Xian-Ming Chen, M.D.
Appointment(s) and Titles:
Associate Professor, Medical Microbiology and Immunology
Education:
M.D. 1985, Medicine, Hubei Medical University Xianning Medical School, Hubei, China
M.S. 1988, Cellular Biology and Pathophysiology, Shanxi Medical University, Taiyuan, China Research Fellowships: 1993-1994, Cellular and Molecular Biology, Kurume
University School of Medicine, Kurume, Japan; 1996-2001, Pathoparasitology and Pathoimmunology, Mayo Clinic College of Medicine, Rochester, Minnesota
Research Interests:
Small non-coding RNA molecules such as microRNAs are emerging as important regulators of gene expression and represent potential targets for new therapeutic strategies for human diseases.
We have identified a panel of microRNAs that are responsive to microbial infection in human epithelial cells and our objectives are to test the functional roles for those microRNAs in epithelial anti-microbial immunity.
Such studies should provide a rational basis for the design and implementation of new therapeutic strategies for infectious diseases.
Recent Publicatons:
Zhou R, Hu G, Liu J, Gong AY, Drescher KM, and Chen XM. NF-kappaB p65-dependent transactivation of miRNA genes following Cryptosporidium parvum infection stimulates epithelial cell immune responses. PLoS PATHOGENS 2009 (in press).
Gong AY, Zhou R, Hu G, Liu J, Sosnowska D, Drescher KM, Dong H, and Chen XM. Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by downregulating microRNA-513. J Infect Dis 2009 (in press).
O’Hara SP, Splinter PL, Gajdos GB, Trussoni CE, Fernandez-Zapico ME, Chen XM, and LaRusso NF. NF-kappaB p50-CAAT/enhancer-binding protein beta (C/EBPb)-mediated transcriptional repression of microRNA let-7i following microbial infection. J Biol Chem 2009 (published on line Nov 10).
Li X, Liu J, Zhou R, Huang S, Huang SA, and Chen XM. Gene silencing of miR-22 in acute lymphoblastic leukemia involves histone modifications independent of promoter DNA methylation. Brit J Haematol 2009 (published on line Oct 5).
Liu J, Drescher KM, and Chen XM. MicroRNAs and epithelial immunity (invited review). Int Rev Immunol 2009;28(3):139-154.
Hu G, Zhou R, Liu J, Gong AY, Eischeid AN, Dittman JW, and Chen XM. MicroRNA-98 and let-7 confer cholangiocyte expression of cytokine-inducible Src homology 2-containing protein in response to microbial challenge. J Immunol 2009;183:1617-1624.
Chen XM. MicroRNA signatures in liver diseases (editorial). World J Gastroenterol 2009;15(14):1665-72.
Gong AY, Zhou R, Hu G, Li X, Splinter PL, O'Hara SP, LaRusso NF, Soukup GA, Dong H, and Chen XM. MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes. J Immunol 2009;182(3):1325-33.
O'Hara SP, Small AJ, Gajdos GB, Badley AD, Chen XM, and LaRusso NF. HIV-1 Tat protein suppresses cholangiocyte toll-like receptor 4 expression and defense against Cryptosporidium parvum. J Infect Dis 2009;199(8):1195-204..
Yang N, Kaur S, Volinia S, Greshock J, Lassus H, Hasegawa K, Liang S, Leminen A, Deng S, Smith L, Johnstone C, Chen XM, Liu CG, Huang Q, Katsaros D, Calin G, Weber B, Bützow R, Croce CM, Coukos G, and L Zhang L. MicroRNA microarray identifies let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Research 2008;68(24):10307-14.
Chen XM, O’Hara SP, and LaRusso NF. The immunobiology of cholangiocytes. Immunol & Cell Biol 2008;86:497-505.
O’Hara SP, Chen XM, and LaRusso NF. Molecular mechanisms of Cryptospiridium-induced actin cytoskeleton dynamics. In: Giardia and Cryptosporidium: From Molecules to Disease. Ortega-Pierres et al. (Eds.). CAB International 2008;418-427.
O’Hara SP, Small AJ, Chen XM, and LaRusso NF. Host cell actin remodeling in response to Cryptosporidium. In: Molecular Mechanisms of Parasite Invasion. Barbara A. Burleigh and Dominique Soldati-Favre (Eds.). Subcell Biochem 2008;47:92-100.
Chen XM, Splinter PL, O’Hara SP, and LaRusso NF. A cellular miRNA, let-7i, regulates toll-like receptor 4 expression and contributes to cholangiocyte immune responses against Cryptosporidium parvum infection. J Biol Chem 2007;282(39):28929-28938.
Zhang HY, Han DW, Zhao ZF, Liu MS, Wu YJ, Chen XM, and Ji C. Multiple pathogenic factor-induced complications of cirrhosis in rats: a new model of hepatopulmonary syndrome with intestinal endotoxemia. World J Gastroenterol 2007;13(25):3500-3507.
