James R Brown
Affiliation: GlaxoSmithKline Research and Development
- Bioinformatics and the discovery of novel anti-microbial targetsCraig Volker
Bioinformatics Division, GlaxoSmithKline, 1250 South Collegeville Road, UP1345 Collegeville, Pennsylvania 19426, USA
Curr Drug Targets Infect Disord 2:279-90. 2002....
- No association found between the detection of either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus and chronic fatigue syndrome in a blinded, multi-site, prospective study by the establishment and use of the SolveCFS BDavid M Irlbeck
Division of Infectious Diseases, GlaxoSmithKline, Research Triangle Park, NC, USA
BMC Res Notes 7:461. 2014....
- Target prediction for an open access set of compounds active against Mycobacterium tuberculosisFrancisco Martínez-Jiménez
Genome Biology Group, Centre Nacional d Anàlisi Genòmica CNAG, Barcelona, Spain Gene Regulation Stem Cells and Cancer Program, Centre for Genomic Regulation CRG, Barcelona, Spain
PLoS Comput Biol 9:e1003253. 2013..The results from our analysis, including the predicted structural models, are available to the wider scientific community in the open source mode, to encourage further development of novel TB therapeutics...
- Identification of common biological pathways and drug targets across multiple respiratory viruses based on human host gene expression analysisSteven B Smith
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
PLoS ONE 7:e33174. 2012..The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning...
- Data mining the human gut microbiota for therapeutic targetsMatthew Collison
Biopharmaceutical Process Development Centre, School of Chemical Engineering and Advanced Materials, Newcastle University, UK
Brief Bioinform 13:751-68. 2012..In addition, integrative bioinformatics analysis will further our understanding of the microbial biotransformation of exogenous compounds or xenobiotics, which could lead to safer and more efficacious drugs...
- Evolutionary relationships of Aurora kinases: implications for model organism studies and the development of anti-cancer drugsJames R Brown
Bioinformatics Division, Genetics Research, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, P, O, Box 5089, Collegeville, Pennsylvania 19426 0989, USA
BMC Evol Biol 4:39. 2004..However, the ortholog and paralog relationships of these kinases across various species have not been rigorously examined. Here, we present comprehensive evolutionary analyses of the Aurora kinase family...
- Phylogeny of gamma-proteobacteria: resolution of one branch of the universal tree?James R Brown
Bioinformatics Division, Genetics Research, GlaxoSmithKline, Collegeville, Pennsylvania 19426 0989, USA
Bioessays 26:463-8. 2004..Thus, any thorough reconstruction of bacterial evolution must not only choose a suitable set of molecular markers but also strive to reduce potential bias in the selection of species...
- Phylogenomics of phosphoinositide lipid kinases: perspectives on the evolution of second messenger signaling and drug discoveryJames R Brown
Computational Biology, Quantitative Sciences, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, P, O, Box 5089, Collegeville, PA 19426 0989, USA
BMC Evol Biol 11:4. 2011..Here, we report the genomic occurrences and evolutionary relationships or phylogenomics of all three PIK families across major eukaryotic groups and suggest potential ramifications for drug discovery...
- Ancient horizontal gene transferJames R Brown
Bioinformatics Division, GlaxoSmithKline, 1250 South Collegeville Road, UP1345 Collegeville, Pennsylvania 19426, USA
Nat Rev Genet 4:121-32. 2003
- Molecular evolutionary analysis of cancer cell linesYan Zhang
Department of Biology, Pennsylvania State University, University Park, Pennsylvania, USA
Mol Cancer Ther 9:279-91. 2010..Our study shows the potential role of molecular evolutionary analyses in tumor classification and the development of novel anticancer strategies...
- Molecular evolution perspectives on intraspecific lateral DNA transfer of topoisomerase and gyrase loci in Streptococcus pneumoniae, with implications for fluoroquinolone resistance development and spreadMichael J Stanhope
Bioinformatics, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA
Antimicrob Agents Chemother 49:4315-26. 2005..pneumoniae population density, such events could be an important means of resistance spread...
- Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogensJames R Brown
Bioinformatics Division, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, Collegeville, Pennsylvania 19426, USA
EMBO Rep 4:692-8. 2003..This study shows the importance of understanding complex evolutionary networks of ancient horizontal gene transfer for the development of novel antibiotics...
