Research

The Sharkey Lab are focused on understanding the physiology and pathophysiology of the neural control of the gastrointestinal tract and brain-gut interactions in health and disease. We are particularly interested in how inflammatory bowel diseases, like Crohn’s disease and ulcerative colitis, alter neural control mechanisms controlling gut function.

The overarching hypothesis that guides the lab, supported by a Canadian Institutes of Health Research (CIHR) Foundation grant, is that enteric nerves and glia synergistically interact to maintain intestinal homeostasis and perturbations in their function lead to gastrointestinal disease. Digestion becomes impaired when there are abnormalities in the control of gastrointestinal motility and/or a breakdown in the intestinal barrier function. This program has two main aims:

Aim 1: To understand how the endocannabinoid system regulates gastrointestinal motility and intestinal barrier function in health and disease. Endocannabinoids are key molecules in the control of gut function, but their physiology remains to be fully determined. Moreover, how this system is altered in disease remains poorly understood and our lab is seeking to better understand how gastrointestinal inflammation alters the endocannabinoid system and how endocannabinoids are involved in restoring homeostasis in gastrointestinal disease.

Aim 2: To establish the physiology of the enteric nervous system in the control of motility and intestinal barrier function. How enteric nerves, enteroendocrine cells and the enteric microbiota interact with enteric glia in order to effect regulatory control of motor and barrier function remains to be fully understood. Our lab is examining these issues using state-of-the-art approaches including live cell imaging and molecular genetics.

In addition, our lab is part of two collaborative teams.  With the labs of Quentin Pittman (PI) and Matt Hill at University of Calgary, we are studying the role of the endocannabinoid system in comorbid anxiety in colitis (funded by CIHR). With the labs of Christophe Altier (University of Calgary) and Aaron Gruber (PI, University of Lethbridge) we are studying the therapeutic potential of non-psychotropic cannabinoids in visceral pain, inflammation and depression (funded by Alberta Innovates).

We are collaborating with the labs of Minh Dang Nguyen and Gerald Pfeffer (University of Calgary) on the role of the gut in amyotrophic lateral sclerosis. 

We are collaborating with the lab of Raylene Reimer De Bruyn (University of Calgary) on the impact of artificial sweeteners on the brain.