Thomas Michel, M.D., PH.D.
|Title||Professor of Medicine|
|Institution||Brigham and Women's Hospital|
|Address||Brigham and Womens Hospital|
Thorn Building, room 1210A
75 Francis St
Boston MA 02115
|Title||Special Advisor to the Dean, Interdisciplinary Education|
|Institution||Harvard Medical School|
|Department||Office for Education|
Available: 06/29/11, Expires: 07/15/20
My lab uses biochemical and cell biological approaches to explore signal transduction pathways in the cells and tissues of the cardiovascular system, with a particular focus on the study of nitric oxide synthase pathways in endothelial cells and cardiac myocytes– and their alterations in disease states.
Nitric oxide (NO) is the active compound formed from important cardiovascular drugs such as nitroglycerin, and is synthesized in the body by a family of nitric oxide synthases. The endothelial isoform of nitric oxide synthase (eNOS) is a key signaling enzyme that is activated by cell surface receptors and modulates vascular smooth muscle relaxation, cardiac myocyte function, and platelet aggregation. My lab studies eNOS and related signaling pathways using biochemical and cellular imaging approaches in cultured cell systems and in mouse models of cardiovascular disease. We are using novel biosensors to understand the roles of reactive oxygen species in modifying eNOS signaling in cardiovascular physiology and pathophysiology. We also are exploring the roles of “statin” drugs (HMG CoA reductase inhibitors commonly used in the treatment of cardiovascular disease) on the targeting and protein associations of eNOS.
Student research projects in my lab involve basic investigations into the intracellular pathways that regulate eNOS and related signaling proteins in endothelial cells, cardiac myocytes, and blood platelets.
Available: 01/12/09, Expires: 01/12/19
Basic research studies using biochemical, molecular biological, and cell imaging approaches to understand the effects of oxidative stress, diabetes, and statins on signaling pathways in vascular endothelium and cardiac myocytes in murine and cultured cell systems, with a focus on nitric oxide synthase-modulated responses.
Available: 10/13/09, Expires: 11/20/18
My laboratory is interested in signal transduction pathways in the mammalian cardiovascular system, with a particular focus on nitric oxide synthases and G protein-coupled receptors in the vascular endothelium, bith in normal cells and in animal models of diabetes. Nitric oxide (NO) has been studied for years as the active compound formed from drugs such as nitroglycerin, but more recently a family of nitric oxide synthases was discovered to catalyze the formation of NO in diverse mammalian tissues. For the past several years, we have used biochemical and cell biological approaches to explore 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.
eNOS undergoes a complex pattern of post-translational regulation, including myristoylation, thiopalmitoylation, and phosphorylation. Some of the proteins that modulate eNOS signaling pathways are modified by statins, which are drugs that are widely used in treatment of cardiovascular disease. The covalent modifications of eNOS modulate the enzyme's subcellular targeting to specialized lipid-rich signal-transducing microdomains in the plasma membrane termed caveolae. Our current efforts are proceeding along several interdependent lines of investigation. In vascular endothelial cells, we are studying the enzymatic pathways that regulate eNOS palmitoylation, phosphorylation, and subcellular targeting, and are exploring novel protein-protein interactions that modulate eNOS enzyme activity. We are also investigating the interplay among protein kinases, G protein subunits and eNOS in plasmalemmal caveolae, and are studying the agonist-regulated translocation of eNOS, G protein subunits and associated signaling proteins using biochemical and cellular imaging approaches.
Available: 11/02/10, Expires: 07/01/15
Clinically important cardiovascular drugs such as nitroglycerin are metabolized in the body to form nitric oxide (NO), which exerts important physiological effects in vascular smooth muscle and in other tissues throughout the body. Reactive oxygen species such as hydrogen peroxide (H2O2) can have deleterious effects in the vasculature, but H2O2 also has many important roles in normal vascular homeostasis. The nitric oxide synthases are a family of enzymes that generate NO in the vascular wall, heart, brain, and throughout the body. Our studies have focused mostly on the endothelial isoform of NO synthase, a versatile enzyme that synthesizes both NO and reactive oxygen species, and which is post-translationally modified by phosphorylation and acylation. NO synthase signaling pathways are impaired in important vascular disease states such as diabetes and atherosclerosis. Statins importantly impact NO synthase activity and abundance, as well as both NO and H2O2 metabolism. Our laboratory is exploring NO-related signaling pathways in vascular endothelium and cardiac myocytes. We have a variety of ongoing research projects that explore the relationship between NO and H2O2 signaling in normal cells and in disease models including diabetes. Over the years, many medical students have pursued summer research projects in our lab, in several cases leading to medical school theses. Students with a background in biochemistry and cell biology who are seeking to pursue basic research into a fascinating signaling system with direct relevance to cardiovascular pathobiology are encouraged to read papers from our lab and to inquire about pursuing research studies here.
Available: 08/01/12, Expires: 09/26/14
Term-time and summer basic science cardiovascular research projects involving biochemical and cell biological approaches to the study of signaling pathways in endothelial cells, cardiac myocytes and blood platelets, with a focus on nitric oxide synthase signaling and their regulation by oxidative pathways and by statins.
Analysis of the Roles of Nitric Oxide and Nitric Oxide Synthases in Apoptosis
Summer, 05/22/00 - 08/31/00
Local representatives can answer questions about the Profiles website or help with editing a profile or issues with profile data. For assistance with this profile: HMS/HSDM faculty should contact Human Resources at faculty_serviceshms.harvard.edu.
Click the "See All" links for more information and interactive visualizations!
People who are also in this person's primary department.