- Computational biology in anti-tuberculosis drug discoveryDennis J Murphy
Computational Biology, Quantitative Sciences, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, P O Box 5089, Collegeville PA 19426 0989, USA
Infect Disord Drug Targets 9:319-26. 2009..However, the translation of in silico predictions to effective clinical therapies remains a significant challenge...
- A global approach to identify novel broad-spectrum antibacterial targets among proteins of unknown functionMagdalena Zalacain
Microbial, Musculoskeletal and Proliferative Diseases CEDD, Collegeville, PA 17426, USA
J Mol Microbiol Biotechnol 6:109-26. 2003..Moreover, this study demonstrates that different experimental procedures can produce apparently contradictory results...
- Identification of gene targets against dormant phase Mycobacterium tuberculosis infectionsDennis J Murphy
Informatics, Molecular Discovery Research, GlaxoSmithKline, Collegeville, PA 19426 0989, USA
BMC Infect Dis 7:84. 2007..Eradication of TB is affected by the ability of the bacterium to survive up to decades in a dormant state primarily in hypoxic granulomas in the lung and to cause recurrent infections...
- Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent ModelsDeepak K Rajpal
Computational Biology, Target Sciences, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America
PLoS ONE 10:e0145499. 2015..More broadly, our study suggests that in vivo modulation of the microbiome warrants further investigation as a potential therapeutic strategy for metabolic diseases. ..
- Phylogenomic and biochemical characterization of three Legionella pneumophila polypeptide deformylasesJianzhong Huang
Microbiology Department, GlaxoSmithKline, 1250 S Collegeville Road, Collegeville, PA 19426, USA
J Bacteriol 188:5249-57. 2006..pneumophila. These results indicate that even though L. pneumophila has three PDFs, they can be effectively inhibited by PDF inhibitors which can, therefore, have potent anti-L. pneumophila activity...
- Comparative genomics of Klebsiella pneumoniae strains with different antibiotic resistance profilesVinod Kumar
Computational Biology, Quantitative Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, USA
Antimicrob Agents Chemother 55:4267-76. 2011..Our study adds new and significant DNA sequence data on K. pneumoniae strains and demonstrates the value of whole-genome sequencing in characterizing multidrug resistance in clinical isolates...
- Novel drug target strategies against Mycobacterium tuberculosisDennis J Murphy
Computational Biology, Molecular Discovery Research, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, P O Box 5089, Collegeville, PA 19426 0989, USA
Curr Opin Microbiol 11:422-7. 2008..Recent work, especially the identification genes involved in regulatory networks and the Enduring Hypoxic Response (EHR), hold promise for developing new drugs targeting dormancy phase MTB...
- The micro RNA target paradigm: a fundamental and polymorphic control layer of cellular expressionMichael R Barnes
Molecular Discovery Research Informatics, Molecular Discovery Research, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park North, Third Avenue, Harlow, Essex, CM 19 5AW, UK
Expert Opin Biol Ther 7:1387-99. 2007..Second, one may be able to identify miRNA target variants in mRNA with a direct role in human disease, which may be valuable therapeutic targets...
- The evolution of core proteins involved in microRNA biogenesisDennis Murphy
Bioinformatics, Molecular Discovery Research, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, Collegeville, Pennsylvania 19426, USA
BMC Evol Biol 8:92. 2008....
- Evidence from the evolutionary analysis of nucleotide sequences for a recombinant history of SARS-CoVMichael J Stanhope
Bioinformatics Division, Genetics Research, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA
Infect Genet Evol 4:15-9. 2004..Our results are consistent with a hypothesis of viral host jumping events, concomitant with the reassortment of bird and mammalian coronaviruses, a scenario analogous to earlier outbreaks of influenzae...
- Microbiome changes in healthy volunteers treated with GSK1322322, a novel antibiotic targeting bacterial peptide deformylaseSeda Arat
Computational Biology, GSK R and D, Collegeville, Pennsylvania, USA Department of Mathematics, Virginia Tech, Blacksburg, Virginia, USA
Antimicrob Agents Chemother 59:1182-92. 2015..This clinical trial was registered at the GlaxoSmithKline Clinical Study Register under study identifier PDF 113376.). ..
