NW Research Center for Excellence in Biodefense and Emerging Infectious Diseases

Summary

Principal Investigator: Samuel I Miller
Abstract: The Region X Northwest Regional Center of Excellence (NWRCE) for Biodefense and Emerging Infectious Diseases is an essential component in a nationwide network of biomedical research programs to combat infectious disease threats to the population. The NWRCE is currently a highly interactive and thematic program focused on Gram-negative bacterial pathogens, and the same general consistent focus has existed since its inception. There are three research themes: (1) mechanisms of Gram-negative bacterial pathogenesis, (2) innate immune responses to Gram-negative bacterial pathogens, and (3) translation of (1) and (2) into early stage therapeutic development to prevent or treat Gram-negative bacterial diseases. The NWRCE is centered at the University of Washington (UW) in Seattle;in this renewal application, multiple sites are proposed in Seattle, two in Oregon, one in Idaho, and one in Maryland. Additional sites for collaboration include the NIAID Rocky Mountain Laboratory in Montana, the University of Victoria, British Columbia, and collaborators at sites in Thailand, Sweden, and Mexico. The projects, cores, domestic and international sites, as well as collaborators, are highly interactive. The individuals that make up this proposal have worked together for many years during the last funding period and before the NWRCE was created. The majority of investigators newly added to this to this application for renewed funding of the NWRCE have had long collaborative relationships with members of the center. The interactive nature and focus of the NWRCE is a major strength of the program and allows the NWRCE to rapidly and nimbly respond to national priorities to achieve important objectives with respect to Gram-negative bacterial infections.
Funding Period: 2003-09-04 - 2015-02-28
more information: NIH RePORT

Top Publications

  1. pmc Homeostatic regulation of Salmonella-induced mucosal inflammation and injury by IL-23
    Muyiwa Awoniyi
    Department of Pathology and Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington, United States of America
    PLoS ONE 7:e37311. 2012
  2. pmc Coordinated host responses during pyroptosis: caspase-1-dependent lysosome exocytosis and inflammatory cytokine maturation
    Tessa Bergsbaken
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    J Immunol 187:2748-54. 2011
  3. pmc Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis
    T E West
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA 98104, USA
    Genes Immun 13:38-46. 2012
  4. pmc PGAT: a multistrain analysis resource for microbial genomes
    M J Brittnacher
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Bioinformatics 27:2429-30. 2011
  5. pmc Role of pagL and lpxO in Bordetella bronchiseptica lipid A biosynthesis
    I Macarthur
    Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
    J Bacteriol 193:4726-35. 2011
  6. pmc Sources of diversity in bactobolin biosynthesis by Burkholderia thailandensis E264
    Gavin Carr
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Org Lett 13:3048-51. 2011
  7. pmc Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis
    Laurence Rohmer
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Trends Microbiol 19:341-8. 2011
  8. pmc Metabolic capabilities and systems fluctuations in Haloarcula marismortui revealed by integrative genomics and proteomics analyses
    Lichieh Julie Chu
    Institute of Biotechnology in Medicine, National Yang Ming University, Taipei, Taiwan, Republic of China
    J Proteome Res 10:3261-73. 2011
  9. pmc Computational design of proteins targeting the conserved stem region of influenza hemagglutinin
    Sarel J Fleishman
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Science 332:816-21. 2011
  10. ncbi Automated lipid A structure assignment from hierarchical tandem mass spectrometry data
    Ying S Ting
    Department of Medicinal Chemistry, University of Washington, Box 357610, Seattle, WA 98195 7610, USA
    J Am Soc Mass Spectrom 22:856-66. 2011

Detail Information

Publications197 found, 100 shown here

  1. pmc Homeostatic regulation of Salmonella-induced mucosal inflammation and injury by IL-23
    Muyiwa Awoniyi
    Department of Pathology and Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington, United States of America
    PLoS ONE 7:e37311. 2012
    ..Our studies demonstrate that IL-23 is a homeostatic regulator of IL-12-dependent, IFN-γ-mediated intestinal inflammation...
  2. pmc Coordinated host responses during pyroptosis: caspase-1-dependent lysosome exocytosis and inflammatory cytokine maturation
    Tessa Bergsbaken
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    J Immunol 187:2748-54. 2011
    ..These studies indicate two conserved secretion pathways are initiated by caspase-1, lysosome exocytosis, and a parallel pathway resulting in cytokine release, and both enhance the antimicrobial nature of pyroptosis...
  3. pmc Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis
    T E West
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA 98104, USA
    Genes Immun 13:38-46. 2012
    ..We conclude that TLR genetic variants may modulate host susceptibility to melioidosis. Confirmation of these findings and further investigation of the mechanisms are required...
