Cardiovascular Signal Transduction Dr. Thomas Michel's laboratory studies signal transduction pathways in the cardiovascular system, with a particular focus on nitric oxide synthases and G protein-coupled receptors. Nitric oxide (NO) has been studied for many years as the active compound that is formed from important cardiovascular drugs such as nitroglycerin, More recently it was discovered that a family of nitric oxide synthases catalyze the formation of NO in diverse tissues. His lab has studied the endothelial isoform of nitric oxide synthase (eNOS), a key signaling enzyme that is activated by a variety of cell surface receptors and is involved in the control of vascular smooth muscle relaxation and platelet aggregation. Endothelium-dependent vascular smooth muscle relaxation is altered or impaired in models of atherosclerosis, hypertension, diabetes and hypercholesterolemia. Insights into these disease states may be gained by a thorough understanding of the structural and regulatory features of the endothelial cell nitric oxide synthase signaling system.
Dr. Michel's laboratory applies a broad range of experimental approaches to characterize intracellular signaling pathways in vascular endothelial cells, from analyses of subcellular targeting to explorations of novel protein modifications that modulate eNOS enzyme activity. His lab also studies the interplay among protein kinases, G protein subunits, eNOS and other signaling proteins in plasmalemmal caveolae using biochemical, biophysical, and cellular imaging approaches. In addition, his laboratory has developed novel transgenic mouse models for the study of NO-dependent signaling pathways.
Dr. Michel is also the Principal Investigator of an NIH Program Project Grant that engages the efforts of several BWH-basic investigators in basic research studies of the molecular basis of diabetic vasculopathy.
References:
Gonzalez E, Kou R and Michel T. Rac1 and modulation of PI3-kinase pathways in vascular endothelial cells. J Biol Chem 2006, 281:3210-3216.
Erwin PA, Mitchell D, Sartoretto J, Marletta M and Michel T. Subcellular targeting and S-nitrosylation of endothelial nitric oxide synthase. J Biol Chem 2006, 281:151-157.
Dudzinski D, Igarashi J, Greif D and Michel T. Pharmacology and molecular regulation of nitric oxide synthases. Annu Rev Pharmacol Toxicol, 2006, 46:235-276.
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