Xing-Zhen Chen

Xing-Zhen Chen

Xing-Zhen Chen (PhD, University of Montreal)

Professor

7-29A Medical Sciences Building
University of Alberta
Edmonton, Alberta
Canada T6G 2H7

Tel: 780.492-2294
Lab Tel: 780-492-1080
Fax: 780-492-0886

xzchen@ualberta.ca


Awards

  • Senior Scholar, Alberta Heritage Foundation for Medical Research (AHFMR), 2006-2011
  • Research Award, Canada Foundation for Innovation New Opportunities (CFI NO), 2002-2004
  • Scholar, AHFMR, 2001-2006
  • New Investigator, Canadian Institutes of Health Research (CIHR), 2000-2005
  • Postdoctoral fellowships, International Human Frontier Science Program (HFSP), 1998-2000; Natural Sciences and Engineering Research Council of Canada (NSERC), 1998-2001

Research Description

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).

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, and the Kidney Foundation of Canada.


Selected publications

Zheng, W., Shen, F., Hu, R., Roy, B., Yang, J., Wang, Q., Zhang, F., King, J.C., Sergi, C., Liu, S.-M., Cordat, E., Tang, J., Cao, Y., Ali, D.W., and Chen, X.-Z.* Far upstream element-binding protein 1 binds the untranslated region of PKD2 and suppresses its translation. J. Am. Soc. Nephrol. Epub ahead of print, 2016. doi:10.1681/ASN.2015070836.

Hussein, S., Zheng, W., Dyte, C., Wang, Q., Yang, J., Zhang, F., Tang, J., Cao, Y., and Chen, X.-Z.* Acid-induced off-response of PKD2L1 channel in Xenopus oocytes and roles of Ca2+. Sci. Rep. 5, 15752, 2015. DOI: 10.1038/srep15752.

Wentong Long, Pankaj Panwar, Kate Witkowska, Kenneth Wong, Debbie O'Neill, Xing-Zheng Chen, M. Joanne Lemieux, Chris I. Cheeseman. (2015) Critical Roles for Two Hydrophobic Residues within Human Glucose Transporter 9 (hSLC2A9) Affecting Substrate Selectivity and the Energetics of Urate Transport J Biol Chem. pii: jbc.M114.611178.

Wang, Q., Dai., X.-Q., Li, Q., Tuli, J., Liang, G., Li, S. and Chen, X.-Z.* (2013) Filamin interacts with ENaC and inhibits its channel function. J. Biol. Chem., 288, 264-273.

Yang, J., Zheng, W., Wang, Q., Lara, C., Hussein, S., and Chen, X.-Z.* (2013) Translational up-regulation of polycystic kidney disease protein PKD2 by endoplasmic reticulum stress. FASEB J. 27, 4998-5009.

Wang, Q., Dai, X.-Q., Wang, Z., Li, Q., Cantero, M.R., Li, S., Shen, J., Tu, J.-C., Cantiello, H.F. and Chen, X.-Z.* (2012) Structural interaction and functional regulation of polycystin-2 by filamin PLoS ONE. 7, e40448.

Yang, J., Wang, Q., Zheng, W., Tuli, J., Li, Q., Wu, Y., Hussein, S., Dai, X.-Q., Shafiei, S., Li, X.-G., Shen, P.Y., Tu, J.-C., and Chen, X.-Z.* (2012) Receptor for activated C kinase 1 (RACK1) inhibits the function of TRP-type channel Pkd2L1 through physical interaction. J. Biol. Chem. 287, 6551-6561.