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Dr. Michael T. Chin is interested in the genetic regulation of cardiovascular development and the role of developmental mechanisms in adult cardiovascular disease.  He has previously identified two novel bHLH transcription factors, CHF1 and CHF2, which are expressed predominantly in the developing cardiovascular system.  CHF1 is expressed primarily in the developing ventricle and arterial vasculature, while CHF2 is expressed primarily in the developing atria.  Dr. Chin’s work has demonstrated that these proteins function as transcriptional repressors and are important regulators of cardiovascular development, cardiac hypertrophy and the development of occlusive vascular disease.  Currently, his laboratory has three major areas of interest: 1. to determine the molecular mechanisms by which CHF1 regulates the development of the interventricular septum, myocardium and vasculature; 2. to determine the molecular mechanisms by which CHF1 affects the smooth muscle proliferative response after vascular injury; and 3. to determine the molecular mechanisms by which CHF1 regulates the myocardial response to hypertrophic stimuli and the subsequent progression to heart failure.  Ongoing projects within the laboratory include generation of CHF1 conditional knockout mice, assessing these mice for developmental phenotypes, testing of these mice in various models of vascular injury, angiogenesis and hypertrophy, and isolation and characterization of primary endocardial cushion, cardiac myocyte, vascular smooth muscle and  endothelial cells from these mice for in vitro assessment of cell function and molecular phenotype. We are also using these in vitro assays to test the ability of small molecules to rescue aspects of the CHF1 null phenotype.  These studies should further our understanding of cardiovascular development and its relationship to adult cardiovascular disease. 

            Sun J, Kamei CN, Layne MD, Jain MK, Liao JK, Lee M-E, Chin MT.  Regulation of myogenic terminal differentiation by the hairy-related transcription factor CHF2.  J Biol Chem 2001;276:18591-18596.

Sakata Y, Kamei CN, Nakagami H, Bronson R, Liao JK, Chin MT. Ventricular  septal defects and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2. Proc. Natl. Acad. Sci. USA 2002; 99: 16197-16202.

Sakata Y, Xiang F, Chen Z, Kiriyama Y, Kamei CN, Simon DI and Chin MT. Transcription factor CHF1/Hey2 regulates neointimal formation in vivo and vascular smooth muscle proliferation and migration in vitro. Arterioscler Thromb Vasc Biol 2004; 24: 2069-2074.

Sakata Y, Koibuchi N, Xiang F, Youngblood JM, Kamei CN and Chin MT. The Spectrum of Cardiovascular Anomalies in CHF1/Hey2 Deficient Mice Reveals Roles in Endocardial Cushion, Myocardial and Vascular Maturation. J. Mol. Cell. Cardiol. 2006; 40: 267-273.

Xiang F, Sakata Y,Cui L, Youngblood JM, Nakagami H, Liao JK, Liao R and Chin MT. Transcription  factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4. Am. J. Physiol. Heart Circ. Physiol. 2006; 290: H1997-H2006.

Koibuchi N and Chin MT. CHF/Hey2 plays a pivotal role in left ventricular maturation through suppression of ectopic atrial gene expression. Circulation Research, in press, 2007.

Shirvani S, Mookanamparambil L, Ramoni MF and Chin MT. Transcription factor CHF1/Hey2 regulates the global transcriptional response to platelet-derived growth factor in vascular smooth muscle cells. Physiological Genomics, in press, 2007.