Michael Caterina, M.D., Ph.D.

My lab is interested in understanding how neuronal and nonneuronal cells in the body detect changes in ambient temperature. Increases or decreases in tissue temperature can cause pain, pleasure, or homeostatic changes in mammals, depending upon their direction, magnitude, and anatomical location. The molecular basis of this thermosensation, however, is very poorly understood. We previously identified two heat-gated ion channels that are expressed in distinct subsets of peripheral neurons within the pain pathway. One of these proteins, TRPV1 (VR1), is a channel that can be activated not only by noxious heat (>43 C), but also by protons and by capsaicin (the main pungent ingredient in 'hot' peppers). The second channel, TRPV2, is activated by temperatures exceeding 52 C, but is insensitive to protons or capsaicin. Since then, we and others have identified several additional members of the TRP ion channel family that can be activated by either increases (TRPV3, TRPV4) or decreases (TRPM8) in temperature. Through a multidisciplinary approach involving molecular biology, biochemistry, calcium imaging, electrophysiology and mouse behavior, we are focusing on the following goals: 1)Using mouse knockouts of temperature-gated ion channels to clarify their roles in pain and temperature sensation. 2) Dissecting the mechanisms by which these molecules are activated by increases or decreases in ambient temperature. 3) Understanding how nonneuronal cells that express temperature-gated channels contribute to the process of thermosensation.