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. A family of nitric oxide synthases has been discovered to catalyze the formation of NO in diverse tissues. The Michel lab has focused on studying 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. Reactive oxygen species (ROS), including the stable ROS hydrogen peroxide, are intimately involved in the modulation of NO-dependent signaling pathways both in normal issues and in disease states. Insights into these disease states may be gained by a thorough understanding of the structural and regulatory features of the nitric oxide synthase signaling pathways and their interplay with the metabolism of ROS.
The Michel laboratory applies a broad range of experimental approaches to characterize intracellular signaling pathways in vascular endothelial cells and cardiac myocytes. Recently, he and his students and trainees have been exploiting novel biosensors to explore the role of hydrogen peroxide in control of NO signaling pathways in cardiovascular tissues and cells using cell imaging methods. His lab also studies the interplay among protein kinases, G protein subunits, eNOS and other signaling proteins in plasmalemmal caveolae and the cytoskeleton using biochemical, biophysical, and cellular imaging approaches. In addition, his laboratory has developed novel transgenic mouse models for the study of NO- and ROS-dependent signaling pathways.