Xian-Ming Chen, MD
Xian-Ming Chen, MD

Xian-Ming Chen, MD

Professor
School of Medicine

Academic Appointments

Department

  • Med. Microbiology & Immunology

Position

  • Professor

Biography

Examples of the most recent publications can be found at this PubMed link.

Publications and Presentations

Articles

  • Wang Y, Gong AY, Ma S, Chen X, Li Y, Su CJ, Norall D, Chen J, Strauss-Soukup JK, and Chen XM. Delivery of parasite RNA transcripts into infected epithelial cells during Cryptosporidium infection and its potential impact on host gene transcription. J Infect Dis (Accepted on Dec 2, 2016 and currently in press), J Infect Dis, 2016
  • Ma S, Ming ZP, Gong AY, Wang Y, Chen X, Hu G, Zhou R, Shibata A, Swanson PC, and Chen XM. A long non-coding RNA, lincRNA-Tnfaip3, acts as a co-regulator of NF-ĸB to modulate inflammatory gene transcription. FASEB J (Accepted on Nov 28, 2016 and currently in press)., FASEB Journal, 2016
  • Ming ZP, Zhou R, and Chen XM.  Regulation of host epithelial responses to Cryptosporidium infection by microRNAs. Parasite Immunol (Invited review, accepted on Dec 2, 2016 and currently in press)., Parasite Immunology, 2016
  • Zhang XT, Gong AY, Wang Y, Chen X, Lim SYS, Dolata CE, and Chen XM. Cryptosporidium parvum infection attenuates the ex vivo propagation of murine intestinal enteroids. Physiol Rep (Accepted on Nov 8, 2016 and currently in press)., Physiological Reports, 2016
  • Mathy NW, and Chen XM. LncRNAs and their transcriptional control of inflammatory responses.  J Biol Chem (Invited review, accepted on Nov 8, 2016 but on hold publishing with the other reviews in the series), J Biol Chem, 2016
  • Hu G, Gong AY, Wang Y, Ma S, Chen X, Chen J, Su CJ, Shibata A, Strauss-Soukup JK, Drescher KM, and Chen XM.  LincRNA-Cox2 promotes late inflammatory gene transcription in macrophages through modulating SWI/SNF-mediated chromatin remodeling., Journal of Immunology, 2016;196, 2799–2808, 2016
  • Tong Q, Gong AY, Zhang X, Lin C, Ma S, Chen J, Hu G, and Chen XM. LincRNA-Cox2 modulates TNFα-induced transcription of Il12b gene in intestinal epithelial cells through regulation of Mi-2/NuRD-mediated epigenetic histone modifications., FASEB Journal, 2016;30, 1187–1197, 2016
  • Xia Z, Lu Y, Li X, Chen XM, and Zhou R. Upregulation of KSRP by miR-27b provides IFN-γ-induced post-transcriptional regulation of CX3CL1 in liver epithelial cells., Scientific Reports, 2015:5, 17590, 2015
  • Checkley W, White Jr AC, Jaganath D, Arrowood MJ, Chalmers RM, Chen X-M, Fayer R, Griffiths J, Guerrant RL, Hedstrom L, Huston C, Kotloff KL, Kang G, Mead JR, Miller M, Petri Jr W, Priest JW, Roos DS, Striepen B, Thompson RCA, Ward HD, Van Voorhis W, Xiao L, Zhu G, Houpt ER. Cryptosporidiosis: Global Burden, Novel Diagnostics, Therapeutics and Vaccine Targets., Lancet Infectious Diseases, 2015;15(1), 85-94, 2015
  • Hu G, Feng Y, O’Hara SP, and Chen XM. Immunology of Cryptosporidiosis. In: Cryptosporidium: parasite and disease.Simone M. Caccio and Giovanni Widmer (eds)., Not Applicable, Springer-Verlag Wien, 2014., 423-454, 2014
  • Zhou R, Feng F, and Chen XM. Non-coding RNAs in epithelial immunity to Cryptosporidium infection., Parasitology, 2014;141(10), 1233-43., 2014
  • Xie H, Lei N, Gong A-Y, Chen XM, and Hu G. Cryptosporidium parvum induces SIRT1 expression in host epithelial cells by downregulating let-7i., Human Immunology, 2014;75(8), 760-5, 2014
  • Hu G, Gong AY, Roth AL, Huang BQ, Ward HD, Zhu G, LaRusso NF, Hanson ND and Chen XM. Release of luminal exosomes contributes to TLR4-mediated epithelial antimicrobial defense., PLoS Pathogens, 9(4), e1003261, 2013
