VERNON BRUCE CARRUTHERS

Summary

Affiliation: University of Michigan
Country: USA

Publications

  1. pmc A novel high throughput invasion screen identifies host actin regulators required for efficient cell entry by Toxoplasma gondii
    Rajshekhar Y Gaji
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS ONE 8:e64693. 2013
  2. pmc Targeted disruption of Toxoplasma gondii serine protease inhibitor 1 increases bradyzoite cyst formation in vitro and parasite tissue burden in mice
    Viviana Pszenny
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Infect Immun 80:1156-65. 2012
  3. pmc Microneme proteins in apicomplexans
    Vern B Carruthers
    Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
    Subcell Biochem 47:33-45. 2008
  4. pmc Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells
    Bjorn F C Kafsack
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 323:530-3. 2009
  5. pmc Tagging of endogenous genes in a Toxoplasma gondii strain lacking Ku80
    My Hang Huynh
    Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
    Eukaryot Cell 8:530-9. 2009
  6. doi request reprint New roles for perforins and proteases in apicomplexan egress
    Marijo S Roiko
    Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 48109, USA
    Cell Microbiol 11:1444-52. 2009
  7. pmc Effects of Toxoplasma gondii infection on the brain
    Vern B Carruthers
    Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor MI 48109, USA
    Schizophr Bull 33:745-51. 2007
  8. pmc Kinetic modeling of Toxoplasma gondii invasion
    Bjorn F C Kafsack
    Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Sciences Bldg II, 1150 West Medical Center Dr, Ann Arbor, MI 48109 0620, USA
    J Theor Biol 249:817-25. 2007
  9. ncbi request reprint Distinct mechanisms govern proteolytic shedding of a key invasion protein in apicomplexan pathogens
    Steven A Howell
    Department of Protein Structure, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Mol Microbiol 57:1342-56. 2005
  10. ncbi request reprint Trans-genera reconstitution and complementation of an adhesion complex in Toxoplasma gondii
    My Hang Huynh
    Johns Hopkins Bloomberg School of Public Health, W Harry Feinstone Department of Molecular Microbiology and Immunology, Baltimore MD, USA
    Cell Microbiol 6:771-82. 2004

Research Grants

  1. Proteolytic modulation of toxoplasma invasion proteins
    VERNON BRUCE CARRUTHERS; Fiscal Year: 2010
  2. MICRONEME FUNCTION IN TOXOPLASMA
    VERNON CARRUTHERS; Fiscal Year: 2009
  3. Proteolytic modulation of toxoplasma invasion proteins
    VERNON CARRUTHERS; Fiscal Year: 2009
  4. Mediators of Toxoplasma surviral during infection
    VERNON CARRUTHERS; Fiscal Year: 2004
  5. MICRONEME FUNCTION IN TOXOPLASMA
    VERNON CARRUTHERS; Fiscal Year: 2004
  6. Proteomics analysis Toxoplasma gene knockout phenotypes
    VERNON CARRUTHERS; Fiscal Year: 2003
  7. Proteolytic modulation of toxoplasma invasion proteins
    VERNON BRUCE CARRUTHERS; Fiscal Year: 2011

Collaborators

  • Yasuhiro Suzuki
  • Isabelle Coppens
  • F M Tomley
  • John C Boothroyd
  • M J Blackman
  • J Aliberti
  • Kami Kim
  • Kristin M Hager
  • My Hang Huynh
  • Jill M Harper
  • Susannah D Brydges
  • Xing W Zhou
  • Bjorn F C Kafsack
  • Meredith Teilhet Morris
  • Viviana Pszenny
  • Rajshekhar Y Gaji
  • Steven A Howell
  • Marijo S Roiko
  • Eleanor F Hoff
  • Fabiola Parussini
  • Chin Fen Teo
  • Xing Wang Zhou
  • G Lucas Starnes
  • L David Sibley
  • Alfica Sehgal
  • Dominique Soldati
  • Stanislas Tomavo
  • Markus Meissner
  • Paul H Davis
  • David S Roos
  • Christopher A Hunter
  • Sandeep Ravindran
  • Janethe D O Pena
  • Matthew Bogyo
  • Fernando J Pineda
  • Gary E Ward
  • Travis J Jewett
  • Koku D Z Adjogble
  • Walter Daubener
  • Jeffrey Mital
  • Silvia Moreno
  • Chrislaine Withers-Martinez
  • Artemio M Jongco
  • Fiona Hackett
  • Phil Beckett
  • Robert N Cole
  • Rong F Shen
  • Lai Yu Kwok
  • Wen Chih Cheng
  • Corinna Opitz
  • Shobhona Sharma
  • Nirbhay Kumar
  • Karen E Rabenau
  • Wandy L Beatty
  • Matthias Reiss
  • James W Ajioka
  • Nicola Viebig
  • Alexandra Coppin
  • Catherine Toursel

