Dr. Brett Finlay

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The human body routinely encounters many threatening infectious agents, including Salmonella and pathogenic E. coli. Most Salmonella and E. coli infections arise from oral ingestion of tainted food or water and are a significant cause of disease and death in animals and humans worldwide. Salmonella bacteria cause typhoid fever, a frequently fatal infectious condition that is common in the developing world. It also causes gastroenteritis, a type of food poisoning characterized by abdominal pain, fever, vomiting, and diarrhoea. Salmonella species are close relatives of E. coli, which cause numerous diseases including meningitis, urinary tract infections diarrhea and fatal kidney disease. The bacteria infect and interfere with normal function of cells in the stomach and intestine to cause disease. However, the molecular mechanism of how these pathogens adhere, enter, survive, replicate, and exit host cells is not well defined.

Although attacks from infectious agents are common, extremely few actually lead to infection. The body possesses a very powerful and efficient set of conserved mechanisms that deal rapidly with nearly all microbial infectious agents. This system, called "innate immunity", is the primary defence mechanism of most multicellular organisms. To cause an infection, a successful pathogen must overcome innate immunity.

Research in my lab is focussed on understanding bacterial pathogenesis from the perspective of both pathogen and host. In addition to studying the molecular mechanisms of pathogenicity for Salmonella and E. coli, we are interested in gaining further understanding of the critical human innate responses to microbial infection. By applying techniques from several disciplines including microbiology, cell biology, biochemistry, immunology, genomics and bioinformatics we have begun to understand the molecular mechanisms of microbial pathogenesis, ultimately allowing development of novel vaccines, diagnostics, and therapeutics that can be used to control infections caused by a wide range of globally important pathogens.

Wickham ME, Brown NF, Boyle EC, Coombes BK, Finlay BB. Virulence is positively selected by transmission success between mammalian hosts. Curr Biol 17(9):783-8. (2007).

Scott MG, Dullaghan E, Mookherjee N, Glavas N, Waldbrook M, Thompson A, Wang A, Lee K, Doria S, Hamill P, Yu JJ, Li Y, Donini O, Guarna MM, Finlay BB, North JR, Hancock RE. An anti-infective peptide that selectively modulates the innate immune response. Nat Biotechnol 25(4):465-72. (2007).

Mason D, Mallo GV, Terebiznik MR, Payrastre B, Finlay BB, Brumell JH, Rameh L, Grinstein S. Alteration of epithelial structure and function associated with PtdIns(4,5)P2 degradation by a bacterial phosphatase. J Gen Physiol 129(4):267-83. (2007).

Wickham ME, Lupp C, Vázquez A, Mascarenhas M, Coburn B, Coombes BK, Karmali MA, Puente JL, Deng W, Finlay BB. Citrobacter rodentium virulence in mice associates with bacterial load and the type III effector NleE. Microbes Infect 9(3):400-7. (2007).

Boyle EC, Bishop JL, Grassl GA, Finlay BB. Salmonella: from pathogenesis to therapeutics. J Bacteriol 189(5):1489-95. (2007).

Vaid KS, Guttman JA, Babyak N, Deng W, McNiven MA, Mochizuki N, Finlay BB, Vogl AW. The role of dynamin 3 in the testis. J Cell Physiol 210(3):644-54. (2007).

Zarivach R, Vuckovic M, Deng W, Finlay BB, Strynadka NC. Structural analysis of a prototypical ATPase from the type III secretion system. Nat Struct Mol Biol 14(2):131-7. (2007).

Guttman JA, Kazemi P, Lin AE, Vogl AW, Finlay BB. Desmosomes are unaltered during infections by attaching and effacing pathogens. Anat Rec (Hoboken) 290(2):199-205. (2007).

Coombes BK, Lowden MJ, Bishop JL, Wickham ME, Brown NF, Duong N, Osborne S, Gal-Mor O, Finlay BB. SseL is a salmonella-specific translocated effector integrated into the SsrB-controlled salmonella pathogenicity island 2 type III secretion system. Infect Immun 75(2):574-80. (2007).

Bishop JL, Boyle EC, Finlay BB. Deception point: peptidoglycan modification as a means of immune evasion. Proc Natl Acad Sci U S A 104(3):691-2. (2007).

Grassl GA, Finlay BB. Shigella rewrites host transcriptional responses. Nat Immunol 8(1):15-6. (2007).

Jandu N, Shen S, Wickham ME, Prajapati R, Finlay BB, Karmali MA, Sherman PM. Multiple seropathotypes of verotoxin-producing Escherichia coli (VTEC) disrupt interferon-gamma-induced tyrosine phosphorylation of signal transducer and activator of transcription (Stat)-1. Microb Pathog 42(2):62-71. (0).

Coburn B, Grassl GA, Finlay BB. Salmonella, the host and disease: a brief review. Immunol Cell Biol 85(2):112-8. (0).