Current positions
Anne Burnett Tandy Chair in Neurology
Member and Laboratory Head, Molecular Pharmacology and Chemistry Program
Memorial Sloan-Kettering Cancer Center
and
Professor of Neurology and Neuroscience, Pharmacology and Psychiatry
Weill Cornell Medical College
Bio-Sketch
Dr. Gavril Pasternak holds the Anne Burnett Tandy Chair in Neurology at Memorial Sloan-Kettering Cancer Center and is a Laboratory Head in the Molecular Pharmacology and Chemistry Program within the Sloan-Kettering Institute. After receiving his M.D. and Ph.D. degrees from the Johns Hopkins University he completed his clinical training in Neurology at Johns Hopkins Hospital and then joined the faculty at Memorial Sloan-Kettering in 1979. He is a Fellow of the American Academy of Neurology and a Fellow of the American Neurological Association.
His research has focused on opioid receptors and their mechanisms of action. He has published over 400 articles. Much of his work has addressed the reasons underlying the subtle, but distinct differences among opioid analgesics. These studies revealed the existence of multiple mu opioid receptor subtypes generated from alternative splicing of a single gene. He demonstrated the importance of different sets of mu receptor subtypes in the actions of various opioid analgesics and identified a set of subtypes that offer a unique target for the development of analgesics lacking opioid side-effects.
He is a recipient of a Senior Scientist Award and a MERIT Award from the National Institute on Drug Abuse and has served on their Board of Scientific Counselors. He is a member of the Johns Hopkins Society of Scholars and has been awarded the Millenium Prize from the Norwegian University of Science and Technology, the John J. Bonica Award from the Eastern Pain Association, the Julius Axelrod Award of the American Society of Pharmacology and Experimental Therapeutics, the S. Weir Mitchell Award from the American Academy of Neurology and the Louise and Allston Boyer Young Investigator Award for Clinical Investigation from MSKCC.
Symposium: Cancer pain management - Up To Date
Multiple Opioid Receptors: Their Impact on Drug Selection, Opioid Rotation and Drug Combination Therapy
Abstract
Cancer pain often requires the use of strong analgesics, such as the opioids. The opioids most often used clinically act through mu opioid receptors. Yet, their actions can be quite variable among patients, leading to the clinical dictum that every drug should be optimized for every patient. Recent advances in the molecular biology of mu opioid receptors now provides insights into why patients vary in their responses to these drugs. Mu opioids do not act through a single receptor. The mu opioid receptor gene undergoes extensive alternative splicing to generate three classes of mu receptor proteins comprised of dozens of splice variants. Using a series of knockout mice in which portions of the mu receptor gene are disrupted to selectively eliminate different receptor classes, we now can demonstrate the importance of different sets of variants in the actions of various mu opioids. While each category of variants is important in analgesia, they vary in the mechanisms they use and in their side-effect profiles. In vivo, the actions of mu opioids are the summation of their interactions with multiple mu receptors. Together with biased agonism, these observations help explain the subtle, but important clinical distinctions among the various opioids and the concept of incomplete cross tolerance that is important in understanding Opioid Rotation.
