-8731
Lab tel.: 215-573-7212
Fax: 215-573-2094
E-mail: epsteinj@mail.med.upenn.edu

Link(s)

The Molecular Cardiology Research Center

Education

Harvard College, A.B.(Biochemistry),1979-83

Harvard Medical School, M.D. (Medicine), 1984-88

Research Interests

• Transcriptional regulation of cardiac development and function using mouse models

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

Search PubMed for articles

Description of Research

The Epstein laboratory is interested in molecular mechanisms of cardiovascular development, 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. 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.

Recent Publications

Lang, D., Lu, M.M., Huang, L., Engleka, K.A., Zhang, M., Chu, E.Y., Lipner, S., Skoutlchi, A., Millar, S., Epstein, J.A. Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature, 433: 884-887, 2005.

Parmacek, M.S., and Epstein, J.A. Pursuing cardiac progenitors: regeneration redux. Cell, 120: 296-298, 2005.

High, F.A., Zhang, M., Proweller, A., Tu, L.L., Parmacek, M.S., Pear, W.S., Epstein, J.A. : An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest. 2007 February 1;117(2): 353–363.

Trivedi, C.M., Luo, Y., Zhan, Y., Zhang, M., Zhu, W., Wang, T., Floss, T., Goettlicher, M., Noppinger, P.R., Wurst, W., Ferrari, V.A., Abrams, C.S., Gruber, P.J., Epstein, J.A.: Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3beta; activity. Nat Med. 2007 Mar;13(3):324-331

Lab

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, Hop, 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 personnel:

Kurt Engleka, Senior Research Investigator
Jun Li, Research Specialist B
Fraz Ismat, CHOP Postdoctoral Fellow
Min Min Lu, Research Specialist C
Li Huang, Research Specialist B
Ying Zhang, Graduate Student
Jason Stoller, CHOP Neonatology Research Fellow
Frances High, Graduate Student
Chinmay Trivedi, Postdoctoral Fellow
Junwang Xu, Postdoctoral Fellow
Arun Padmanabhan, Sarnoff Fellow
Meilin Wu, Postdoctoral Fellow