  • Duan M, Yao H, Hu G, Chen XM, Lund AK, Buch S. HIV Tat induces expression of ICAM-1 in HUVECs: implications for miR-221/-222 in HIV-associated cardiomyopathy., PLoS One, 8(3), e60170, 2013
  • Yu C, Gong AY, Chen D, Sotelo Leon D, Young CYF, and Chen XM. Phenethyl isothiocyanate inhibits androgen receptor-regulated transcriptional activity in prostate cancer cells through suppressing PCAF., Molecular Nutrition & Food Research, 57(10), 1825-1833, 2013
  • Zhou R, Gong AY, Chen D, Eischeid AN, and Chen XM. Histone deacetylases and NF-kB signaling coordinate expression of CX3CL1 in epithelial cells in response to microbial challenge by suppressing miR-424 and miR-503, PLoS One, 2013;8(5):, e65153. , 2013
  • Liu J, Hu G, Chen D, Gong AY, Soori GS, Dobleman TJ, and Chen XM. Suppression of SCARA5 by Snail1 is essential for EMT-associated cell migration of A549 cells., Oncogenesis, 3013;2:, e73, 2013
  • Liu J, Eischeid AN, and Chen XM. Col1A1 production and apoptotic resistance in TGF-â1-induced epithelial-to- mesenchymal transition-like phenotype of 603B cells., PLoS One, 2012; 7(12):, e51371, 2012
  • Zhao J, Gong AY, Zhou R, Liu J, Eischeid A, and Chen XM. Downregulation of PCAF by miR-181s provides feedback regulation to TNF-á-induced transactivation of pro-inflammatory genes in gastrointestinal epithelial cells, Journal of Immunology, 2012;188(3): , 1266–1274. , 2012
  • Hu G, Drescher KM, and Chen XM. Exosomal MicroRNAs: Biology, Function and Therapeutic Potential., Fronters in Genetics, 2012;3:56. , 56-67. , 2012
  • Xiao J, Gong AY, Eischeid AN, Chen D, Deng CS, Young CYF, and Chen XM. miR-141 modulates androgen receptor transcriptional activity in human prostate cancer cells through targeting the small heterodimer partner protein., Prostate, 2012;72:, 1514–1522, 2012
  • Zhou R, Gong AY, Eischeid AN, and Chen XM. miR-27b targets KSRP to coordinate TLR4-mediated epithelial defense against Cryptosporidium parvum infection., PLoS Pathogens, 2012;8(5): , e1002702, 2012
  • Gong AY, Eischeid AN, Xiao J, Zhao J, Chen D, Wang ZY, Young CYF, and Chen XM. miR-17-5p targets the p300/CBP-associated factor and modulates androgen receptor transcriptional activity in cultured prostate cancer cells., BMC Cancer, 2012;12:, e492. , 2012
  • O'Hara SP, Tietz Bogert PS, Trussoni CE, Chen XM, and LaRusso NF. TLR4 promotes Cryptosporidium parvum clearance in a mouse model of biliary cryptosporidiosis., Journal of Parasitology, 2011; 97(5):, 813-821, 2011
  • Chen X, Song CH, Feng BS, Li TL, Li P, Zheng PY, Chen XM, Xing Z, and Yang PC. Intestinal epithelial cell-derived integrin ávâ6 plays an important role in the induction of regulatory T cells and inhibits an antigen specific Th2 response., Journal of Leukocyte Biology, 2011; 90(4):, 751-759. , 2011
  • Zhu R, O’Hara SP, Chen XM. MicroRNA regulation of innate immune responses in epithelial cells., Cell Mol Immunol, 2011;8(5):, 371-9. , 2011
  • O’Hara S, Chen XM, and LaRusso NF. Cell biology of Cryptosporidium parvum infection. O’Hara SP, Chen XM. Cell biology of Cryptosporidium parvum infection., Microbes and Infection, 2011;13(8-9): , 721-30. , 2011
  • Gong AY, Hu G, Zhou R, Liu J, Feng Y, Soukup GA, and Chen XM. MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection., International Journal of Parasitology, 2011;41(3-4):, 397-403. , 2011
  • O’Hara SP, Splinter PS, Gajdos GB, Trussoni CK, Fernandez-Zapico ME, Chen XM, and LaRusso NF. NF-kappaB p50-CCAAT-enhancer binding protein beta (C/EBP{beta})-mediated transcriptional repression of microRNA let-7i following microbial infection., J Biol Chem, 2010;285(1):, 216-225. , 2010
