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James J. Chou简历_Harvard Medical School, USAProf.James J. Chou受邀参会演讲_活动家

Posted on 2021年5月11日 By dongge

James J. Chou is a Professor in Biological Chemistry and Molecular Pharmacology at Harvard Medical School. He received his BS in Physics from University of Michigan at Ann Arbor; Ph.D. in Biophysics from Harvard University; and postdoctoral training from NIH. Since 2002, he joined the faculty at Harvard Medical School. Professor Chou’s group at Harvard pioneered the use of solution NMR spectroscopy to obtain structures of membrane ion channels, receptors and transporters. The biology community never thought this was possible but their work changed our view. His group’s first breakthrough was de novo structure determination of the 30 kDa pentameric assembly of phosphoplamban, a helical membrane protein that regulates heart muscle contractility (PNAS 2005, 102, 10870-10875). This work demonstrated for the first time that solution NMR is capable of generating a new structure of an intact helical membrane protein. In another application, his laboratory revealed the structural details of the membrane-associated region of the T cell receptor, which have important consequences for how we envision immune signals to be propagated across the cell membrane (Cell 2006, 127, 355-368; Cell 2008, 135, 702-713; Nature Immunology, 2010, 11, 1023-1029). Prof. Chou and his group also brought NMR to the age of nanotechnology, by developing a new liquid crystal made of DNA nanotubes for providing global structural restraints in NMR studies of membrane proteins (PNAS 2007, 104, 6644-6648). For quite a long period in history, many intense efforts have been made to determine the 3D structure of the M2 proton channel because it is the key target for finding effective drugs against influenza A virus. In 2008, he and his postdocs have successfully determined the long-sought structure. Meanwhile, they also discovered a novel allosteric mechanism of drug inhibition and drug resistance of the proton channel (Nature 2008, 451, 591-595; PNAS 2009, 106, 7379-7384). These discoveries have provided new insights and stimulated new strategies to overcome the drug resistance problem of flu. Recently, James Chou has made yet another breakthrough; his lab developed a new NMR method that enabled structure determination of UCP2, a 300-residue proton translocator in the inner membrane of mitochondria that resisted years of crystallization efforts. The new development, which includes fabrication of DNA nanotubes and RDC-based molecular fragment replacement, overcame many technical challenges involved in solving large membrane proteins by conventional NMR methods (Nature 2011, 476, 109-113). This NMR method will have strong impact on probing conformational switches of membrane transporters. Professor Chou has received many prestigious awards such as the Pew Scholar Award in Biomedical Sciences, the Smith Family Award, and the Genzyme Outstanding Achievement in Biomedical Science Award.

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