TIMOTHY COVER

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. ncbi J-Western forms of Helicobacter pylori cagA constitute a distinct phylogenetic group with a widespread geographic distribution
    Stacy S Duncan
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    J Bacteriol 194:1593-604. 2012
  2. ncbi In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription
    Feifei Shen
    Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK
    BMC Microbiol 10:210. 2010
  3. ncbi Analysis of a beta-helical region in the p55 domain of Helicobacter pylori vacuolating toxin
    Susan E Ivie
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    BMC Microbiol 10:60. 2010
  4. ncbi Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer
    Mark S McClain
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 2605, USA
    BMC Genomics 10:3. 2009
  5. ncbi Helicobacter pylori VacA, a paradigm for toxin multifunctionality
    Timothy L Cover
    Departments of Medicine, and Microbiology and Immunology, Division of Infectious Diseases, Vanderbilt University School of Medicine and Veterans Administration Medical Center, Nashville, Tennessee 37232, USA
    Nat Rev Microbiol 3:320-32. 2005
  6. ncbi Beta2 integrin mediates entry of a bacterial toxin into T lymphocytes
    Timothy L Cover
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Cell Host Microbe 3:5-6. 2008
  7. ncbi Helicobacter pylori in health and disease
    Timothy L Cover
    Department of Medicine, Vanderbilt University School of Medicine and Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee 37232, USA
    Gastroenterology 136:1863-73. 2009
  8. ncbi Regulation of Helicobacter pylori cagA expression in response to salt
    John T Loh
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Cancer Res 67:4709-15. 2007
  9. ncbi Analysis of hopQ alleles in East Asian and Western strains of Helicobacter pylori
    Ping Cao
    Department of Medicine, Division of Infectious Diseases, A2200 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    FEMS Microbiol Lett 251:37-43. 2005
  10. ncbi Host response to Helicobacter pylori infection before initiation of the adaptive immune response
    Holly M Scott Algood
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    FEMS Immunol Med Microbiol 51:577-86. 2007

Research Grants

  1. Structure-function analysis of H. pylori VacA
    TIMOTHY COVER; Fiscal Year: 2005
  2. H. Pylory factors associated with peptic ulcer disease
    TIMOTHY COVER; Fiscal Year: 2006
  3. Structure-function analysis of H. pylori VacA
    TIMOTHY COVER; Fiscal Year: 2007
  4. Analysis of the H. Pylori cag pathogenicity island
    TIMOTHY COVER; Fiscal Year: 2009
  5. Structure-function analysis of H. pylori VacA
    Timothy L Cover; Fiscal Year: 2010
  6. Analysis of the H. Pylori cag pathogenicity island
    Timothy L Cover; Fiscal Year: 2010
  7. STRUCTURE AND REGULATION OF H PYLORI CYTOTOXIN
    TIMOTHY COVER; Fiscal Year: 2000
  8. BINDING AND UPTAKE OF H PYLORI VACUOLATING CYTOTOXIN
    TIMOTHY COVER; Fiscal Year: 2001
  9. Structure-function analysis of H. pylori VacA
    Timothy L Cover; Fiscal Year: 2011

Collaborators

Detail Information

Publications63

  1. ncbi J-Western forms of Helicobacter pylori cagA constitute a distinct phylogenetic group with a widespread geographic distribution
    Stacy S Duncan
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    J Bacteriol 194:1593-604. 2012
    ..pylori...
  2. ncbi In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription
    Feifei Shen
    Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK
    BMC Microbiol 10:210. 2010
    ..In this study, we investigated whether and how LuxS controls motility of H. pylori, specifically if it has its effects via luxS-required cysteine metabolism or via AI-2 synthesis only...
  3. ncbi Analysis of a beta-helical region in the p55 domain of Helicobacter pylori vacuolating toxin
    Susan E Ivie
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    BMC Microbiol 10:60. 2010
    ..To test this hypothesis, we introduced eight deletion mutations (each corresponding to a single coil within a beta-helical segment spanning VacA amino acids 433-628) into the H. pylori chromosomal vacA gene...
