The sense of touch is unique in perceiving stimuli both physical (temperature, mechanical) and chemical (compounds that cause pain, itch, et cetera) in nature. In each modality, touch neurons distinguish noxious (painful) from innocuous stimuli, and the sensitization of touch neurons in response to injury and inflammation is the basis for many clinically-relevant chronic pain states. The molecules that mediate detection of touch stimuli have been a long-standing mystery. Our lab has identified and characterized ion channels activated by distinct changes in thermal energy (in the noxious to innocuous range), thus functioning as the molecular thermometers of our body. A subset of these same ion channels also act as polymodal chemosensors, playing an essential role in pain and inflammation. Small molecule antagonists of TRPA1, one of the ion channels identified in the Patapoutian lab, are currently in phase I clinical studies.

Mechanotransduction is perhaps the last sensory modality to be understood at the molecular level. Ion channels that sense mechanical force are postulated to play critical roles in sensing touch/pain (somatosensation), sound (hearing), sheer stress (cardiovascular tone), and more; however, the identity of such ion channels has remained elusive. We recently identified Piezo1 and Piezo2, mechanically-activated cation channels that are expressed in many mechanosensitive cell types. Current efforts focus on understanding structure-function relationships of Piezo proteins and elucidating their physiological roles in biological processes and diseases that involve mechanotransduction. We are also searching for novel ion channels involved in thermosenation and mechanosensation.