Dr Safina Gadeock

Research

Intestinal mucosal healing is rapidly becoming the primary therapeutic goal of medical treatments for inflammatory bowel disease (IBD). Epithelial stem cells are key players in the healing process for a wide variety of injury models, including Crohn’s and colitis, radiation, helminth infection, and T-cell activation. Despite extensive investigation of inflammation-induced epithelial repair processes, currently there is a lack of epithelial targeted therapies for IBD. Epithelial stem cell-derived 3D organoids provide a powerful physiological model to study stem cell regulation, epithelial barrier integrity and its interactions with the micro-environment.

Using IBD patient-derived intestinal organoids, we show for the first time that there is an inherent stem cell-dependent developmental defect in the epithelium and barrier function of these patients. We also reveal novel mechanisms through which TNF signaling via TNFR1 is essential for the proper specification and stem-cell niche function of colonic mesenchymal cells and epithelial deep crypt secretory cell regulation. Our current studies focus on investigating IFN targets to predict clinical non-response to anti-TNF treated IBD patients and determine its role in modulation of the epithelial innate response to commensal metabolites.

Thus, on a whole, organoids play a key role in modelling mucosal healing in IBD and offer personalized medicine as a tool for screening therapeutics for inflammatory diseases. By developing the human 3D organoid modelling system, we seek to develop new therapies targeting epithelial wound healing to improve patient outcomes in IBD.