  4. pmc PGAT: a multistrain analysis resource for microbial genomes
    M J Brittnacher
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Bioinformatics 27:2429-30. 2011
    ....
  5. pmc Role of pagL and lpxO in Bordetella bronchiseptica lipid A biosynthesis
    I Macarthur
    Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
    J Bacteriol 193:4726-35. 2011
    ..These data refine the structure of B. bronchiseptica lipid A and demonstrate that pagL and lpxO are involved in its biosynthesis...
  6. pmc Sources of diversity in bactobolin biosynthesis by Burkholderia thailandensis E264
    Gavin Carr
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Org Lett 13:3048-51. 2011
    ..Studies on the deletion mutants also led to four new bactobolin analogs that provide additional structure-activity relationships for this interesting antibiotic family...
  7. pmc Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis
    Laurence Rohmer
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Trends Microbiol 19:341-8. 2011
    ..Greater understanding of bacterial metabolism within host tissues should be important for increased understanding of host-pathogen interactions and the development of future therapeutic strategies...
  8. pmc Metabolic capabilities and systems fluctuations in Haloarcula marismortui revealed by integrative genomics and proteomics analyses
    Lichieh Julie Chu
    Institute of Biotechnology in Medicine, National Yang Ming University, Taipei, Taiwan, Republic of China
    J Proteome Res 10:3261-73. 2011
    ....
  9. pmc Computational design of proteins targeting the conserved stem region of influenza hemagglutinin
    Sarel J Fleishman
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Science 332:816-21. 2011
    ..Such designed binding proteins may be useful for both diagnostics and therapeutics...
  10. ncbi Automated lipid A structure assignment from hierarchical tandem mass spectrometry data
    Ying S Ting
    Department of Medicinal Chemistry, University of Washington, Box 357610, Seattle, WA 98195 7610, USA
    J Am Soc Mass Spectrom 22:856-66. 2011
    ..Additionally, HiTMS correctly assigned 85% of the structures in a smaller library of lipid A species from Yersinia pestis demonstrating that it may be used across species...
  11. pmc Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism
    Kristin N Adams
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Cell 145:39-53. 2011
    ..Efflux pump inhibitors like verapamil reduce this tolerance. Thus, the addition of this currently approved drug or more specific efflux pump inhibitors to standard antitubercular therapy should shorten the duration of curative treatment...
  12. pmc The Proteome Folding Project: proteome-scale prediction of structure and function
    Kevin Drew
    Center for Genomics and Systems Biology, Department of Biology, New York University, New York, New York 10003, USA
    Genome Res 21:1981-94. 2011
    ..We demonstrate that predicted structures can be combined with annotations from the Gene Ontology database to predict new and more specific molecular functions...
  13. pmc Caspase-1-induced pyroptotic cell death
    Edward A Miao
    Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Immunol Rev 243:206-14. 2011
    ..We further review the importance of pyroptosis in vivo as a potent mechanism to clear intracellular pathogens...
  14. pmc Chemical cross-linking, mass spectrometry, and in silico modeling of proteasomal 20S core particles of the haloarchaeon Haloferax volcanii
    Ivanka Karadzic
    Department of Chemistry, School of Medicine, University of Belgrade, Belgrade, Serbia
    Proteomics 12:1806-14. 2012
    ..volcanii proteasomal CPs composed of α1-, α2-, and β-homoheptameric rings from several different possible structures from Protein Data Bank...
  15. pmc Evolution of Burkholderia pseudomallei in recurrent melioidosis
    Hillary S Hayden
    Department of Microbiology, University of Washington, Seattle, Washington, United States of America
    PLoS ONE 7:e36507. 2012
    ..Our findings provide new insights into pathogen evolution during long-term infections and have important implications for the development of intervention strategies to combat recurrent melioidosis...
  16. pmc A widespread bacterial type VI secretion effector superfamily identified using a heuristic approach
    Alistair B Russell
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Cell Host Microbe 11:538-49. 2012
    ....
  17. pmc LPS remodeling is an evolved survival strategy for bacteria
    Yanyan Li
    State Key Laboratory of Food Science and Technology, School of Biotechnology, Jiangnan University, Wuxi 214211, China
    Proc Natl Acad Sci U S A 109:8716-21. 2012
    ....
  18. pmc Molecular and biological characterization of Streptococcal SpyA-mediated ADP-ribosylation of intermediate filament protein vimentin
    Laura M Icenogle
    Department of Microbiology, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 287:21481-91. 2012
    ..We conclude that SpyA modification of vimentin occurs in an important regulatory region of the head domain and has significant functional effects on vimentin assembly...
  19. ncbi Surface acoustic wave nebulization produces ions with lower internal energy than electrospray ionization
    Yue Huang
    Department of Chemistry, University of Washington, Seattle, WA 98195 1700, USA
    J Am Soc Mass Spectrom 23:1062-70. 2012
    ..Under all conditions tested, SAWN-generated BzPy ions displayed a higher tendency for survival and thus have lower internal energies than those formed by ESI...
