Abstract
The pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is incompletely understood, and patients have variable responses to available medications. IBD is thought to arise from aberrant host-microbial interactions that lead to a cascade of innate and adaptive immune activation, followed by fibrosis. In my dissertation project, I aimed to provide insight into the role of some of the “forgotten players” in this complex disease process: phagocytes, pathobionts, and stromal cells.
My colleagues and I have identified key innate immune pathways involved in IBD pathogenesis and uncovered potential disease biomarkers and targets for therapeutic intervention. We highlighted distinct pathways in ileal and colonic phagocytes that may underpin the differences between ileal and colonic CD and revealed targetable pathways that are upregulated in anti-TNF refractory patients. We also used innovative methods to identify plausible pathobionts in CD and suggested both microbial and host targets based on their upregulation in CD patients. Finally, we identified a new population of circulating stromal-like cells that may be a biomarker of IBD. Taken together, these findings advance our understanding of IBD and may help us to achieve better outcomes for IBD patients.