  4. ncbi Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer
    Mark S McClain
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 2605, USA
    BMC Genomics 10:3. 2009
    ..In this study, we analyzed the genome sequences of an H. pylori strain (98-10) isolated from a patient with gastric cancer and an H. pylori strain (B128) isolated from a patient with gastric ulcer disease...
  5. ncbi Helicobacter pylori VacA, a paradigm for toxin multifunctionality
    Timothy L Cover
    Departments of Medicine, and Microbiology and Immunology, Division of Infectious Diseases, Vanderbilt University School of Medicine and Veterans Administration Medical Center, Nashville, Tennessee 37232, USA
    Nat Rev Microbiol 3:320-32. 2005
    ..The actions of H. pylori VacA represent a paradigm for how bacterial secreted toxins contribute to colonization and virulence in multiple ways...
  6. ncbi Beta2 integrin mediates entry of a bacterial toxin into T lymphocytes
    Timothy L Cover
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Cell Host Microbe 3:5-6. 2008
    ..Downregulation of T cell responses by VacA may allow H. pylori to evade the adaptive immune response and establish persistent infection...
  7. ncbi Helicobacter pylori in health and disease
    Timothy L Cover
    Department of Medicine, Vanderbilt University School of Medicine and Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee 37232, USA
    Gastroenterology 136:1863-73. 2009
    ....
  8. ncbi Regulation of Helicobacter pylori cagA expression in response to salt
    John T Loh
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Cancer Res 67:4709-15. 2007
    ..pylori grown under low salt conditions. Up-regulation of H. pylori cagA expression in response to high salt concentrations may be a factor that contributes to the development of gastric adenocarcinoma...
  9. ncbi Analysis of hopQ alleles in East Asian and Western strains of Helicobacter pylori
    Ping Cao
    Department of Medicine, Division of Infectious Diseases, A2200 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    FEMS Microbiol Lett 251:37-43. 2005
    ..Geographic variation in the genetic characteristics of H. pylori strains may be a factor contributing to geographic variation in gastric cancer incidence...
  10. ncbi Host response to Helicobacter pylori infection before initiation of the adaptive immune response
    Holly M Scott Algood
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    FEMS Immunol Med Microbiol 51:577-86. 2007
    ..It is speculated that inappropriate waning of the innate immune response during early stages of infection may be a factor that contributes to H. pylori persistence...
  11. ncbi Structural analysis of the DNA-binding domain of the Helicobacter pylori response regulator ArsR
    Shobhana S Gupta
    Department of Microbiology and Immunology, Vanderbilt University and Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee 37232, USA
    J Biol Chem 284:6536-45. 2009
    ..Molecular modeling of an ArsR-DBD-DNA complex permits identification of protein elements that are predicted to bind target DNA sequences and thereby regulate gene transcription in H. pylori...
  12. ncbi Induction of gastric epithelial cell apoptosis by Helicobacter pylori vacuolating cytotoxin
    Timothy L Cover
    Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA
    Cancer Res 63:951-7. 2003
    ..pylori-infected persons may result from strain-dependent variations in VacA structure...
  13. ncbi Functional analysis of neutralizing antibodies against Clostridium perfringens epsilon-toxin
    Mark S McClain
    Department of Medicine, Division of Infectious Diseases, A2200 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Infect Immun 75:1785-93. 2007
    ..Identifying the epitopes recognized by these neutralizing antibodies constitutes an important first step in the development of therapeutic agents that could be used to counter the effects of the epsilon-toxin...
  14. ncbi Regulation of gastric B cell recruitment is dependent on IL-17 receptor A signaling in a model of chronic bacterial infection
    Holly M Scott Algood
    Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA
    J Immunol 183:5837-46. 2009
    ..In contrast to many chronic inflammatory diseases in which IL-17RA signaling promotes an inflammatory response, IL-17RA signaling down-regulates the chronic mononuclear inflammation elicited by H. pylori infection...
  15. ncbi Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth
    Fang Yan
    Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Gastroenterology 132:562-75. 2007
    ..Here, we purify and characterize 2 secreted LGG proteins that regulate intestinal epithelial cell antiapoptotic and proliferation responses...
