Brian Kobilka is Hélène Irwin Fagain Chair of Cardiology and Professor of Molecular and Cellular Physiology at Stanford University. He received Bachelor of Science Degrees in Biology and Chemistry from the University of Minnesota, Duluth in 1977. He graduated from Yale University School of Medicine in 1981, and completed residency training in Internal Medicine at the Barnes Hospital, Washington University School of Medicine, St. Louis, Missouri in 1984. From 1984-1989 he was a postdoctoral fellow in the laboratory of Robert Lefkowitz at Duke University. In 1990 he joined the faculty of Medicine and Department of Molecular and Cellular Physiology at Stanford University. Research in the Kobilka lab focuses on the structure and mechanism of action of G protein coupled receptors. He is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences. In 2012, Kobilka was awarded the Nobel Prize in Chemistry with Robert Lefkowitz for their work on GPCRs.
Structural insights into the complex biology of mu-opioid receptor agonists
The management of acute and chronic pain is one of the greatest challenges in modern medicine. While effective, many of the currently used opioid analgesics are highly addictive and their increased clinical use over the past 20 years is partially responsible for the opioid epidemic. The properties of more recently discovered µ-opioid receptor (µOR) agonists suggest that it may be possible to separate analgesia from liabilities including addiction, tolerance and respiratory suppression. The µOR can signal through six G protein isoforms (Gi1,2,3, GoA,B, Gz), and though arrestin 2 and 3. We have observed that different µOR agonist differentially activate these signaling pathways. I will discuss what we have learned about the structural basis for G protein isoform and arrestin biased signaling by the µOR.