Professor of Microbiology, Genome Sciences, and Medicine
Phone:(206) 616-5107, (206) 616-5108, (206) 616-5110
Office Location: Health Sciences K-140
Campus Box: 357710
Dr. Miller holds a B.A. from Johns Hopkins University and a M.D. from Baylor College of Medicine. Dr. Miller is a former faculty member of the Harvard Medical School. In addition to his Microbiology Department appointment, he is a Professor in the Department of Medicine, Division of Allergy and Infectious Diseases, and in the Department of Genome Sciences. He functions as the Director of a Research Center of Excellence in Biodefense and Emerging Infectious Diseases for the region as well as the Director of the Cystic Fibrosis Research and Development Program at the University of Washington.
The Miller laboratory is focused on defining the molecular basis of bacterial pathogenesis and interactions with eukaryotic cells. The laboratory has a particular interest in bacterial interactions with innate immunity. This work involves the use of animal and tissue culture (mice, macrophages, epithelial cells) models of infection using Salmonella, Pseudomonas, and Yersinia. Research interests include Salmonellae-induced typhoid fever and gastroenteritis, the chronic Pseudomonas airway disease of cystic fibrosis patients, and Gram-negative organisms important to biodefense, including Francisella tularensis and the plague bacillis Yersinia pestis.
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; (5) Analysis of bacterial genes and proteins using bioinformatics; (6) Development of new antimicrobial compounds inhibiting pathogenic factors. Current projects organized by group include the study of: (1) Salmonellae translocated effectors (which are delivered across the phagosome membrane and recruited to the actin cytoskeleton, nucleus, and phagosome) (2) Assembly of the type III secretion system inner membrane ring of the needle complex and structure-function analysis of the type III secretion chaperone InvB; (3) Remodeling of the surface of lipid A after bacterial infection of host tissues and analysis of the recognition of diverse lipid A by human Toll-like receptor 4; (4) Proteomic analysis and transcriptional profiling of Pseudomonas aeruginosa adaptation during CF; (5) Bioinformatic analysis and comparison of Francisella genomes; (6) Screening for chemical compounds that inhibit aminoarabinose modification of Lipid A.
You can email Dr. Miller at: firstname.lastname@example.org
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 U S A 2003 Mar 4;100(5):2771-6.
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. 2003 Apr;48(2):401-15.
Miller SI, Ernst RK, Bader MW. LPS, TLR4 and infectious disease diversity. Nat Rev Microbiol. 2005 Jan;3(1)36-46.
Bader MW, Sanowar S, Daley ME, Schneider AR, Cho U, Wenqing X, Klevit RE, Moual H, Miller SI. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell, in press.
Hoffman L, D’Argenio D, MacCoss M, Zhang Z, Jones RA, and Miller SI. Aminoglycoside antibiotics induce bacterial biofilm formation. Nature, in press.
Calvin K. Yip, Tyler G. Kimbrough, Heather B. Felise, Marija Vuckovic, Nikhil A. Thomas, Richard A. Pfuetzner, Elizabeth A. Frey, B. Brett Finlay, Samuel I. Miller, Natalie C.J. Strynadka. Structural characterization of the molecular platform for type III secretion system assembly. Nature, in press.