Xing-Zhen Chen

Professor
PhD, University of Montreal

Office: 7-29A Medical Sciences Building
Laboratory: 7-29 and 7-30 Medical Sciences Building 
Tel: 780-492-2294
Lab Tel: 780-492-2307
Email address: xzchen@ualberta.ca

Research Interests / Academic Activities

The transient receptor potential (TRP) superfamily of cation channels plays important roles in sensory physiology (such as vision and pain/mechano/chemo sensations), through responding to various stimuli, such as light, temperature, force and different chemicals.

Our laboratory mainly studies the function and regulation of TRPP2, -P3 and -V6 channels, of which dysfunction are associated with polycystic kidney disease, abnormal acid sensing, imbalance of calcium homeostasis and cancer, etc. In particular, we focus on 

  1. Characterization of how they interact with and are regulated by interacting partner proteins
  2. Determination the amino acid residue(s) that constitutes the pore gate that controls the channel opening and closing, and
  3. Identification of intramolecular interactions that are critical for their channel function and mediate the regulation by upstream factors including phosphatidylinositol 4,5-bisphosphate (PIP2) and extracellular stimuli, and determination of whether this represents a shared mechanism for different TRPs.

Experimental methods and models: Molecular biology, protein-protein interaction, biotinylation, gene over-expression and knockdown, CRISPR/Cas9, immunostaining, electrophysiology (patch-clamp, two-microelectrode voltage-clamp, and lipid bilayer reconstitution), radiotracer transport measurements, pulse chase, cell proliferation and apoptosis assays. Experimental models include Xenopus oocytes, cultured mammalian cells, lipid bilayer, zebrafish and mice. 

Select Publications

  1.       Cai, R. and Chen, X.-Z. Roles of intramolecular interactions in the regulation of TRP channels. Reviews Physiol. Biochem. Pharmacol. doi: 10.1007/112_2022_74, 2022.
  2.       Huang, Y., Li, S., Liu, Q., Wang, Z., Li, S., Liu, L., Zhao, W., Wang, K., Zhang, R., Wang, L., Wang, M., Ali, D.W., Michalak, M., Chen, X.-Z., Zhou, C., and Tang, J. The LCK-14-3-3ζ-TRPM8 axis regulates TRPM8 function/assembly and promotes pancreatic cancer malignancy. Cell Death Dis. 13, 524, 2022.
  3.       Cai, R., Wang, L., Liu, X., Michalak, M., Tang, J., Peng, J.-B., and Chen, X.-Z. Auto-inhibitory intramolecular S5/S6 interaction in the TRPV6 channel regulates breast cancer cell migration and invasion. Commun. Biol. 4, 990, 2021.
  4.       Cai, R., Tang, J., and Chen, X.-Z. Hydrophobic gates and proton binding in proton-activated chloride channel. iScience. 24, 103395, 2021.
  5.       Zhou, C., Liang, Y., Zhou, L., Yan, Y., Zhang, R., Huang, Y., Wang, M., Tang, Y., Ali, D., Wang, Y., Michalak, M., Chen, X.-Z., and Tang, J. TSPAN1 promotes autophagy flux and mediates cooperation between WNT-CTNNB1 signaling and autophagy via the MIR454-FAM83A-TSPAN1 axis in pancreatic cancer. Autophagy. 17, 3175-3195, 2021.
  6.       Cai, R., Liu, X., Zhang, R., Hofmann, L., Zheng, W., Amin, M.R., Wang, L., Hu, Q., Peng, J.-B., Michalak, M., Flockerzi, V., Ali, D., Chen, X.-Z., and Tang, J. Autoinhibition of TRPV6 channel and regulation by PI(4,5)P2. iScience. 23, 101444, 2020.
  7.   Zhou, C., Yi, C., Yi, Y., Qin, W., Yan, Y., Dong, X., Zhang, X., Huang, Y., Zhang, R., Wei, J., Ali, A., Michalak, M., Chen, X.-Z., and Tang, J. LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes. Mol. Cancer. 19, 118, 2020.
  8.       Wang, Z., Ng, C., Liu, X., Wang, Y., Li, B., Kashyap, P., Chaudhry, H.A., Castro, A., Kalontar, E.M., Ilyayev, L., Walker, R., Alexander, R.T., Qian, F., Chen, X.‑Z., and Yu, Y. The ion channel function of polycystin-1 in the polycystin-1/polycystin-2 complex. EMBO Rep. 20, e48336, 2019. 
  9.       Lee, J.J., Liu, X., O’Neill, D., Beggs, M.R., Flockerzi, V., Chen, X.-Z., Dimke, H., and Alexander, R.T. Activation of the calcium sensing receptor attenuates TRPV6-dependent intestinal calcium absorption. JCI Insight. 5, 128013, 2019.
  10.   Zheng, W., Yang, X., Hu, R., Cai, R., Hofmann, L., Wang, Z., Hu, Q., Liu, X., Bulkley, D., Yu, Y., Tang, J., Flockerzi, V., Cao, Y., Cao, E., and Chen, X.-Z. Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels. Nat. Commun. 9, 2302, 2018.
  11.   Zheng, W., Cai, R., Hofmann, L., Nesin, V., Hu, Q., Long, W., Fahiti, M., Liu, X., Hussein, S., Kong, T., Li, J., Light, P.E., Tang, J., Flockerzi, V., Tsiokas, L., and Chen, X.-Z. Direct binding between pre-S1 and TRP-like domain in TRPP channels mediates gating and functional regulation by PIP2. Cell Rep. 22, 1560-1573, 2018.
  12. 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. 27, 2645-2657, 2016.

 

Laboratory Members

Graduate students
Zoe Qinyi Xu
Lillian Wanyi Fang
Yuzi Wang
Amiee Yifang Wang
Xiaoling Deng
Rui Tian

Visiting scholar
Lin Xu