Simon Hirota

Dr. Simon Hirota

Ph.D.
Pronouns: he/his/him

Positions

Associate Professor

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

Full Member

Inflammation Research Network

Full Member

Gastrointestinal Research Group

Full Member

The Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases

Child Health & Wellness Researcher

Alberta Children's Hospital Research Institute

Contact information

Phone number

Office: 403.210.7888
Lab: 403.210.8588

Location

Office: HSC1845
Lab: HSC1802

For media enquiries, contact

Kelly Johnston
Senior Communications Specialist

Please submit your media request here

 

Background

Educational Background

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

Biography

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.

Research

Areas of Research

The intestinal mesenchyme as a regulator of inflammation and tissue remodelling, Intestinal organoids as tools for precision medicine, Pathogenesis of Johne's disease, Host-microbe interactions and the regulation of drug metabolism/absorption

Participation in university strategic initiatives

Courses

Course number Course title Semester
MDSC 638 Mucosal Pathophysiology Winter 2024

Projects

Intestinal mesenchymal regulation of mucosal inflammation

CIHR Project Grant (PI: Hirota; Operating Grant) – 2021-2026


Targeting intestinal mesenchymal cell populations in fibrostenotic Crohn's disease - modulation of proliferative, fibrotic and inflammatory processes by NR4A1

CIHR Project Grant (PI: Hirota; Operating Grant) – 2017-2022


Harnessing microbe-induced immune signaling mechanisms to modify drug metabolism – novel approaches to enhancing drug efficacy and avoiding systemic drug toxicity

Weston Family Microbiome Initiative – Proof-of-principle Program (PI: Hirota; Operating Grant) – 2020-2022


Targeting bacterial metabolism to diagnose and prevent toxicity associated with the immunosuppressive drug mycophenolate mofetil

Weston Family Microbiome Initiative – Proof-of-principle Program (PI: Greenway; Co-PI: Hirota; Operating Grant) – 2020-2022


Developing organoid-based screening assays as precision medicine tools for the management of cystic fibrosis

Alberta Children’s Hospital Research Institute – Child Health and Wellness Grand Challenge Catalyst Award (PI: Hirota; Seedling Award) – 2021-2023


Proteomic Biomarkers and Intestinal Ultrasound; Innovative Tools to Differentiate Fibrostenotic from Inflammatory Crohn’s Disease

Alberta Innovates – Accelerating Innovations into CarE – Concepts (Co-PI: Hirota; Operating Grant) – 2021-2024


Quantitative Proteomic Profiling of Fibrostenotic Crohn’s Disease Patients

Helmsley Charitable Trust – (PI: Lu; Co-PI – Hirota; Operating Grant) – 2021-2024

Awards

  • CAG Visiting Professor Award, Canadian Association of Gastroenterology. 2023
  • 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

Publications

More Information

Darasimi Kola-Ilesanmi
MSc Student
darasimi.kolailesanm@ucalgary.ca

Joshua Lee
MSc Student
joshua.lee1@ucalgary.ca

Eva Shenoda
MSc Student
eva.shenoda@ucalgary.ca

Lauren Smith
Lab Technician
lauren.smith3@ucalgary.ca

Améline Delanne, PhD
Postdoctoral Associate
ameline.delanne@ucalgary.ca

Andrew Thorne, PhD
Postdoctoral Associate
andrew.thorne@ucalgary.ca

C. Elizabeth Hughes
Research Technician
chughes@ucalgary.ca

Barbara Chyz
HSC 1663
Email: chyz@ucalgary.ca
Phone: 403.220.4555