Gregory Petsko

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Greg Petsko
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Born (1948-08-07) August 7, 1948 (age 75)
Washington, D.C., USA
Education Princeton University (BS)
Merton College, Oxford (MS, PhD)
Spouse Laurie Glimcher [1]
Awards Rhodes Scholarship
Member of the U.S. National Academy of Sciences
Member of the U.S. National Academy of Medicine
Member of the American Academy of Arts and Sciences
Member of the American Philosophical Society
Scientific career
Institutions Harvard Medical School
Brigham and Women's Hospital
Weill Cornell Medical College
Cornell University
Brandeis University
Wayne State University School of Medicine
MIT
Max Planck Institute
University of Oxford
Princeton University
Thesis Structural studies of triose phosphate isomerase.  (1974)
Doctoral advisor David Chilton Phillips
Website Official website

Gregory A. Petsko (born August 7, 1948) is an American biochemist and member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society. He is currently Professor of Neurology at the Ann Romney Center for Neurologic Diseases at Harvard Medical School and Brigham and Women's Hospital. He formerly had an endowed professorship (the Arthur J. Mahon Chair) in Neurology and Neuroscience at Weill Cornell Medical College and is still an adjunct professor of Biomedical Engineering at Cornell University, and is also the Gyula and Katica Tauber Professor, Emeritus, in biochemistry and chemistry at Brandeis University. On October 24, 2023, in a ceremony in the East Room of the White House, President Joe Biden presented Gregory Petsko and eight others with the National Medal of Science, the highest honor the United States can bestow on a scientist and engineer.

Contents

As of 2020 Petsko's research interests are understanding the biochemical bases of neurological diseases like Alzheimer's, Parkinson's, and ALS, discovering drugs (especially by using structure-based drug design) and biologics, especially gene therapy, that could therapeutically affect those biochemical targets, and seeing any resulting clinical candidates tested in humans. He has made key contributions to the fields of protein crystallography, biochemistry, biophysics, enzymology, and neuroscience.

Education

Petsko was an undergraduate at Princeton University, where he graduated summa cum laude in 1970. He received a Rhodes Scholarship, and obtained his doctorate in Molecular Biophysics from Merton College, Oxford supervised by David Phillips, studying the structure and mechanism of the enzyme triosephosphate isomerase.

He did a brief postdoctoral fellowship in Paris with Pierre Douzou, studying enzymology at low temperatures. In 1996 he did a sabbatical at the University of California at San Francisco with Ira Herskowitz, where he learned yeast genetics and molecular biology with the support of a Guggenheim Foundation Fellowship.

Career

President Joe Biden awards the National Medal of Science to Professor Gregory A. Petsko of Harvard Medical School and Brigham & Women's Hospital on October 24, 2023. Photo by Jay Premack/USPTO. President Biden awards the National Medal of Science to Professor Gregory A. Petsko of Harvard Medical School and Brigham & Women's Hospital.jpg
President Joe Biden awards the National Medal of Science to Professor Gregory A. Petsko of Harvard Medical School and Brigham & Women's Hospital on October 24, 2023. Photo by Jay Premack/USPTO.

Petsko's independent academic career has included stints at Wayne State University School of Medicine, the Massachusetts Institute of Technology, the Max Planck Institute for Medical Research in Heidelberg, and, from 1991 until 2012, Brandeis University, where he was Professor of Biochemistry and of Chemistry and director of the Rosenstiel Basic Medical Sciences Research Center. He is past-president of the American Society for Biochemistry and Molecular Biology and of the International Union of Biochemistry and Molecular Biology. He is an elected member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences. He is a foreign member of the Hungarian Academy of Sciences and has an honorary Doctor of Laws from Dalhousie University. In April 2010, he was elected to the American Philosophical Society. [2] In 2012, he announced that he was moving to Weill Cornell Medical College in New York City, where his wife, the world-renowned immunologist Dr. Laurie Glimcher, had been appointed dean. [3] He was appointed at Weill Cornell Medical College as the director of the Helen and Robert Appel Alzheimer's Disease Research Institute and the Arthur J. Mahon Professor of Neurology and Neuroscience in the Feil Family Brain and Mind Research Institute, and at Cornell University as adjunct professor of Biomedical Engineering, and retained an appointment at Brandeis University as Gyula and Katica Tauber Professor of Biochemistry and Chemistry, Emeritus. [4] [5] His wife was named president and CEO of the Dana–Farber Cancer Institute in October 2016, and in January 2019 he followed her back to Boston, assuming his present position as Professor of Neurology at the Ann Romney Center for Neurologic Diseases at Brigham and Women's Hospital and Harvard Medical School. On October 24, 2023, he and eight other scientists received the National Medal of Science from President Joe Biden. The National Medal of Science is the highest honor the United States can confer on a scientist; since the first was awarded in 1963 by President John F. Kennedy, only 506 individuals have received it.