  • Hu G, Zhou R, Liu J, Gong AY, and Chen XM. MicroRNA-98 and let-7 regulate expression of suppressor of cytokine signaling-4 in biliary epithelial cells in response to Cryptosporidium parvum infection., J Infect Dis, 2010;202(1):, 125-35. , 2010
  • Hu G, Gong AY, Zhou R, Liu J, and Chen XM. MicroRNA-221/222 regulates ICAM-1 expression in cholangiocytes to modulate inflammation-associated cholangiocyte-T cell interactions., Am J Physiol Gastro & Liver, 2010;298(4):, G542-50. , 2010
  • Zhou R, Hu G, Gong AY, and Chen XM. Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS-induced transactivation of miRNA genes in human biliary epithelial cells., Nucleic Acids Research, 2010;38(10):, 3222-32. , 2010
  • Liu J, Hu G, Zhou R, Drescher KM, Chen XM. MicroRNAs in Epithelial Antimicrobial Immunity. . In: V.A. Erdmann and J. Barciszewski (eds.), RNA Technologies and Their Applications, RNA Technologies, Not Applicable, RNA Technologies and Their Applications, RNA Technologies, 355-367, 2010
  • 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, 2010;201(1):, 160-169. , 2010
  • 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., British Journal of Haematology, 2010;148:, 69-79. , 2010
  • 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;5(12): , e1000681. , 2009
  • Hu G, Zhou R, Liu J, Gong AY, Eischeid A, Dittman J, and Chen XM. MicroRNA-98 and let-7 confer cholangiocyte expression of cytokine-inducible Src homology 2-containing protein in response to microbial challenge., Journal of Immunology, 2009;183: , 1617-1624. , 2009
  • 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 interferon-gamma-induced B7-H1 expression in cholangiocytes., Journal of Immunology, 2009;182:, 1325-1333. , 2009
  • O’Hara SP, Small AJ, Badley AD, Chen XM, and LaRusso NF. HIV-1 Tat protein suppresses cholangiocyte TLR4 expression and defense against Cryptosporidium parvum., J Infect Dis, 2009;199(8):, 1195-1204. , 2009
  • Chen XM. MicroRNA signatures in liver diseases, World Journal of Gastroenterology, 2009;15(14):, 1665-1672. , 2009
  • Liu J, Drescher KM, and Chen XM. MicroRNAs and epithelial immunity (invited review)., International Review of Immuniology, 2009; 28(3):, 139-154. , 2009
  • O’Hara SP, Chen XM and LaRusso NF. Molecular mechanisms of Cryptospiridium-induced actin cytoskeleton dynamics. In: Giardia and Ctyptosporidium: From Molecules to Disease. Ortega-Pierres et al. (Eds.)., Not Applicable, CAB International. 2008;, 418-427, 2008
  • Chen XM, O’Hara SP, and LaRusso NF. The immunobiology of cholangiocytes., Immunology and Cell Biology, 2008;86:, 497-505. , 2008
  • O’Hara SP, Small AJ, Chen XM and LaRusso NF. Host cell actin remodeling in response to Cryptosporidium., Subcell Biochem, 2008;47:, 92-100, 2008
  • 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 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. , 2008
  • 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. , 2007
  • 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 Journal of Gastroenterology, 2007;13(25):, 3500-3507, 2007
  • 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. , 2007
  • 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., Cellular Immunology, 2006; 8(12): , 1932-1945. , 2006
  • Dong HD and Chen XM. Immunoregulatory role of B7-H1 in chronicity of inflammatory responses., Cell Mol Immunol, 2006;3(3):, 179-187, 2006
  • Warren S, Chen XM, LaRusso NF, and Badley AD. Apoptosis as a pathogenic mechanism of HIV-associated opportunistic infection. Cell Death During HIV Infection. Badley A. ed.,, Not Applicable, 2006, 421-440. , 2006