  20. pmc Role of Francisella lipid A phosphate modification in virulence and long-term protective immune responses
    Duangjit Kanistanon
    Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
    Infect Immun 80:943-51. 2012
    ..All mice survived primary infection; however, RAG1(-/-) mice did not survive WT challenge, highlighting a role for T and B cells in the protective immune response...
  21. pmc Protein identification using top-down
    Xiaowen Liu
    Department of Computer Science and Engineering, University of California, San Diego, 9500 Gilman Drive, San Diego, California 92093, USA
    Mol Cell Proteomics 11:M111.008524. 2012
    ..Although MS-Align+ and ProSightPC have similar performance on the Salmonella typhimurium data set, MS-Align+ outperforms ProSightPC on the (more complex) Saccharomyces cerevisiae data set...
  22. pmc Hotspot-centric de novo design of protein binders
    Sarel J Fleishman
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    J Mol Biol 413:1047-62. 2011
    ..We show that the method generates binding surfaces that are more conformationally restricted than previous design methods, reducing opportunities for off-target interactions...
  23. pmc Faster, quantitative, and accurate precursor acquisition independent from ion count
    Alexandre Panchaud
    Department of Medicinal Chemistry, University of Washington, Seattle, Washington, United States
    Anal Chem 83:2250-7. 2011
    ..Finally, we confirm in yeast the dynamic range capabilities of such a method where proteins down to less than 50 copies per cell can be monitored without sample prefractionation...
  24. pmc Interactions between CusF and CusB identified by NMR spectroscopy and chemical cross-linking coupled to mass spectrometry
    Tiffany D Mealman
    Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, United States
    Biochemistry 50:2559-66. 2011
    ..The proteins transiently interact in a metal-dependent fashion, and contacts between CusF and CusB are localized to regions near their respective metal-binding sites...
  25. pmc An Enterotoxin-Bearing Pathogenicity Island in Staphylococcus epidermidis
    Jyoti Madhusoodanan
    Department of Oral Biology, NYS Center of Excellence in Bioinformatics and Life Sciences, The State University of New York, NY, USA
    J Bacteriol 193:1854-62. 2011
    ..We also describe the genome sequence, excision, replication, and packaging of a novel bacteriophage in S. epidermidis FRI909, as well as attempts to mobilize the SePI element by this phage...
  26. pmc Phenotypic diversity of Escherichia coli O157:H7 strains associated with the plasmid O157
    Ji Youn Lim
    Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844, USA
    J Microbiol 48:347-57. 2010
    ..The O157:H7 serotype diversity was further highlighted by phenotypic microarray comparisons of the two outbreak strains with a genotype 6 bovine E. coli O157:H7 isolate, rarely associated with human disease...
  27. pmc Asymmetrical distribution of the second messenger c-di-GMP upon bacterial cell division
    Matthias Christen
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Science 328:1295-7. 2010
    ..Thus, asymmetrical distribution of c-di-GMP was observed as part of cell division, which may indicate an important regulatory step in extracellular organelle biosynthesis or function...
  28. pmc Detecting cross-linked peptides by searching against a database of cross-linked peptide pairs
    Sean McIlwain
    Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    J Proteome Res 9:2488-95. 2010
    ..We show that our fully automated procedure successfully reidentifies spectra from a previous study, and we provide evidence that our statistical confidence estimates are accurate...
  29. pmc xComb: a cross-linked peptide database approach to protein-protein interaction analysis
    Alexandre Panchaud
    Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA
    J Proteome Res 9:2508-15. 2010
    ..A further benefit of decoupling from the search engine is that protein cross-linking studies may be conducted with readily available informatics tools for which scoring routines already exist within the proteomic community...
  30. ncbi Comprehensive structure characterization of lipid A extracted from Yersinia pestis for determination of its phosphorylation configuration
    Jace W Jones
    Department of Medicinal Chemistry, University of Washington, Seattle, Washington, USA
    J Am Soc Mass Spectrom 21:785-99. 2010
    ..The prevalent aminoarabinose modification was determined to be exclusively attached to the lipid A disaccharide via a phospho-diester linkage at either or both the C-1 and C-4' positions...
  31. pmc A brief overview of Escherichia coli O157:H7 and its plasmid O157
    Ji Youn Lim
    Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, ID 83844, USA
    J Microbiol Biotechnol 20:5-14. 2010
    ..Among these virulence factors, the role of the pO157 is least understood. This review provides a board overview of E. coli O157:H7 with an emphasis on the pO157...
  32. pmc Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome
    Edward A Miao
    Institute for Systems Biology, Seattle, WA 98103, USA
    Proc Natl Acad Sci U S A 107:3076-80. 2010
    ..Furthermore, the specific detection of the virulence machinery permits the discrimination between pathogenic and nonpathogenic bacteria...
  33. pmc A type VI secretion system of Pseudomonas aeruginosa targets a toxin to bacteria
    Rachel D Hood
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Cell Host Microbe 7:25-37. 2010
    ..This demonstration that the T6SS targets a toxin to bacteria helps reconcile the structural and evolutionary relationship between the T6SS and the bacteriophage tail and spike...
  34. pmc Quorum-sensing-regulated bactobolin production by Burkholderia thailandensis E264
    Mohammad R Seyedsayamdost
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Org Lett 12:716-9. 2010
    ..The antibiotic is identified as a mixture of four bactobolins. Annotation of the bta cluster allows us to propose a biosynthetic scheme for bactobolin and reveals unusual enzymatic reactions for further study...
  35. pmc A quantitative real time PCR method to analyze T cell receptor Vbeta subgroup expansion by staphylococcal superantigens
    Keun Seok Seo
    Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, ID 83844, USA
    J Transl Med 8:2. 2010
    ....
  36. pmc Detection of classical and newly described staphylococcal superantigen genes in coagulase-negative staphylococci isolated from bovine intramammary infections
    Joo Youn Park
    Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA 99164 6610, USA
    Vet Microbiol 147:149-54. 2011
    ..chromogenes, S. xylosus, S. haemolyticus, S. sciuri subsp. carnaticus, S. simulans and S. succinus. The genes for SAgs appear to be widely distributed amongst CNS isolated from bovine IMI...
  37. pmc Genome-scale identification of resistance functions in Pseudomonas aeruginosa using Tn-seq
    Larry A Gallagher
    Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    MBio 2:e00315-10. 2011
    ..The results thus show the effectiveness of the Tn-seq method in defining the genetic basis of a complex resistance trait of P. aeruginosa and indicate that it can be used to analyze a variety of growth-related processes...
  38. ncbi Fragmentation-free LC-MS can identify hundreds of proteins
    Pascal Bochet
    Laboratoire de Biologie Systémique, Département Génomes et Génétique, Institut Pasteur, Paris, France
    Proteomics 11:22-32. 2011
    ....
  39. pmc Escherichia coli O157:H7: animal reservoir and sources of human infection
    Witold A Ferens
    Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844 3052, USA
    Foodborne Pathog Dis 8:465-87. 2011
    ..Transmission to people occurs primarily via ingestion of inadequately processed contaminated food or water and less frequently through contact with manure, animals, or infected people...
  40. pmc Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
    Edward A Miao
    Institute for Systems Biology, Seattle, Washington, USA
    Nat Immunol 11:1136-42. 2010
    ..This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system...
  41. pmc What is type VI secretion doing in all those bugs?
    Sandra Schwarz
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Trends Microbiol 18:531-7. 2010
    ..The crucial role of T6S in bacterial interactions, along with its presence in many organisms relevant to disease, suggests that it might be a key determinant in the progression and outcome of certain human polymicrobial infections...
  42. pmc Burkholderia type VI secretion systems have distinct roles in eukaryotic and bacterial cell interactions
    Sandra Schwarz
    Department of Microbiology, University of Washington, Seattle, Washington, United States of America
    PLoS Pathog 6:e1001068. 2010
    ....
  43. pmc Outer membrane protein X (Ail) contributes to Yersinia pestis virulence in pneumonic plague and its activity is dependent on the lipopolysaccharide core length
    Anna M Kolodziejek
    Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844 3052, USA
    Infect Immun 78:5233-43. 2010
    ..coli, independently of other Yersinia proteins and/or LPS. Also, autoaggregation was required for efficient OmpX-mediated adhesiveness and internalization but not serum resistance...
  44. pmc Acquisition of iron by alkaliphilic bacillus species
    Duncan G G McMillan
    Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
    Appl Environ Microbiol 76:6955-61. 2010
    ....
  45. pmc Comparison of phenotypic and genotypic methods for the species identification of coagulase-negative staphylococcal isolates from bovine intramammary infections
    Joo Youn Park
    Department of Veterinary Clinical Science, Washington State University, Pullman, WA 99164 6610, USA
    Vet Microbiol 147:142-8. 2011
    ....
  46. pmc Characterization of BNT2, an intrinsically curved DNA of Escherichia coli O157:H7
    Jang W Yoon
    Department of Microbiology and Research Institute for Translational System Biomics, Chung Ang University College of Medicine, Seoul 156 756, Republic of Korea
    Biochem Biophys Res Commun 391:1792-7. 2010
    ..This implies that such a local intrinsic curvature within the unusual promoter of BNT2 is important for thermoregulation of the ecf operon...
