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JOHN SHYY, PH.D.Professor of Biomedical Sciences
Ph.D., Ohio State University
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Research Summary
The major aim of my research is to elucidate the molecular mechanisms by which fluid shear stress and mechanical stretch activate gene expression in cells in the cardiovascular system. A variety of devices have been designed and engineered to subject a monolayer of cultured endothelial cells, vascular smooth muscle cells, and cardiac myocytes to well-defined mechanical forces. These include a rectangular flow channel with a uniform shear stress, a tapered flow channel with shear stress varying along the channel length, a step flow channel with disturbed flow patterns to stimulate vessel branch regions, and a cyclic stretch device to apply uniform biaxial strain to simulate oscillatory pressure. The expression of a number of genes related to atherogenesis, hypertension and hypertrophy, as well as the upstream signal transduction in response to variations in the magnitude of shear stress and stretch and flow pattern is studied. We have identified a number of genes related to atherogenesis, hypertension, abdominal aortic aneurysm, and hypertrophy, which are particularly activated by well-defined mechanical stimuli. Transgenic approaches are currently underway to test the function of genes in the pathogenic processes of these diseases. |
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Selected Publications
Lin, T., L. Zeng, Y. Liu, K. DeFea, M. A. Schwartz, S. Chien, and J. Y-J. Shyy. The Rho-ROCK-LIMK-Cofilin pathway regulates shear stress activation of sterol regulatory element binding proteins. Circ. Res. 92:1296-1304, 2003.
Zeng, L., Y. Zhang, S. Chien, X. Liu, and J. Y-J. Shyy. Deacetylation of p53 by laminar flow: The role in p21Waf1 regulation. J. Biol. Chem. 278:24594-24599, 2003.
Zhou, R-H., T-S. Lee, T-C. Tsou, F. Rannou, Y-S. Li, S. Chien, and J. Y-J. Shyy. Stent implantation activates Akt in the vessel wall: The role of mechanical stretch in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 23:2015-2020, 2003.
Rannou, F., T-S. Lee, R-H. Zhou, J. Chin, J. C. Lotz, M. Mayoux-Benhamou, J. P. Barbet, A. Chevrot, and J Y-J. Shyy. Intervertebral disc degeneration: The role of the mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload. Am. J. Pathol. 164: 915-924, 2004.
Zeng, L., M. Lu, K. Mori, S. Luo, A. S. Lee, Y. Zhu, and J. Y-J. Shyy. ATF6 modulates SREBP2-mediated lipogenesis. EMBO J. 23:950-958, 2004. Liu, Y., Y. Zhu, F. Rannou, T-S. Lee, K. Formentin, L. Zeng, X. Yuan, Y. Zhu, N. Wang, S. Chien, B. Forman, and J. Y-J. Shyy. Laminar flow activates peroxisome proliferator-activator receptor gamma in vascular endothelial cells. Circulation. 110:1128-1133, 2004.
Lee, T-S., C-C. Chang, Y. Zhu, and J. Y-J. Shyy. Simvastatin induction of heme oxygenase-1: A novel mechanism of vessel protection. Circulation 110:1296-1302, 2004.
Zhou, R-H., M. Yao, T-S. Lee, Y. Zhu, M. Martins-Green, and J. Y-J. Shyy. Vascular endothelial growth factor activation of sterol regulatory element binding protein: a potential role in angiogenesis. Circ. Res. 95: 471-478, 2004.
Published On-Line Data:
Oxidative Stress is Involved in the Development of Experimental Abdominal Aortic Aneurysm: A Study of the Transcription Profile by cDNA Microarray |
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