Publications

  • Liu J, Gong A-Y, Zhou R, and Chen XM. TGF-beta-1 induces EMT, stimulates production of Col1A1 and decreases expression of pro-apoptotic genes in cholangiocytes in vitro., Molecular Biology of the Cell, 2010, 2010, 2010
  • Zhou R, Gong A-Y, Zhao J, and Chen XM. HIV-1 Tat protein impairs epithelial antimicrobial defense through modulating KSRP expression, Molecular Biology of the Cell, 2010, 2010, 2010
  • Gong A-Y, Hu G, Zhou R, Liu J, Soukup GA, Feng Y, and Chen XM. miR-221 controls ICAM-1 expression in epithelial cells in response to Cryptosporidium parvum infection., Molecular Biology of the Cell, 2010, 2010, 2010
  • Guoku Hu, Rui Zhou, Ai-Yu Gong, and Chen XM. MicroRNA-98 and let-7 Modulate Cryptosporidium parvum-induced Expression of Suppressor of Cytokine Signaling-4 (SOCS4) in Biliary Epithelial Cells., Molecular Biology of the Cell, 2008, 2008
  • Rui Zhou, Guoku Hu, Ai-Yu Gong, and Chen XM. NF-kappaB p65-dependent Transactivation of miRNA Genes Following Cryptosporidium parvum Infection Stimulates Epithelial Cell Immune Responses., Molecular Biology of the Cell, 2008, 2008
  • Li XQ, Liu J, Zhou R He YL, Huang S, Huang S, and Chen XM. Silencing of Mir-22 Is Linked to H3K27 Trimethylation and Independent of DNA Methylation in Pre-B Acute Lymphoblastic Leukemia Cells., Blood, 2008, 2008
  • Ai-Yu Gong, Rui Zhou, Guoku Hu, Xiaoqing Li, Patrick L. Splinter, Steven P. O’Hara, Nicholas F. LaRusso, Garrett A. Soukup, Haidong Dong, and Chen XM. MicroRNA-513 Regulates Interferon-gamma-induced B7-H1 Expression in Cholangiocytes., Molecular Biology of the Cell, 2008, 2008
  • Guoku Hu, Rui Zhou, Ai-Yu Gong, and Chen XM. MicroRNA-98 and let-7 Regulate Expression of Cytokine-induced SH2 Protein and Modulate Microbial-stimulated NF-kappaB Activation in Epithelial Cells, Molecular Biology of the Cell, 2008, 2008
  • Bogert PS, O'Hara SP, Trussoni CE, Stroope AJ, Lewis JT, Chen XM, LaRusso NF. Toll-like receptor 4-mediated immune response is required for in vivo eradication of C. parvum infection of the biliary tract, Gastroenterology, 2008, 2008
  • O'Hara SP, Gajdos GB, Huang BQ, Splinter PL, Chen XM, LaRusso NF. Myosin II-dependent membrane translocation of SGLT1 and Aqp1 is required for efficient C. parvum cellular invasion of cholangiocytes., Gastroenterology, 134, A353-A353, 2008
  • O’Hara SP, Small AJ, Splinter PL, Trussoni CE, Gajdos GB, Chen XM, and LaRusso NF. HIV-1 Tat Protein Decreases Cholangiocyte TLR4 Expression and Abrogates Epithelial Immune Responses against Cryptosporidium parvum Infection, Molecular Biology of the Cell, 2007, 2007
  • Splinter PL, O’Hara SP, Trussoni CE, Gajdos G., Chen XM, and LaRusso NF. NF-kB Regulation of a Cellular MicroRNA, Let-7i, Contributes to Biliary Epithelial Immunity Against Cryptosporidium parvum Infection., Molecular Biology of the Cell, 2007, 2007
  • Chen XM, Splinter P. L., O’Hara S. P. and LaRusso N. F. MicroRNA-mediated Post-transcriptional Gene Silencing is Involved in Cholangiocyte Defense against Cryptosporidium parvum Infection, Molecular Biology of the Cell, 2006, 2006
  • O’Hara SP, HuangBQ, Splinter PL, Nelson JB, Chen XM, and LaRusso NF. Myosin II-dependent Membrane Translocation of SGLT1 and AQP1 is Required for Efficient Host-cell Membrane Protrusion during C. parvum Cellular Invasion., Molecular Biology of the Cell, 2006
  • Splinter PL, O'Hara SP, Chen XM, LaRusso NF. Let-7i Expression is Regulated by NF-kB Pathway and is Involved in Cholangiocyte Defense Against Cryptosporidium parvum Infection., Hepatology, 44(4), 388A, 2006
  • Small AJ, O'Hara SP, Splinter PL, Chen XM, LaRusso NF. Tat, an HIV-1-associated Protein, Impairs Cholangiocyte Innate Immune Responses to Cryptosporidium parvum., Hepatology, 44(4), 389A, 2006