  16. ncbi Helicobacter pylori HopQ outer membrane protein attenuates bacterial adherence to gastric epithelial cells
    John T Loh
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
    FEMS Microbiol Lett 289:53-8. 2008
    ..These data indicate that in some strains of H. pylori, the HopQ protein can attenuate bacterial adherence to gastric epithelial cells...
  17. ncbi Epidermal growth factor receptor activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis
    Fang Yan
    Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0696, USA
    Gastroenterology 136:1297-1307, e1-3. 2009
    ..Because EGFR signaling regulates cell survival, we investigated whether activation of EGFR following H pylori infection promotes gastric epithelial survival...
  18. ncbi Molecular analysis of sarcoidosis tissues for mycobacterium species DNA
    Wonder Puryear Drake
    Vanderbilt University School of Medicine and Veteran Affairs Medical Center, Nashville, Tennessee 37232, USA
    Emerg Infect Dis 8:1334-41. 2002
    ..tuberculosis were negative for IS6110. We provide evidence that one of a variety of Mycobacterium species, especially organisms resembling M. tuberculosis, is found in most patients with sarcoidosis...
  19. ncbi Two different families of hopQ alleles in Helicobacter pylori
    Ping Cao
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Microbiol 40:4504-11. 2002
    ..pylori strains. Further studies in multiple populations of patients are indicated to evaluate the usefulness of this approach for distinguishing potentially ulcerogenic H. pylori strains from less virulent strains...
  20. ncbi Promoter analysis of Helicobacter pylori genes with enhanced expression at low pH
    Catherine C McGowan
    Division of Infectious Diseases, Department of Medicine, A 3310 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232 2605, USA
    Mol Microbiol 48:1225-39. 2003
    ..pylori transcript abundance at acid pH. These studies document the complex response of H. pylori to environmental pH changes, and provide insight into mechanisms used for intragastric survival...
  21. ncbi Global analysis of Helicobacter pylori gene expression in human gastric mucosa
    James E Graham
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Gastroenterology 123:1637-48. 2002
    ..Helicobacter pylori inhabits a highly restricted ecological niche in the human gastric mucosa. Microbial gene expression in the context of persistent infection remains largely uncharacterized...
  22. ncbi Analysis of protein expression regulated by the Helicobacter pylori ArsRS two-component signal transduction system
    John T Loh
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Bacteriol 192:2034-43. 2010
    ..These results provide further definition of the ArsRS regulon and underscore the importance of the ArsRS system in regulating expression of H. pylori proteins during bacterial growth at both neutral pH and acidic pH...
  23. ncbi Resistance of primary murine CD4+ T cells to Helicobacter pylori vacuolating cytotoxin
    Holly M Scott Algood
    Departments of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Infect Immun 75:334-41. 2007
    ..This suggests that the resistance of primary murine CD4+ T cells to VacA is attributable, at least in part, to impaired VacA binding to these cells...
  24. ncbi Mapping of a domain required for protein-protein interactions and inhibitory activity of a Helicobacter pylori dominant-negative VacA mutant protein
    Victor J Torres
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Infect Immun 74:2093-101. 2006
    ....
  25. ncbi Molecular evolution of the Helicobacter pylori vacuolating toxin gene vacA
    Kelly A Gangwer
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Bacteriol 192:6126-35. 2010
    ..Taken together, these results indicate that positive selection has shaped the phylogenetic structure of VacA and CagA, and each of these virulence determinants has evolved separately from the core genome...
  26. ncbi Helicobacter pylori persistence: an overview of interactions between H. pylori and host immune defenses
    Holly M Scott Algood
    Division of Infectious Diseases, A2200 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Clin Microbiol Rev 19:597-613. 2006
    ..pylori resists immune clearance and also are relevant for understanding the pathogenesis of diseases caused by H. pylori (peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma)...