O’Hara SP, Small AJ, Nelson JB, Badley AD, Chen XM, Gores GJ, and LaRusso NF. The human immunodeficiency virus type 1 Tat protein enhances Cryptosporidium parvum-induced apoptosis in cholangiocytes via a Fas ligand-dependent mechanism. Infect Immun 2007;75(2):684-696.
Nelson JB, O’Hara SP, Small AJ, Tietz PS, Choudhury AK, Pagano RE, Chen XM, and LaRusso NF. Cryptosporidium parvum infects human cholangiocytes via sphingolipid-enriched membrane microdomains. Cell Microbiol 2006;8(12):1932-1945.
Dong HD and Chen XM. Immunoregulatory role of B7-H1 in chronicity of inflammatory responses. Cell Mol Immunol 2006;3(3):179-187.
Chen XM, O’Hara SP, Nelson JB, Splinter PL, Small AJ, Tietz PS, Limper AH, and LaRusso NF. Multiple toll-like receptors are expressed in human cholangiocytes and mediate host epithelial responses to Cryptosporidium parvum via activation of NF-kB. J Immunol 2005;175(11):7447-7456.
Chen XM, O’Hara SP, Huang BQ, Splinter PL, Nelson JB, and LaRusso NF. Localized glucose and water influx facilitates Cryptosporidium parvum cellular invasion via modulation of host-cell membrane protrusion. Proc Nat Acad Sci USA 2005;102(18):6338-6343.
O’Hara SP, Huang BQ, Chen XM, Nelson JB, and LaRusso NF. Distribution of Cryptosporidium parvum sporozoite apical organelles during attachment to and internalization by cultured biliary epithelial cells. J Parasitol 2005;91(5):995-999.
Chen XM and LaRusso NF. Cryptosporidium and bile duct injury. Pathophysiology of the Biliary Epithelia. Alpini G., Alvaro D., LeSage G., and LaRusso NF. eds., Landes Biosciences and Eurekah.com, Georgetown, TX 2004; pp357-367.
Chen XM, O’Hara SP, Huang BQ, Nelson JB, Zhu G, Ward HD, and Nicholas NF. Apical organelle discharge by Cryptosporidium parvum is temperature, cytoskeleton, and intracellular calcium dependent and required for host cell invasion. Infect Immun 2004;72(12):6806-6816.
Chen XM, Splinter PL, Tietz PS, Billadeau DD, and LaRusso NF. Phosphatidylinositol 3-kinase and frabin mediate Cryptosporidium parvum cellular invasion via activation of cdc42. J Biol Chem 2004;279(30):31671-31678.
Chen XM, Huang BQ, Splinter PL, Orth JD, Billadeau DD, McNiven MA, and LaRusso NF. Cdc42 and the Arp/N-WASP Network Mediate Cellular Invasion of Cryptosporidium parvum. Infect Immun 2004;72(5):3011-3021.
Huang BQ, Chen XM, and LaRusso NF. Mechanisms of attachment and internalization of Cryptosporidium parvum by biliary epithelia: a morphologic study. J Parasitol 2004;90(2):212-221.
Chen XM, Huang BQ, Splinter PL, Cao H, Zhu G, McNiven MA, LaRusso NF. Cryptosporidium parvum invasion of biliary epithelia requires host cell tyrosine phosphorylation of cortactin via c-Src. Gastroenterology 2003;125(1):216-28.
Gong AY, Tietz PS, Muff MA, Splinter PL, Huebert RC, Strowski MZ, Chen XM, and LaRusso NF. Somatostatin stimulates ductal bile absorption and inhibits ductal bile secretion in mice via SSTR2 on cholangiocytes. Am J Physiol Cell Physiol 2003;284(5):C1205-14.
Tietz PS, Marinelli RA, Chen XM, Huang B, Cohn J, Kole J, McNiven MA, Alper S, and LaRusso NF. Agonist-induced coordinated trafficking of functionally related transport proteins for water and ions in cholangiocytes. J Biol Chem 2003;278(22):20413-9.
Chen XM and LaRusso NF. Cryptosporidiosis and the pathogenesis of AIDS-cholangiopathy. Semin Liver Dis 2002;22(3):277-89.
Chen XM, Keithly JS, Paya CV, and LaRusso NF. Cryptosporidiosis. N Engl J Med 2002;346(22):1723-31.
Tietz PS, Chen XM, Gong AY, Huebert RC, Masyuk A, Masyuk T, Splinter PL, and LaRusso NF. Experimental models to study cholangiocyte biology. World J Gastroenterol 2002;8(1):1-4.
Chen XM, Levine SA, Splinter PL, Tietz PS, Ganong AL, Jobin C, Gores GJ, Paya CV, and LaRusso NF. Cryptosporidium parvum activates nuclear factor kappaB in biliary epithelia preventing epithelial cell apoptosis. Gastroenterology 2001;120(7):1774-83.
Chen XM and LaRusso NF. Mechanisms of attachment and internalization of Cryptosporidium parvum to biliary and intestinal epithelial cells. Gastroenterology 2000;118(2):368-79.
Links:
Chen Lab