Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic and frequently disabling intestinal inflammatory disorders that affect more than a million individuals in the US. One of the most dreaded complications of UC and Crohn's colitis is the greatly increased risk of developing colorectal cancer (CRC), which accounts for approximately 15% of all deaths in IBD patients. So far, while endoscopy remains as the only established and vital tool for IBD diagnosis/prognosis, it is an invasive and highly resource-intensive procedure. Therefore, a less expensive, less laborious, less invasive tool is needed for IBD diagnosis/prognosis. Here, we propose a novel high-throughput proteomic approach to screen and identify new serological biomarkers for IBD. We hypothesize that disease- specific antibodies, either anti-intestinal microorganisms or anti-human endogenous proteins (autoantibodies), are present in the sera of IBD patients, and these specific antibodies can be used as serological biomarkers for either IBD diagnosis, or as indicative of disease prognosis and/or responsiveness to therapy. With a complete access to a large number of sera from normal subjects and IBD patients, serum antibodies will be used directly to screen high-density protein chips (also called protein arrays) to identify IBD-specific protein antigens. Our yeast protein chips that cover the entire yeast proteome (with 5,800 unique proteins) and robotically produced at Johns Hopkins will be used in the initial stage of our proposed screening. We are currently in the developing phase of generating E. coli proteome chips (with 4288 unique proteins) and human protein chips (4,000 unique proteins), which are expected to be ready in 3- 5 months. E. coli and human protein chips will be used in the second phase of biomarker screening. The goal is to identify CD- and UC-specific serological biomarkers and to use these biomarkers to develop a clinically reliable, comprehensive one-step diagnostic protein chip/kit for IBD diagnosis and subtyping. Moreover, identification of IBD-specific antibodies might not only reveal new pathogenic mechanisms of IBD, but also provide potential molecular targets for therapeutic intervention of IBD.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-DIG-A (10))
Program Officer
Hamilton, Frank A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Jin, Peng; Wang, De-Zhi; Lyu, Chen-Xi et al. (2017) Mismatch Repair Protein hMLH1, but not hMSH2, Enhances Estrogen-Induced Apoptosis of Colon Cancer Cells. J Cancer 8:3232-3241
Lin, Rong; Ding, Zhen; Ma, Huan et al. (2015) In Vitro Conditioned Bone Marrow-Derived Mesenchymal Stem Cells Promote De Novo Functional Enteric Nerve Regeneration, but Not Through Direct-Transdifferentiation. Stem Cells 33:3545-57
Jiang, Weiwei; Li, Xuhang (2015) Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy. Mol Diagn Ther 19:141-58
Kaul, Amit; Hutfless, Susan; Liu, Ling et al. (2012) Serum anti-glycan antibody biomarkers for inflammatory bowel disease diagnosis and progression: a systematic review and meta-analysis. Inflamm Bowel Dis 18:1872-84
Alex, Philip; Ye, Mei; Zachos, Nicholas C et al. (2010) Clcn5 knockout mice exhibit novel immunomodulatory effects and are more susceptible to dextran sulfate sodium-induced colitis. J Immunol 184:3988-96
Alex, Philip; Zachos, Nicholas C; Nguyen, Thuan et al. (2009) Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflamm Bowel Dis 15:341-52
Sullivan, Sean; Alex, Philip; Dassopoulos, Themos et al. (2009) Downregulation of sodium transporters and NHERF proteins in IBD patients and mouse colitis models: potential contributors to IBD-associated diarrhea. Inflamm Bowel Dis 15:261-74
Chen, Chien-Sheng; Sullivan, Sean; Anderson, Troy et al. (2009) Identification of novel serological biomarkers for inflammatory bowel disease using Escherichia coli proteome chip. Mol Cell Proteomics 8:1765-76
Alex, Philip; Gucek, Marjan; Li, Xuhang (2009) Applications of proteomics in the study of inflammatory bowel diseases: Current status and future directions with available technologies. Inflamm Bowel Dis 15:616-29
Li, Xuhang; Conklin, Laurie; Alex, Philip (2008) New serological biomarkers of inflammatory bowel disease. World J Gastroenterol 14:5115-24