Presentations

  • LincRNAs and NF-kappaB-mediated immune responses. East China Unviersity of Science and Technology, Shanghai, China., 2014
  • C. parvum-host cell interactions and pathogenesis of intestinal cryptosporidiosis. Wuhan University, Wuhan, China., 2014
  • Molecular basis of C. parvum-host cell interactions and pathogenesis. CDC, Shanghai, China, 2014
  • Non-coding RNA regulation of innate immune responses. Biochemistry and Molecular Biology, University of Nebraska Medical Center (UNMC)., 2014
  • Epithelial exosomes, ncRNAs and TLR-mediated mucosal defense. NIH/NIAID MIST Steering Committee meeting. Washington DC, 2014
  • Non-coding RNA regulation of NF-kappaB-mediated immune responses. Creighton University Medical Center., 2014
  • C. parvum-host cell interactions and pathogenesis of intestinal cryptosporidiosis. Wuhan University, Wuhan, China., 2014
  • RNA regulation of innate immune responses. Xianning College, Xianning, China, 2014
  • Non-coding RNAs and NF-kappaB-mediated immune responses. Chengdu, China, 2014
  • Molecular basis of C. parvum-host cell interactions. Lanzhou, China, 2014
  • LincRNAs and NF-kappaB-mediated inflammatory responses. Wuhan, China., 2014
  • Epithelial exosomes, ncRNAs and TLR-mediated mucosal defense. NIH/NIAID MIST Steering Committee meeting. Portland, OR, 2013
  • Non-coding RNAs and mucosal immunity to Cryptosporidium infection. The Fifth International Symposium of Parasitology/14th Biennial Meeting of the Chinese Society of Parasitology (CSP)., 2013
  • Non-coding RNAs are important regulatory molecules in mammalian cells. Nebraska CROBP program, 2013
  • Non-coding RNAs and NF-kappaB-mediated immune response. Department of Pharmacology, Creighton University School of Medicine., 2013
  • Luminal release of exosomal vesicles from biliary epithelium contributes to TLR4-mediated mucosal anti-Cryptosporidium parvum defense. Annual Meeting of American Society of Cell Biology. San Francisco, CA., 2012
  • Epithelial exosomes and TLR-mediated mucosal defense. NIH/NIAID MIST first face-to-face Steering Committee meeting. NIH, Bethesda, MD., 2012
  • Exosomes: cellular function and therapeutic potential. Creighton LB595 seminar series., 2011
  • New perspectives in microRNA regulation of biliary innate immunity. Digestive Health Center Seminar Series. Division of Gastroenterology, Hepatology & Nutrition. Cincinnati Children’s Hospital. Cincinnati., 2011
  • Boosting epithelial innate immunity as a potential solution to C. parvum infection. Cryptosporidium: Global burden, novel diagnostics and therapeutics, and preventive strategies. Workshop organized by the NIH and Bill & Melinda Gates Foundation. Philadelphia., 2011
  • Non-coding RNA regulation of androgen receptor-regulated transactivation in prostate cancer cells. Creighton LB595 Program., 2011
