2010 Passano Laureate & Physician Scientists

 

2010 Passano Laureate

David Julius, Ph.D., a pioneer in sensory neurobiology, will receive the 2010 Passano Award for his discovery of the molecular mechanism of thermosensation and his elucidation of the manner in which temperature and pain sensation are integrated. Dr. Julius’ research was conducted at the University of California at San Francisco, where he is Chairman of the Department of Physiology. Dr. Julius’ work on thermosensation began when he and his colleagues identified an ion channel, TRPV1, that is highly expressed in pain sensing neurons and that can be specifically activated by capsaicin, the chemical responsible for the “hot” taste of chili peppers. The Julius laboratory showed that TRPV1 acts as a molecular thermometer, with channel opening induced at temperatures somewhat above normal body temperature. Interestingly, TRPV1 can also be activated by products of tissue damage and inflammation, suggesting that it functions to integrate both temperature and pain sensation. In support of this hypothesis, the Julius laboratory demonstrated that mice genetically engineered to lack TRPV1 exhibit diminished sensitivity to both heat and noxious chemicals. In an analogous series of experiments, Julius and his colleagues identified a related ion channel, TRPM8, as the cold receptor, based on its activation by menthol and other chemicals that elicit a cool sensation. Mice genetically engineered to lack the TRPM8 receptor exhibit diminished sensitivity to cold temperatures. Closely related members of the same TRP channel family have since been shown to mediate thermosensation in a wide variety of organisms, including invertebrates. These experiments cap a decades-long quest to understand the molecular basis of this sensory modality. Recent work from the Julius laboratory has focused on the integrative function of TRP channels in pain sensation and the role of these channels in medically important conditions. For example, the Julius lab has shown that TRPA1, a channel closely related to TRPV1, mediates the pain associated with a variety of noxious chemicals, including those in tear gas and vehicle exhaust, as well as the metabolic byproducts of chemotherapy. TRPA1 also functions as a critical mediator of bradykinin-induced hyperalgesia, a major mechanism by which inflammation sensitizes the pain pathway. The Julius laboratory has also discovered that the burning sensation associated with several spider venoms reflects their direct activation of TRPV1 channels. These and related discoveries reveal a broad role for TRP channels in the sensation and integration of noxious stimuli, and they set the stage for the development of novel strategies to control both chronic and acute pain.