University of Pennsylvania
Perelman School of Medicine
602 PCAM South Expansion
3400 Civic Center Blvd.
Philadelphia, PA 19104
Office: 215-898-8731
Fax: 215-573-2030
epsteinj@pennmedicine.upenn.edu
The Epstein laboratory studies molecular mechanisms of cardiovascular development and stem cell biology, and the implications of these mechanisms for understanding human disease. The lab has a longstanding interest in the genetic causes of congenital heart disease and transcriptional regulation of cell fate determination. Most recently, we have focused on epigenetics, including the role of histone deacetylases in cardiac development and adult heart function. Aims of current projects include gaining an understanding of the three-dimensional packaging of DNA and chromatin in the nucleus (“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 interactions between the nuclear lamina and the chromatin contribute to the regulation of entire gene programs that define cardiac cell types.
We have elucidated the role of epigenetics in heart development and we have applied this knowledge to explore novel therapies for adult cardiac disease including ischemia-reperfusion and congestive heart failure. In particular, we demonstrated that histone deacetylase inhibitors can prevent pathologic cardiac hypertrophy, which was counter to the prevailing dogma at the time.
My laboratory has contributed to our understanding of how the neural crest influences cardiac development and to the embryologic and genetic basis of congenital heart disease.Neural crest contribution to the heart was described in the early 1980s by Kirby and colleagues, and our laboratory extended these observations to mammalian systems, performed genetic fate-mapping in mouse models, identified candidate genes for congenital heart defects and described molecular pathways including Notch, Fgf, Wnt and Hippo that regulate cross-talk between neural crest, endothelium and second heart field derivatives in the heart.
We described the molecular basis for cardiovascular manifestations in Type 1 Neurofibromatosis using mouse and zebrafish models, including valvular pulmonic stenosis, endothelial defects and cardiac hypertrophy.We generated a zinc-finger knockout of the Nf1 genes in zebrafish, and demonstrated behavioral defects amenable to small molecule drug screening.
We were among the first to show that guidance molecules known to regulate the migration of axons in the central nervous system can also regulate angiogenesis and cardiac development. We have shown that members of the semaphorin and plexin families help to pattern the outflow tract of the heart, the pulmonary veins and coronary arteries, and the peripheral vasculature.
I have contributed to the dissemination of scientific knowledge across disciplines and to the public, as evidenced by service as President of the American Society for Clinical Investigation, Deputy Editor of the Journal of Clinical Investigation, contributions to the Institute of Medicine, and author of numerous scholarly commentaries on public policy and health care.
My dedication to community service in academic medicine is evidenced by my service as chairman of an NIH study section (CDD) and multiple roles on study sections at the NIH, DOD and AHA, and as a frequent journal reviewer, member of editorial boards, member of NHLBI Council and co-chair of NHLBI strategic planning.
FIRST NAME: | LAST NAME: | TITLE: | EMAIL: |
---|---|---|---|
Jonathan | Epstein | Executive Vice Dean & CSO | epsteinj@pennmedicine.upenn.edu |
Carolyn | Henry | Executive Assistant | carolynp@pennmedicine.upenn.edu |
Haig | Aghajanian | Post Doc Researcher | haig@pennmedicine.upenn.edu |
Kurt Allen | Engleka | Senior Research Investigator | kengleka@pennmedicine.upenn.edu |
Cheryl | Smith | Senior Research Investigator | chsmit@pennmedicine.upenn.edu |
Jun | Li | Research Specialist D | junli2@pennmedicine.upenn.edu |
Feiyan | Liu | Technician | feiyan@pennmedicine.upenn.edu |
Andrey | Poleshko | Post Doc Researcher | poleshko@pennmedicine.upenn.edu |
Kelvin | See | Post Doc Researcher | kelvins@pennmedicine.upenn.edu |
Nikhita | Bolar | Post Doc Researcher | nbolar@pennmedicine.upenn.edu |
Aidan | Hancock | Post Doc Researcher | aidans@pennmedicine.upenn.edu |
Joshua | Rhoades | Bioinformatician | Joshua.Rhoades@pennmedicine.upenn.edu |
Joel | Rurik | Graduate Student | joel.rurik@penmmedicine.upenn.edu |
Karen | Wong | Graduate Student | karewong@pennmedicine.upenn.edu |
Anna | Kiseleva | Post Doc Researcher | anna.kiseleva@pennmedicine.upenn.edu |
Li | Li | Technician | li10@pennmedicine.upenn.edu |