  • MicroRNAs: Regulatory function and potential applications for cancer gene therapy. Creighton Molecular Carcinogenesis Symposium, 2011
  • TGFbeta-1 induces EMT, stimulates production of Col1A1 and decreases expression of pro-apoptotic genes in cholangiocytes in vitro. Annual Meeting of American Society of Cell Biology. Philadelphia., 2011
  • HIV-1 Tat protein impairs epithelial antimicrobial defense through modulating KSRP expression. Annual Meeting of American Society of Cell Biology. Philadelphia, 2011
  • miR-221 controls ICAM-1 expression in epithelial cells in response to C. parvum infection. Annual Meeting of American Society of Cell Biology. Philadelphia, 2011
  • MicroRNA regulation of epithelial antimicrobial defense. Xianning Medical College. China, 2010
  • MicroRNAs and anti-parasitic immunity. 10th International Conference of Coccidiosis., 2010
  • miR-221 controls ICAM-1 expression in epithelial cells in response to Cryptosporidium parvum infection. 10th International Conference of Coccidiosis., 2010
  • MicroRNA-98 and let-7 Modulate Cryptosporidium parvum-induced Expression of Suppressor of Cytokine Signaling-4 (SOCS4) in Biliary Epithelial Cells. Annual Meeting of American Society of Cell Biology. San Diego., 2009
  • NF-kappaB p65-dependent Transactivation of miRNA Genes Following Cryptosporidium parvum Infection Stimulates Epithelial Cell Immune Responses. Annual Meeting of American Society of Cell Biology. San Diego., 2009
  • Pathophysiology of Cryptosporidium infection. III International Giardia and Cryptosporidium Conference. 11-15 Oct 2009, Orvieto, Italy., 2009
  • MicroRNA-513 Regulates Interferon-gamma-induced B7-H1 Expression in Cholangiocytes. Annual Meeting of American Society of Cell Biology. San Francisco., 2008
  • MicroRNA-98 and let-7 Regulate Expression of Cytokine-induced SH2 Protein and Modulate Microbial-stimulated NF-kappaB Activation in Epithelial Cells. Annual Meeting of American Society of Cell Biology. San Francisco., 2008
  • HIV Tat protein decreases cholangiocyte TLR4 expression and abrogates epithelial immune responses against Cryptosporidium parvum infection. Annual Meeting of American Society of Cell Biology. Washington DC., 2007
  • NF-kB regulation of a cellular microRNAs, let-7i, contributes to biliary epithelial immunity against Cryptosporidium parvum infection. Annual Meeting of American Society of Cell Biology. Washington DC., 2007
  • MicroRNA-mediated Post-transcriptional Gene Silencing is Involved in Cholangiocyte Defense against Cryptosporidium parvum Infection. Annual Meeting of American Society of Cell Biology. San Diego, 2006
  • Let-7i expression is regulated by the NF-kB pathway and is involved in cholangiocyte defense against Cryptosporidium parvum infection. The 71st Symposium: Regulatory RNAs. Cold Spring Harbor Laboratory. New York, 2006

