Description of CVI Expertise

Director, Cardiovascular Institute
Chief, Division of Cardiovascular Medicine

Research Interests
Transcriptional programs that regulate cardiovascular development

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

Description of Research
The Parmacek Lab examines the molecular mechanisms underlying cardiovascular development with particular focus on elucidating the transcriptional programs controlling specification and differentiation of the muscle cell lineages. These studies are fundamentally important at a basic level and have provided important insights into the pathogenesis of congenital heart disease, cardiac hypertrophy and vascular proliferative syndromes including atherosclerosis.

In the Parmacek laboratory, which is located in the Molecular Cardiology Research Center, gene targeting in embryonic stem (ES) cells and mice is routinely utilized to examine the molecular basis of cardiac myocyte and vascular smooth muscle cell development and differentiation.

Members of the Parmacek laboratory first cloned and characterized the GATA-4/5/6 subfamily of zinc finger transcription factors that have been shown to play critical roles in the developing heart and vascular system. Mutations in GATA-4 are associated with common forms of congenital heart disease observed in humans. Parmacek also defined the serum response factor (SRF)-dependent transcriptional program that regulates vascular smooth muscle cell differentiation and modulation of smooth muscle cell phenotype which occurs in atherosclerosis. In recent years, the Parmacek laboratory has focused on examining the function(s) of the SAP domain transcription factor, myocardin, and two myocardin-related transcription factors (MRTFs)-A and –B in the cardiovascular system.

Graduate students and postdoctoral fellows interested in obtaining training in molecular cardiology, stem cell biology, transgenic and genetically engineered models of cardiovascular disease are encouraged to apply for positions.

Recent Publications:
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. 2006 Apr;116(4):929-39.

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 U S A. 2005 Jun 21;102(25):8916-21.

Parmacek MS, Epstein JA. Pursuing cardiac progenitors: regeneration redux. Cell. 2005 Feb 11;120(3):295-8.

Proweller A, Pear WS, Parmacek MS. Notch signaling represses myocardin-induced smooth muscle cell differentiation. J Biol Chem. 2005 Mar 11;280(10):8994-9004.

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. 2003 Apr;23(7):2425-37.

Rotation Projects for 2006-2007
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:
Aaron Proweller MD, PhD - Postdoctoral Research Fellow, Instructor, Dept. of Medicine
Jian Li, MD - Senior Research Scientist
John Huang MD, PhD - Postdoctoral Research Fellow
Mary Chen - Senior Research Technician
Xiaohong Zhu - Senior Research Technician