Research

Petsko's current research interests are understanding the biochemical bases of neurological diseases like Alzheimer's, Parkinson's, and ALS, discovering drugs (especially by using structure-based drug design) that could therapeutically affect those biochemical targets, and seeing any resulting drug and gene therapy candidates tested in humans. [5] [6]

Petsko's past research interests [7] have been in protein crystallography and enzymology. He is co-author with Dagmar Ringe of Protein Structure and Function. [8] He was also the author of a monthly column in Genome Biology [9] [10] modelled after an amusing column in Current Biology penned by Sydney Brenner. [11] The first ten years of that column are available as an eBook. [12]

Petsko is best known for his collaborative work with Dagmar Ringe, in which they used X-ray crystallography to solve important problems in protein function including protein dynamics as a function of temperature and problems in mechanistic enzymology, [13] [14] [15] and for his collaborative work with Dr. Scott Small of Columbia University, which focuses on the retromer endosomal protein trafficking pathway and its role in Alzheimer's and Parkinson's diseases. [16] [17] [18] [19] [20] [21] [22] [23] [24]

At MIT and Brandeis, he and Dagmar Ringe trained a large number of current leaders in structural molecular biology who now have leadership roles in science. These individuals include:

Related Research Articles

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Vacuolar protein sorting ortholog 35 (VPS35) is a protein involved in autophagy and is implicated in neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). VPS35 is part of a complex called the retromer, which is responsible for transporting select cargo proteins between vesicular structures and the Golgi apparatus. Mutations in the VPS35 gene (VPS35) cause aberrant autophagy, where cargo proteins fail to be transported and dysfunctional or unnecessary proteins fail to be degraded. There are numerous pathways affected by altered VPS35 levels and activity, which have clinical significance in neurodegeneration. There is therapeutic relevance for VPS35, as interventions aimed at correcting VPS35 function are in speculation.

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Huda Yahya Zoghbi, born Huda El-Hibri, is a Lebanese-born American geneticist, and a professor at the Departments of Molecular and Human Genetics, Neuroscience and Neurology at the Baylor College of Medicine. She is the director of the Jan and Dan Duncan Neurological Research Institute. She became the editor of the Annual Review of Neuroscience as of 2018.

Laurie Hollis Glimcher is an American physician-scientist who was appointed president and CEO of Dana–Farber Cancer Institute in October 2016. She was elected a Member of the American Philosophical Society in 2019.

Maria Grazia Spillantini, is Professor of Molecular Neurology in the Department of Clinical Neurosciences at the University of Cambridge. She is most noted for identifying the protein alpha-synuclein as the major component of Lewy bodies, the characteristic protein deposit found in the brain in Parkinson's disease and dementia with Lewy bodies. She has also identified mutations in the MAPT gene as a heritable cause for frontotemporal dementia.

Maiken Nedergaard is a Danish neuroscientist most well known for discovering the glymphatic system. She is a jointly appointed professor in the Departments of Neuroscience and Neurology at the University of Rochester Medical Center. She holds a part-time appointment in the Department of Neurosurgery within the University of Rochester Center for Translational Neuromedicine, where she is the principal investigator of the Division of Glial Disease and Therapeutics laboratory. She is also Professor of Glial Cell Biology at the University of Copenhagen, Center for Translational Neuromedicine.

David Chaim Rubinsztein FRS FMedSci is the Deputy Director of the Cambridge Institute of Medical Research (CIMR), Professor of Molecular Neurogenetics at the University of Cambridge and a UK Dementia Research Institute Professor.

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Elizabeth Mary Claire Fisher is a British geneticist and Professor at University College London. Her research investigates the degeneration of motor neurons during amyotrophic lateral sclerosis and Alzheimer's disease triggered by Down syndrome.

