Description of Research Expertise:
Chair, Department of Medicine
Director, Cardiovascular Institute
Transcriptional programs that regulate cardiovascular development
Key Words: smooth muscle cell, cardiac myocyte, GATA, myocardin, transcription, notch
Description of Research
The Parmacek laboratory examines the molecular and genetic programs that regulate heart and vascular development with particular focus on defining the molecular programs regulating development, differentiation and survival of vascular smooth muscle cells and cardiac myocytes. The Parmacek laboratory utilizes a variety of experimental methodologies including the generation and characterization of genetically-engineered mouse and embryonic stem (ES) cell models to elucidate the function(s) of critical transcription factors and transcriptional co-activators in the cardiovascular system. The Parmacek laboratory cloned and/or characterized the function of the GATA-4/5/6 subfamily of cardiovascular transcription factors and the Myocardin/MKL-1/MKL-2 family of transcriptional coactivators. These data provided unanticipated insights into how cells populating the cardiovascular system transduce signals regulating development and response to hemodynamic stress. While fundamentally important at a basic level, this research has provided insights into the pathogenesis of cardiovascular diseases including atherosclerosis, aortic aneurysm and dissection, heart failure and congenital heart disease.
Rotation Projects for 2012-13
1. Characterization of the function of MKL2/MRTF-B in the heart and vasculature
2. Examine the molecular basis of myocardin function in the heart and in visceral and 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
Jian Li, MD - Senior Research Scientist
John Huang MD, PhD - Postdoctoral Research Fellow
Xiaohong Zhu - Senior Research Technician
Huang J, Elicker J, Bowens N, Liu X, Cheng L, Cappola TP, Zhu X: Myocardin regulates BMP10 expression and is required for heart development The Journal of Clinical Investigation 122 (10): 3678-91,2012.
Li J, Bowens N, Cheng L, Zhu X, Chen M, Hannenhalli S, Cappola TP: Myocardin-like protein 2 regulates TGFβ signaling in embryonic stem cells and the developing vasculature Development (Cambridge, England) 139 (19): 3531-42,2012.
Rong L, Liu J, Qi Y, Graham AM, Parmacek MS: GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation Molecular Biology of the Cell 23 (18): 3754-63,2012.
Rader DJ: Secreted miRNAs suppress atherogenesis Nature Cell Biology 14 (3): 233-5,2012.
Shen D, Li J, Lepore JJ, Anderson TJ, Sinha S, Lin AY, Cheng L, Cohen ED, Roberts JD Jr, Dedhar S, Parmacek MS: Aortic aneurysm generation in mice with targeted deletion of integrin-linked kinase in vascular smooth muscle cells Circulation Research 109 (6): 616-28,2011.
Huang J, Lu MM, Cheng L, Li J, Zhu X, Stout A, Chen M, Li J: Myocardin is required for cardiomyocyte survival and maintenance of heart function Proc Natl Acad Sci USA (106): 18734-18739,2009.
Parmacek MS: Cardiomyocyte Renewal N Engl J Med 2 (361): 86-8,2009.
Zhang Z, Goss AM, Cohen ED, Kadzik R, Lepore JJ, Muthukumaraswamy K, Yang J, DeMayo F, Whitsett JA, Parmacek MS: A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration Nature Genetics 40 (7): 862-70,2008.
Huang J, Cheng L, Li J, Chen M, Zhou D, Lu MM, Proweller A, Epstein JA: Myocardin regulates smooth muscle cell contractile genes required for closure of the ductus arteriosus J Clin Invest 118 (2): 515-25,2008.
Proweller A, Wright AC, Horng D, Cheng L, Lu MM, Lepore JJ, Pear WS: Notch signaling in vascular smooth muscle cells is required to pattern the cerebral vasculature Proc Natl Acad Sci USA 104 (41): 16275-80,2007.
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