- Computational biology approaches for selecting host-pathogen drug targetsJames R Brown
Computational Biology, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, PO Box 5089, Collegeville, PA 19426 0989, USA
Drug Discov Today 16:229-36. 2011..Using the hepatitis C virus interactome as an example, here we suggest a computational biology framework for identifying and prioritizing potential human host targets against infectious diseases...
- Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infectionsKaren O'Dwyer
Antibacterial Discovery Performance Unit, GlaxoSmithKline R and D, Collegeville, Pennsylvania, USA
Antimicrob Agents Chemother 59:289-98. 2015..gov under registration no. NCT01381549 for the study of complicated urinary tract infections and registration no. NCT01381562 for the study of complicated intra-abdominal infections.). ..
- Host response to respiratory bacterial pathogens as identified by integrated analysis of human gene expression dataSteven B Smith
Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America Institute for Genome Science, University of Maryland, Baltimore, Maryland, United States of America
PLoS ONE 8:e75607. 2013..Furthermore, 36 host-bacterial pathways were also shared with our previous results for respiratory virus host gene expression. Based on our pathway analysis we propose several drug-repurposing opportunities supported by the literature. ..
- Variable sensitivity to bacterial methionyl-tRNA synthetase inhibitors reveals subpopulations of Streptococcus pneumoniae with two distinct methionyl-tRNA synthetase genesDaniel R Gentry
Department of Microbiology, Microbial, Musculoskeletal, and Proliferative Diseases Center of Excellence for Drug Discovery, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA
Antimicrob Agents Chemother 47:1784-9. 2003..pneumoniae is the result of horizontal gene transfer which has been driven by selection for resistance to some unknown class of naturally occurring antibiotics with similarities to recently reported synthetic MetS inhibitors...
- Human microbial metabolites as a source of new drugsSomdutta Saha
Computational Biology, Target Sciences, R and D, GlaxoSmithKline, 1250 S Collegeville Road, Collegeville, PA 19426 0989, USA
Drug Discov Today 21:692-8. 2016..In this review, we discuss the rapidly growing research into the role of microbial metabolites in human health and suggest potential strategies for developing these molecules into therapeutic agents. ..
- Lung microbiome dynamics in COPD exacerbationsZhang Wang
Computational Biology, Target Sciences, GSK R and D, Collegeville, PA, USA These authors contributed equally
Eur Respir J 47:1082-92. 2016..Our study furthers the understanding of lung microbiome dynamics in COPD patients and highlights its potential as a biomarker, and possibly a target, for future respiratory therapeutics...
- A computational view of microRNAs and their targetsJames R Brown
GlaxoSmithKline, Bioinformatics Discovery and Analysis, Upper Providence, 1250 South Collegeville Road, UP1345, PO Box 5089, Collegeville, PA 19426 0989, USA
Drug Discov Today 10:595-601. 2005..In this review, the nature and function of microRNAs will be discussed, with special emphasis on the computational tools and databases available to predict microRNAs and the genes they target...
- Modulating the human gut microbiome as an emerging therapeutic paradigmDeepak K Rajpal
Computational Biology, GlaxoSmithKline, Research Triangle Park, NC 27709, USA
Sci Prog 96:224-36. 2013..Here we provide an overview of present knowledge about the gut microbiome, its putative role in metabolic diseases and the potential for microbiome focused treatments from the drug development perspective...
- Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and developmentJessica J Vamathevan
Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage, UK
Toxicol Appl Pharmacol 270:149-57. 2013..These data will facilitate the more effective use of animals in biomedical research...
- Inhibitors of pantothenate kinase: novel antibiotics for staphylococcal infectionsAnthony E Choudhry
Microbial, Musculoskeletal and Proliferative Diseases and Bioinformatics, GlaxoSmithKline Pharmaceuticals, Collegeville Pennsylvania 19426, USA
Antimicrob Agents Chemother 47:2051-5. 2003..Here we report the identification of the Staphylococcus aureus coaA gene and characterization of the enzyme. We have also identified a series of low-molecular-weight compounds which are effective inhibitors of S. aureus CoaA...
- The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutantsSilvino Sousa
Department of Comparative Genomics, Glaxo SmithKline, King of Prussia, PA 19406, USA
Microbiology 148:1291-303. 2002..It is concluded that, like S. cerevisiae, C. albicans contains two DAHP synthases required for the first step in the aromatic amino acid biosynthetic pathway...