The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2 inflammasomes.
Rodrigue-Gervais IG, Doiron K, Champagne C, Mayes L, Leiva-Torres GA, Vanié P Jr, Douglas T, Vidal SM, Alnemri ES, Saleh M.
Sci Rep. 2018 May 31;8(1):8446. doi: 10.1038/s41598-018-26603-1.
An updated view on the functions of caspases in inflammation and immunity.
Songane M, Khair M, Saleh M.
Semin Cell Dev Biol. 2018 Oct;82:137-149. doi: 10.1016/j.semcdb.2018.01.001. Epub 2018 Feb 3. Review.
Previous Highlights: Cell Host and Microbe, January 15, 2014 (cover)
Cellular Inhibitor of Apoptosis Protein cIAP2 Protects against Pulmonary Tissue Necrosis during Influenza Virus Infection to Promote Host Survival
Volume 15, Number 1
Ian Gaël Rodrigue-Gervais, Katherine Labbé, Maryse Dagenais, Jeremy Dupaul-Chicoine, Claudia Champagne, Alexandre Morizot, Alexander Skeldon, Erik L. Brincks, Silvia Vidal, Thomas S. Grifﬁth and Maya Saleh | Full text | PDF |
Highlights: Immunity, 26 March 2010 (cover)
Control of Intestinal Homeostasis, Colitis, and Colitis-Associated Colorectal Cancer by the Inflammatory Caspases
Volume 32, Issue 3
Jeremy Dupaul-Chicoine, Garabet Yeretssian, Karine Doiron, Kirk S.B. Bergstrom, Christian R. McIntire, Philippe M. LeBlanc, Charles Meunier, Claire Turbide, Philippe Gros, Nicole Beauchemin, Bruce A. Vallance, Maya Saleh Summary | Full Text | PDF (1954 kb)
|We are investigating key pathways of innate immunity and cell death towards the discovery of new biologic therapies for inflammatory-mediated immune disorders. We are exploring the molecular mechanisms and roles of cytosolic Pattern Recognition Receptors in host defense, diseases of chronic inflammation, and cancer.
The strengths of our laboratory are based in fundamental research in apoptosis and cellular immunology, mouse models (genetic and other) of infectious diseases and inflammatory disorders and access to well-defined cohorts of patients with clinical and therapeutic subtypes of many inflammatory disorders.
Structure/Function Characterization of Inflammatory factors and Genetic basis of inflammatory disorders.
This theme is based on the observations that many inflammatory diseases are under the control of ‘master switches’ that operate not only in specific inflammatory diseases, but also across multiple immune disorders. These master switches operate at the innate as well as adaptive immune levels as either stimulators or suppressors of inflammation. 1) Toll-like receptors [TLRs] and Nod-like receptors [NLRs], highly conserved families of proteins termed pattern recognition receptors (PRRs) that detect microbial/danger-associated molecular patterns (MAMPs/DAMPs) and trigger acute inflammation, 2) Inflammatory caspases activated within macromolecular complexes known as the “inflammasomes”, and required for cytokine maturation and cell death, and 3) Apoptosis effectors such as the cellular inhibitors of apoptosis proteins (cIAPs) and Bcl-2 family proteins that modulate cell death and cancer progression but function physiologically as central regulators of innate immunity pathways. The work in this theme, which represents a large part of the research in my lab, aims to further characterize the above pathways at the molecular and functional levels in animal models and possibly in patients.
Identification of novel players in apoptotic and non-apoptotic cell death.
Apoptosis is a physiological process necessary for the survival of an organism. Apoptosis must be kept in check, as defects in its regulation are associated with pathogenesis. Too much apoptosis is evident in AIDS, ischemic injury and neurodegenerative diseases, while too little causes cancer and autoimmunity. In addition to apoptosis, non-apoptotic cell death pathways including caspase-independent cell death (CICD) and autophagic cell death contribute to tissue homeostasis and development of disease. Identification of novel regulators of cell death is expected to provide important insights into tumor biology and immune disorders.