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Welcome to the Michel Lab Website!        

My lab explores signal transduction pathways in the cells and tissues of the cardiovascular system. We have a particular focus on applying biochemical methods and cell imaging approaches using informative biosensors to probe nitric oxide synthase signaling pathways and their interactions with reactive oxygen species in endothelial cells and cardiac myocytes, studying cultured cell systems, animal models of cardiovascular disease states, and human cells and tissues.

Some of our recent studies have exploited novel biosensors in cellular imaging studies to explore the relationship between nitric oxide and reactive oxygen species.  For example

  • We have been studying receptor-modulated nitric oxide (NO) and hydrogen peroxide (H2O2) metabolism using live cell imaging approaches in cardiac myocytes and in endothelial cells.
  • We have also been exploring the roles of “statin” drugs (HMG CoA reductase inhibitors commonly used in the treatment of cardiovascular disease) in eNOS and H2O2 signaling
  • We developed “chemogenetic” approaches that allow us to selectively generate oxidative stress in cardiac myocytes or vascular endothelial cells in vivo using a yeast D-amino acid oxidase, which generates hydrogen peroxide when provided with D-amino acids. We can generate heart failure in transgenic mice expressing DAAO in the heart simply by providing D-alanine in the animals’ drinking water.
  • We are using similar chemogenetic approaches along with multispectral imaging technologies to probe the roles of hydrogen peroxide in endothelial signal transduction pathways that modulate nitric oxide.

Lab Members

My team is made up of post docs and students from around the world

Left to right : Jonas Kaynert, Sai Thulabandu, Taylor Covington, Markus Waldeck-Weiermair, Thomas Michel, Shambhu Yadav, Fotios Spyropoulos, Arvind Pande

PUBLICATIONS

Selected recent reports

  • Andrea Sorrentino, Benjamin Steinhorn, Luca Troncone, Seyed Soheil Saravi, Sachin L Badole, Emrah Eroglu, Marie Foley Kijewski, Sanjay Divakaran, Marcelo Di Carli, Thomas Michel. Reversal of heart failure in a chemogenetic model of persistent cardiac redox stress AJP-Heart and Circulatory Physiology, 2019
  • Steinhorn B, Sartoretto J, Sorrentino A, Kalwa H, Romero N, 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, 113:16-25.
  • Tarrago L, Péterfi Z , Lee BC, Michel T, and Gladyshev V. Monitoring methionine sulfoxide with stereospecific mechanism-based fluorescent sensors. Nature Chem Biol 2015, 11: 332-338. PMID: 25799144.
  • Kalwa H, Sartoretto J, Martinelli R, Romero N, Steinhorn B, Tao M, Ozaki K, Carman C, Michel T A central role for hydrogen peroxide in P2Y1 ADP receptor-mediated cellular responses in vascular endothelium. Proc Nat Acad Sci USA 2014, Mar 4;111(9):3383-8. doi: 10.1073/pnas.1320854111.  PMID:24550450
  • Steinhorn B, Loscalzo J and Michel T. Rondo in E: Nitroglycerin, nitric oxide, and endothelial therapeutics.  New England Journal of Medicine  2015; 373:277-280.

Contact

If you wish to get in touch, use the form below, or write me an e-mail

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    Whats Up?

    We are located in the Thorn Building at Brigham and Women’s Hospital.

    Snail mail address
    Brigham and Women’s Hospital, Cardiovascular Division,
    Harvard Medical School
    75 Francis Street, Thorn Building, Room 1210A,
    Boston MA, 02115, USA

    Phone: 617-732-7376

    E-mail: thomas_michel@hms.harvard.edu

    Directions:

    From the HMS Quadrangle, cross Shattuck Street (behind Gordon Hall) and enter the Brigham and find your way to the BWH Pike (the long hallway that runs the length of the Brigham).  The entrance to the Thorn Building is midway between the old PBBH building and the Hospital Tower.  Ask the security guard to let you in (entrance is staffed 7AM-5PM weekdays); you will probably need to show I.D. or have me called at 617-732-7376.  Take the Thorn elevators to the 12th floor, turn left down the hall to room 1210, and walk through the lab to reach my office, room 1210A.

    Via the M2 shuttle from Harvard/MIT, get off at the final stop (Vanderbilt Hall), and cross Longwood Avenue to arrive at the base of HMS Quadrangle.  Walk the length of the Quad, and go behind Gordon Hall at the head of the Quad to find yourself on Shattuck Street (more an alley than a proper street).  You will now be facing the various buildings of the Brigham.  The best entrance is reached by crossing left diagonally across Shattuck Street, walk up the steps and go down the hall to find yourself in the rotunda of the old Peter Bent Brigham Hospital.  Go down the Pike to your right (ask the security guard if it’s not clear to you), and you will find the entrance to the Thorn Building ~100 yards down the Pike on your right.  Then follow the directions above.

    By public transportation (MBTA Green Line E train), get off at the Brigham Circle stop, and walk into the PBBH entrance, and find your way down the Pike to the Thorn Building entrance.

    If coming by car, park (valet) at the 45 Francis Street (Ambulatory) entrance, and go through the Cabot Atrium to find the Pike beyond, turn right, and you will soon find your way to the Thorn Building entrance on your left.