Dr. Cheng’s Research

Structural Pharmacology of the Nociceptive Ion Channel TRPM3

The Transient Receptor Potential Melastatin-3 (TRPM3) ion channel plays a critical role in heat nociception and pathological pain, and is specifically activated by the neurosteroid, pregnenolone sulfate (PS). Antagonists of TRPM3 produce analgesia without significant adverse effects, suggesting that TRPM3 is a promising target for the development of analgesics. However, few TRPM3 antagonists are known, and there is an absence of information about the structural mechanisms by which agonists and antagonists activate/inhibit this ion channel. To address this knowledge gap, we will determine the structure of TRPM3 and the sites of agonist/antagonist binding using cryo-EM and photo-affinity labeling. This structural information will be used to screen for novel TRPM3 ligands. Identification of TRPM3 antagonists will facilitate research into the role of TRPM3 in pathological pain, and advance development of analgesics that specifically target TRPM3.