Special Centre for Molecular Medicine
Seminar
Title: Chaperoning G protein-coupled receptors: from cell biology to therapeutics
Speaker
Dr. Ya-Xiong Tao, Ph.D.
Professor
Department of Anatomy, Physiology and Pharmacology
College of Veterinary Medicine. Auburn University
Auburn, AL 36849, USA
taoyaxi@auburn.edu
Date: Thursday 21st November, 2019 Time: 3.00 PM
Venue: Seminar Hall, SCMM, JNU
Introduction : Dr. Tao joined the Auburn University College of Veterinary Medicine in 2004. He obtained his PhD from the Institute of Zoology, Chinese Academy of Sciences, Beijing, China. He completed post-doctoral training at the University of Louisville and at the University of Iowa with Dr. Deborah L. Segaloff. Since 2014 , He is professor, Dept. of Anatomy, Physiology & Pharmacology, Auburn University College of Veterinary Medicine, Auburn, Alabama.
Research : Research in his lab is directed to elucidate the structure-function relationships of G protein-coupled receptors, especially the neural melanocortin receptors, melanocortin-3 and -4 receptors. These receptors are critically involved in the regulation of energy homeostasis.
In presentation, he will review how molecular, chemical, and pharmacological chaperones promote the folding of G protein-coupled receptors (GPCRs), membrane proteins that traverse the plasma membrane seven times (hence, are also called 7TM receptors). The polytopic structure of GPCRs makes the folding of GPCRs difficult and complex. Indeed, many wild-type GPCRs are not folded optimally, and defects in folding are the most common cause of genetic diseases due to GPCR mutations. Both general and receptor-specific molecular chaperones aid the folding of GPCRs. Chemical chaperones have been shown to be able to correct the misfolding in mutant GPCRs, proving to be important tools for studying the structure-function relationship of GPCRs. However, their potential therapeutic value is very limited. Pharmacological chaperones (pharmacoperones) are potentially important novel therapeutics for treating genetic diseases caused by mutations in GPCR genes that resulted in misfolded mutant proteins. Pharmacoperones also increase cell surface expression of wild-type GPCRs; therefore, they could be used to treat diseases that do not harbor mutations in GPCRs. He will highlight his own work on the pharmacological chaperones for the melanocortin-4 receptor. Recent studies have shown that indeed pharmacoperones work in both experimental animals and patients. High-throughput assays have been developed to identify new pharmacoperones that could be used as therapeutics for a number of endocrine and other genetic diseases.
