Lay Summary

Proposal No.  IBD-0006
Principal Investigator:  M. Bishr Omary, Ph.D., M.D.
Applicant Organization:  Stanford University (California, U.S.A.)
Project Title:  Keratin mutations as a risk factor for inflammatory bowel disease
Period of Award:  April 1, 2002 - September 30, 2003

The genetic causes of inflammatory bowel disease (IBD) are only beginning to be appreciated.  This proposal entails carrying out a collaborative effort that brings together the expertise of my laboratory, which focuses on studying the family of proteins called keratins, with the expertise of Dr. Judy Cho, an established investigator in IBD genetic research.

The keratins are primarily found within the skin and the inner linings of organs such as the intestine and liver.  This project proposes to test the possibility that mutations in the keratin proteins may predispose individuals to the subsequent development of IBD.  I will use sophisticated genetic techniques to search for keratin mutations in DNA that is isolated from patients with ulcerative colitis or Crohn’s disease.  Our prediction, that keratin mutations will be identified in patients with IBD, is based on findings in mice whereby keratin mutations cause either liver or intestinal disease depending on the genetic background of the mice.  My laboratory has recently identified keratin mutations as a major risk factor for the subsequent development of liver disease in humans, thereby paralleling the animal findings and providing support for our proposed study.

If successful, this study will result in a new and novel association of keratin mutations with IBD, and may provide a unique mechanism for the subsequent development of IBD.  This mechanism entails a primary defect in cells lining the intestine, which subsequently triggers an undesired immune response with consequent inflammation and other downstream clinical manifestations of IBD.  This information could be the basis for new therapeutic and preventive measures in IBD.