Description of Research Expertise

Our research focuses on the interplay of bacterial virulence mechanisms and host innate immune recognition strategies. In particular, we are interested in understanding how bacterial pathogens are detected by host cells as well as strategies utilized by bacterial pathogens to evade innate immune recognition.

Bacterial pathogens utilize specialized virulence-associated secretion systems or pore-forming toxins to deliver bacterial proteins into host cells. These proteins typically function to disrupt or modulate critical cellular processes in order to enable successful bacterial colonization of host niches. Two broad types of innate immune recognition exist for the purpose of detecting bacteria – pattern recognition, which detects conserved microbial structures present in all microbes of a given class, and detection of microbial virulence activities, triggered by microbial disruption of host cell processes or membranes. Macrophages infected with a variety of unrelated bacterial pathogens, but not avirulent or non-pathogenic bacteria, undergo a pro-inflammatory form of cell death termed pyroptosis, which depends on the cellular protease Caspase-1. Caspase-1 plays an important role in the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18 and is therefore important in immune defense against various microbial infections. Caspase-1 activation has also been linked to a process termed ‘unconventional protein secretion’ involving secretion of proteins without leader sequences. A subset of these unconventionally secreted proteins have roles in tissue repair and redox homeostasis, suggesting a possible role for caspase-1 in these processes. Recent studies in a number of laboratories identified members of the Nod-like receptor (NLR) family as being responsible for recruiting Caspase-1 into multi-protein activating platforms termed ‘inflammasomes’. Inflammasome complexes are activated in response to a variety of bacterial, viral, and fungal infections and inflammasome activation plays an important role in host defense.

We use the Gram-negative bacterial pathogen Yersinia pseudotuberculosis as a model to understand the immune response to bacterial pathogens. Our laboratory takes genetic, biochemical, and molecular biology approaches on both the bacterial and host side to understand the bacterial signals that trigger inflammasome activation, how inflammasome activation is coupled to innate and adaptive immune responses, and how bacterial pathogens prevent inflammasome activation.

Current projects in our lab investigate the following topics related to host-pathogen interactions:


1. Inhibition of inflammasome activation by bacterial pathogens and the features of bacterial pathogens that trigger inflammasome activation
2. The role of caspase-1 in unconventional protein secretion
3. Cross-talk between inflammasome activation and other innate immune signaling pathways

Lab Members:
Post-doctoral Fellow: Meghan Wynosky-Dolfi
Graduate Student (MVP): Erin Zwack
Rotation Student (IGG): Naomi Philip
Research Specialist: Annelise Snyder