Description of CVI Expertise

Chief, Division of Cardiovascular Medicine
Director, Cardiovascular Institute

Research Interests
Transcriptional programs that regulate cardiovascular development

Key Words: smooth muscle cell, cardiac myocyte, GATA, myocardin, transcription, notch

Description of Research
The Parmacek laboratory has a longstanding interest in examining the molecular programs that regulate vascular smooth muscle cell and cardiac myocyte development and differentiation. Dr. Parmacek cloned and characterized members of the GATA-4/5/6 family of zinc finger transcription factors and used gene targeting techniques in mice to elucidate the distinct functions of GATA-4 and GATA-6 in the cardiovascular system. The Parmacek laboratory also utilized transgenic techniques to show that an SRF-dependent transcriptional program regulates vascular SMC differentiation.

More recently Parmacek reported that myocardin is a critical SRF cofactor that regulates vascular smooth muscle cell differentiation and modulation of smooth muscle cell phenotype. These studies are relevant to understanding the molecular basis of angiogenesis and the pathophysiology of vascular proliferative syndromes including atherosclerosis.

In collaboration with other Penn cardiologists, Dr. Parmacek performs translational research studies focusing on stem cells and other novel agents that may be used to treat cardiovascular disease.

Rotation Projects
1. Characterization of the function of MRTF-B in the heart and vasculature
2. Examine the molecular basis of Myocardin function in the heart and in vascular smooth muscle cells
3. Characterization of mice harboring a conditional mutation in the lineage-restricted transcription factors GATA-6
4. Examine the role of Notch signaling and Notch-regulated genes during angiogenesis and in the vasculature

Lab Personnel:
Jian Li, MD - Senior Research Scientist
John Huang MD, PhD - Postdoctoral Research Fellow
Mary Chen - Senior Research Technician
Xiaohong Zhu - Senior Research Technician

Selected Publications:
Morrisey EE, Tang Z, Sigrist K, Lu MM, Jiang F, Ip HS, Parmacek MS: GATA-6 regulates HNF-4 and is required for differentiation of visceral endoderm in the mouse embryo. Genes and Dev 12(22): 3579-90, Nov 15 1998.

Du KL, Ip HS, Li J, Chen M, Dandre F, Yu W, Lu MM, Owens GK, Parmacek MS: Myocardin is a critical serum response factor cofactor in the transcriptional program regulating smooth muscle cell differentiation. Mol Cell Biol 23(7): 2425-37, Apr 2003.

Li J, Zhu X, Chen M, Cheng L, Zhou D, Lu MM, Du K, Epstein JA, Parmacek MS: Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development. Proc Natl Acad Sci USA 102(25): 8916-21, Jun 21 2005.

Lepore JJ, Mericko PA, Cheng L, Lu MM, Morrisey EE, Parmacek MS: GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis. J Clin Invest 116(4): 929-39, Apr 2006.

Proweller A, Wright AC, Horng D, Cheng L, Lu MM, Lepore JJ, Pear WS, Parmacek MS: Notch signaling in vascular smooth muscle cells is required to pattern the cerebral vasculature. Proc Natl Acad Sci USA 104(41): 16275-80, Oct 2007.

High FA, Zhang M, Proweller A, Tu L, Parmacek MS, Pear WS, Epstein JA: An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest 117(2): 353-63, Feb 2007.

Parmacek MS: Myocardin-related transcription factors: critical coactivators regulating cardiovascular development and adaptation. Circ Res 100(5): 633-44, Mar 2007.

Huang J, Cheng L, Li J, Chen M, Zhou D, Lu MM, Proweller A, Epstein JA, Parmacek MS: Myocardin regulates smooth muscle cell contractile genes required for closure of the ductus arteriosus. J Clin Invest 118(2): 515-25, Feb 2008.

Zhang Z, Goss AM, Cohen ED, Kadzik R, Lepore JJ, Muthukumaraswamy K, Yang J, DeMayo F, Whitsett JA, Parmacek MS, Morrisey EE: A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration. Nature Genetics 40(7): 862-70, July 2008.

Parmacek MS, Epstein JA: Cardiomyocyte Renewal. N Engl J Med 2(361): 86-8, July 2009.