What we did…
The MacNaughton lab studied the role of the epithelium in inflammatory diseases for over 30 years. We investigated several aspects of epithelial cell biology and how they are involved in inflammatory bowel diseases and colorectal cancer. We used epithelial cell lines and patient-derived epithelial organoids to model human disease.
Epithelial barrier function
We studied the cellular mechanisms that regulate barrier function, focusing on the factors and pathways that control how tight junction proteins traffic in and out of the tight junction (the main structure controlling epithelial permeability).
When the epithelium is inflamed, inflammation needs to be resolved, and when it is injured, repair has to occur. We studied how the behaviour of epithelial cells changes during inflammation and when repair needs to occur. Specifically we investigated the roles of serine proteases, peptides and their receptors in these processes.
The role of the epithelium in inflammation-associated colorectal cancer
Chronic inflammation is associated with an increased risk of cancer, not just in the gut, but in many organs and tissues. The link between inflammation and cancer is complex and not well understood. We studied how inflammatory proteases may trigger an epithelial-mesenchymal transition (EMT) through the generation of proteolytic cleavage fragments of junctional proteins such as E-cadherin.
Why is this important…
It is important that all these functions of the epithelium are tightly controlled to maintain homeostasis. Dysregulation of these complex processes leads to diseases that afflict hundreds of thousands of Canadians – Crohn’s disease, ulcerative colitis, celiac disease, irritable bowel syndrome, colorectal cancer and more. We are only now learning how important maintaining proper epithelial function is to disease prevention and treatment.