Grant: Project Grant

Digestive diseases, particularly inflammatory bowel disease (IBD), place a significant financial burden on Canadians, costing $3.3 billion annually in healthcare as of 2023. With one in 150 Canadians affected by IBD, the country has the highest prevalence in the world. Additionally, digestive cancers, constituting 10% of new cancer cases in Canada in 2023, are a growing concern. Colorectal cancer, with the 2nd highest death rate among men and the 3rd highest among women, is a major health issue. The seed and soil hypothesis proposes that the intricate functioning of the gastrointestinal (GI) tract relies on interactions between epithelial cells (seeds) and their subepithelial microenvironment and mesenchymal cells (soil). Traditionally, mesenchymal cells were seen as supporting the GI epithelium, but recent findings indicate their crucial role in GI disorders. Genetic changes or immune disturbances alone cannot fully explain GI disease initiation and progression. The project's main hypothesis is that mesenchymal cells are pivotal for maintaining microenvironment signals that regulate epithelial homeostasis, influencing gut pathophysiology. This research aims to uncover the precise role of mesenchymal cells in establishing this dynamic environment and the resulting molecular events. Enhancing our understanding of the microenvironment guiding epithelial responses in gut diseases could lead to new therapeutic interventions targeting relevant molecules in the subepithelial milieu.