Antoine Dufour, PhD

Antoine Dufour

Assistant Professor

Cumming School of Medicine, Department of Physiology and Pharmacology

Full Member

The Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases

Full Member

McCaig Institute for Bone and Joint Health

Full Member

Hotchkiss Brain Institute

Full Member

Hotchkiss Brain Institute

Web presence

Phone number

office: 403-210-7426

Background

Educational Background

B.A. Chemistry, State U of New York at Oswego, 2005

Doctor of Philosophy Chemistry Chemical Biology, Stony Brook University, 2010

Biography

EXPERIENCE                                                                                                                                              

 

Assistant Professor                                                                                                                        2017-present

University of Calgary, Calgary, AB, Canada

Department of Physiology and Pharmacology, McCaig Institute

 

Scientific Director                                                                                                                          2019-present

Southern Alberta Mass Spectrometry (SAMS) core facility

 

Post-Doctoral Fellowship                                                                                                                   2010-2017

University of British Columbia, Vancouver, BC, Canada             

Supervised by Dr. Chris Overall, Department of Oral and Biological Sciences

 

Stony Brook University, Stony Brook, NY, USA                                                                                     2005-2010

 

PhD in Chemical Biology, Chemistry

Thesis title: “The Role of the Hemopexin Domain of Matrix Metalloproteinases in Cell Migration.”

http://hdl.handle.net/1951/55415

 

SUNY Oswego, Oswego, NY, USA                                                                                                      2003-2005

Bachelor of Arts, Chemistry

Thesis title: “Comparison of the structure and dynamics of the antibiotic peptide polymyxin B”

Research

Areas of Research

Activities

The goal of my lab is to understand how proteolytic post-translational modifications lead to the activation or inactivation of immune responses in inflammatory diseases. By the irreversible processing of bioactive proteins and signaling molecules, proteases modulate all aspects of biology. We focus on proteases and their substrates on a cell, tissue, or organism-wide scale.

Projects

Calpains

Unraveling how calcium signalling regulates calpain proteolytic networks. Selected proteins have evolved to bind Ca2+ to buffer its levels, and alterations in Ca2+ homeostasis initiate or terminate multiple cellular signalling pathways that govern cell shape, adhesion, migration, and viability. Activation of G protein-coupled receptors (GPCRs) can trigger intracellular Ca2+ release through the downstream generation of 1,4,5-inositol triphosphate (IP3). When IP3 binds to its cognate-receptor (IP3R) in the endoplasmic reticulum, Ca2+ concentrations rise from ~100 nM to more than 1 mM (>10-fold increase) dictating profound changes on cellular functions. Among the key downstream effectors of Ca2+ signalling are a family of 15 cysteine proteases called calpains, which are directly activated at their catalytic sites by changes in intracellular Ca2+ levels. These proteases regulate diverse cellular processes through targeted proteolysis and precise processing of multiple protein substrates. We are using systems biology approaches to identify novel calpain substrates and understand their effect on cellular functions and immune signalling.


Macrophages

Tissues are an interactive, multi-cell and dynamic environment linked to the surrounding stroma by signalling networks that regulate gene and protein expression as well as post-translational modifications. Within inflamed joints, wounds or tumors, immune cells collaborate to this highly dynamic environment by modulating the genetic landscape and web of proteins as they are reacting to the threat. Among the multitude of infiltrating immune cells, mononuclear phagocytes (macrophages) are necessary for the clearance of pathogens and the resolution of inflammation during innate and adaptive immunity. The mononuclear phagocyte system is a highly dynamic and complex system that can be unified based upon progenitor cells but disjointed based upon the stimuli they are responding to. They are responsive and activated by various cell products and cytokines thus giving rise to a panoply of populations with distinct functions. The classically activated macrophages are induced by IFNgamma and/or LPS (TH1) whereas alternatively activated macrophages (TH2) have several activators including IL4, IL13, IL10, glucocorticoids (GC), immune complexes (IC) and/or transforming growth factor β (TGFβ). To understand the global changes of macrophage reactivity and their substrates within whole tissues or fluids, wide-scale systems biology approaches offer the opportunity to integrate and capture such complexity. Extensive transcriptomics information has been published in the last decade but still little is known about the partitioned macrophage populations’ proteome and their protease substrates.

Awards

  • Top 40 under 40 Calgary, Avenue Magazine. 2020
  • Young Investigator Award, canadian society for mass spectrometry. 2021