Dr. John Mercer
The CCBD group is focused on inherited cardiomyopathies to better understand cardiovascular disease. Our international collaboration is led by Jim Spudich (Stanford University, NCBS & inStem) and includes Norio Nakatsuji (iCeMS, Kyoto), Kouichi Hasegawa (iCeMS and inStem), R.Sowdhamini (NCBS), Maneesha Inamdar (JNCASR and inStem) and K.VijayRaghavan (NCBS). Our primary interest is to understand how changing a single amino-acid residue in a sarcomeric protein (myosin, actin, tropomyosin or the troponins) causes dilated or hypertrophic inherited cardiomyopathy. Focusing on alpha-tropomyosin and troponin T, our initial approach is to detect functional changes using binding and fluorescence assays, in vitro motility assays, laser trapping, and single-cell contractility assays. These contractility assays require the production of cardiomyocytes, the source can be from patient induced pluripotential stem cells (iPSC) or from genetically-modified embryonic stem cells (ESC). Our goal is to group the mutants mechanistically to facilitate the development of small molecule treatments. Our team also studies cytoskeletal remodeling during hypertrophy and developmental aspects of cardiac disease. This work is funded by the Shanta Wadhwani Centre for Cardiac and Neural Research and by inStem intramural funds.