Intestinal Barrier Regulation by Host Gene – Bacterial Crosstalk

Abstract: Increased intestinal permeability (leakiness) and alterations in the abundance of intestinal bacteria are critical factors contributing to many autoimmune diseases such as Inflammatory Bowel Disease (IBD), celiac disease and Type 1 diabetes. Genetic contributions to these autoimmune diseases include the increased association with loss-of-function mutations in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene. A major deficit in our understanding of chronic inflammatory disease lies in identifying how the interactions between autoimmune susceptibility genes and gut bacteria contribute to disease pathogenesis. We have identified that mice constitutively lacking PTPN2 have increased intestinal barrier permeability. In addition, loss of PTPN2 increased the intestinal abundance of a disease-associated adherent-invasive E. coli (AIEC), referred to as a “pathobiont” bacterium. In this talk, I will discuss how the host PTPN2 gene regulates intestinal barrier function while also restricting host cell expression of susceptibility factors that can increase binding and invasion of this pathobiont.  I will demonstrate that PTPN2 serves as a “microbial modulator” by protecting the gut against disease-causing bacteria, and highlight the mechanisms by which PTPN2 protects the intestinal epithelium against inflammatory cytokine and microbe-induced barrier dysfunction.

Biography: Dr. McCole is an Associate Professor of Biomedical Sciences at UCR. In addition to the Biomedical Sciences Graduate Program, he is also a member of the Biochemistry & Molecular Biology Graduate Program. He is vice-Chair of the School of Medicine Faculty Executive Committee and serves as the campus-wide Faculty Assistant for Partner Employment Opportunities. He obtained his B.Sc. and Ph.D. in Pharmacology & Veterinary Medical Research from University College Dublin, Ireland. He then held postdoctoral research positions at UC San Diego before joining the faculty in the Division of Gastroenterology at UCSD. In 2013, he was in the first group of recruited faculty members to join the new UCR School of Medicine. His research is supported by the National Institutes of Health, the Crohn’s and Colitis Foundation and the American Gastroenterological Association (AGA). He also holds leadership positions in the American Gastroenterological Association and the American Physiological Society. In 2018, he received the AGA-Pfizer Young Investigator Pilot Research Award in Inflammatory Bowel Disease.