Did you know…
The epithelium is the layer of cells that separates your body from the external environment. In the intestine, the epithelium is only one cell layer thick. That layer of cells must form a barrier against the harsh external environment of your gut lumen, while at the same time participating in digestion and absorption of nutrients. The epithelium also acts as a sensor of its environment, transmitting information from the vast microbiota in the gut to the underlying mucosal immune system.
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.
What are we doing…
The MacNaughton lab has been studying the role of the epithelium in inflammatory diseases for over 20 years. We are currently studying several aspects of epithelial cell biology and how they are involved in inflammatory bowel diseases and colorectal cancer.
Epithelial barrier function
We are studying 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 are studying how the behaviour of epithelial cells changes during inflammation and when repair needs to occur. Specifically were are studying the roles of serine proteases and their receptors in these processes. Can we prevent injury? Can we accelerate the resolution of inflammation and the initiation of injury repair?
Aquaporins as regulators of epithelial homeostasis
Aquaporins are water channels found in all epithelia. But they’re not just water channels anymore – aquaporins are now known to be regulators of several different cellular processes including proliferation and cell death. We are studying how aquaporins fulfill these functions in intestinal epithelial cells. Are there AQP-dependent processes that could be therapeutic targets?
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 are studying how inflammatory proteases may trigger an epithelial-mesenchymal transition (EMT) through the generation of proteolytic cleavage fragments of junctional proteins such as E-cadherin. Do these fragments have biological activity? Could they be targets for the development of preventative drugs?
Our research and trainees are supported by: