Xing-zhen Chen

Biography

7-29A Medical Sciences Building University of Alberta Edmonton, Alberta Canada T6G 2H7 Tel: 780 492-2294 (office) Tel: 780 492-2307 (lab) Fax: 780 248-1995.

Research Interest

Cellular function and regulation of polycystins Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD and occurs in 0.1-0.2% of adults. ADPKD is due to mutations in polycystin-1 and -2, which are membrane receptor and ion channel, respectively. ADPKD also leads to cysts in liver, pancreas and spleen, and to non-cystic manifestations, including vascular abnormalities, organ left-right asymmetry development, and hypertension. Other proteins, such as inversin, cystin, polaris, kinesin and tubulin, are also cystogenic in mice. At the cellular level, cystic epithelial cells show abnormalities in proliferation, differentiation, adhesion, polarity, fluid transport and apoptosis. The family of cystoproteins is also associated with other phenotypes, including fertility, mating behavior and muscle contraction, etc. Therefore, studies on polycystins may elucidate common molecular mechanisms underlying distinct physiological functions (phenotypes). Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD and occurs in 0.1-0.2% of adults. ADPKD is due to mutations in polycystin-1 and -2, which are membrane receptor and ion channel, respectively. ADPKD also leads to cysts in liver, pancreas and spleen, and to non-cystic manifestations, including vascular abnormalities, organ left-right asymmetry development, and hypertension. Other proteins, such as inversin, cystin, polaris, kinesin and tubulin, are also cystogenic in mice. At the cellular level, cystic epithelial cells show abnormalities in proliferation, differentiation, adhesion, polarity, fluid transport and apoptosis. The family of cystoproteins is also associated with other phenotypes, including fertility, mating behavior and muscle contraction, etc. Therefore, studies on polycystins may elucidate common molecular mechanisms underlying distinct physiological functions (phenotypes). Polycystin-1 possesses a long extracellular N-terminus and acts as a receptor while polycystin-2 exhibits similar membrane organization to voltage-gated cation channels and transient receptor potential (TRP) channels. Polycystin-2 (also called PKD2 or TRPP2) and its homologue, polycystin-L (also called PKD2L1 or TRPP3), are non-selective cation channels, permeable to Ca, Na and K. Polycystin-L is not related to PKD. Increasing evidence indicates that polycystin-1 and -2 may be part of a mechano-sensor in epithelial cells while polycystin-L may be part of an acid sensor in neurons. My laboratory studies function and regulation of polycystin-2 and -L, and interaction with other proteins, using molecular biology and cell physiology approaches, such as electrophysiology and protein-protein interaction, in combination with cellular and animal models. In particular, as project #1, we study cross-talk between polycystin-2 and cellular machineries related to translation or responses to stress conditions. As project #2, we try to determine functional roles of polycystin-L, in particular in neurons of retina and brain. Techniques Molecular biology, protein-protein interaction, gene knockdown, immunostaining, mutagenesis, electrophysiology (patch-clamp, two-microelectrode voltage-clamp, and lipid bilayer reconstitution), radiotracer transport measurements, pulse chase, heterologous expression/purification of soluble and membrane proteins (in mammalian cells, E. coli and Xenopus oocytes), cell proliferation and apoptosis assays. Experimental models include Xenopus oocytes, cultured mammalian cells, mouse models, and organ culture of embryonic kidneys. Support Our research has been funded by the Canadian Institutes of Health Research, the Alberta Innovates Health Solutions, the Natural Sciences and Engineering Council of Canada, and the Kidney Foundation of Canada.