Research Interests
Claudins are the major structural and functional components of tight junctions and are widely expressed in epithelial and endothelial cells and they show tissue-specific distribution patterns. Altered expression and distribution of different claudins have been found in a wide variety of human cancer. Claudin-7 is highly expressed in lung and kidney. Deletion of claudin-7 gene in mice (claudin-7-/-) resulted in hyperproliferation of lung alveolar epithelial cells and the infiltration of neutrophilic leukocytes. While homozygous claudin-7-/- mice die within two weeks after birth, heterozygous claudin-7+/- mice showed an increased incidence of developing lung and kidney tumors. Based on these observation, we are testing the hypothesis that claudin-7 may play a role as a tumor suppressor in cancer.
Lung cancer accounts for more than one-fourth of all cancer deaths and is the leading cause of cancer death worldwide for both men and women. In our current research, we are using a variety of cell based assays to determine if the properties of cell cycle, apoptosis, and cell adhesion and invasion are altered when claudin-7 is stably expressed in human lung cancer cell line NCI-H1299. We are investigating whether claudin-7 expression can suppress NCI-H1299 cell growth in athymic nude mice. We are also analyzing the growth and metastatic properties of Lewis Lung Cancer cell line (LLCL1) with or without stably expressing clauidn-7 after they are inoculated into our heterozygous claudin-7+/- mice, to determine if claudin-7 expression is sufficient to inhibit LLC1 tumor growth in an immuno-competent mouse model.
Identification of claudin-7 as a tumor suppressor and to understand its mechanisms in inhibiting cancer cell growth will help shed lights on how to block lung cancer from progression to metastasis, and therefore, have significant implications for lung cancer therapy.

Recent Accomplishments and Honors
1989 Grass Foundation Scholarship recipient, Hopkins Marine Station of Stanford University
1991 Travel Award for International Gap Junction Conference, Asilomar, CA
1992 Travel Award for 32nd ASBMB/Biophysical Society Joint Meeting, Houston, TX
1994-1995 NIH Fellowship recipient
1996 Travel Award for International Gap Junction Conference, France. (Invited Speaker)
2000 Travel Award for Keystone Symposia. Intercellular Junction. (Invited Speaker)
2003-2005 Faculty Research Award from East Carolina University Brody School of Medicine
2005-2006 Faculty Author Recognition Award Division of Health Sciences at East Carolina University
2007-2008 Research Development Award from the Division of Research and Graduate Studies of East Carolina University

Training
East China Normal University, Shanghai, P. R. China B.S. 1982 Biology
Emory University School of Medicine, Atlanta, GA M.S. 1992 Cell Biology
Emory University School of Medicine, Atlanta, GA Ph.D. 1993 Cell Biology and Biophysics
Emory University School of Medicine, Atlanta, GA Post-doctor 1993-94 Cell Biology and Biophysics
Harvard Medical School, Boston MA Post-doctor 1994-2000 Molecular and Cell Biology

