Étudiants-chercheurs étoiles June 2012



Christian McIntire

Master's student in Biochemistry
McGill University

Katherine Labbé

PhD student in Microbiology and Immunology
McGill University


Award-winning publicationCellular Inhibitors of Apoptosis Proteins cIAP1 and cIAP2 Are Required for Efficient Caspase-1 Activation by the Inflammasome

Published in: Immunity, Volume 35, Issue 6, p. 897-907, 23 December 2011
 

Abstract

"In this article, we demonstrate that the cellular inhibitors of apoptosis proteins (cIAPs) are fundamental to the immune response triggered when danger signals are sensed by the cytosolic complex known as inflammasome. Molecular mechanism studies reveal the major role of the cIAPs in the inflammasome-dependent activation of caspase-1, a key effector protein in inflammation and cell death, which lead to pathogen elimination and cell repair."

Clinical studies on the use of pharmacological cIAPs inhibitors to treat certain types of cancer are currently underway. The work of the two student-researchers in animal models shows that the compounds weaken the innate immune response. With a significant potential for immunosuppressive effects, these inhibitors should be used with caution. However, certain inflammatory diseases stem directly from inflammasome overactivation in response to endogenous signals (gout) or genetic mutations (familial cold autoinflammatory syndrome, Muckle-Wells syndrome, familial Mediterranean fever, CINCA/NOMID, etc.). Pharmacological cIAPs targeting could therefore prove to be an effective therapeutic alternative to treat these diseases. In addition, the compounds could be used to treat multifactorial diseases with an inflammatory component involving inflammasome (diabetes, malaria, silicosis, etc.)