  27. ncbi Helicobacter pylori vacuolating cytotoxin inhibits activation-induced proliferation of human T and B lymphocyte subsets
    Victor J Torres
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232 2605, USA
    J Immunol 179:5433-40. 2007
    ..We propose that the immunomodulatory actions of VacA on T and B lymphocytes, the major effectors of the adaptive immune response, may contribute to the ability of H. pylori to establish a persistent infection in the human gastric mucosa...
  28. ncbi Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain
    Kelly A Gangwer
    Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 104:16293-8. 2007
    ..Docking of the p55 structure into a 19-A cryo-EM map of a VacA dodecamer allows us to propose a model for how VacA monomers assemble into oligomeric structures capable of membrane channel formation...
  29. ncbi Growth phase regulation of flaA expression in Helicobacter pylori is luxS dependent
    John T Loh
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
    Infect Immun 72:5506-10. 2004
    ..Mutating the luxS gene eliminates growth-phase-dependent control of flaA, and this growth phase dependence is restored when the luxS mutant strain is complemented with the wild-type luxS gene...
  30. ncbi Requirement of histidine kinases HP0165 and HP1364 for acid resistance in Helicobacter pylori
    John T Loh
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Infect Immun 74:3052-9. 2006
    ..These results indicate that intact HP0165 and HP1364 histidine kinases are required for acid resistance in H. pylori...
  31. ncbi Protein-protein interactions among Helicobacter pylori cag proteins
    Valerie J Busler
    Department of Microbiology and Immunology, Division of Infectious Diseases, A2200 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Bacteriol 188:4787-800. 2006
    ..Protein-protein interactions among Cag proteins are likely to have an important role in the assembly of the H. pylori type IV secretion apparatus...
  32. ncbi Heterogeneity among Helicobacter pylori strains in expression of the outer membrane protein BabA
    Ewa E Hennig
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Infect Immun 72:3429-35. 2004
    ..Heterogeneity among H. pylori strains in expression of the BabA protein may be a factor that contributes to differing clinical outcomes among H. pylori-infected humans...
  33. ncbi Clustering and redistribution of late endocytic compartments in response to Helicobacter pylori vacuolating toxin
    Yi Li
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Mol Biol Cell 15:1946-59. 2004
    ..We speculate that VacA-induced alterations in late endocytic membrane traffic contribute to the capacity of H. pylori to persistently colonize the human gastric mucosa...
  34. ncbi Helicobacter pylori VacA subdomain required for intracellular toxin activity and assembly of functional oligomeric complexes
    Susan E Ivie
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2605, USA
    Infect Immun 76:2843-51. 2008
    ..These data indicate that the assembly of functional oligomeric VacA complexes is dependent on specific sequences, including amino acids 346 and 347, within the p55 amino-terminal subdomain...
  35. ncbi Helicobacter pylori VacA toxin inhibits human immunodeficiency virus infection of primary human T cells
    Kyra Oswald-Richter
    Division of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Virol 80:11767-75. 2006
    ..These results suggest that VacA inhibits T-cell activation and HIV infection via a novel mechanism. Identifying the host cell targets of VacA could be useful for elucidating the HIV life cycle within primary T cells...
  36. ncbi Random mutagenesis of Helicobacter pylori vacA to identify amino acids essential for vacuolating cytotoxic activity
    Mark S McClain
    Department of Medicine, Vanderbilt University School of Medicine, and Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232, USA
    Infect Immun 74:6188-95. 2006
    ..In addition, these are the first examples of mutant VacA proteins that have defects in vacuolating activity despite exhibiting channel activities similar to those of wild-type VacA...
  37. ncbi Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion
    Mark S Sundrud
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2605, USA
    Proc Natl Acad Sci U S A 101:7727-32. 2004
    ..We suggest that VacA may inhibit the clonal expansion of T cells that have already been activated by H. pylori antigens, thereby allowing H. pylori to evade the adaptive immune response and establish chronic infection...
  38. ncbi Interactions between p-33 and p-55 domains of the Helicobacter pylori vacuolating cytotoxin (VacA)
    Victor J Torres
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2605, USA
    J Biol Chem 279:2324-31. 2004
    ..These results provide evidence that interactions between p-33 and p-55 domains play an important role in VacA assembly into oligomeric structures...
