Associate Professor and Director of Graduate Studies
Adjunct Associate Professor, Department of Pediatrics
East Carolina University Scholar 2017
office: Brody 7N-55A
B.S., East China Normal University
M.S., Emory University
Ph.D., Emory University
Postdoctoral Fellow, Harvard Medical School
Our laboratory studies roles of tight junction proteins in epithelial cell functions and their involvement in human diseases such as hypertension, inflammation, and cancer. Tight junctions serve as a permeability barrier regulating the passage of ions and small molecules through the paracellular pathway (between cells). Tight junction plays a crucial role in maintaining tissue homeostasis by keeping the extracellular fluid within the physiological range. Disruption of tight junction integrity leads to a number of human diseases such as renal magnesium wasting. We use various approaches including targeted gene deletion, molecular and cell biology, and electrophysiology to study protein-protein interactions, paracellular permeability regulation, and the role of protein kinases in the regulation of tight junction formation and functions.
Using our claudin-7 knockout mouse model and cell culture system, we are currently working on the following projects: (1) Phosphorylation of tight junction proteins and the role of protein kinases in modulating paracellular ion permeability in kidneys. We are investigating the regulation of tight junction functions by WNK4 kinase, mutations of which cause hypertension in PHAII; (2) Claudin functions in intestines. Deletion of claudin-7 in mouse intestines leads to mucosal ulcerations, epithelial cell sloughing and intestinal inflammation. Our laboratory is investigating the underlying molecular mechanism causing these defects using microarrays, RT-PCR, biochemistry, and imaging technology; (3) Roles of claudin proteins in cancer. Our recent publications indicate that overexpression of claudin-7 reduces cell growth in human lung cancer cells, and that suppression of claudin-7 expression promotes human lung cancer cell proliferation and detachment. We are currently investigating how claudin-7 interactions with integrin signaling influences cancer cell growth, adhesion, and invasion.
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.
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: 13-21.
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. (Editorial focus of this issue)
Zhang, G, L. Ding, R. Renegar, X.M. Wang, Q. Lu, S.Q. Huo, and Y.-H. Chen. 2011. Hydroxycamptothecin-loaded Fe3O4 nanoparticles induce human lung cancer cell apoptosis through Caspase-8 pathway activation and disrupt tight junctions. Cancer Sci. 102: 1216-1222.
Lu, Z., L. Ding, H. Hong, J. Hoggard, Q. Lu, and Y.-H. Chen. 2011. Claudin-7 inhibits human lung cancer cell migration and invasion through ERK/MAPK signaling pathway. Exp. Cell Res. 317: 1395-1946.
Ding, L., Z. Lu, O. Foreman, R. Tatum, Q. Lu, R. Renegar, J. Cao, and Y.-H. Chen. 2012. Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice. Gastroenterology. 142: 305-315. (Editorial highlight of this issue)
Ding, L., Z. Lu, Q. Lu, and Y.-H. Chen. 2013. The claudin family of proteins in human malignancy: A clinical perspective. Cancer Manag. Res. 5: 367-375.
Hoggard, J., J.M. Fan, Z. Lu, Q. Lu, L. Sutton, and Y.-H. Chen. 2013. Claudin-7 increases chemosensitivity to cisplatin through the upregulation of caspase pathway in human NCI-H522 lung cancer cells. Cancer Sci. 104: 611-618. (Editorial Highlight of this issue)
Lu, Z., L. Ding, Q. Lu, and Y.-H. Chen. 2013. Claudins in intestines: Distribution and functional significance in health and diseases. Tissue Barriers. 1: e24978.
Lu, Z., D.H. Kim, J.M. Fan, Q. Lu, K. Verbanac, L. Ding, R. Renegar, and Y.-H. Chen. 2015. A non-tight junction function of claudin-7 – Interaction with integrin signaling in suppressing lung cancer cell proliferation and detachment. Mol. Cancer. 14:120.
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