Home Faculty and Research Faculty by Name Russell Vance

Russell Vance

Assistant Professor of Immunology and Pathogenesis

Lab Homepage: http://mcb.berkeley.edu/labs/vance/

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Research Interests

How do mammals defend themselves against the diverse world of microbial pathogens? This is a fundamental question that has intrigued biologists for over a century, yet some of the most important advances in our understanding have occurred only in the past decade. Given the continuing global burden of infectious disease, the study of host-pathogen interactions continues to be a pressing area of investigation.

My lab is interested in all aspects of the complex interrelationship between pathogens and their hosts. In particular, we apply the modern tools of biology and genetics to answer a variety of questions at a molecular level: how is the presence of pathogenic bacteria sensed by hosts? Are pathogenic bacteria distinguished from harmless bacteria, and if so, how? What innate immune mechanisms protect cells from pathogens? How do cells coordinate defenses that are appropriate for various categories of pathogen? What mechanisms have pathogens evolved to evade host defenses?

Current Projects

Many of our studies focus on a gram-negative bacterium, Legionella pneumophila, the causative agent of a severe pneumonia called Legionnaires’ Disease. Legionella has evolved a variety of sophisticated mechanisms for manipulating host cells, and is representative of a class of bacterial pathogens that grow intracellularly within specialized vacuoles that evade fusion with lysosomes. Legionella is also experimentally accessible, as it grows readily in vitro and can be genetically manipulated at will.

Role of Naip5 in immune defense against intracellular bacteria. Classical genetic studies in mice have demonstrated that a host protein, Naip5, is essential for resistance to Legionella. Naip5 is a member of a large class of ‘pathogen-detector’ proteins that are believed to coordinate host immune responses upon recognition of pathogen-derived molecules. The mechanism by which Naip5 protects host macrophages is still largely mysterious, but our recent studies indicate that Naip5 regulates activation of caspase-1. We are generating and characterizing mice deficient in Naip5 to determine its function in immune responses and resistance to Legionella and other pathogens.

Intracellular detection of bacterial flagellin by macrophages. It is well established that mammalian cells can detect the presence of microbes by recognizing the presence of microbially-derived molecules such as lipopolysaccharide. We have recently shown that mouse macrophages appear to respond to the intracellular presence of bacterial flagellin, the primary structural component of flagella. We have further shown that recognition of flagellin is essential for initiation of macrophage resistance to Legionella. We are seeking to extend these studies to establish the general importance of flagellin-detection and its molecular basis.

Genetic screens in mice and bacteria. Only very few host genes required for the resistance to Legionella and other intracellular pathogens have been identified. We are commencing longer-term projects using ENU mutagenesis to identify novel mouse genes essential for resistance to various intracellular pathogens. We are also taking advantage of the genetic accessibility of Legionella to identify bacterial genes important for pathogenesis.

Selected Publications

Ren T, Zamboni DS, Roy CR, Dietrich WF, Vance, RE (2006) Flagellin-deficient Legionella mutants evade caspase-1 and Naip5-mediated macrophage immunity. PLoS Pathogens, in press.

Zamboni DS, Kobayashi KS, Kohlsdorf T, Ogura Y, Long EM, Vance RE, Kuida K, Mariathasan S, Dixit VM, Flavell RA, Dietrich WF, Roy CR. (2006) The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat Immunology, in press.

Vance RE, Rietsch A, Mekalanos JJ (2005) Role of type III-secreted exoenzymes S, T and Y in systemic spread of Pseudomonas aeruginosa in vivo. Infection and Immunity 73(3):1706-13

Vance RE, Hong S, Gronert K, Serhan CN, Mekalanos JJ (2004) The opportunistic pathogen Pseudomonas aeruginosa carries a secretable arachidonate 15-lipoxygenase. Proc. Natl. Acad. Sci 101(7):2135-2139.

Vance RE, Zhu J, Mekalanos JJ. (2003) A constitutively active variant of the quorum-sensing regulator LuxO affects protease production and biofilm formation in Vibrio cholerae. Infection & Immunity 71(5):2571-6.

Last Updated 2006-02-06