Gregory A. Petsko, D. Phil.

Ann Romney Center for Neurologic Diseases Harvard Medical School and Brigham & Women’s Hospital; Adjunct Professor of Biomedical Engineering, Cornell University

Gregory A. Petsko, D. Phil.

Ann Romney Center for Neurologic Diseases Harvard Medical School and Brigham & Women’s Hospital; Adjunct Professor of Biomedical Engineering, Cornell University

Biography

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. From 2021-2018 he was the Arthur J. Mahon Professor of Neurology and Neuroscience at Weill Cornell Medical College in New York City, and Director of the Helen and Robert Appel Alzheimer’s Disease Research Institute.  He also holds appointments as Adjunct Professor of Biomedical Engineering at Cornell University and Tauber Professor of Biochemistry and Chemistry, Emeritus, at Brandeis University. He is married to Dr. Laurie Glimcher, the President and CEO of the Dana-Farber Cancer Institute. 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 both 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 scientific advisory boards of MeiraGTx, Amicus Therapeutics, Proclara Biosciences, and QR Pharma. His many awards include the Max Planck Prize, the Pfizer Award of the American Chemical Society, the Buerger Award of the American Crystallographic Association, and the Fyodor Lynen Medal.

The research interests of his group, which operates jointly with the group of Brandeis University Professor Dagmar Ringe, are focused on the development of treatments for age-related neurodegenerative diseases, including ALS (Lou Gehrig’s), Alzheimer’s and Parkinson’s diseases, the tauopathies, and frontotemporal dementias.  His public lectures on the aging of the population and its implications for human health have attracted a wide audience on the Internet (one of his TED talks, for example, has been viewed almost a million times). He has also written a widely-read and much reprinted 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 much more popular than those he writes himself.

Endosomal Trafficking as a Determinant of Selective Cellular Vulnerability in Alzheimer’s and Parkinson’s Diseases

Every major neurodegenerative disease has familial sub-types that are characterized by mutations in genes expressed in all cells in the body. Why, then, are only certain cell types vulnerable to them? Although one could argue in principle that neurons, being quiescent cells with long axons, may be inherently more sensitive to certain kinds of disturbances than cells in other tissues, that argument fails to explain why, for example, some alleles of the VPS35 gene cause Parkinson’s disease (death of dopaminergic neurons) while others cause Alzheimer’s disease (death of cortical neurons). It also fails to explain why Alzheimer’s disease always starts in the trans-entorhinal cortex and spread to the hippocampal formation and amygdala while Parkinson’s disease tends to start in the vagus nerve and spreads to the locus coeruleus and thence to the basal ganglia. My collaborator Scott Small (Columbia University School of Medicine) and I believe that endosomal protein trafficking provides a possible explanation. I will review what is known about such trafficking in neurons and how human genetics, cell biology and anatomical biology all integrate to link this pathway to both Alzheimer’s and Parkinson’s diseases, and how different disturbances of this pathway may account for the selective cellular vulnerabilities observed in these diseases, as well as their strong comorbidity.

All sessions by Gregory A. Petsko, D. Phil.