Candie Paulsen, PhD

Pain is a fundamental protective mechanism initiated in response to harmful thermal, mechanical, or chemical stimuli that is necessary for survival of a species. When pain sensory neurons become hyper-sensitized, pain can outlive its protective utility and become chronic and debilitating. 100 million Americans suffer from chronic pain, yet, little progress has been made to develop new pain remedies beyond non-steroidal anti-inflammatory agents and opioids, which harbor significant side effects and the risk of addiction. The wasabi receptor, TRPA1, is a non-selective homotetrameric cation channel expressed in primary pain sensory neurons where its activation by diverse chemical irritants initiates pain signals and neurogenic inflammation. This central role of TRPA1 in initiating and enhancing pain signaling through neurogenic inflammation has deemed it a gatekeeper to the development of chronic pain and mark it a viable target for new pain therapeutics. Despite its importance, there is much we do not understand about how TRPA1 is regulated, how it becomes hyper-activated, and how hyper-activated TRPA1 uniquely contributes to the development of chronic pain. Our current research program focuses on determining how TRPA1 is regulated by proteins, lipids, and small molecules and how modifications to those regulatory mechanisms contribute to channel hypersensitivity and aberrant pain signaling. To answer these questions, we employ a multidisciplinary approach that includes chemical biology, molecular biology, protein biochemistry, ion channel electrophysiology, and single-particle electron cryo-microscopy.