Chemical probes inspired by natural products and TRP channel structural biology

Research in the Journigan laboratory focuses on the de novo design and discovery of small molecules for the transient receptor potential melastatin 8 (TRPM8) ion channel based on the natural product menthol, for clinically unmet disease states. TRPM8 is a polymodal nociceptor in the somatosensory nervous system and the major sensor of cold in humans. Our drug discovery efforts are aimed at correcting defects in sensory perception to cold, seen in chemotherapy-induced peripheral neuropathy (CIPN). To accomplish our ultimate goals of discovering novel small molecule chemical probes and therapeutics using current knowledge of TRP channel structural biology, we combine computational, synthetic medicinal chemistry and biochemical techniques. We collaborate with several research groups working in the TRP channel area on electrophysiology and rodent neurobehavioral and telemetry assays, to evaluate the effects of our designed ligands in translational models.