Publications
1. R.L. DeHaan, Chen, Y.-H. and R. L. Penrod. 1989. Voltage dependence of junctional conductance in the embryonic heart. In: Molecular and Cellular Mechanisms of Antiarrhythmic Agents. L. Hondeghem, ed. Futura, Mount Kisco, NY pp. 19-43
2. DeHaan, R.L. and Y.-H. Chen. 1990. Development of gap junctions. In: Embryonic Origins of Defective Heart Development. D.E. Bockman and M.L. Kirby, Eds. Ann. N.Y. Acad. Sci. 588:164-173
3. Chen, Y.-H. and R.L. DeHaan. 1991. The role of channel sub-states in voltage-induced decay of junctional conductance. In: 1991 International Meeting on Gap Junctions. Asilomar, CA
4. Chen, Y.-H. and R.L. DeHaan. 1992. Multiple-channel conductance states and voltage regulation of embryonic chick cardiac gap junctions. J. Membrane Biol. 127:95-111.
5. 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.
6. 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
7. R.L. DeHaan and Y.-H. Chen. 1995. Multiple connexins and asymmetric currents in embryonic cardiac gap junction. In: Process in Cell Research, ed. Y. Kanno, Elsevier Science, B.V., Amsterdam. 4: 187-200
8. Chen, Y.-H. and R.L. DeHaan. 1996. Asymmetric voltage-dependence of embryonic cardiac gap junction channels. American Journal of physiology, Cell Physiology. 270: C276-C285.
9. 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 Biology. 138: 891-899.
10. Merzdorf, C.S., Y.-H. Chen and D.A. Goodenough. 1998. Formation of functional tight junctions in Xenopus embryos. Developmental Biology. 195: 187-203.
11. Chen, Y.-H., 2000. Diverse Functions of Vertebrate Junctional Complexes in Human Health and neurological disorders. Fudan Lectures in Neurobiology. 235:93-104.
12. Chen, Y.-H., Q. Lu, E. E. Schneeberger and D.A. Goodenough. 2000. Restoration of Tight Junction Structure and Barrier Function by Down-Regulation of the Mitogen-activated Protein Kinase Pathway in Ras-transformed Madin-Darby Canine Kidney Cells. Mol Biol Cell. 11: 849-862.
13. 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
14. Jones, S.B., Lanford, G.W., Chen, Y.H., Moribito, M., Kim, K., and Lu, Q. 2002. Glutamate-Induced Catenin Redistribution and Dissociation from Postsynaptic Receptor Complexes. Neuroscience. 115 (4): 1009-1021.
15. Kim, K., A. Sirota, Y.-H. Chen, S. B. Jones, R. Dudek, G.W. Lanford, C. Thakore, and Q. Lu. 2002. Dendrite-like Process Formation and Cytoskeletal Remodeling Regulated by -Catenin Expression. Exp Cell Res. 275:171-184.
16. Chen, Y.H. and Lu, Q. 2002. Association of Nonreceptor Tyrosine Kinase c-Yes with Tight Junction Protein Occludin by Coimmunoprecipitation Assay. In: Cancer Cell Signaling, Methods in Molecular Biology. 218: 127-132.
17. Jeansonne, B., Lu, Q., Goodenough, D.A. and Chen, Y.H. 2003. Claudin-8 Interacts with Multi-PDZ Protein 1 (MUPP1) and Reduces Paracellular Conductance in Epithelial Cells. Cell and Mol Biol. 49: 13-21
18. Chen, Y.-H., D.A. Goodenough, and Q. Lu. 2004. Occludin, a Constituent of Tight Junctions. In: Tight Junctions, 3rd edition. Ronald G. Landes. pp. 1-14.
19. Lu, Q., Dobbs, L. J., Gregory, C. W., Lanford, B. A., Revelo, M. P., Shappell, S., Chen, Y. H. 2005. Increased expression of Catenin/neural plakophilin-related armadillo protein is associated with the down-regulation and redistribution of E-cadherin and p120ctn in human prostate cancer. Human Pathology. 36: 1037-1048.
20. Alexandre, M.D., Lu, Q., and Chen, Y.H. 2005. Overexpression of Claudin-7 Decreases the Paracellular Cl- Conductance and Increases the Paracellular Na+ Conductance in LLC-PK1 Cells. J. Cell Sci. 118:2683-93.
21. Alexandre, M. D., Jeansonne, B. G., Renegar, R. H., Tatum, R and Chen, Y. H. 2007. The First Extracellular Domain of Claudin-7 Affects the Paracellular Cl- Permeability. Biochemical and Biophysical Research Communications. 357:87-91.
22. Tatum, R., Zhang, Y., Lu, Q., Kim, K., Jeansonne, B. J., and Chen, Y. H. 2007. WNK4 Phosphorylates Ser206 of Claudin-7 and Promotes Paracellular Cl- Permeability. FEBS Letters. 581:3887-3891.

E-mail: cheny@ecu.edu
Telephone: 252-744-1341
Address: Brody 7N-55A, East Carolina University Greensboro, NC 27858

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