Yan-hua Chen, Ph.D.

Yan-hua Chen
Associate Professor

office: Brody 7N-55A
phone: 252-744-1341
email: cheny@ecu.edu

B.S., East China Normal University
M.S., Emory University
Ph.D., Emory University
Postdoctoral Fellow, Harvard Medical School

Research

Our laboratory is interested in the regulation of tight junction barrier function and the signaling pathway(s) involved in tight junction assembly and disassembly. Tight junctions serve as a permeability barrier in epithelial and endothelial cells regulating the passage of ions and small molecules through the paracellular pathway. Tight junction plays a crucial role in maintaining tissue homeostasis by keeping the extracellular fluid within the physiological range. Recent studies indicate that disruption of tight junction function leads to a number of human diseases such as autosomal recessive deafness and renal magnesium wasting resulting in nephrocalcinosis.

We use various techniques including molecular biology, cell biology and physiology to study protein-protein interactions, paracellular permeability regulation, and the role of non-receptor tyrosine kinases and MAP kinase pathway in the regulation of tight junction formation and functions.

Current projects include:

  1. Tyrosine phosphorylation of tight junction proteins and the role of non-receptor tyrosine kinase(s) in regulating paracellular permeability.
  2. Using yeast two-hybrid system, we have identified a multiple PDZ protein (MPDZ) that interacts with claudin-8, a tight junction membrane protein localized at kidney and lung. Currently, we are working on: (a) their interaction in vivo; (b) the functional consequence of this protein-protein interaction; and (c) how this MPDZ protein is involved in tight junction function.
  3. We have previously shown that the inhibition of MAP kinase pathway restored tight junction structure and barrier function in oncogenic ras-transformed epithelial cells, and reverted their morphology from an overlapping, fibroblastic-like phenotype back to a normal epithelial cell monolayer. Currently, we are investigating the downstream elements of MAP kinase pathway and the molecular and cellular mechanisms in this phenotypic reversion process.

Selected Publications

Chen, Y.-H. and R.L. DeHaan. 1993. Temperature-dependence of embryonic cardiac gap junction conductance and channel kinetics. J. Membrane Biol. 136: 125-134.

Chen, Y.-H. and R.L. DeHaan. 1993. Multiple channel conductance states in gap junctions. In: Gap Junctions (J.S. Hall, G.A. Zampighi, and R.M. Davis, eds.) Elsevier, Amsterdam. pp. 97-103.

DeHaan, R.L. and Y.-H. Chen. 1995. Multiple connexins and asymmetric currents in embryonic cardiac gap junction. In: Process in Cell Research (Y. Kanno, ed.). Elsevier Science, B.V., Amsterdam. 4: 187-200.

Chen, Y.-H. and R.L. DeHaan. 1996. Asymmetric voltage-dependence of embryonic cardiac gap junction channels. Am. J. Physiol. 270: C276-C285.

Chen, Y.-H., C.S. Merzdorf, D.L. Paul, and D.A. Goodenough. 1997. COOH terminus of occludin is required for tight junction barrier function in early Xenopus embryos. J. Cell Biol. 138: 891-899.

Merzdorf, C.S., Y.-H. Chen, and D.A. Goodenough. 1998. Formation of functional tight junctions in Xenopus embryos. Develop. Biol. 195: 187-203.

Chen, Y.-H. and Q. Lu (equal contribution), E. Scheneeberg, and D. Goodenough. 2000. Restoration of junction assembly and barrier function by down regulation of MAP kinase pathway in ras-transformed MDCK cells. Molec. Biol. Cell 11: 849-862.

Chen, Y.-H., Q. Lu, D.A. Goodenough, and B. Jeansonne. 2002. Non-receptor tyrosine kinase c-yes interacts with occludin during tight junction formation in canine kidney epithelial cells. Mol. Biol. Cell. 13: 1227-1237.

Chen, Y.-H. and Q. Lu. 2002. Association of non-receptor tyrosine kinase c-yes with tight junction protein occludin by co-immunoprecipitation assay. In: Cancer Cell Signaling: Methods and Protocols. Methods in Molecular Biology. 218: 127-132.

Jeansonne, B., Q. Lu, D.A. Goodenough, and Y.-H. Chen. 2003. Claudin-8 interacts with multi-PDZ domain protein 1 (MUPP1) and reduces paracellular conductance in epithelial cells. Cell. Mol. Biol. 49(1): 13-21.

Chen, Y.-H., D.A. Goodenough, and Q. Lu. 2004. Occludin, a constituent of tight junction. In: Tight Junctions (R.G. Landes, ed.). Landes Bioscience, Georgetown, TX. pp. 1-14.

Alexandre, M.D., Q. Lu, and Y.-H. Chen. 2005. Overexpression of claudin-7 decreases the paracellular Cl- conductance and increases the paracellular Na+ conductance in LLC-PK1 cells. J. Cell Science 118: 2683-2693.

Alexandre, M. D., B.G. Jeansonne, R.H. Renegar, R. Tatum, and Y.-H. Chen. 2007. The first extracellular domain of claudin-7 affects the paracellular Cl- permeability. Biochem. Biophys. Res. Commun. 357: 87-91.

Tatum, R., Y. Zhang, Q. Lu, K. Kim, B.G. Jeansonne, and Y.-H. Chen. 2007. WNK4 phosphorylates Ser206 of claudin-7 and promotes paracellular Cl- permeability. FEBS Lett. 581: 3887-3891.

Chen, Y.-H., J-J. Lin, B.G. Jeansonne, R. Tatum, and Q. Lu. 2009. Analysis of claudin genes in pediatric patients with Bartter’s Syndrome. Ann. N. Y. Acad. Sci. 1165: 126-134.

Tatum, R., Y. Zhang, K. Salleng, Z. Lu, J.-J. Lin, Q. Lu, B.G. Jeansonne, L. Ding, and Y.-H. Chen. 2010. Renal salt wasting and chronic dehydration in claudin-7-deficient mice. Am. J Physiol. Renal Physiol. 298: F24-34.

View PubMed Publications for further listings.


Staff and Students

Location: 7N-55

Name Title Phone Email
Beverly Jeansonne Research Technician 252-744-2866 jeansonneb@ecu.edu
Do Hyung Kim IDPBS Graduate Student 252-744-2864 kimdo11@students.ecu.edu
Srikanth Ravisankar Visiting Scientist (Department of Pediatrics) 252-744-2846 ravisankars@ecu.edu
Rodney Tatum Research Technician 252-744-2866 tatumr@ecu.edu

Former Students and Post-Doctoral Fellows

Name Title Location
Lei Ding, Ph.D., M.D. Associate Professor Department of Oncology, Beijing Capital Medical University, Beijing, China
Michele Delencour-Alexandre, Ph.D. Biology Instructor Durham Technical College, Durham, NC
Junming Fan, Ph.D. Assistant Professor Wenzhou Medical University, Wenzhou, China
Parvesh Garg, M.D. Physician Elmhurst Hospital Center, Ichan School of Medicine, New York, NY
John Hoggard, M.S. Dental Student School of Dental Medicine, East Carolina University, Greenville, NC
Zhe Lu, Ph.D. Assistant Professor Department of Basic Medicine, Hangzhou Normal University, Hangzhou, China
Jongdee Nopparat, Ph.D. Lecturer Department of Anatomy. Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla, Thailand
Dileep Vessu, Ph.D (IDPBS) Scientist DSM Pharmaceuticals, Greenville, NC
Gen Zhang, Ph.D. Assistant Professor Nanjing Medical University, Nanjing, China

List of Faculty