Dr. Simon Hirota, Ph.D.
Cumming School of Medicine, Department of Physiology and Pharmacology
Associate Dean of Research Infrastructure
Cumming School of Medicine
Canada Research Chair, Canada Research Chair, Tier 2
in Host-Microbe Interactions and Chronic Disease
Inflammation Research Network
Gastrointestinal Research Group
The Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases
Child Health & Wellness Researcher
Alberta Children's Hospital Research Institute
Post-doctoral Fellowship Gastrointestinal Immunology & Pharmacology, University of Calgary, 2012
Ph.D. Pharmacology & Physiology, McMaster University, 2007
B.Sc. Honours Biology & Pharmacology, McMaster University, 2002
Throughout my research training I have studied a variety of organ systems, including the vascular system and the respiratory and gastrointestinal tracts. I was first trained as a smooth muscle electrophysiologist, assessing ion currents and calcium signals in vascular and airway smooth muscle, in the context of hypertension and asthma, respectively. I began specialized training in the gastrointestinal tract as a post-doctoral fellow. Originally recruited to assess gastrointestinal motility in the context of intestinal inflammation, I began to pursue studies focused on the regulation of intestinal epithelial barrier function and mucosal immune signaling in the context of the inflammatory bowel diseases (IBD) and infectious colitis. To this end, I published a series of papers assessing the innate immune responses involved in C. difficile toxin-associated tissue damage and was among the first groups to report on the functional role of the NLRP3 inflammasome in the pathogenesis of IBD. The complete study, published in the IBD Journal, has been cited 390 times since 2011. In addition to my contributions in the gastrointestinal tract, my expertise in inflammasome biology allowed for fruitful collaborations with groups working on inflammatory diseases of the liver, kidney and cardiovascular system.
My laboratory’s current research interests lie in the mechanisms that govern optimal gastrointestinal health through the maintenance of intestinal mucosal homeostasis, in the context of infectious colitis and IBD. We focus on host-microbe/host-pathogen interactions at the intestinal epithelium and how these processes contribute to optimal gut health, and how aberrant interactions contribute to the pathophysiology of IBD and infectious colitis. Enhanced intestinal epithelial permeability is observed in a number of gastrointestinal pathologies, including the IBD, and during acute infectious colitis (e.g., C. difficile colitis). Thus, I am interested in the systems that regulate the intestinal epithelium and preserve barrier function through enhancing epithelial cell survival, maintaining cell-cell contacts and regulating epithelial wound healing. To this end, my laboratory is focused on the role that nuclear receptors play in host-microbe/host-pathogen/host-environment interactions in the gastrointestinal tract. I believe that nuclear receptors act as xenobiotic sensors and respond to environmental contaminants, microbial metabolites and other small molecules, and regulate cellular processes in intestinal epithelial cells and mucosal immune cells. We are currently directing our efforts to understand how the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both xenobiotic/endobiotic sensors that regulate the body’s detoxification responses, contribute to the regulation of intestinal mucosal homeostasis, host-defense, tissue repair and the regulation of fibrosis. In other studies, my laboratory is examining the role that NR4A1 (an orphan nuclear receptor also known as NUR77, TR3, NGFI-B, or NAK-1) plays in regulating intestinal epithelial barrier function, mucosal repair responses and intestinal fibrosis, to determine whether it could be an attractive therapeutic target for treating gastrointestinal diseases associated with mucosal damage, increased permeability and aberrant tissue remodeling.
Areas of Research
CIHR Project Grant (PI: Hirota; Operating Grant) – 2021-2026
CIHR Project Grant (PI: Hirota; Operating Grant) – 2017-2022
Weston Family Microbiome Initiative – Proof-of-principle Program (PI: Hirota; Operating Grant) – 2020-2022
Weston Family Microbiome Initiative – Proof-of-principle Program (PI: Greenway; Co-PI: Hirota; Operating Grant) – 2020-2022
Alberta Children’s Hospital Research Institute – Child Health and Wellness Grand Challenge Catalyst Award (PI: Hirota; Seedling Award) – 2021-2023
Alberta Innovates – Accelerating Innovations into CarE – Concepts (Co-PI: Hirota; Operating Grant) – 2021-2024
Helmsley Charitable Trust – (PI: Lu; Co-PI – Hirota; Operating Grant) – 2021-2024
- CAG/INMD/CIHR - New Investigator Prize, Canadian Association of Gastroenterology & CIHR. 2021
- British Journal of Pharmacology Early Career Research Prize, British Pharmacological Society. 2017
- Crohn’s & Colitis Canada Rising Star Award, Crohn's & Colitis Canada. 2016
- CAG Visiting Professor Award, Canadian Association of Gastroenterology. 2023
Lauren Smith (Co-supervised by Dr. Wally MacNaughton)
Améline Delanne, PhD
C. Elizabeth Hughes
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