Gregory A. Petsko
Harvard University
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Primary Section: 29, Biophysics and Computational Biology Secondary Section: 21, Biochemistry Membership Type:
Member
(elected 1995)
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Biosketch
Gregory A. Petsko is Professor of Neurology in the Ann Romney Center for Neurologic Diseases at Harvard Medical School and Brigham & Women’s Hospital in Boston, and Adjunct Professor of Biomedical Engineering at Cornell University. He has been elected to the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society. He is Past-President of the American Society for Biochemistry and Molecular Biology and of the International Union of Biochemistry and Molecular Biology. He has founded several publicly traded companies and serves on the advisory boards of MeiraGTx, Retromer Therapeutics, Amicus Therapeutics, Proclara Biosciences, and Annovis Bio. His current work aims to develop treatments for the major neurodegenerative diseases, including ALS (Lou Gehrig’s), Alzheimer’s, and Parkinson’s. His public lectures on brain health have attracted a wide audience (one of his TED talks has been viewed over a million times). He has also written a widely-read column on science and society, the first ten years of which are available in book form. He admits, however, that the columns guest-written by his two dogs, Mink and Clifford, are more popular than those he writes himself.
Research Interests
For over forty years, I have been trying to understand how enzymes achieve their extraordinary catalytic power. I began by developing X-ray crystallographic methods for direct observation of productive enzyme-substrate and enzyme-intermediate complexes, which led to general techniques for studying protein crystal structures at very low temperatures. I used these methods to obtain atomic-resolution information about several enzyme intermediates. I also discovered that protein flexibility could be studied crystallographically, and mapped the spatial distribution of protein motions as a function of temperature. In collaboration with Professor Dagmar Ringe of Brandeis University, I extended this work, helping develop methods for time-resolved protein crystallography, and finally applied all of these techniques to obtain the first time-lapse pictures, at atomic resolution, of an enzyme (cytochrome P450) in action. In 2003 Dagmar and I completely changed the direction of our joint research program to focus on finding treatments for the major age-related neurodegenerative diseases: Alzheimer’s, Parkinson’s, and ALS. We took an integrative biology approach that combined structural biology with genetics, biochemistry, and cell biology to identify novel targets and develop novel therapeutics. The first result was a gene therapy for the most common forms of ALS, which is about to be tested in humans. In 2005 we began to collaborate with Dr. Scott Small of Columbia University, a pioneer in anatomical neurobiology who first linked endosomal protein trafficking to neurodegeneration, and together we identified potential small molecule and gene therapies for Alzheimer’s and Parkinson’s diseases, which are also nearing human clinical trials.
