UCR’s Associate Professor of Biomedical Sciences at the School of Medicine Declan McCole, has received a two-year grant of $150,000 which will support research for inflammatory bowel disease (IBD) patients. The grant was awarded by Pfizer Inc., a company dedicated to distributing affordable medicine and products for various diseases. McCole will be joined by UCR’s Moorthy Krishnan, assistant project scientist and Anica Sayoc, fourth-year graduate student in biomedical science.
IBD is a broad term used to describe chronic or recurring diseases in the immune system which causes inflammation in the gastrointestinal tract. IBD includes Crohn’s disease and ulcerative colitis. An important protective protein that McCole and his team will be focusing on is the “T-cell protein tyrosine phosphatase,” or TCPTP. TCPTP protects the intestinal epithelial barrier function, by blocking bacteria from surpassing the gut and spreading to the rest of the body. A mutated TCPTP can result in IBD, celiac disease and type 1 diabetes.
“We are trying to understand the signaling pathways, networks and physiological consequences affected by TCPTP loss-of-function mutations,” McCole told The Highlander. “We anticipate that our studies will identify novel and/or known molecules that can be targeted by therapeutic agents (existing or newly developed), to correct the consequences of TCPTP mutations.”
McCole’s lab plans to interrupt a signaling pathway called Janus Kinase Signal Transducer and Activator of Transcription (JAK-STAT) which plays a major role in increasing intestinal barrier defects. McCole explained, when asked how his team plans to target the inhibitors of the JAK-STAT pathway, “We are already conducting studies with a drug that inhibits two of the JAK proteins whose activity is increased when TCPTP does not function properly … This inhibitor is approved to treat rheumatoid arthritis patients and is in clinical trials in IBD patients.”
Studies planned for the first year of research will include using cell lines and intestinal tissue in mice lacking the TCPTP gene and characterizing the proteins in JAK-STAT that show increased activation in TCPTP-deficient cells. For the second year of research, McCole’s lab will determine if the proteins associated with JAK-STAT can improve the barrier function of the TCPTP-deficient epithelial cells.
Aside from determining whether the proteins in JAK-STAT are particularly effective, McCole explained that a successful outcome of these studies will further lead to conducting clinical trials of existing and novel JAK-STAT inhibitors in IBD patients identified as having TCPTP mutations.
These studies also align with the goals of the new UCR Center for Molecular and Translational Medicine which strives to improve the health of individuals by translating basic findings into diagnostic tools or therapeutics which will be brought upon by clinicians and resarches from across the UCR campus. “Hopefully these studies will strengthen the reputation of UCR for translational research that connects fundamental basic research with clinical disease,” McCole concluded.