  47. pmc Mechanisms of post-transcriptional gene regulation in bacterial biofilms
    Luary C Martínez
    Paul G Allen School for Global Animal Health, Washington State University Pullman, WA, USA
    Front Cell Infect Microbiol 4:38. 2014
    ..In this review, we discuss post-transcriptional mechanisms that influence the biofilm developmental cycle in a variety of pathogenic bacteria. ..
  48. pmc A high-throughput screen for quorum-sensing inhibitors that target acyl-homoserine lactone synthases
    Quin H Christensen
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 110:13815-20. 2013
    ..Our screen and identification of acyl-HSL synthase inhibitors serve as a basis for efforts to target quorum-sensing signal synthesis as an antivirulence approach. ..
  49. pmc A chemical biology approach to interrogate quorum-sensing regulated behaviors at the molecular and cellular level
    Colin A Lowery
    The Skaggs Institute for Chemical Biology, Departments of Chemistry, Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Chem Biol 20:903-11. 2013
    ..typhimurium, thus attesting that QS inhibitors may be used to confirm proposed and elucidate previously unidentified QS pathways without relying on genetic manipulation. ..
  50. pmc Detection of pyroptosis by measuring released lactate dehydrogenase activity
    Manira Rayamajhi
    Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Methods Mol Biol 1040:85-90. 2013
    ..J Immunol Methods 115:61-69, 1988)...
  51. pmc Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection
    Youssef Aachoui
    Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Curr Opin Microbiol 16:319-26. 2013
    ..In addition, recent work shows that inflammasomes can also recruit procaspase-8, initiating apoptosis. The induction of multiple pathways of cell death has probably evolved to counteract microbial evasion of cell death pathways. ..
  52. pmc Physiological levels of glucose induce membrane vesicle secretion and affect the lipid and protein composition of Yersinia pestis cell surfaces
    Anna M Kolodziejek
    School of Food Science, University of Idaho, Moscow, Idaho, USA
    Appl Environ Microbiol 79:4509-14. 2013
    ..These effects were independent of temperature and the biofilm-related locus pgm and were not observed in Yersinia pseudotuberculosis. ..
  53. ncbi A rapid one-step method for the characterization of membrane lipid remodeling in Francisella using matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry
    Yanyan Li
    State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
    Rapid Commun Mass Spectrom 25:2641-8. 2011
    ..This analysis showed that the bacterial membranes remodeled rapidly to adapt to changes in environmental growth conditions and may be important for Francisella pathogenesis...
  54. pmc Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors
    Alistair B Russell
    Department of Microbiology, University of Washington, Seattle, Washington 98195, USA
    Nature 496:508-12. 2013
    ..The surprising finding that virulence-associated phospholipases can serve as specific antibacterial effectors suggests that interbacterial interactions are a relevant factor driving the continuing evolution of pathogenesis...
  55. pmc Proteomic profiling of bronchoalveolar lavage fluid in critically ill patients with ventilator-associated pneumonia
    Elizabeth V Nguyen
    Department of Medicinal Chemistry, University of Washington, Seattle, Washington, United States of America
    PLoS ONE 8:e58782. 2013
    ..Identifying protein profiles specific to VAP in bronchoalveolar lavage fluid (BALF) may aid in earlier diagnosis, elucidate mechanisms of disease, and identify putative targets for therapeutic intervention...
  56. pmc Toll-like receptor 1 polymorphisms and associated outcomes in sepsis after traumatic injury: a candidate gene association study
    Callie M Thompson
    Department of Surgery Division of Pulmonary and Critical Care Medicine, University of Washington, Harborview Medical Center, Seattle, WA
    Ann Surg 259:179-85. 2014
    ..To determine whether single nucleotide polymorphisms (SNPs) in TLR1 are associated with mortality, specifically sepsis-associated mortality, in a traumatically injured population...
  57. pmc Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock
    Jon A Hagar
    Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Science 341:1250-3. 2013
    ..Together, our data reveal a new pathway for detecting cytoplasmic LPS. ..
  58. pmc Mechanisms of NOD-like receptor-associated inflammasome activation
    Haitao Wen
    The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Immunity 39:432-41. 2013
    ..This work will highlight key progress in understanding the mechanisms that activate the best-studied NLRs (NLRP3, NLRC4, NAIP, and NLRP1) and in uncovering inflammasome NLRs. ..
  59. pmc Detection of cytosolic bacteria by inflammatory caspases
    Jon A Hagar
    Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Curr Opin Microbiol 17:61-6. 2014
    ..These findings underscore bacterial coevolution with the innate immune system, which has resulted in few, but highly specialized cytosolic pathogens. ..
