Yabing Chen, PhD
Molecular and Cellular Pathology
University of Vermont
Regulation of vascular smooth muscle cells (VSMC) contributes significantly to the development of cardiovascular diseases, including atherosclerosis and pulmonary hypertension. Vascular calcification is a feature of advanced atherosclerosis, a process of differentiation of VSMC to “bone-like” cells that resembles the process of osteogenesis. Increased oxidative stress accelerates the progression of atherosclerosis and vascular calcification. Projects involve characterization of molecular signals that regulates osteogenic transcription factor Runx2 in vascular calcification, as well as mechanisms underlying Runx2 in modulating the pathogenesis of atherosclerosis and vascular calcification. We use cell culture systems and conditional Runx2 knock out mouse models to elucidate the definitive role of Runx2 in regulating vascular calcification, which may lead to novel strategies and targets to treat atherosclerosis. In pulmonary hypertension, VSMC play a central role in the structural remodeling of pulmonary arteries. Projects include the characterization of cross talk between innate immune signals and oxidative stress signaling in regulating vascular remodeling during pulmonary hypertension. Studies involve in vitro cell culture and in vivo mouse models. Mechanisms underlying phospholipase C gamma-mediated calcium signaling in bone formation and resorption highlight Dr. Chen’s interest in bone research. Tissue specific gene knockout mice will be used to determine the function of phospholipase C gamma in regulating skeletal development. In collaboration with Dr. Jay M McDonald, we investigate the mechanism by which calmodulin regulates Fas-mediated apoptosis in cholangiocarcinoma. Projects include defining the role of calmodulin in regulating formation of Fas-induced death inducing signaling complex in cholangiocarcinoma cells and in the pathogenesis of cholangiocarcinoma in animal models.
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