Xing-Zhen Chen (PhD, University of Montreal)

ProfessorChen
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
xzchen@ualberta.ca


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).

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.


Awards

  • Senior Scholar, Alberta Heritage Foundation for Medical Research (AHFMR), 2006-2013
  • 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


Selected publications

Additional 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.* Identification of FUBP1 as a PKD2 mRNA 3’UTR binding protein that suppresses its translation. J. Am. Soc. Nephrol. In press.
  • 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. link
  • Zheng, W., Hussein, S., Yang, J., Huang, J., Zhang, F., Hernandez-Anzaldo, S., Fernandez-Patron, C., Cao, Y., Zeng, H., Tang, J., and Chen, X.-Z.* A novel PKD2L1 C-terminal domain critical for trimerization and channel function. Sci. Rep. 5, 9460, 2015. DOI: 10.1038/srep09460. link
  • Wang, Q., Cantero, M.R., Zheng, W., Wang, Z., Yang, J., Hussein, S., Cantiello, H.F., Tang, J., and Chen, X.-Z.* Filamin-A increases the stability and plasma membrane expression of polycystin-2. PLOS ONE. 10, e0123018, 2015. DOI: 10.1371/journal.pone.0123018. Link
  • Yang, J., Zheng, W., Wang, Q., Lara, C., Hussein, S., and Chen, X.-Z.* Translational up-regulation of polycystic kidney disease protein PKD2 by endoplasmic reticulum stress. FASEB J. 27, 4998-5009, 2013. Link
  • Wang, Q., Dai, X.-Q., Li, Q., Tuli, J., Liang, G., Li, S., and Chen, X.-Z.* Filamin interacts with ENaC and inhibits its channel function. J. Biol. Chem. 288, 264-273, 2013. Link