Detail Information

Publications34

  1. pmc A novel high throughput invasion screen identifies host actin regulators required for efficient cell entry by Toxoplasma gondii
    Rajshekhar Y Gaji
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS ONE 8:e64693. 2013
    ..These findings support the emerging notion that host actin dynamics are important for Toxoplasma invasion along with identifying several novel host factors that potentially participate in parasite entry...
  2. pmc Targeted disruption of Toxoplasma gondii serine protease inhibitor 1 increases bradyzoite cyst formation in vitro and parasite tissue burden in mice
    Viviana Pszenny
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Infect Immun 80:1156-65. 2012
    ..These results demonstrate that TgPI1 influences both parasite virulence and bradyzoite differentiation, presumably by inhibiting parasite and/or host serine proteases...
  3. pmc Microneme proteins in apicomplexans
    Vern B Carruthers
    Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
    Subcell Biochem 47:33-45. 2008
    ..New access to complete genome sequences and ongoing advances in genetic manipulation should provide fertile ground for refining current models and defining exciting new roles for MICs in apicomplexan biology...
  4. pmc Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells
    Bjorn F C Kafsack
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 323:530-3. 2009
    ..Perforin-like proteins from other intracellular pathogens may play a similar role in microbial egress and virulence...
  5. pmc Tagging of endogenous genes in a Toxoplasma gondii strain lacking Ku80
    My Hang Huynh
    Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
    Eukaryot Cell 8:530-9. 2009
    ..LIC constructs reduces both the time and cost required to determine localization of a new gene of interest. This should allow the opportunity for performing larger-scale studies of novel T. gondii genes...
  6. doi request reprint New roles for perforins and proteases in apicomplexan egress
    Marijo S Roiko
    Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 48109, USA
    Cell Microbiol 11:1444-52. 2009
    ..Together these discoveries reveal important new molecular players involved in the principal steps of egress by apicomplexans...
  7. pmc Effects of Toxoplasma gondii infection on the brain
    Vern B Carruthers
    Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor MI 48109, USA
    Schizophr Bull 33:745-51. 2007
    ....
  8. pmc Kinetic modeling of Toxoplasma gondii invasion
    Bjorn F C Kafsack
    Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Sciences Bldg II, 1150 West Medical Center Dr, Ann Arbor, MI 48109 0620, USA
    J Theor Biol 249:817-25. 2007
    ..We conclude that mathematical modeling provides a powerful new tool for characterizing the stages of host-cell invasion by intracellular parasites...
  9. ncbi request reprint Distinct mechanisms govern proteolytic shedding of a key invasion protein in apicomplexan pathogens
    Steven A Howell
    Department of Protein Structure, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Mol Microbiol 57:1342-56. 2005
    ..This work reveals unexpected differences in the manner in which Plasmodium and Toxoplasma shed AMA1 from the surface of invasive zoites, and demonstrates the presence at the malaria merozoite surface of a rhomboid-like protease...
  10. ncbi request reprint Trans-genera reconstitution and complementation of an adhesion complex in Toxoplasma gondii
    My Hang Huynh
    Johns Hopkins Bloomberg School of Public Health, W Harry Feinstone Department of Molecular Microbiology and Immunology, Baltimore MD, USA
    Cell Microbiol 6:771-82. 2004
    ....
  11. ncbi request reprint Multimerization of the Toxoplasma gondii MIC2 integrin-like A-domain is required for binding to heparin and human cells
    Jill M Harper
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street E5132, Baltimore, MD 21205, USA
    Mol Biochem Parasitol 134:201-12. 2004
    ..Multimerization of MIC2 may increase the number of interactions with host cell receptors, thereby forming a multivalent adhesive junction during parasite entry...
  12. ncbi request reprint Proteomic analysis of cleavage events reveals a dynamic two-step mechanism for proteolysis of a key parasite adhesive complex
    Xing W Zhou
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Mol Cell Proteomics 3:565-76. 2004
    ..Our data support a novel two-step proteolysis model that includes primary processing of the MIC2/M2AP complex followed by secondary cleavage to shed the complex from the parasite surface during the final steps of invasion...
