Education

Ph.D., 1993, Emory University

Postdoc., 1999, Harvard Medical School

Honors and Awards

Brody Brothers Endowment Research Award, 2019; Celebrating Women - East Carolina University Feature, 2019; The University Scholar, 2017; The Daily Reflector Feature, 2017; Inaugural Induction, National Academy of Inventors, 2013; East Carolina University Inaugural Inventor Award, 2009; The Daily Reflector Feature, 2008; East Carolina Alumni Magazine Feature, 2008; Research Development Award, 2007; Faculty Research Award, 2003; NIH NRSA Award, 1995; Grass Foundation Scholarship,1989.

Research

My research focuses on the roles of tight junction (TJ) proteins in human diseases such as inflammatory bowel disease (IBD) and cancer. We use various approaches including targeted gene deletion, molecular cell biology, and biochemistry to study protein-protein interactions, paracellular permeability regulation, and the role of protein kinases in the regulation of tight junction formation and functions.

Using TJ integral membrane protein claudin-7 tissue-specific inducible knockout mouse model and organoid culture system, we discovered that claudin-7 is essential for intestinal stem cell self–renewal and differentiation. Deletion of claudin-7 in intestines causes the significant alteration of gene expression profiles with striking downregulation of intestinal crypt stem cell markers and disrupted epithelial cell differentiation. Claudin-7 knockout mice show bloody stool, weight loss, mucosal ulcerations, and severe intestinal inflammation, resembling symptoms of IBD in human. Currently, we are investigating the molecular mechanism and signaling pathways that cause claudin-7 deletion-induced defects.

We are also interested in the roles of intestinal TJ in gut-brain axial regulations under health and disease conditions. We investigate potential effects of claudin-7 deletion and TJ disruptions in intestines on central nervous system. We apply small molecules as chemical biology tools to modulate and improve tissue barrier function and gut-brain axis regulations.

Selected Publications

Naser A, Xing TS, Tatum R, Lu, Q, Boyer PJ and Chen Y-H. 2024. Colonic crypt stem cell functions are controlled by tight junction protein claudin-7 through Notch/Hippo signaling. Ann NY Acad Sci. 1-17, DOI: 10.1111/nyas.15137

Xing TS, Benderman LJ, Sabu S, Parker J, Yang J, Lu Q, Ding L, and Chen, Y-H. 2020. Tight Junction Protein Claudin-7 Is Essential for Intestinal Epithelial Stem Cell Self-Renewal and Differentiation. Cell Mol Gastroenterol Hepatol. 9 (4): 641-659. This paper is an Editorial Featured Article of this issue with a cover page.

Garg PM, Tatum R, Ravisankar S, Shekhawat PS, and Chen, Y-H. 2015. Necrotizing enterocolitis in a mouse model leads to widespread renal inflammation, acute kidney injury, and disruption of renal tight junction proteins. Pediatric Research. 146:1-6.

Lu Z, Kim DH, Fan JM, Lu Q, Verbanac K, Ding L, Renegar R, and Chen, Y-H. 2015. A non-tight junction function of claudin-7 - Interaction with integrin signaling in suppressing lung cancer cell proliferation and detachment. Molecular Cancer. 14:(120) 1-15.

Vezzu, D.A.K., Lu, Q., Chen, Y.-H., Huo, S. 2014. Cytotoxicity of Cyclometalated Platinum Complexes Based on Tridentate NCN and CNN-coordinating ligands: Remarkable Coordination Dependence. J. Inorganic. Biochemistry. 134:49-56.

Friesland A, Zhao Y, Chen YH, Wang L, Zhou H, and Lu Q. Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility. Proc Natl Acad Sci USA. 2013; 110(4):1261-1266.

Hoggard, J., Fan, JM; Lu, Z; Lu, Q; Sutton, L; Chen, Y.-H. 2013. Claudin-7 increases chemosensitivity to cisplatin through the upregulation of caspase pathway in human NCI- H522 lung cancer cells. Cancer Science. 104(5): 611-618. This paper is the Editorial Highlight of this issue.

Ding, L., Lu, Z., Foreman, O., Tatum, R., Lu, Q., Renegar, R., Cao, J., and Chen, Y.-H.  2012. Inflammation and Disruption of the Mucosal Architecture in Claudin-7-Deficient Mice. Gastroenterology. 142: 305-315. This paper is the Editorial Highlight of this issue.

Zhang, G, Lai, BB, Zhou, YY, Chen, BA, Wang, XM, Lu, Q, Chen, YH. 2011. Fe3O4 Nanoparticles With Daunorubicin Induce Apoptosis Through Caspase-8/PARP Pathway And Inhibit K562 Leukemia Cell-Induced Tumor Growth In Vivo. Nanomedicine: nanotechnology, biology, and medicine. 7: 595-603.

Tatum, R., Zhang, Y., Salleng, K., Lu, Z., Lin, JJ., Lu, Q., Jeansonne, B. G., Ding, L. and Chen Y.-H.  2010. Renal Salt Wasting and Chronic Dehydration in Claudin-7-Deficient Mice. Am J Physiol Renal Physiol 298: F24-34. This paper is the Editorial Focus of this issue.