Biology and function of inflammasomes

Inflammasomes are cytosolic multiprotein complexes that activate the cysteine protease caspase-1 controlling the maturation of two inflammatory cytokines (IL-1 and IL-18), as well as an unusually rapid form of cell death (pyroptosis). Inflammasomes are a central component of host defense and major contributors to a myriad of inflammatory diseases. A major goal of our research program aims to describe the microbial and host triggers of inflammasomes, define the molecular mechanisms of inflammasome assembly and uncover new regulators of these complexes. We have focused our studies on AIM2 and NLRP3. Our work on the AIM2 inflammasome was the first to establish direct ligand binding by an inflammasome sensor, providing a simplified model for downstream activation. Ongoing efforts in our lab are also geared toward understanding how NLRP3 is activated. In particular, we are interested in defining how the NLRP3 inflammasome is activated during infection with Gram-negative bacteria.