Ardem Patapoutian, Ph.D.
Director of Discovery Research
Physical pain is one of the oldest and most universal issues in human health, and improving the clinical management of pain remains a great medical challenge today. Pain perception originates within the central nervous system (CNS) in response to activity of peripheral nociceptors. This is something that scientists have understood for a long time. Even as far back as 1898, Charles Sherrington defined nociception as the ability of specialized neurons within the peripheral nervous system (PNS) to sense damage to tissues such as the skin. But the detailed molecular picture of nociception and pain sensation were a mystery then and are only beginning to emerge.
At GNF, we are leading the search for the elusive molecular sensors involved in pain and our ability to sense our environment through touch. The significant insights gained from these studies may have an impact on novel treatments for pain.
Our laboratory is employing powerful new technologies for identifying and characterizing the genes that encode sensory molecules, such as those responsible for detecting damage-causing noxious stimuli. For example, we identified TRPA1, which encodes for a protein that belongs to the Transient Receptor Potential (TRP) ion channel family. Interestingly, TRPA1 is activated by noxious cold, a variety of pungent compounds present in plant extracts such as allicin from garlic, and by environmental irritants such as acrolein. We are currently working towards understanding the mechanism of activation of these ion channels and exploring their role in vivo. In addition, we are continuing to search for additional sensory receptors.
Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 2007;445(7127):541-5.
Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, Spencer KS, Andahazy M, Story GM, Patapoutian A. Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science 2005;307(5714):1468-72.
Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 2003;112(6):819-29.