Lay Summary

Proposal No.  IBD-0119R2
Principal Investigator:  Xuhang Li, Ph.D.
Applicant Organization:  Johns Hopkins University (Baltimore, Maryland, U.S.A.)
Project Title:  Initial proteomic studies of inflammatory bowel diseases
Period of Award:  January 1, 2005 – December 31, 2007

Currently, there are two major approaches to elucidate the molecular mechanisms of inflammatory bowel disease (IBD) pathogenesis.  One is gene profiling to identify abnormal gene expression by analyzing mRNA expression.  The other is proteomics to identify abnormal protein expression and posttranslational modifications.  Generally, when genes are expressed, they are first transcribed into mRNA (this process is called transcription), and then made into proteins (this process is called translation).  Gene microarray technologies are highly efficient approaches to identify changes in gene expression by detecting changes in mRNA levels and they have been used at a preliminary stage in the study of IBD.  However, since transcription and translation are often independently regulated, for a given gene, the level of its mRNA does not always reflect the level of its protein.  Moreover, after being translated, proteins often undergo modifications, such as phosphorylation/dephosphorylation (addition/removal of phosphate groups) or glycosylation (addition of sugar groups).  These processes are called posttranslational modifications, which often define functions of proteins and cannot be identified by gene profiling.  When proteins are abnormally expressed or modified, diseases or symptoms often develop.  Here, we propose to take the proteomic approach to identify proteins that are differentially expressed or modified in IBD vs. normal intestine mucosa.  No effort has been reported so far to use the proteomic approach in IBD studies.  We hypothesize that by identifying changes in proteins in IBD vs. normal intestine, we will increase our current understanding of the causes of IBD and of the associated diarrhea.

Using various technologies, we have obtained promising preliminary data to demonstrate that:  1) a large number of proteins are differentially expressed in human IBD vs. normal mucosa and we have begun their identification, and 2) several membrane transport proteins, which are proteins responsible for maintaining the balance of water and electrolytes in the gut, are significantly downregulated in IBD mucosa.  This suggests a potential explanation of IBD-associated diarrhea. 

The ultimate goal is to identify potential diagnostic biomarkers and therapeutic targets to cure IBD or alleviate the symptoms of IBD.