- 2018 Award in Excellence in Pharmacology/Toxicology
- 1979 Research Starter Grant in Pharmacology/Toxicology
Dr. Gavril Pasternak has been a leader in the opioid field for over 40 years. He holds the Anne Burnett Tandy Chair of Neurology at Memorial Sloan Kettering Cancer Center and is Professor of Neurology & Neuroscience, Pharmacology and Psychiatry at the Weill Cornell Medical College.
As a graduate student in the Snyder laboratory at Johns Hopkins in the 1970’s, he was part of the original team that identified and characterized the opiate receptor. During that time, he discovered the ‘Sodium Effect’ and was the first to propose a role of sodium ions in the inter-conversion of agonist and antagonist receptor conformations, a discovery that now extends to almost all G-protein coupled receptors. After moving to Memorial Sloan Kettering, Dr. Pasternak focused upon subtypes of opiate receptors, synthesizing antagonists that separated opioid analgesia from side-effects, such as respiratory depression and constipation. Following the discovery of the mu opioid receptor gene Oprm1, his group identified a vast array of mu receptor splice variants that have played a major role in understanding opioid action and the variable responses of patients to different mu opioid drugs. In addition to the traditional GPCR variants, he identified two sets of truncated isoforms and established their pharmacological relevance both in vitro and in vivo. As with the Sodium Effect, the importance of the truncated forms may extend beyond the opioid field to GPCRs in general based upon predictions that up to 10% of non-olfactory GPCRs may generate similar truncated variants.
His discoveries have markedly altered our understanding of how opiates act and have led to novel, potent analgesics targeting novel receptor targets with greatly reduced side effects. He synthesized a series of compounds targeting one of the truncated isoforms that yielded new opiate drugs up to 100-fold more potent than morphine with a broader spectrum of analgesic activity that includes neuropathic pain and that lack respiratory depression, physical dependence and reward behavior. From these, a lead compound has been chosen and is entering clinical development.
Dr. Pasternak’s accomplishments have been recognized by numerous awards, including The Millenium Prize from the Norwegian University of Science and Technology, the John Bonica Award of the Eastern Pain Association, the S. Weir Mitchell Award of the American Academy of Neurology, the Julius Axelrod Award in Pharmacology (ASPET), The Founders Award of the International Narcotics Research Conference, a Senior Scientist and a MERIT Award from the National Institute on Drug Abuse, Fellowships in the American Academy of Neurology and in the American Neurological Association and election to the Johns Hopkins University Society of Scholars. He sat on the Board of Scientific Counselors of the National Institute on Drug Abuse and serves on a wide range of editorial boards. He has consulted widely for industry and is listed among ‘Highly Cited Researchers” by ISI/Thomson Scientific and has been on the list of “Best Doctors in America” for over 15 years. He has published over 430 research articles, over a dozen patents and five books. He is heavily involved in education, serving as the Program Director of the Neuroscience Program for a decade and teaching in three pharmacology courses at Weill Cornell Medical College/MSKCC. For many years he directed the summer diversity program, overseeing several dozen college students each summer interested in science careers. He has mentored over a dozen thesis students and over three dozen fellows, as well as introducing numerous high school students to scientific research in his laboratory.