Anthony J. Muslin, M.D.

DEPARTMENT OF Internal Medicine
Keywords: cardiovascular physiology, cell signaling, development, signal transduction, stem cell, vascular biology

My research focuses on the regulation of growth factor signal transduction cascades and the role of these cascades in the pathogenesis of congestive heart failure and atherosclerotic vascular disease. My group established a series of murine transgenic and knockout models of altered signal transduction to determine the role of G proteins, scaffolding molecules, and protein kinases in the pathogenesis of cardiovascular disease. In particular, we recently generated mice with targeted disruption of the RGS3 and RGS4 genes that encode proteins that deactivate heterotrimeric G proteins. In addition, we are analyzing the cardiovascular phenotypes of mice with targeted disruption of the Akt1 and Akt2 protein kinases and the 14-3-3 adaptor proteins that are involved in the regulation of cell growth, metabolism, and survival. We utilize experimental murine models of hypertension, hyperlipidemia, myocardial infarction, vascular injury, and exercise training. Our phenotypic analysis of these mice includes transthoracic echocardiography, cardiac catheterization, electrophysiological studies, ex vivo hanging heart studies, PET scanning, proteomics and metabolomics. We also utilize chemical biology robotic screening techniques to identify novel pathways involved in the pathogenesis of atherosclerosis and congestive heart failure. For example, we recently identified over 20 compounds that inhibit foam cell formation in cultured macrophages by use of a fluorescently-labeled form of modified low density lipoprotein.