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The Institute for Systems Biology
Current research interests: Our focus is on the innate immune system; how it recognizes and formulates responses to infectious agents, and how it instructs the adaptive immune system to provide long-lived immunity to the pathogen. Our initial studies defined how pattern recognition receptors, in particular the Toll-like receptors, identify bacteria: in essence, how the immune cell reads the molecular bar-code of the microbe and thereby precisely defines the nature of the threat. This precise recognition triggers a specific, highly regulated, response to the pathogen by the host. Our current focus is the molecular definition of these responses. To do so we are using the tools of systems biology to develop predictive models of the immune and inflammatory responses. We are also using nanotechnology to build devices with sufficient sensitivity to allow multi-parameter analysis of single cells. The long-term goals are predictive and preventive medicine. Students currently training in the Aderem Lab: Sarah Warren Representative publications: Underhill, D.M., A. Ozinsky, A.M. Hajjar, A. Stevens, C.B. Wilson, M. Bassetti, A. Aderem. 1999. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401:811-815. Hayashi, F., D.M. Underhill, A. Ozinsky, K.D. Smith, E.C. Yi, D.R. Goodlett, J.K. Eng, and A. Aderem. 2001. The innate immune response to bacterial flagellin is mediated by Toll-like receptor-5. Nature 410(6832):1099-1103. Smith KD, Andersen-Nissen E, Hayashi F, Strobe K, Bergman MA, Barrett SL, Cookson BT, Aderem A. 2003. Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat Immunol. (12):1247-53. Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, Skerrett SJ, Beutler B, Schroeder L, Nachman A, Ozinsky A, Smith KD, Aderem A. 2003. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease. J. Exp. Med. 198:1563-72. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, and Aderem A. 2004. Lipocalin 2 mediates a novel innate immune response to bacterial infection by sequestrating iron. Nature. 16:917:21. Andersen-Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A. 2005. Evasion of Toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci USA. 102:9247-52. Aderem A. 2005. Systems biology: its practice and challenges. Cell. 121:511-13. Gilchrist M, Thorsson V, Li B, Rust AG, Korb M, Kennedy K, Hai T, Bolouri H, Aderem A. 2006. Systems Biology Approaches Identify ATF3 as a Negative Regulator of Innate Immunity. Nature. 441:173-8. Miao, EA, CM Alpuche-Aranda, M Dors, AE Clark, MW Bader, SI Miller, and A Aderem. 2006. Cytoplasmic flagellin activates Caspase 1 and IL-1β secretion through Ipaf. Nature Immunology. 7:569-75. Andersen-Nissen E, Smith KD, Bonneau R, Strong RK, Aderem A. 2007. A conserved surface on Toll-like receptor 5 recognized bacterial flagellin. J Exp Med. 204:393-403.
COS Expertise
Profile Updated July 2007
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