  60. pmc VgrG-5 is a Burkholderia type VI secretion system-exported protein required for multinucleated giant cell formation and virulence
    Sandra Schwarz
    Department of Microbiology, University of Washington, Seattle, Washington, USA
    Infect Immun 82:1445-52. 2014
    ..We propose a model whereby the CTD of VgrG-5-, propelled by T6SS-5-, plays a key role in inducing membrane fusion, either by the recruitment of other factors or by direct participation. ..
  61. pmc E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis
    Jonathan N Pruneda
    Department of Biochemistry, University of Washington, Seattle, WA, USA
    EMBO J 33:437-49. 2014
    ..Recognizing conserved E2 features, OspG can interact with at least ten distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub conjugates act as novel regulators of OspG effector kinase function in eukaryotic host cells. ..
  62. pmc Type VI secretion system effectors: poisons with a purpose
    Alistair B Russell
    Department of Microbiology, University of Washington, Seattle, Washington 98195, USA
    Nat Rev Microbiol 12:137-48. 2014
    ....
  63. pmc Survey of innate immune responses to Burkholderia pseudomallei in human blood identifies a central role for lipopolysaccharide
    Narisara Chantratita
    Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    PLoS ONE 8:e81617. 2013
    ..Our findings suggest that B. pseudomallei lipopolysaccharide may play a central role in stimulating the host response in melioidosis. ..
  64. pmc The role of NOD2 in murine and human melioidosis
    Nicolle D Myers
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195
    J Immunol 192:300-7. 2014
    ..pseudomallei. To our knowledge, these findings are the first to characterize the role of NOD2 in host defense in mammalian melioidosis. ..
  65. pmc Proteomic landscape of bronchoalveolar lavage fluid in human immunodeficiency virus infection
    Elizabeth V Nguyen
    Computational Medicine Core, Center for Lung Biology, 850 Mercer St, Box 358052, Seattle, WA 98109
    Am J Physiol Lung Cell Mol Physiol 306:L35-42. 2014
    ..These findings implicate mechanisms whereby HIV invokes local immunosuppression in the lung and increases the susceptibility of HIV(+) patients to develop a wide range of infectious and noninfectious pulmonary diseases. ..
  66. pmc Sequence-defined transposon mutant library of Burkholderia thailandensis
    Larry A Gallagher
    Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    MBio 4:e00604-13. 2013
    ..nwrce.org/tn_mutants/ and http://www.gs.washington.edu/labs/manoil/. The library should facilitate comprehensive mutant screens and serve as a source of strains to test predicted genotype-phenotype associations...
  67. pmc A cellular genome-wide association study reveals human variation in microtubule stability and a role in inflammatory cell death
    Raul E Salinas
    Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC 27710 Department of Medicine and Center for Human Genome Variation, School of Medicine, Duke University, Durham, NC 27710 Department of Microbiology, University of Washington, Seattle, WA 98195 Departments of Medicine, Genome Sciences, and Immunology, University of Washington, Seattle, WA 98195
    Mol Biol Cell 25:76-86. 2014
    ..Furthermore, the finding that there is common diversity in TUBB6 expression and microtubule stability could have broad consequences for other microtubule-dependent phenotypes, diseases, and pharmacological responses. ..
  68. pmc Impaired TLR5 functionality is associated with survival in melioidosis
    T Eoin West
    International Respiratory and Severe Illness Center, University of Washington, Seattle, WA 98104, USA
    J Immunol 190:3373-9. 2013
    ..This conclusion suggests a deleterious immunoregulatory effect of TLR5 that may be mediated by IL-10 and identifies this receptor as a potential therapeutic target in melioidosis...
  69. pmc Virulence of Burkholderia mallei quorum-sensing mutants
    Charlotte Majerczyk
    Department of Microbiology, University of Washington School of Medicine, Seattle, Washington, USA
    Infect Immun 81:1471-8. 2013
    ..mallei infections of mice. QS may be involved in some stage of chronic infections in the natural host of horses, or the QS genes may be remnants of the QS network in B. pseudomallei from which this host-adapted pathogen evolved...
  70. pmc Caspase-11 protects against bacteria that escape the vacuole
    Youssef Aachoui
    Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Science 339:975-8. 2013
    ..thailandensis and B. pseudomallei. Thus, caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens...
  71. pmc Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon
    Sudha Chugani
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 109:E2823-31. 2012
    ..This study also provides a framework for understanding the molecular mechanisms by which quorum-sensing systems operate, the evolutionary pressures by which they are maintained, and their importance in disparate ecological contexts...
  72. pmc An in vivo platform for rapid high-throughput antitubercular drug discovery
    Kevin Takaki
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Cell Rep 2:175-84. 2012
    ..The methods developed here should be widely applicable to small-molecule screens for other infectious and noninfectious diseases...