Donald L. Price (1935-2023) was an American neuropathologist and professor at the Johns Hopkins School of Medicine. His research aimed to understand the molecular basis of neurodegenerative diseases, particularly Alzheimer’s disease. Price received a number of awards for his work and served as the President of both the American Association of Neuropathologists and the Society for Neuroscience.

Lary Walker is an American neuroscientist and researcher at Emory University in Atlanta, Georgia. He is Associate Director of the Goizueta Alzheimer's Disease Research Center at Emory, and he is known for his research on the role of abnormal proteins in the causation of Alzheimer’s disease.

<span class="mw-page-title-main">Dagmar Ringe</span> American biochemist, educator

Dagmar Ringe is an American biochemist, educator, and researcher. She is the Harold and Bernice Davis Professor in Aging and Neurodegenerative Disease at Brandeis University in Waltham, Massachusetts, and holds appointments in the departments of chemistry and biochemistry.

<span class="mw-page-title-main">Scott A. Small</span> American neurologist and neuroscientist

Scott A. Small is an American neurologist and neuroscientist known for his work in Alzheimer's disease and normal cognitive aging. His research focuses on the hippocampus, a circuit in the brain targeted by Alzheimer's disease, aging, and schizophrenia. Small is the Director of the Alzheimer's Disease Research Center at Columbia University, where he is the Boris and Rose Katz Professor of Neurology. He is also appointed in Radiology and in Psychiatry, where he directs the Schizophrenia Research program.

Gerard David Schellenberg is an academic neuropathologist who specializes in the research of Alzheimer's disease. He is the director of Penn Neurodegeneration Genomics Center as well as a professor of Pathology and Laboratory Medicine at the University of Pennsylvania. He is a leading contributor to Alzheimer's disease research.

Li Gan is a neuroscientist and professor at Weill Cornell Medical College. She is known for her discovery of pathogenic tau protein acetylation in tauopathies and mechanisms of microglia dysfunction in neurodegeneration.

Constance Joan Jeffery is an American biophysicist and an associate professor of biological sciences at the University of Illinois Chicago. She was elected a fellow of the American Association for the Advancement of Science in 2022. Jeffery is known for her work with multifunctional proteins.

