EMPLOYMENT AND TRAINING
Professor. 07/2011 –, Department of Physiology, University of Alberta, Canada.
Associate Professor. 07/2006 – 06/2011, Department of Physiology, University of Alberta.
Assistant Professor. 05/2000 – 06/2006, Department of Physiology, University of Alberta.
Instructor. 05/1999 – 05/2000, Harvard Medical School, USA.
Postdoctoral Fellow. 02/1997 – 05/1999, Brigham & Women’s Hospital, Harvard Medical School.
Supervisor: Dr. Matthias A. Hediger.
Instructor. 08/1987 – 08/1991, Department of Biology, Zhejiang University, China.
PhD in Physics. 09/1991 – 02/1997, Université de Montréal, Canada.
Supervisor: Dr. Jean-Yves Lapointe.
MSc in Physics. 09/1984 – 07/1987, Zhejiang University.
BSc in Physics. 02/1982 – 07/1984, Zhejiang University.
License candidate in Physics. 09/1981 – 02/1982, Université Pierre et Marie Curie - Paris VI, France.
DEUG A in Mathematics. 09/1979 – 07/1981, Université Claude Bernard - Lyon I, France.
French language learning. 02/1979 – 08/1979, Université de Rennes I, France.
BSc candidate in Computing Science. 10/1978 – 02/1979, Zhejiang University.
HONORS AND AWARDS
Senior Scholar, Alberta Heritage Foundation for Medical Research (AHFMR), 2006-2013.
Senior Scholar research prize, AHFMR, 2006-2013.
Research Award, Canada Foundation for Innovation New Opportunities (CFI NO).
Scholar, AHFMR, 2001-2006.
Scholar research prize, AHFMR, 2001-2006.
New Investigator, Canadian Institutes of Health Research (CIHR), 2000-2005.
Postdoctoral fellowship, International Human Frontier Science Program, 1998-2000.
Postdoctoral fellowship, Natural Sciences and Engineering Research Council of Canada (NSERC), 1998-2001, declined.
Awards of excellence, Université de Montréal, 1993 and 1994.
"Molecular and Cellular Physiology", PHYSL 407/507, instructor and coordinator
"Physiology of Transport Systems", PHYSL 545, instructor and coordinator
"Discovery Learning Pulmonary", DMED 514, facilitator
"Discovery Learning Renal", DMED 517, facilitator
"Undergraduate Research Project", PHYSL 467/468, instructor and supervisor
"Mammalian and Human Physiology", PHYSL 210/211, instructor
"Elementary Physiology", PHYSL 161, instructor
"Undergraduate Tutorial", PHYSL 466, instructor
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.
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, zebrafish and mouse models
Ion channel, electrophysiology, molecular biology, TRP channel, xenopus oocyte, culture cell, zebrafish, mouse, structure-function-regulation, protein-protein interaction, intramolecular interaction
1. Zhou, C., Hu, M., Qian, X., Zhang, R., Huang, Y., Yang, J., Zhang, J., Bai, H., Yang, Y., Wang, Y., Ali, D., Michalak, M., Chen, X.-Z., and Tang, J. STYK1 promotes autophagy through enhancing the assembly of ATG14L-Beclin1-VPS34 core complex. Autophagy. In press.
2. Wang, Z., Ng, C., Liu, X., Wang, Y., Chaudhry, H.A, Li, B., Castro, A., Kalontar, E.M., Ilyayev, L., Walker, R., Alexander, R.T., Qian, F., Chen, X.-Z., and Yu, Y. The ion channel role of the polycystin protein PKD1 in the PKD1/TRPP2 complex. EMBO Report. In press.
3. 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.
4. 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.
5. Zheng, W., Hu, R., Cai, R., Hofmann, L., Hu, Q., Fatehi, M., Long, W., Kong, T., Tang, J., Light., P., Flockerzi, V., Cao., Y., and Chen, X.-Z.* Identification and characterization of hydrophobic gates in TRP channels. FASEB J. 32, 639-653, 2018.
6. Frei, B., Eisenach, C., Martinoia, E., Hussein, S., Chen, X.-Z., Arrivault, S., and Neuhaus, H.E. Purification and functional characterization of the vacuolar malate transporter tDT from Arabidopsis. J Biol Chem. 293, 4180-4190, 2018.