  73. pmc Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death
    Dennis C Ko
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 109:E2343-52. 2012
    ..Our study shows that in vitro association screens of disease-related traits can not only reveal human genetic differences that contribute to disease but also provide unexpected insights into cell biology...
  74. pmc Identification of a p-coumarate degradation regulon in Rhodopseudomonas palustris by Xpression, an integrated tool for prokaryotic RNA-seq data processing
    Somsak Phattarasukol
    Department of Microbiology, University of Washington, Seattle, Washington, USA
    Appl Environ Microbiol 78:6812-8. 2012
    ..In this paper, we show the utility of Xpression to process strand-specific RNA-seq data to identify genes regulated by CouR, a transcription factor that controls p-coumarate degradation by the bacterium Rhodopseudomonas palustris...
  75. pmc Acyl-homoserine lactone-dependent eavesdropping promotes competition in a laboratory co-culture model
    Josephine R Chandler
    Department of Microbiology, University of Washington School of Medicine, Seattle, WA, USA
    ISME J 6:2219-28. 2012
    ..Our work supports the idea that quorum sensing is important for interspecies competition and that promiscuous signal receptors allow eavesdropping on competitors in mixed microbial habitats...
  76. pmc Structure and regulation of the type VI secretion system
    Julie M Silverman
    Department of Microbiology, University of Washington, Seattle, 98195, USA
    Annu Rev Microbiol 66:453-72. 2012
    ..This review discusses recent progress toward characterizing T6S structure and regulation...
  77. ncbi Surface acoustic wave nebulization facilitating lipid mass spectrometric analysis
    Sung Hwan Yoon
    Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195 7610, USA
    Anal Chem 84:6530-7. 2012
    ..The ease of generating SAWN-MS(n) data combined with HiTMS interpretation offers the potential for high throughput lipid A structure analysis...
  78. pmc A Salmonella typhimurium-translocated glycerophospholipid:cholesterol acyltransferase promotes virulence by binding to the RhoA protein switch regions
    Doris L LaRock
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    J Biol Chem 287:29654-63. 2012
    ..The dependence of a bacterial effector on regulation by a mammalian GTPase defines further how intimately host pathogen interactions have coevolved through similar and divergent evolutionary strategies...
  79. pmc Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting
    Didier Hocquet
    Department of Immunology, Medicine and Microbiology, University of Washington, Seattle, Washington, United States of America
    PLoS Pathog 8:e1002778. 2012
    ..Our results demonstrate that in human hosts, the antibiotic-induced SOS response in pathogens could play a pivotal role in adaptation process of the bacteria...
  80. pmc Proteomic analysis of bronchoalveolar lavage fluid proteins from mice infected with Francisella tularensis ssp. novicida
    Susan M Varnum
    Biological Science Division, Pacific Northwest National Laboratory, Richland, Washington 99354, USA
    J Proteome Res 11:3690-703. 2012
    ..Finally, this study identifies several candidate biomarkers, including Chitinase 3-like-1 (CHI3L1 or YKL-40) and peroxiredoxin 1, that are associated with F. tularensis ssp. novicida but not P. aeruginosa infection...
  81. pmc Extensive evolutionary and functional diversity among mammalian AIM2-like receptors
    Rebecca L Brunette
    Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA
    J Exp Med 209:1969-83. 2012
    ..These findings validate ALRs as key activators of the antiviral response and provide an evolutionary and functional framework for understanding their roles in innate immunity...
  82. pmc Endogenous retroelements and autoimmune disease
    Daniel B Stetson
    Department of Immunology, University of Washington, School of Medicine, Seattle, WA 98195, USA
    Curr Opin Immunol 24:692-7. 2012
    ..Understanding this potentially pathologic role for retroelements and the precise mechanisms by which their genomes are sensed and metabolized has important implications for the diagnosis and treatment of numerous autoimmune disorders...
  83. pmc The Yersinia virulence effector YopM binds caspase-1 to arrest inflammasome assembly and processing
    Christopher N LaRock
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Cell Host Microbe 12:799-805. 2012
    ..Thus, a bacterium obstructs pyroptosis utilizing a direct mechanism of caspase-1 inhibition that is distinct from known viral or host inhibitors...
  84. pmc YopM puts caspase-1 on ice
    Ine Jørgensen
    Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cell Host Microbe 12:737-8. 2012
    ..Caspase-1-mediated detection of pathogens is a potent arm of the innate immune system. LaRock and Cookson (2012) show that the Yersinia type III secretion effector, YopM, directly inhibits caspase-1...
  85. pmc Genome sequence of Francisella tularensis subspecies holarctica strain FSC200, isolated from a child with tularemia
    Kerstin Svensson
    CBRN Defence and Security, Swedish Defence Research Agency, Umea, Sweden
    J Bacteriol 194:6965-6. 2012
    ..This genome is important because strain FSC200 has been extensively used for functional and genetic studies of Francisella and is well-characterized...