  39. ncbi Expression of Helicobacter pylori vacuolating toxin in Escherichia coli
    Mark S McClain
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Infect Immun 71:2266-71. 2003
    ..The capacity to analyze VacA in this heterologous-expression system should greatly facilitate efforts to elucidate the structure and function of this toxin...
  40. ncbi Reconstitution of Helicobacter pylori VacA toxin from purified components
    Christian González-Rivera
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Biochemistry 49:5743-52. 2010
    ..We propose that the oligomerization observed in these experiments mimics the process by which VacA oligomerizes when in contact with membranes of host cells...
  41. ncbi Functional properties of the p33 and p55 domains of the Helicobacter pylori vacuolating cytotoxin
    Victor J Torres
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2605, USA
    J Biol Chem 280:21107-14. 2005
    ..Reconstitution of toxin activity from two separate domains, as described here for VacA, has rarely been described for pore-forming bacterial toxins, which suggests that VacA is a pore-forming toxin with unique structural properties...
  42. ncbi Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity
    John T Loh
    Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Cancer Epidemiol Biomarkers Prev 20:2237-49. 2011
    ..Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis...
  43. ncbi Helicobacter pylori VacA induces programmed necrosis in gastric epithelial cells
    Jana N Radin
    Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 2605, USA
    Infect Immun 79:2535-43. 2011
    ....
  44. ncbi Essential role of a GXXXG motif for membrane channel formation by Helicobacter pylori vacuolating toxin
    Mark S McClain
    Department of Medicine, Vanderbilt University School of Medicine and the Veterans Affairs Medical Center, Nashville, Tennessee 37232, USA
    J Biol Chem 278:12101-8. 2003
    ....
  45. ncbi Association of Helicobacter pylori vacuolating toxin (VacA) with lipid rafts
    Wayne Schraw
    Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Biol Chem 277:34642-50. 2002
    ..These data indicate that VacA associates with lipid raft microdomains in the absence of GPI-anchored proteins and suggest that association of the toxin with lipid rafts is important for VacA cytotoxicity...
  46. ncbi L-arginine availability regulates inducible nitric oxide synthase-dependent host defense against Helicobacter pylori
    Rupesh Chaturvedi
    Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee 37212, USA
    Infect Immun 75:4305-15. 2007
    ..These findings indicate that L-Arg is rate limiting for iNOS translation and suggest that the levels of L-Arg that occur in vivo do not permit sufficient NO generation by the host to kill H. pylori...
  47. ncbi Helicobacter pylori VacA disrupts apical membrane-cytoskeletal interactions in gastric parietal cells
    Fengsong Wang
    Morehouse School of Medicine, Atlanta, Georgia 30310, USA
    J Biol Chem 283:26714-25. 2008
    ..pylori-induced inhibition of acid secretion. Our results indicate that VacA disrupts the apical membrane-cytoskeletal interactions in gastric parietal cells and thereby causes hypochlorhydria...
  48. ncbi Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells
    Song Ze Ding
    Department of Microbiology, The University of Virginia Health System, 1300 Jefferson Park Avenue, Charlottesville, VA 22908, USA
    FEMS Immunol Med Microbiol 53:385-94. 2008
    ..These results provide more insight into how H. pylori and MAPK modulate AP-1 subcomponents in gastric epithelial cells to alter the expression of downstream target genes and affect cellular functions...
  49. ncbi Serological assays for identification of human gastric colonization by Helicobacter pylori strains expressing VacA m1 or m2
    Chandrabali Ghose
    Department of Microbiology, New York University School of Medicine, New York, New York, USA
    Clin Vaccine Immunol 14:442-50. 2007
    ..In an Asian-American population, serologic responses to VacA m region-specific antigens were not able to predict the risk of development of gastric cancer...
  50. ncbi Genome-wide transcriptional profiling in a histidine kinase mutant of Helicobacter pylori identifies members of a regulon
    Mark H Forsyth
    Department of Biology, The College of William and Mary, Williamsburg, Virginia 23187, USA
    J Bacteriol 184:4630-5. 2002
    ..Strain-dependent variations in differential expression were also detected. These results indicate that the signal transduction circuit utilizing HK0164 controls the transcription of at least seven genes in H. pylori...
