Grant: Project Grant

Digestive diseases represent an important financial burden for Canadians with an expense of $5,7 billion annually (2008) in health care cost and lost productivity. One in 150 people in Canada suffer from inflammatory bowel diseases (IBD) making Canadians suffering from the disease the highest than anywhere in the world. Moreover, digestive cancers represent one out of every five new cancer cases diagnosed in the country (2009) with colorectal cancer having the 2nd highest death rate of all cancers in Canada. The seed and soil hypothesis suggests that the successful function of a complex organ, such as the one found in the gastrointestinal (GI) tract, depends on the interactions and properties of the epithelial cells (seeds) and their sub-epithelial microenvironment and mesenchymal cells (soil). Until recently, mesenchymal cells have been recognized mainly for their role in sustaining the GI epithelium rather than for their potential contribution to GI pathologies. It is now well established that genetic changes in troubled epithelium or disturbance in immune cells regulation are insufficient to recapitulate entirely GI disease initiation and progression. Thus far, it is beginning to be accepted that the mesenchymal cells and the sub-epithelial microenvironment may play a critical role in many GI disorders. The main hypothesis for this project is that mesenchymal cells are central for the preservation of the microenvironment mechanical and biochemical cues regulating the epithelial homeostasis with consequences on gut pathophysiology. This project will unravel the precise contribution of mesenchymal cells in the establishment of this chemically and mechanically dynamic environment and the molecular cascade of events emerging from this interaction. Improving our knowledge on the microenvironment instructing the epithelial responses during gut diseases opens possibilities for new therapeutic intervention targeting relevant molecules in the sub-epithelial milieu.