  86. pmc Variation in the TLR10/TLR1/TLR6 locus is the major genetic determinant of interindividual difference in TLR1/2-mediated responses
    C Mikacenic
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, WA 98104, USA
    Genes Immun 14:52-7. 2013
    ..These findings establish the TLR10/1/6 locus as the dominant common genetic factor controlling interindividual variability in Pam(3)CSK(4)-induced whole blood responses in the healthy population...
  87. pmc Quantitative single-cell characterization of bacterial interactions reveals type VI secretion is a double-edged sword
    Michele LeRoux
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 109:19804-9. 2012
    ..Our discoveries highlight the utility of single-cell approaches for measuring interbacterial phenomena and provide a foundation for studying the contribution of a widespread bacterial interaction pathway to community structure...
  88. pmc Bacterial quorum sensing, cooperativity, and anticipation of stationary-phase stress
    Eunhye Goo
    Department of Agricultural Biotechnology, Seoul National University, Seoul 151 921, Korea
    Proc Natl Acad Sci U S A 109:19775-80. 2012
    ....
  89. pmc Murine pulmonary infection and inflammation induced by inhalation of Burkholderia pseudomallei
    T Eoin West
    Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, WA 98104 2499, USA
    Int J Exp Pathol 93:421-8. 2012
    ..pseudomallei. This model has utility for the study of bacterial and host factors that contribute to the virulence of melioidosis...
  90. pmc Humanized TLR4/MD-2 mice reveal LPS recognition differentially impacts susceptibility to Yersinia pestis and Salmonella enterica
    Adeline M Hajjar
    Department of Comparative Medicine, University of Washington, Seattle, Washington, USA
    PLoS Pathog 8:e1002963. 2012
    ..Thus, Y. pestis exploits temperature-dependent shifts in LPS acylation to selectively evade recognition by human TLR4/MD-2 uncovered with "humanized" TLR4/MD-2 transgenic mice...
  91. pmc Exploiting a natural auxotrophy for genetic selection
    Elizabeth Ramage
    Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    Appl Environ Microbiol 78:5926-8. 2012
    ..During this work, we formulated a simplified defined growth medium for Francisella novicida...
  92. ncbi Identification, cloning, expression, and purification of Francisella lpp3: an immunogenic lipoprotein
    Maria C Parra
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Microbiol Res 165:531-45. 2010
    ..coli-expressed Flpp3 is palmitoylated and closely resembles the native protein in structure and immunogenicity. Taken together, these data suggest that Flpp3 could be a candidate for inclusion in a F. tularensis vaccine...
  93. ncbi Determination and comparison of the Francisella tularensis subsp.novicida U112 proteome to other bacterial proteomes
    Laurence Rohmer
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    J Proteome Res 7:2016-24. 2008
    ..Comparison of this protein profile with other profiles previously published suggested that the genome size and number of genes involved in regulation have little effect on the number of proteins expressed in a given stable condition...
  94. ncbi Assessing bias in experiment design for large scale mass spectrometry-based quantitative proteomics
    Amol Prakash
    Departments of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA
    Mol Cell Proteomics 6:1741-8. 2007
    ..Moreover we show that reducing bias by correcting for just a few steps, for example randomizing the run order, does not provide much gain in statistical power for biomarker discovery...

Research Grants30

  1. Molecular Analyses and Interventions for Biodefense and Emerging Pathogens
    Olaf Schneewind; Fiscal Year: 2013
    ..Research and training at the GLRCE is governed by a mechanism involving ongoing review of scientific excellence and translational goals, inter-institutional advisory boards and external scientific advisory bodies. ..
  2. BEHAVIORAL GENOMICS OF ALCOHOL NEUROADAPTATION
    John C Crabbe; Fiscal Year: 2013
    ..An Education and Outreach component trains pre- and post-doctoral students in alcohol research, disseminates research findings to the public, and engages in a range of activities with elementary-to-high school students. ..
  3. Vermont Center on Behavior and Health
    Stephen T Higgins; Fiscal Year: 2013
    ..S. public health. ..
  4. EtOH-induced Immunomodulation: Role of Histone Deacetylases and Cannabinoid Genes
    Marisela Agudelo; Fiscal Year: 2013
    ..D.DCs treated with alcohol.Thus, an understanding of the alcohol-associated epigenetic changes and its implications in immune modulation will have translational significance for therapeutic targeting and control of AUDs. ..
  5. MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISM
    Fulton T Crews; Fiscal Year: 2013
    ..The ARC will conduct, promote, support, and mentor research on alcoholic pathology and educate broad groups of health professionals and youth in North Carolina. ..