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Thomas Mark Michel, MD, PhD
Senior Physician, Brigham and Women's Hospital
Professor of Medicine, Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
Cardiovascular
75 Francis Street
Boston, MA 02115

Research Location: Thorn Research Building

Research Email: thomas_michel@hms.harvard.edu

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Research Narrative:

Dr. Thomas Michel's laboratory studies signal transduction pathways in the cardiovascular system, with a particular focus on nitric oxide synthases and intracellular oxidant pathways. 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 and cardiac myocytes, from analyses of subcellular targeting to explorations of novel protein modifications.  His lab also studies the interplay among protein kinases, intracellular oxidants, eNOS and other signaling proteins using biochemical, biophysical, and cellular imaging approaches.  In addition, his laboratory has developed novel chemogenetic approaches and exploited informative biosensors to study the interplay of intracellular oxidants and NO-modulated pathways in the control of cell signaling  in normal cardiovascular tissues and in pathophysiological states caused by oxidative stress.

 


Education:
Duke University, 1984, MD
Duke University, 1983, PhD (Biochemistry)
Harvard Colege, 1977, A.B.

Courses Taught:
Spring semester, annually, HMS, BCMP234, Cellular metabolism and human disease

annually in July, BWH/HMS Catalyst, Models of Disease Boot Camp, 3 week boot camp for physician-scientists completing their clinical subspecialty training and returning to the lab for a basic/translational research fellowship


Publications (Pulled from Harvard Catalyst Profiles):

1. Steinhorn B, Sorrentino A, Badole S, Bogdanova Y, Belousov V, Michel T. Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction. Nat Commun. 2018 10 02; 9(1):4044.

2. Steinhorn B, Sartoretto JL, Sorrentino A, Romero N, Kalwa H, Abel ED, Michel T. Insulin-dependent metabolic and inotropic responses in the heart are modulated by hydrogen peroxide from NADPH-oxidase isoforms NOX2 and NOX4. Free Radic Biol Med. 2017 12; 113:16-25.

3. Kinlay S, Michel T, Leopold JA. The Future of Vascular Biology and Medicine. Circulation. 2016 Jun 21; 133(25):2603-9.

4. Goettsch C, Hutcheson JD, Aikawa M, Iwata H, Pham T, Nykjaer A, Kjolby M, Rogers M, Michel T, Shibasaki M, Hagita S, Kramann R, Rader DJ, Libby P, Singh SA, Aikawa E. Sortilin mediates vascular calcification via its recruitment into extracellular vesicles. J Clin Invest. 2016 Apr 01; 126(4):1323-36.

5. Machlus KR, Wu SK, Stumpo DJ, Soussou TS, Paul DS, Campbell RA, Kalwa H, Michel T, Bergmeier W, Weyrich AS, Blackshear PJ, Hartwig JH, Italiano JE. Synthesis and dephosphorylation of MARCKS in the late stages of megakaryocyte maturation drive proplatelet formation. Blood. 2016 Mar 17; 127(11):1468-80.

6. Wang L, Hagemann TL, Kalwa H, Michel T, Messing A, Feany MB. Nitric oxide mediates glial-induced neurodegeneration in Alexander disease. Nat Commun. 2015 Nov 26; 6:8966.

7. Steinhorn BS, Loscalzo J, Michel T. Nitroglycerin and Nitric Oxide--A Rondo of Themes in Cardiovascular Therapeutics. N Engl J Med. 2015 Jul 16; 373(3):277-80.

8. Kraus BJ, Sartoretto JL, Polak P, Hosooka T, Shiroto T, Eskurza I, Lee SA, Jiang H, Michel T, Kahn BB. Novel role for retinol-binding protein 4 in the regulation of blood pressure. FASEB J. 2015 Aug; 29(8):3133-40.

9. Tarrago L, Péterfi Z, Lee BC, Michel T, Gladyshev VN. Monitoring methionine sulfoxide with stereospecific mechanism-based fluorescent sensors. Nat Chem Biol. 2015 May; 11(5):332-8.

10. Barroso M, Florindo C, Kalwa H, Silva Z, Turanov AA, Carlson BA, de Almeida IT, Blom HJ, Gladyshev VN, Hatfield DL, Michel T, Castro R, Loscalzo J, Handy DE. Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression. J Biol Chem. 2014 May 30; 289(22):15350-62.