During the first phase of the project (2022), TRPM8 orthologs from four reptile species were synthesized and functionally validated. The functional characterization of these reptile orthologs is ongoing.
Alongside, we performed detailed investigations regarding the ion currents elicited by the simultaneous exposure TRPM8 (from mammals and birds) to cooling and chemical agonists. Future investigations into the physiological roles that TRPM8 plays in vivo (e.g. in the animal behavior) will benefit from the use of these pharmacolgical tools that we validated in vitro. Click here for the Stage 1 Executive Summary
In the second phase of the project (2023), the synthesized TRPM8 orthologs were further characterized. Targeted point mutations of these proteins were performed to find the molecular determinants of their pharmacological properties. Click here for the Stage 2 Executive Summary
The final phase of the project (2024) was dedicated to further characterizing TRPM8 mutants from several species. Click here for the Stage 3 Executive Summary
Results of the activities funded by the grant, investigating the roles of human, rodent and avian TRPM8 were published in the following articles and preprints (team members in bold):
Selescu T, Bivoleanu RA, Iodi Carstens M, Manolache A, Caragea VM, Hutanu DE, Meerupally R, Wei ET, Carstens E, Zimmermann K, Babes A. TRPM8-dependent shaking in mammals and birds. bioRxiv [Preprint]. 2024 Jan 16:2023.12.27.573364. doi: 10.1101/2023.12.27.573364. PMID: 38234797
Lee S, Wei ET, Selescu T, Babes A, Park J, Kim J, Chung B, Park C, Kim HO. Histamine- and pruritogen-induced itch is inhibited by a TRPM8 agonist: a randomized vehicle-controlled human trial. Br J Dermatol. 2024 May 17;190(6):885-894. doi: 10.1093/bjd/ljae054. PMID: 38345103.
Carstens MI, Mahroke A, Selescu T, Carstens E. Role of thermosensitive transient receptor potential (TRP) channels in thermal preference of male and female mice. J Therm Biol. 2024 May;122:103868. doi: 10.1016/j.jtherbio.2024.103868. Epub 2024 Jun 4. PMID: 38852485.