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The Miller laboratory is focused on defining the molecular basis of bacterial pathogenesis and interactions with eukaryotic cells. This work involves the use of animal and tissue culture (mice, macrophages, epithelial cells) models of infection using
Salmonella, Pseudomonas, Yersinia, and other Gram-negative bacterial diseases. The diseases of interest to us at the moment include Salmonellae-induced typhoid fever and gastroenteritis and the chronic
Pseudomonas airway disease of cystic fibrosis patients. The lab is organized into research groups focusing on the study of (1) the effect of bacterial type III effector proteins on mammalian cells, (2) the assembly and regulation of the type III secretion system of
Salmonella typhimurium, which translocates proteins into mammalian cells on contact, (3) the environmental remodeling of the gram-negative bacterial surface that occurs when bacteria infect host tissues, and (4) the characterization of the phenotypic adaptation of Pseudomonas aeruginosa to the unique environmental niche of the CF airway. Current projects within each group include the study of (1) Salmonellae translocated effectors (which are delivered across the phagosome membrane and recruited to the phagosome, actin cytoskeleton, and nucleus), (2) assembly of the type III secretion system inner membrane ring of the needle complex, (3) remodeling of the surface of lipid A after bacterial infection of host tissues and analysis of the recognition of structural variants of lipid A by human toll-like receptor 4, and (4) proteomic analysis and transcriptional profiling of Pseudomonas aeruginosa isolated from children with CF and Pseudomonas colonization.
PUBLICATIONS Haraga A, Miller SI. A Salmonella enterica serovar typhimurium translocated leucine-rich repeat effector protein inhibits NF-kappa B-dependent gene expression. Infect Immun 71:4052-8, 2003. Miao EA, Brittnacher M, Haraga A, Jeng RL, Welch MD, Miller SI. Salmonella effectors translocated across the vacuolar membrane interact with the actin cytoskeleton. Mol Microbiol 48:401-15, 2003. Guina T, Purvine SO, Yi EC, Eng J, Goodlett DR, Aebersold R, Miller SI. Quantitative proteomic analysis indicates increased synthesis of a quinolone by Pseudomonas aeruginosa isolates from cystic fibrosis airways. Proc Natl Acad Sci USA 100:2771-6, 2003. Freeman JA, Ohl ME, Miller SI. The Salmonella enterica serovar typhimurium translocated effectors SseJ and SifB are targeted to the Salmonella-containing vacuole. Infect Immun 71:418-27, 2003. Hajjar AM, Ernst RK, Tsai JH, Wilson CB, Miller SI. Human toll-like receptor 4 recognizes host-specific LPS modifications. Nat Immunol 3:354-9, 2002. |
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