  51. ncbi Effects of Helicobacter pylori on intracellular Ca2+ signaling in normal human gastric mucous epithelial cells
    Katie L Marlink
    Department of Surgery, Oregon Health Sciences University, 3181 Sam Jackson Park Road, Portland, OR 97201, USA
    Am J Physiol Gastrointest Liver Physiol 285:G163-76. 2003
    ..These findings are the first to show that H. pylori alters [Ca2+]i in normal GMEC through a Ca2+ release/influx mechanism that depends on expression of cagA and picB/cagE genes...
  52. ncbi Characterization of the MHC class I cross-presentation pathway for cell-associated antigens by human dendritic cells
    Jean Francois Fonteneau
    School of Medicine, New York University, New York, NY 10016, USA
    Blood 102:4448-55. 2003
    ..Altogether, these data suggest that antigens derived from apoptotic and necrotic cells require access to the cytosol to intersect with the conventional MHC class I pathway for presentation of cytosolic proteins...
  53. ncbi Multiple oligomeric states of the Helicobacter pylori vacuolating toxin demonstrated by cryo-electron microscopy
    Marc Adrian
    Laboratoire d'Analyse Ultrastructurale, Batiment de Biologie, Universite de Lausanne, Lausanne, Switzerland
    J Mol Biol 318:121-33. 2002
    ..These results indicate that VacA is able to undergo major conformational changes, accompanied by major changes in its state of oligomerization, under different natural and experimental conditions...
  54. ncbi Genomic Comparison of cag pathogenicity island (PAI)-positive and -negative Helicobacter pylori strains: identification of novel markers for cag PAI-positive strains
    Courtney E Terry
    Department of Biology, The College of William and Mary, 214 Millington Hall, Landrum Drive, Williamsburg, VA 23187-8795, USA
    Infect Immun 73:3794-8. 2005
    ..A low G+C content of these two genes suggests they were acquired by horizontal transfer events...
  55. ncbi Quantitative effect of luxS gene inactivation on the fitness of Helicobacter pylori
    Woo-Kon Lee
    Department of Molecular Microbiology, Campus Box 8230, 4940 Parkview Place, Washington University Medical School, St. Louis, MO 63110, USA
    Appl Environ Microbiol 72:6615-22. 2006
    ..pylori strains. Also tenable is a model in which AI-2 affects other microbes in H. pylori's gastric ecosystem and thereby modulates the gastric environment in ways to which certain H. pylori strains are particularly sensitive...
  56. ncbi Mimicry of a host anion channel by a Helicobacter pylori pore-forming toxin
    Daniel M Czajkowsky
    Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
    Biophys J 89:3093-101. 2005
    ..As a result, VacA can perturb, but not necessarily abolish, the homeostatic ionic imbalance across a membrane and so change cellular physiology without necessarily jeopardizing vitality...
  57. ncbi High resolution structural analysis of Helicobacter pylori VacA toxin oligomers by cryo-negative staining electron microscopy
    Catherine el-Bez
    Laboratoire d Analyse Ultrastructurale, Batiment de Biologie, Universite de Lausanne, Lausanne, Switzerland
    J Struct Biol 151:215-28. 2005
    ....
  58. ncbi Multiple chromosomal loci for the babA gene in Helicobacter pylori
    Ewa E Hennig
    Department of Gastroenterology, Medical Center for Postgraduate Education, Cancer Center, Warsaw, Poland
    Infect Immun 74:3046-51. 2006
    ..These data indicate that there is marked heterogeneity among H. pylori strains in babA genetic content and BabA expression...
  59. ncbi Targeting of Helicobacter pylori vacuolating toxin to lipid raft membrane domains analysed by atomic force microscopy
    Nicholas A Geisse
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK
    Biochem J 381:911-7. 2004
    ..Therefore it is probable that the association of VacA with rafts in DOPC/SM/cholesterol bilayers represents a useful model for understanding the interactions of VacA with membranes in vivo...
