Assistant Professor, Department of Paediatrics; Paediatric Gastroenterologist
Cumming School of Medicine
3330 Hospital Dr NW
Calgary, AB T2N 4N1
Chronic intestinal inflammatory diseases including inflammatory bowel disease (IBD) affect a growing number of children in Alberta and across the country. While genetic predisposition plays a significant role in how these diseases develop, environmental factors are also important. One key environmental factor in disease development is our intestinal bacterial flora, or the "microbiota". The human intestine contains trillions of bacteria that, in most cases, provide significant health benefits. In chronic disease states, however, we become intolerant to these bacteria, and the immune response that is mounted against the microbiota results in disease perpetuation. The way that our bodies perceive bacteria, then, is important for a full understanding of how we respond both in health and disease to our microbiota.
The Toll-Like Receptors (TLRs) are a group of proteins that recognize conserved components of various microbes, including bacteria. In the intestine, TLRs play a major role in intestinal health and recovery following injury, as well as contributing to host defence in the context of infection. In disseminated infections, however, TLRs are a major effector of the inflammatory response and contribute to many of the clinical features seen in sepsis. Given the enormous burden of bacteria in the GI tract, TLR signalling in the gut must be carefully regulated, with multiple checks and balances, in order to ensure that homeostasis is maintained.
My research interests focus on two signalling pathways downstream of the TLRs, one controlled by the adaptor protein MyD88, and the other by the adaptor TRIF. Our evidence suggests that each pathway serves a distinct role in the GI tract during inflammation, with TRIF acting to downregulate inflammatory responses in the GI tract. In addition, we are studying the expression and activity of proteins that inhibit the MyD88 pathway in the intestine during inflammatory responses. Our results suggest that these regulatory proteins may be very important in downregulating the inflammatory response in experimental colitis.
The insights gained in these studies will greatly increase our understanding of how TLR signalling is regulated in the GI tract, and provide important insight into how we can harness particular TLR signalling pathways as therapies in IBD and other intestinal disorders.
Role of the innate immune system in animal models of colitis, particularly with regard to microbial recognition by pattern recognition receptors