7. 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.
8. Zheng, W., Yang, J., Beauchamp, E., Cai, R., Hussein, S., Hofmann, L., Li, Q., Flockerzi, V., Berthiaume, L.G., Tang, J., and Chen, X.-Z.* Regulation of TRPP3 channel function by N-terminal domain palmitoylation and phosphorylation. J. Biol. Chem. 291, 25678-25691, 2016.
9. 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.
10. 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.* Receptor for activated C kinase 1 (RACK1) inhibits the function of TRP-type channel Pkd2L1 through physical interaction. J. Biol. Chem. 287, 6551-6561, 2012.
11.. Yu, Y., Ulbrich, M.H., Li, M.-H., Buraei, Z., Chen, X.-Z., Ong, A.C.M., Tong, L., Isacoff, E.Y., and Yang, J. Structural and molecular basis of the assembly of the TRPP2/PKD1 complex. Proc. Natl. Acad. Sci. 106, 11558-11563, 2009.
12. Liang, G., Yang, J., Wang, Z., Li, Q., Tang, Y., and Chen, X.-Z.* Polycystin-2 down-regulates cell proliferation via promoting PERK-dependent phosphorylation of eIF2α. Hum. Mol. Genet. 17, 3254-3262, 2008.
13. Liang, G., Li, Q., Tang, Y., Kokame, K., Kikuchi, T., Wu, G., and Chen, X.-Z.* Polycystin-2 is regulated by endoplasmic reticulum-associated degradation. Hum. Mol. Genet. 17, 1109-1119, 2008.
14. Wu, Y., Li, Q., and Chen, X.-Z.* Detecting protein-protein interactions by Far Western blotting. Nature Protocols. 2, 3278-3284, 2007.78. Chen, X.-Z., Vassilev, P.M., Basora, N., Peng, J.-B., Nomura, H., Segal, Y., Brown, E.M., Reeders, S.T., Hediger, M.A., and Zhou, J. Polycystin-L is a calcium-regulated cation channel permeable to calcium ions. Nature 401, 383-386, 1999.
15. Tsukaguchi, H., Tokui, T., Mackenzie, B., Berger, U.V., Chen, X.-Z., Wang, Y.-X., Brubaker, R.F., and Hediger, M.A. A family of mammalian Na+-dependent L-ascorbic acid transporters. Nature 399, 70 75, 1999.
16. Chen, X., Tsukaguchi, H., Chen, X.-Z., Berger, U.V., and Hediger, M.A. Molecular and functional analysis of SDCT2, a novel rat sodium-dependent dicarboxylate transporter. J. Clin. Invest. 103, 1159-1168, 1999.
Member of grant panel review for
Department of Defense Congressionally Directed Medical Research Programs (CDMRP), PKD pre-application peer review panel of the Medical Research Program (PRMRP), 2013, 2015, 2019
KFC, Biomedical Scientific Committee, Dec 2018
PKD Foundation grant, May 2018
CIHR Stage 1 Project Grant, 2017
NSERC, Scholarships and Fellowships Selection Committee for Cellular and Molecular Biology, 2015-2018
CIHR College of Reviewers, 2017-
National Natural Science Foundation of China, Operating Grants for Junior Investigators, 2016
CIHR, Haematology, Digestive and Kidney (HDK), Committee Invitee member, 2010, 2011
Reviewer, for ASN abstracts, 2012
KFC, Biomedical Scientific Committee, 2009-2012
KFC, KCRESCENT Program, 2007
CIHR, Experimental Medicine, internal review, 2006
NIH special review panel ZRG1 RUS E02, 2006
NIH special emphasis panel RUS G (02), 2005
External grant review for
MRC Research Grant, 2017; NSERC, Discovery Grant, 2010-2012; NSF Electronic Proposal Review, USA, 2009; MRC Career Development Award, UK, 2008; KFC, 2006; CIHR, KFC, 2005; NSERC, Collaborative Health Research Project (CHRP) Program, 2004; KFC, 2002
Reviews of more than 50 manuscripts submitted to different peer-reviewed journals.