Igor E. Brodsky

faculty photo
Assistant Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

Contact information
3800 Spruce Street
Old Vet Quad 390EE
Email: ibrodsky@vet.upenn.edu
Philadelphia, PA 19104
Office: 215-746-8426
Fax: 215-898-5301
Lab: 215-573-7735
AB (Molecular Biology)
Princeton University, 1997.
PhD (Microbiology&Immunology)
Stanford University, 2004.
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Description of Research Expertise

Our research focuses on the interplay of bacterial virulence mechanisms and host innate immune recognition strategies. We are interested in defining how bacterial pathogens are sensed by host cells, how this sensing contributes to antimicrobial immune defense, and how bacterial pathogens evade these innate immune recognition pathways.

The immune system utilizes two types of recognition strategies to detect microbes – membrane-bound pattern recognition receptors (PRRs), such as Toll-like Receptors, detect conserved microbial structures present in all microbes of a given class. Conversely, cytosolic receptors sense microbial virulence activities that result from the disruption of celluar processes or the inappropriate contamination of the host cell cytosol by microbial products. Notably, innate immune cells 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. Members of the Nucleotide binding domain-Lecuine Rich Repeat (NLR) family of cytosolic signaling proteins recruit 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. However, successful pathogens have also evolved mechanisms to evade or subvert inflammasome activation, thereby avoiding caspase-1-dependent immune responses.

We use the Gram-negative bacterial pathogens Yersinia pseudotuberculosis and Salmonella typhimurium in combination with genetic, biochemical, and imunological 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 evade inflammasome-dependent immune responses.

Recent studies in our laboratory have revealed unexpected links between caspase-1 activation and activation of other cell death pathways (Philip et al., PNAS 2014), and have identified a novel mechanism for sensing of TCA cycle metabolites by the NLRP3 inflammasome pathway (Wynosky-Dolfi et al., J Exp Med, 2014). Further studies have also demonstrated that bacterial pathogens tune the delivery of specific virulence factors into the host cell, so as to avoid triggering inflammasome response pathways (Zwack et al., MBio 2015)

Ongoing Projects in the Brodsky Lab involve (1) Dissecting the role of extrinsic cell death pathway components in inflammation. (2) Defining the contribution of inflammasome activation to anti-Salmonella immunity. (3) Determining the role of cell death in anti-bacterial immunity in vivo (4) Understanding the role of bacterial secretion system pore proteins in inflammasome activation

Current Brodsky Lab Members:
Meghan Wynosky-Dolfi (Post-doctoral fellow)
Erin Zwack (Graduate Student - MVP)
Naomi Philip (Graduate Student - IGG)
Lance Peterson (Graduate Student - IGG)
Elisabet Bjanes (Graduate Student - MVP)
Alexandra Delaney (Graduate Student - MVP)

Research Specialist: Baofeng Hu

Former Brodsky Lab Members:
Annelise Snyder (PhD Student, UW Immunology)
Marta Andres-Terre (PhD Student, Stanford University, Monack Lab)
Dorothy Tovar (PhD Student, Stanford University Microbiology&Immunology)
Lindsay Theodore (PhD Student, Harvard University BBS program)
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Last updated: 05/26/2015
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