Pfizer Awards Grant to UC Riverside Researchers for Discovery of IBD Therapeutic Target

Pfizer Awards Grant to UC Riverside Researchers for Discovery of IBD Therapeutic Target
Pfizer has awarded $150,000 to Declan McCole, PhD, and his team to find a therapeutic target for correcting intestinal barrier defects for patients with inflammatory bowel disease (IBD) who have mutations in the T-cell protein tyrosine phosphatase (TCPTP) protein. TCPTP, which plays a key role in IBD, protects the intestinal epithelial barrier function and is encoded by a gene associated with IBD, type 1 diabetes and celiac disease. Some patients with these conditions have mutations in this gene, stripping TCPTP of its protective function. With the two-year grant, McCole — an associate professor of biomedical sciences at the University of California Riverside — will lead his colleagues in testing different approaches to restore barrier function in intestinal epithelial cells that have a reduced activity of the TCPTP protein. The intestinal epithelium lines the surface of the gut as a single layer of closely adhering cells and forms an efficient physical boundary to the body’s interior, ensuring that gut bacteria  do not pass into the rest of the body. In their experiments, researchers will use these intestinal epithelial cells to test what happens when they interrupt a signaling pathway termed JAK-STAT, which is known to increase intestinal barrier defects. When TCPTP is functioning properly, this pathway is deactivated, but in individuals with TCPTP mutations, the JAK-STAT pathway remains activated. "These defects result in increased intestinal permeability, a major contributor to chronic inflammatory diseases of the intestine such as IBD," McCole said in a
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