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Directory >> Samuel I. Miller, MD


Contact Information

Samuel I. Miller, MD

  • Professor, Division of Allergy and Infectious Diseases, Department of Medicine and
    Departments of Microbiology and Genome Sciences
    Adjunct Professor, Department of Immunology
  • University of Washington

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 is an Adjunct Professor of Immunology. He is a past Director of a Research Center of Excellence in Biodefense and Emerging Infectious Diseases for the region and Director of the Cystic Fibrosis Research and Development Program at the University of Washington.

The lab is organized into research groups focusing on the study of:

  1. Salmonellae translocated effectors which are delivered across the phagosome membrane and function to modify host processes by binding host GTPases, and acting as glycerol-cholesterol acyltransferases and ubiquitin ligases.
  1. Bioinformatic analysis, DNA sequencing and phenotypic comparison of Shigella and Salmonella outbreak strains from diverse geographic locations including Central America and Africa and specifically the emergence of non-typhoidal Salmonella strains in Africa.
  1. The environmental remodeling of the gram-negative bacterial envelope that occurs when bacteria infect host tissues and specifically the regulated alteration of glycerolphospholipids in the bacterial outer membrane by using a combination of bacterial genetics and mass spectrometry analysis of lipids.
  1. Using NMR and crystallography to define structural mechanisms by which PhoQ responds to antimicrobial peptides and low pH and specifically testing the hypothesis that signal transduction involves the loss of structure on one side of the membrane with specific gain of structure on the other side of the membrane.
  1. Identification of human genome polymorphisms that alter susceptibility to bacterial infection and diversity of human immune responses by using the human cellular genome wide association study (GWAS) platform using bacteria and the HapMap cell collection of normal human diversity.
  1. How the bacterial second messenger di-c-GMP controls cellular processes and use of a FRET based biosensor for c-di-GMP to understand bacterial cellular  function and diversity, and development of compounds that alter human interferon signaling by competing with mammalian molecules that bind cyclic nucleotides.
  1. Human studies that involve analysis of the microbiota.  The diseases analyzed using a metagenomic approach and DNA sequencing include inflammatory bowl disease and cystic fibrosis, as well as stool transplantation.

Selected Publications

Mills E, Petersen E, Kulasekara BR, Miller SI, A direct screen for c-di-GMP modulators reveals a Salmonella Typhimurium periplasmic ?-arginine-sensing pathway;Science signaling. 2015 ; 8 380: ra57

Matamouros S, Hager KR, Miller SI, HAMP Domain Rotation and Tilting Movements Associated with Signal Transduction in the PhoQ Sensor Kinase; mBio. 2015 ; 6 3: e00616-15
PubMed Abstract

Hicks KG, Delbecq SP, Sancho-Vaello E, Blanc MP, Dove KK, Prost LR, Daley ME, Zeth K, Klevit RE, Miller SI, Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence; eLife. 2015 ; 4 :
PubMed Abstract

Buchko GW, Edwards TE, Hewitt SN, Phan IQ, Van Voorhis WC, Miller SI, Myler PJ, Backbone chemical shift assignments for the sensor domain of the Burkholderia pseudomallei histidine kinase RisS: "missing" resonances at the dimer interface; Biomolecular NMR assignments. 2015 May.
PubMed Abstract

Dalebroux ZD, Edrozo MB, Pfuetzner RA, Ressl S, Kulasekara BR, Blanc MP, Miller SI; Delivery of cardiolipins to the Salmonella outer membrane is necessary for survival within host tissues and virulence;Cell host & microbe. 2015 Apr; 17 4: 441-51.
PubMed Abstract

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