Research and Scholarship

Research and Scholarship Interests

  • The Chen laboratory is interested in the molecular basis underlying ncRNA regulation of immune homeostasis and its relevance to the pathogenesis of inflammatory and infectious diseases at the mucosal surfaces. Such studies should provide mechanistic insights into the pathogenesis of a variety of important human diseases and will help identify potential new targets for therapeutic intervention. The major areas of the lab research are:
     
    • Expression of ncRNA genes and their role in regulation of immune responses of innate immune cells and epithelial cells at mucosal surfaces.
    • Interactions between gastrointestinal epithelial cells and Cryptosporidium spp. and the involvement of ncNRAs in the pathogenesis of Cryptosporidiosis.
    • The ncRNA signatures that may link chronic mucosal inflammation to the initiation and development of epithelial carcinoma.
    Description of the program
    Mucosal surfaces, such as the gastrointestinal (GI), respiratory, and urogenital tracts, are a key portal of entry for the majority of medically relevant infectious diseases. Epithelial cells along the mucosal surface provide the front line of defense against luminal pathogen infection and are an important component of mucosal immunity. Toll-like receptors (TLRs) and the NF-kappaB signaling pathway are key to mucosal immune defense and have been implicated in secretion of antimicrobial peptides, release of cytokines/chemokines to mobilize immune effector cells, and activation of adaptive immunity. Specifically, the TLR/NF-kappaB signaling carries out a finely controlled procedure that orchestrates the transactivation of immune genes "at the right place at the right time," but the underlying molecular mechanisms of this regulation are not fully understood. Genomic research has revealed the existence of a large number of non-coding RNAs (ncRNAs) in mammalian cells. Several classes of ncRNAs, such as miRNAs and the long intergenic ncRNAs (lincRNAs), have been shown to play key regulatory roles in diverse biological functions. Our general working hypothesis is that ncRNAs participate in the regulation of TLR/NF-kappaB-mediated immune responses in innate immune cells and mucosal epithelial cells; disorder of such regulation contributes to the pathogenesis of various inflammatory and infectious diseases (e.g., intestinal cryptosporidiosis) at the mucosal surfaces in humans; thus, ncRNAs may be new targets for therapeutic interventions.
     
    First, we are investigating the role of TLR/NF-kappaB-responsive ncRNAs in the regulation of inflammatory and defense responses in innate immune cells and intestinal epithelial cells, in particular transcriptional and posttranscriptional regulation of key inflammatory genes and release of epithelial cell-derived exosomes. Exosomes are extracellular vesicles derived from cells that function as "bioactive vesicles" to promote cell-cell communications. We have demonstrated that microbial challenge stimulates exosome release from the apical side of cultured GI epithelial monolayers in a TLR4-dependent manner. Released exosomes shuttle a variety of antimicrobial peptides and display antimicrobial activity ex vivo (e.g., anti-C. parvum activity). Moreover, TLR/NF-kappaB-responsive ncRNAs may regulate the transcription of inflammatory genes (through lincRNAs) and also the exocytotic process (through miRNAs) relevant to the release of exosomes in epithelial cells. Using complementary biochemical, molecular, and morphologic approaches, we are testing: i) how TLR/NF-kappaB-responsive lincRNAs modulate the transcription of inflammatory genes in innate immune cells and epithelial cells upon microbial challenge; ii) how the TLR signaling pathway regulates release of apical exosomes from epithelial cells; iii) how TLR signaling controls exosomal shuttling of antimicrobial peptides; and iv) how epithelial cell-derived exosomes participitate in TLR-mediated epithelial antimicrobial defense.
     
