Microbial metabolite sensors and the regulation of gut function
Funded by Crohn's & Colitis Canada (2017-2020), this area of research focuses on the distinct receptors that sense and respond to metabolites released from the intestinal microbiota. Our main focus is the pregnane X receptor (PXR), a nuclear receptor expressed in a variety of cell types within the gut (epithelial cells, fibroblasts, immune cells), which responds to microbial metabolites, such as indole-3-propionic acid. Our early work (2014-2017) has implicated the PXR as a key regulator of mucosal healing following inflammation-associated intestinal tissue damage. Our current projects relate to the regulation of intestinal fibrosis by the PXR, implicating a role for the intestinal microbiota and its metabolic products in regulating the response to tissue injury and limiting pathogenic tissue remodelling.

The regulation of mesenchymal cell populations by NR4A1 - identifying new treatments for intestinal fibrosis and remodelling in IBD
Funded by the Canadian Institutes for Health Research (2017-2022), this area of research is focused on identifying new therapeutic targets to treat the fibrosis and tissue remodeling associated with the inflammatory bowel diseases (IBD). Our preliminary work, along with data from the vascular field, point towards NR4A1, an orphan nuclear receptor, as a negative regulator of fibrogenesis and smooth muscle growth. These studies utilize experimental models of intestinal inflammation and primary tissues obtained from patients with IBD.

Generating novel models to assess the pathogenesis of Johne’s disease
Funded by the Natural Sciences and Engineering Research Council of Canada (2016-2021), this area of research seeks to develop new models to study the clinical manifestation of mycobacterium avium subspecies paratuberculosis (MAP) infections, referred to as Johne’s disease. We are currently developing a chronic trickle infection model that better mimics the acquisition of MAP by cattle in feedlots over the course of their life. Furthermore, we are using new technologies to develop primary culture systems to assess MAP invasion into enterocytes and M cells, and assess potential changes in virulence using macrophage co-culture systems.