Grant: Operating Grant

Two of the main challenges that multicellular organisms faced during evolution were to cope with invading microorganisms and eliminate and replace dying cells. Our innate immune system evolved to handle both tasks. Key aspects of innate immunity are 1) the detection of invaders or tissue injury and 2) the activation of inflammation that alarms the system by producing factors called cytokines and chemokines. While inflammation is essential for host resistance to infections, it is detrimental when produced chronically or in excess and is linked to various diseases, most notably auto-immune diseases, auto-inflammatory disorders, cancer and septic shock. Essential regulators of inflammation are enzymes termed « the inflammatory caspases » : They are activated by cellular sensors of danger signals, such as the presence of pathogen-derived molecules or damaged tissue, and consequently convert pro-inflammatory cytokines into their mature active forms. In addition, they induce death of infected cells as a defense strategy to clear pathogens. Our research program is aimed at understanding how the inflammatory caspases are activated and what are the consequences of their activation. Our ultimate goal is to find ways to manipulate their activity or modulate their downstream effects for therapeutic interventions in immune-mediated inflammatory diseases.