References

  1. ↑ Bailey, Melissa (2016-03-01). "Recruited to lead Harvard med, 'fearless' scientist chose Dana-Farber". STAT. Retrieved 2023-01-02.
  2. ↑ "Biochemist Greg Petsko elected to American Philosophical Society".
  3. ↑ Tate Herbert for The Justice November 13, 2012 Petsko set to leave University for New York City in 2014
  4. ↑ Weill Cornell Newsroom. April 16, 2014 No Stone Unturned: Interview with Gregory Petsko
  5. 1 2 Petsko Laboratory Homepage
  6. ↑ Columbia University Newsroom. April 20, 2014 'Chaperone' compounds offer new approach to Alzheimer's treatment
  7. ↑ Gregory Petsko publications indexed by Microsoft Academic
  8. ↑ Petsko, Gregory A. (2008). Protein Structure and Function (Primers in Biology). Oxford [Oxfordshire]: Oxford University Press. ISBN   978-0-19-955684-7.
  9. ↑ Petsko, G. A. (2010). "A Faustian bargain". Genome Biology. 11 (10): 138. doi: 10.1186/gb-2010-11-10-138 . PMC   3218652 . PMID   21062515.
  10. ↑ Petsko, G. A. (2011). "Food of the dogs". Genome Biology. 12 (7): 122. doi: 10.1186/gb-2011-12-7-122 . PMC   3218821 . PMID   21787380.
  11. ↑ Brenner, S. (2002). "The worm's turn". Current Biology. 12 (21): R713. doi: 10.1016/s0960-9822(02)01241-1 . PMID   12419193.
  12. ↑ Petsko, Gregory (2010-10-10). Gregory Petsko in Genome Biology: The first 10 years. BioMed Central.
  13. ↑ Frauenfelder, H.; Petsko, G. A.; Tsernoglou, D. (1979). "Temperature-dependent X-ray diffraction as a probe of protein structural dynamics". Nature. 280 (5723): 558–563. Bibcode:1979Natur.280..558F. doi:10.1038/280558a0. PMID   460437. S2CID   4280206.
  14. ↑ Schlichting, I.; Berendzen, J.; Chu, K.; Stock, A. M.; Maves, S. A.; Benson, D. E.; Sweet, R. M.; Ringe, D.; Petsko, G. A.; Sligar, S. G. (2000). "The Catalytic Pathway of Cytochrome P450cam at Atomic Resolution". Science. 287 (5458): 1615–1622. Bibcode:2000Sci...287.1615S. doi:10.1126/science.287.5458.1615. PMID   10698731.
  15. ↑ Karplus, M.; Petsko, G. A. (1990). "Molecular dynamics simulations in biology". Nature. 347 (6294): 631–639. Bibcode:1990Natur.347..631K. doi:10.1038/347631a0. PMID   2215695. S2CID   6143542.
  16. ↑ Young, Jessica E.; Holstege, Henne; Andersen, Olav M.; Petsko, Gregory A.; Small, Scott A. (2023). "On the causal role of retromer-dependent endosomal recycling in Alzheimer's disease". Nature Cell Biology. 25 (10): 1394–1397. doi:10.1038/s41556-023-01245-2. ISSN   1465-7392. PMID   37803174. S2CID   263741870.
  17. ↑ Jensen, Anne Mette G.; Kitago, Yu; Fazeli, Elnaz; Vægter, Christian B.; Small, Scott A.; Petsko, Gregory A.; Andersen, Olav M. (2023-01-24). "Dimerization of the Alzheimer's disease pathogenic receptor SORLA regulates its association with retromer". Proceedings of the National Academy of Sciences. 120 (4): e2212180120. Bibcode:2023PNAS..12012180J. doi:10.1073/pnas.2212180120. ISSN   0027-8424. PMC   9942828 . PMID   36652482.
  18. ↑ Qureshi, Yasir H.; Berman, Diego E.; Marsh, Samuel E.; Klein, Ronald L.; Patel, Vivek M.; Simoes, Sabrina; Kannan, Suvarnambiga; Petsko, Gregory A.; Stevens, Beth; Small, Scott A. (2022). "The neuronal retromer can regulate both neuronal and microglial phenotypes of Alzheimer's disease". Cell Reports. 38 (3): 110262. doi:10.1016/j.celrep.2021.110262. PMC   8830374 . PMID   35045281.
  19. ↑ Small, Scott A.; Petsko, Gregory A. (2020-12-02). "Endosomal recycling reconciles the Alzheimer's disease paradox". Science Translational Medicine. 12 (572). doi:10.1126/scitranslmed.abb1717. ISSN   1946-6234. PMC   8025181 . PMID   33268506.
  20. ↑ Petsko, Gregory A.; Small, Scott A. (2022). "Elucidating the causes of neurodegeneration". Science. 377 (6601): 31–32. Bibcode:2022Sci...377...31P. doi:10.1126/science.adc9969. ISSN   0036-8075. PMID   35771902. S2CID   250175089.
  21. ↑ Young, Jessica E.; Fong, Lauren K.; Frankowski, Harald; Petsko, Gregory A.; Small, Scott A.; Goldstein, Lawrence S.B. (2018). "Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein". Stem Cell Reports. 10 (3): 1046–1058. doi:10.1016/j.stemcr.2018.01.031. PMC   5919412 . PMID   29503090.
  22. ↑ Small, Scott A.; Simoes-Spassov, Sabrina; Mayeux, Richard; Petsko, Gregory A. (2017). "Endosomal Traffic Jams Represent a Pathogenic Hub and Therapeutic Target in Alzheimer's Disease". Trends in Neurosciences. 40 (10): 592–602. doi:10.1016/j.tins.2017.08.003. PMC   5654621 . PMID   28962801.
  23. ↑ Small, Scott A.; Petsko, Gregory A. (2015). "Retromer in Alzheimer disease, Parkinson disease and other neurological disorders". Nature Reviews Neuroscience. 16 (3): 126–132. doi:10.1038/nrn3896. ISSN   1471-003X. PMID   25669742. S2CID   5166260.
  24. ↑ Mecozzi, Vincent J; Berman, Diego E; Simoes, Sabrina; Vetanovetz, Chris; Awal, Mehraj R; Patel, Vivek M; Schneider, Remy T; Petsko, Gregory A; Ringe, Dagmar; Small, Scott A (2014). "Pharmacological chaperones stabilize retromer to limit APP processing". Nature Chemical Biology. 10 (6): 443–449. doi:10.1038/nchembio.1508. ISSN   1552-4450. PMC   4076047 . PMID   24747528.
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