Medicine & Dentistry-Physiology
University of Alberta
Summary of research:
Dr. Xing-Zhen Chen’s laboratory focuses on structure, function and regulation of transient receptor potential (TRP) channels and membrane transporters, in particular, TRP polycystin (TRPP) and TRP vanilloid (TRPV) channels that are implicated in various physiological processes. For example, elevated TRPV6 expression and gain-of-function (GOF) mutation in TRPV6 are found in breast cancer. His research uses various techniques encompassing electrophysiology, molecular biology and protein-protein/RNA interaction, in combination with various models including Xenopus oocytes, cultured cells, zebrafish and mice. One research direction is to investigate how TRPs intramolecular interactions together with phospholipid PIP2 mediate the regulation of the channel function. In particular, we are studying how intramolecular interactions in TRPV6 cross-talk with phospholipid PIP2 and together regulate the channel function, and how GOF of TRPV6 promotes breast cancer development. Another direction is to functionally characterize TRPs hydrophobic pore gate and express derived gain-/loss-of-function (GOF/LOF) gate mutants in zebrafish to study TRPs physiological function. A third, long term research direction has been on TRPP2 and TRPP3 (also called PKD2 and PKD2L1, respectively, with 54% sequence identity). Mutations in TRPP2 account for 15% of autosomal dominant polycystic kidney disease (ADPKD) which has extra-renal manifestations such as abnormalities in liver, heart, vascular systems and and organ left-right asymmetry development, while TRPP3, not implicated in ADPKD, plays important roles in acid sensing (eg sour tasting) and calcium signaling in primary cilia. ADPKD cells are characterized by over-proliferation, de-differentiation and apoptosis. His team investigates how TRPP2 and TRPP3 channel function is regulated by protein- and RNA-binding partners, and how TRPP2 regulates cell growth and cross-talks with cellular stresses. His research is currently funded by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) and a Biomedical Grant from the Kidney Foundation of Canada (KFoC).