The caspase-8/RIPK1 axis regulates cell survival and death decisions during infection and inflammation. Activation of TNF receptors or Toll-like receptors engages one of three mutually-exclusive cell fate decisions: cell survival and induction of inflammatory gene expression, activation of cell-extrinsic apoptosis via caspase-8, or activation of programmed necrosis via RIPK1/RIPK3. Dysregulation of these pathways is associated with a variety of pathologies, including IBD, psoriasis, ischemia/reperfusion injury-induced organ damage, as well as increased susceptibility to infection. This seminar will present new and unpublished findings on the regulation and role of caspase-8 apoptotic and non-apoptotic functions in immunity against microbial pathogens.
The overall goals of the Brodsky Lab are to understand innate immune defense against bacterial pathogens, and conversely, virulence mechanisms enable pathogen evasion of host defenses. Igor Brodsky obtaining his undergraduate degree in Molecular Biology from Princeton University in 1997, and went on to do PhD studies in the laboratory of Dr. Stanley Falkow at Stanford University, where he studied resistance of Salmonella to host antimicrobial peptides. In 2005, he obtained a research training fellowship to study innate immune recognition in the laboratory of Dr. Ruslan Medzhitov, where he began his investigations on the interactions between bacterial virulence factors and the inflammasome system. In 2011, Dr. Brodsky joined the faculty of the Department of Pathobiology at the UPenn School of Veterinary Medicine as an Assistant Professor, and was promoted to Associate Professor with Tenure in 2017. Over the past 8 years the Brodsky lab has investigated the interface between bacterial pathogens and inflammatory cell death pathways. In particular, the Brodsky lab has identified bacterial metabolic pathways that mediate inflammasome evasion by Salmonella, and has recently identified a novel pathway of RIPK1-induced inflammatory cell death. Recent studies in the Brodsky lab have revealed a novel role for RIPK1-induced cell death in protection from Yersinia infection in vivo, providing novel insight into immune mechanisms that overcome pathogen interference with immune signaling.