  60. ncbi Cellular vacuolation and mitochondrial cytochrome c release are independent outcomes of Helicobacter pylori vacuolating cytotoxin activity that are each dependent on membrane channel formation
    David C Willhite
    Department of Biology and Biochemistry, University of Houston, 369 Science and Research Building II, Houston, Texas 77204-5001, USA
    J Biol Chem 278:48204-9. 2003
    ..These data indicate that cellular vacuolation and mitochondrial cytochrome c release are two independent outcomes of VacA intoxication and that both effects are dependent on the formation of anion-selective membrane channels...
  61. ncbi Role of Helicobacter pylori outer membrane proteins in gastroduodenal disease
    Timothy L Cover
    J Infect Dis 194:1343-5. 2006
  62. ncbi PIKfyve Kinase and SKD1 AAA ATPase define distinct endocytic compartments. Only PIKfyve expression inhibits the cell-vacoulating activity of Helicobacter pylori VacA toxin
    Ognian C Ikonomov
    Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    J Biol Chem 277:46785-90. 2002
    ....
  63. ncbi Recovery from lactacidosis-induced glial cell swelling with the aid of exogenous anion channels
    Takashi Nabekura
    Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki, Japan
    Glia 41:247-59. 2003
    ..Introduction of anion channel activity into glial cells might provide a novel approach for treating cerebral edema, which is associated with lactacidosis in cerebral ischemia or head injury...

Research Grants27

  1. Structure-function analysis of H. pylori VacA
    TIMOTHY COVER; Fiscal Year: 2005
    ..Ultimately, these studies may lead to advances in the treatment or prevention of H. pylori-associated human diseases. ..
  2. H. Pylory factors associated with peptic ulcer disease
    TIMOTHY COVER; Fiscal Year: 2006
    ..These studies should result in a better understanding of the H. pylori factors that help to determine clinical outcome, and ultimately, may lead to advances in the treatment or prevention of H. pylori-associated human diseases. ..
  3. Structure-function analysis of H. pylori VacA
    TIMOTHY COVER; Fiscal Year: 2007
    ..This research seeks to understand how a bacterial infection can lead to these diseases, and seeks to develop new approaches for the prevention and therapy of stomach cancer and peptic ulcer disease. ..
  4. Analysis of the H. Pylori cag pathogenicity island
    TIMOTHY COVER; Fiscal Year: 2009
    ..This research seeks to understand how a bacterial infection can lead to these diseases. The long-term goals are to develop effective means for the prevention and treatment of stomach cancer and peptic ulcer disease. ..
  5. Structure-function analysis of H. pylori VacA
    Timothy L Cover; Fiscal Year: 2010
    ..This research seeks to understand how a bacterial infection can lead to these diseases, and seeks to develop new approaches for the prevention and therapy of stomach cancer and peptic ulcer disease. ..
  6. Analysis of the H. Pylori cag pathogenicity island
    Timothy L Cover; Fiscal Year: 2010
    ..This research seeks to understand how a bacterial infection can lead to these diseases. The long-term goals are to develop effective means for the prevention and treatment of stomach cancer and peptic ulcer disease. ..
  7. STRUCTURE AND REGULATION OF H PYLORI CYTOTOXIN
    TIMOTHY COVER; Fiscal Year: 2000
    ..Understanding the structure and regulation of the vacuolating cytotoxin may aid in the development of strategies to prevent and treat H. pylori-associated gastroduodenal illnesses. ..
  8. BINDING AND UPTAKE OF H PYLORI VACUOLATING CYTOTOXIN
    TIMOTHY COVER; Fiscal Year: 2001
    ..Understanding the mechanisms whereby VacA binds to and enters cells may ultimately result in the development of strategies to prevent and treat H. pylori-associated gastroduodenal illnesses. ..
  9. Structure-function analysis of H. pylori VacA
    Timothy L Cover; Fiscal Year: 2011
    ..This research seeks to understand how a bacterial infection can lead to these diseases, and seeks to develop new approaches for the prevention and therapy of stomach cancer and peptic ulcer disease. ..