Basic and Translational Research in Inflammatory Bowel Disease (IBD) and Autoimmune Liver Diseases
Lab members (current):
Douglas Adler, M.S.
Romina P. Berinat, Ph.D.
Weiwei Jiang, M.D.
Elizabeth Mann, Ph.D.
Xiaoou Yang, M.D.
Huihong Zhai, M.D./Ph.D.
Ted Bayless, M.D.
Steven Brant, M.D.
Sharon Brown, Ph.D./FNP-BC
Carmen Cuffari, M.D.
Mark Lazarev, M.D.
Michael Marohn, M.D.
Xuhang Li, Ph.D.
Assistant Professor of Medicine
Johns Hopkins University School of Medicine
Department of Medicine
746 Ross Research Bldg, 720 Rutland Ave
Baltimore, MD 21205
Tel: 443-287-4804 (Office)
Inflammatory bowel disease (IBD) is a common, idiopathic, chronic and frequently disabling inflammatory disorder of the intestines characterized by a dysregulated mucosal immune response. It is generally classified into two subtypes: Crohn’s disease (CD) and ulcerative colitis (UC). While UC occurs in the colonic mucosa, CD is transmural and often involves both colon and distal ileum. Nevertheless, CD can affect any part of the gastrointestinal (GI) track. IBD affects more than a million Americans. It has a prevalence of ~0.2% of the Western population. Moreover, IBD incidence is dramatically increasing in Asian and traditional underdeveloped countries. In spite of intense researches, the pathogenesis of IBD is still elusive, and there is no cure for IBD.
Biomarker discoveries and development for diagnosis and prognosis of IBD and other autoimmune diseases (AILDs): Through various state-of-art technologies, including high-throughput protein chip technology and multiplex ELISA, we are identifying novel and potentially high-value protein/antibody as diagnostic and or prognostic biomarkers for IBD and AILDs. Biomarkers of GI disorders, such as irritable bowel syndrome (IBS) and celiac disease, are also under investigation.
Exploring molecular pathogenesis and developing novel therapeutics of IBD: Using various biochemical and molecular technologies, including quantitative proteomics, microarray gene profiling and RNA Seq, we are identifying novel signaling pathways, genes, proteins and posttranslational protein modifications that are potentially involved in pathogenesis of IBD and/or used as therapeutic targets for development of new IBD therapy. Research involves both human and animal models of IBD.
Significant efforts are also being made by our laboratory to:
- Understand the molecular mechanisms of why 25 percent to 30 percent of IBD patients fail to respond to the mainstay therapeutics, such as azathioprine (6-MP) or anti-TNFα (such as infliximab)
- Develop diagnostic assays that are capable of predict non-responders before initiation of these therapies. So far biomarker studies have led to the application of four U.S. and international patents.
Selected Publications (from more than 40)
- Liu, L., Ye, M. Yang, J., Joosse, M., Sun, Y., Jin, S., Zhang, J., Marohn, M., and Li, X. 2013. Spontaneous and persistent activation of NLRP3/NALP3 inflammasome plays a critical pathological role in the colitis of IL-10 deficient mice. Accepted to Journal of Clinical Investigation.
- Chu, K., Watermeyer, G., Shelly, L., Janssen, J., May T. D., Brink, K., Benefeld, G., Li, X. 2013. Childhood Helminth Exposure is Protective Against Inflammatory Bowel Disease: A Case Control Study in Cape Town, South Africa. Accepted to Inflammatory Bowel Disease.
- Kaul, A., Hutfless, S., Liu, L., Bayless, T. M., Marohn, M.R., and Li, X. 2012. Glycan Antibody Biomarkers for Inflammatory Bowel Disease Diagnosis and Progression: A Systematic Review and Meta-analysis. Inflammatory Bowel Disease. 18 (10), 1872-1884.
- Conklin, L.S., Cuffari, C., Okazaki, t., Miao, Y., Saatian, B., Chen T.E., TSE, T., Brant, S.R., Li, X. 2012. 6-MP Transport in Human Lymphocytes: Correlation with Drug-Induced Cytotoxicity. Journal of Digestive Diseases. 13 (2): 82-93.
- Alex, P., Ye, M., Sipes, J., Nguyen, T., Gonzales, L., Saksonov-Suhodrev, M., Zhang, T., Arora, Z., Centola, M., Guggino, S.E., Li, X. 2010. Clc-5 Knockout Mice Are More Susceptible to Dextran Sulphate Sodium Induced Colitis. Journal of Immunology. 187, 3988-3996.
- Chen, J., Sullivan, S., Anderson, T., Tan, A.C., Alex, J., Brant, S.R., Cuffari, C., Bayless, T. M., Taylor, M. V., Burek, C.L., Wang, H., Li, R., Datta, L. W., Wu, Y., Winslow, R.L, Zhu, H. and Li, X. 2009. Identification of novel serological biomarkers for inflammatory bowel disease using a protein chip of whole E. coli proteome. Molecular and Cellular Proteomics. 8(8), 1765-76.
- Sullivan, S., Alex P., Dassopoulos, T., Zachos, N.C., Iacobuzio-Donahue, C., Donowitz, M., Brant, S.R., Cuffari, C., Harris, M.L., Datta L.W., Conklin, L., Chen, Y., and Li, X. 2009. Down-Regulation of Sodium Transporters and NHERF Proteins in IBD Patients and Mouse Colitis Models: Potential Contributors to IBD-associated Diarrhea. Inflammatory Bowel Disease. 15(2), 261-274.
- Alex, P, Zacho, N., Nguyen, T., Gonzales, L., Chen, T.E., Conklin, L.S., Centola, M, and Li, X. 2009. Distinct cytokine patterns identified from multiplex profiles of experimental colitis. Inflammatory Bowel Disease. 15(3), 341-352.
- Alex, P., Gucek, M., Li, X. 2009. Applications of Proteomics in Study of Inflammatory Bowel Diseases: Current Status and Future Potential with Available Technologies. Inflammatory Bowel Disease. 15(4), 616-629.
- Li, X., Conklin, L., and Alex, P. 2008. New Serological Biomarkers of Inflammatory Bowel Diseases. World Journal of Gastroenterology. 14 (33), 5115-5124.