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Brenda Anne Wilson B.A. (Biochemistry & German), Barnard College/Columbia University, 1981 Bacterial protein toxins, their interaction with host cells, their effects on intracellular signal transduction, and development of novel alternative anti-toxin therapeutics. |
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Research in the Wilson laboratory involves studying the molecular interactions and biochemical mechanisms by which protein toxins produced by pathogenic bacteria cause their toxic effects on animal cells. When the bacterial toxins are released into the media of the host, they can interact with or even enter host cells and interfere with normal signal transduction and physiological function, thereby disrupting the delicate balance of cellular metabolism, often lethally. One project involves studying the structure, function and pathogenic mechanisms of the potent dermonecrotic toxins produced by Pasteurella multocida, Bordetella sp., and E. coli. Like many other toxins, these toxins are currently being used as potent tools for studying signal transduction pathways and physiological processes within cells. The laboratory is interested in understanding the underlying mechanism of how these toxins carry out their effects on these processes. For example, the laboratory has discovered that the pleiotropic effects on different tissue cells caused by the toxin from P. multocida is due to the diverse roles that the toxin’s targets have in different cell types, which in turn influence the cellular and organismic outcomes of toxin action. Of particular interest to the laboratory is development of post-exposure anti-toxin therapeutics. This requires a global understanding of the downstream metabolic and signaling pathways that are affected by toxins, so as to identify potential sites for intervention. We have initiated proteomic and metabolomic research projects to identify biomarkers of cellular toxicity (i.e. toxicogenomics), which will be part of our new IGB Theme on Mining Microbial Genomics for Novel Antibiotics. Two other projects in the laboratory are part of an inter-institutional and inter-departmental collaborative effort (the NIH-sponsored Great Lakes Regional Center for Excellence in Biodefense and Emerging Infectious Diseases) to combat botulism: one to develop improved recombinant vaccines and novel alternative anti-toxin therapeutics against botulism and the other to develop highly sensitive detection and diagnostic devices for distinguishing among botulinum neurotoxins. There is currently no effective antidote for preventing or reversing botulism or paralysis once exposure has occurred and symptoms of disease have initiated. A major goal of the research is to design novel anti-toxins for neuronal cell-specific delivery of post-exposure therapeutics. Finally, we have just begun research to study the dynamic interactions between the host and its commensal as well as pathogenic microbes to elucidate basic processes of disease and commensalisms. This research will initially focus on the complex ecosystem of the vaginal microbiota and its impact on health and disease in women, which will be part of our new IGB Theme on Host-Microbe Systems.
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Wilson, B.A. and Salyers, A.A. (2002) "Ecology and physiology of infectious bacteria. Implications for biotechnology," Curr. Opin. Biotech. 13: 267-274. [Abstract] Sabri, A., Wilson, B.A., and Steinberg S.F. (2002) "Dual actions of the Gaq agonist Pasteurella multocida toxin to promote cardiomyocyte hypertrophy and enhance apoptosis susceptibility," Circ. Res. 90: 850-857. [Abstract] Sleight, S.B., Wilson, B.A., Heimark, D.B., and Larner J. (2002) "Gq/11 is involved in insulin-stimulated inositol phosphoglycan putative mediator generation in rat liver membranes: co-localization of Gq/11 with the insulin receptor in membrane vesicles," Biochem. Biophys. Res. Comm. 295: 561-569. [Abstract] Sagi, S.A., Seasholtz, T.M., Kobiashvili, M., Wilson, B.A., Toksoz, D., and Brown J.H. (2001) "Physical and functional interactions of Gaq with Rho and its exchange factors," J. Biol. Chem. 276: 15445-15452. [Abstract] Seo, B., Choy, E.W., Maudsley, S., Miller, W.E., Wilson, B.A., and Luttrell, L.M. (2000) "Pasteurella multocida toxin stimulates mitogen-activated protein kinase via Gq/11-dependent transactivation of the epidermal growth factor receptor," J. Biol. Chem. 275: 2239-2245. [Abstract] Sabri, A., Pak, E., Alcott, S.A., Wilson, B.A. and Steinberg, S.F. (2000) "Coupling function of endogenous a1- and b-adrenergic receptors in mouse cardiomyocytes," Circ. Res. 86: 1047-1053. [Abstract] View Publications by Brenda Anne Wilson listed on the National Library of Medicine (PubMed) |
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