    Second, we have conducted ground-breaking studies on the molecular mechanisms by which the protozoan parasite Cryptosporidium spp. interacts with host epithelial cells and causes intestinal cryptosporidiosis. Cryptosporidium is a ubiquitous pathogen that infects the GI epithelium in humans and ruminants. This parasite is of great medical importance as infections in immunocompromised humans, including AIDS, cancer, and infections in transplant patients, often lead to life-threatening illness. A recent massive clinical and epidemiological study revealed that Cryptosporidium is actually one of the most common pathogens (second only after rotavirus) responsible for moderate-to-severe diarrhea in children under two years of age in developing countries. There is currently no fully effective therapy available for the infection. Using in vitro and in vivo models of cryptosporidiosis, we are investigating how ncRNA-mediated gene regulation is altered in infected host cells, contributing to epithelial antimicrobial defense. We are also interested in how Cryptosporidium invades host epithelial cells and the pathologic significance of specific delivery of parasite molecules into host cells during and after internalization, including modulation of epigenetic gene regulation in the infected host cells. We believe that our studies will reveal new molecular mechanisms by which Cryptosporidium infection causes disease in AIDS patients and young children and lead to the development of new therapeutic strategies.
     
    In related studies focusing on the ncRNA signatures that may link chronic mucosal inflammation to the initiation and development of epithelial carcinoma, we are testing the role of lincRNAs in the progression of prostate cancer. Evidence supports that oncogenic NF-kappaB activation promotes prostate cancer progression. We propose that oncogenic activation of NF-?B signaling downregulates expression of metastatic suppression genes to promote prostate cancer progression through lincRNA-mediated epigenetic chromatin remodeling, a process facilitated by the nuclear-to-cytoplasmic translocation of 14-3-3 proteins. Discerning the underpinning mechanisms of the link between inflammation and malignancy of prostate cancer could advance the knowledge of tumor progression of epithelial carcinoma.

Current Research Projects

Grant Funding Received

  • National Institutes of Health, 1U01AI095532-05, EPITHELIAL EXOSOMES AND TLR-MEDIATED MUCOSAL DEFENSE
  • State of NE-LB595, LINCRNAS AND ONCOGENIC ACTIVATION OF NF-KB IN PROSTATE CANCER PROGRESSION
  • National Institutes of Health, 1R01AI116323-02, MOLECULAR BASIS OF INTESTINAL CRYPTOSPORIDIOSIS
  • National Institutes of Health, 1R01AI128854-01, LINCRNAS AND INFLAMMATORY GENE REPROGRAMMING IN SEPSIS
  • State of NE-LB606, INTESTINAL STEM CELL RESPONSES TO C. PARVUM INFECTION
  • State of NE-LB692, EPITHELIAL LINCRNAS AND GASTROINTESTINAL MUCOSAL DEFENSE
  • National Institutes of Health, 2U01AI095532-06, EPITHELIAL LINCRNAS AND GASTROINTESTINAL MUCOSAL DEFENSE
  • National Institutes of Health, 1U01AI095532-05, EPITHELIAL EXOSOMES AND TLR-MEDIATED MUCOSAL DEFENSE
  • State of NE-LB595, LINCRNAS AND ONCOGENIC ACTIVATION OF NF-KB IN PROSTATE CANCER PROGRESSION
  • National Institutes of Health, 1R01AI116323-02, MOLECULAR BASIS OF INTESTINAL CRYPTOSPORIDIOSIS
  • National Institutes of Health, U01AI095532-S1, Prim Recp: Oregon Health & Science University, EXOSOMAL RNA SHUTTLING IN GI MUCOSAL IMMUNITY TO CRYPTOSPORIDIAL INFECTION
  • State of NE-LB606, INTESTINAL STEM CELL RESPONSES TO C. PARVUM INFECTION
  • National Institute of Health, U01AI131283, Mechanisms of gastrointestinal defense suppression in neonates and infants
  • Bill & Melinda Gates Foundation; A model to assess gut factors on anti-parasite drug efficacy