  13. ncbi request reprint Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells
    Julio Aliberti
    Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Immunol 4:485-90. 2003
    ..The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts...
  14. ncbi request reprint A family of transmembrane microneme proteins of Toxoplasma gondii contain EGF-like domains and function as escorters
    Markus Meissner
    Imperial College of Science, Technology and Medicine, Department of Biology, Sir Alexander Fleming Building, Imperial College Road, London, SW7 2AZ, UK
    J Cell Sci 115:563-74. 2002
    ..TgMIC6 and TgMIC8 are expressed in the rapidly dividing tachyzoites, while TgMIC7 and TgMIC9 genes are predominantly expressed in bradyzoites, where they presumably also serve as escorters...
  15. ncbi request reprint Two separate, conserved acidic amino acid domains within the Toxoplasma gondii MIC2 cytoplasmic tail are required for parasite survival
    G Lucas Starnes
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63130 1093, USA
    J Biol Chem 281:30745-54. 2006
    ..Both acidic domains are conserved throughout TRAP orthologs, implicating a central role for these motifs in apicomplexan motility...
  16. pmc A transient forward-targeting element for microneme-regulated secretion in Toxoplasma gondii
    Susannah D Brydges
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Biol Cell 100:253-64. 2008
    ..Microneme discharge during parasite apical attachment plays a pivotal role in cell invasion by delivering adhesive proteins for host receptor engagement...
  17. pmc MARveling at parasite invasion
    Kristin M Hager
    Department of Biological Sciences, Center for Global Health and Infectious Disease, University of Notre Dame, Notre Dame, IN 46556 0369, USA
    Trends Parasitol 24:51-4. 2008
    ..Comparison with Plasmodium erythrocyte-binding antigen 175 reveals that terminal sialic acid residues might represent a shared but tailored invasion pathway among apicomplexan parasites...
  18. pmc Cysteine protease inhibitors block Toxoplasma gondii microneme secretion and cell invasion
    Chin Fen Teo
    Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA
    Antimicrob Agents Chemother 51:679-88. 2007
    ..Our findings suggest that cysteine protease activity is required for microneme secretion and cell invasion by T. gondii...
  19. pmc Targeted deletion of MIC5 enhances trimming proteolysis of Toxoplasma invasion proteins
    Susannah D Brydges
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, MD 21205, USA
    Eukaryot Cell 5:2174-83. 2006
    ..Together, our findings suggest that MIC5 either directly regulates MPP2 activity or it influences MPP2's ability to access substrate cleavage sites on the parasite surface...
  20. pmc Toxoplasma MIC2 is a major determinant of invasion and virulence
    My Hang Huynh
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
    PLoS Pathog 2:e84. 2006
    ..Our findings demonstrate that the MIC2 protein complex is a major virulence determinant for Toxoplasma infection and that MIC2-deficient parasites constitute an effective live-attenuated vaccine for experimental toxoplasmosis...
  21. pmc A cleavable propeptide influences Toxoplasma infection by facilitating the trafficking and secretion of the TgMIC2-M2AP invasion complex
    Jill M Harper
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Mol Biol Cell 17:4551-63. 2006
    ..Therefore, the propeptide and its cleavage site influence distinct aspects of TgMIC2-M2AP function, with both impacting the outcome of infection...
  22. ncbi request reprint Is Toxoplasma egress the first step in invasion?
    Eleanor F Hoff
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA
    Trends Parasitol 18:251-5. 2002
    ....
  23. ncbi request reprint Functional analysis of Toxoplasma gondii protease inhibitor 1
    Meredith Teilhet Morris
    The W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    J Biol Chem 277:45259-66. 2002
    ..TgPI-1 is the first anti-trypsin/chymotrypsin inhibitor to be identified in bradyzoites and sporozoites, stages of the parasite that would be exposed to proteolytic enzymes in the digestive tract of the host...
  24. ncbi request reprint Identification and partial characterization of a second Kazal inhibitor in Toxoplasma gondii
    Meredith Teilhet Morris
    The W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD 21205, USA
    Mol Biochem Parasitol 128:119-22. 2003
  25. pmc Rapid invasion of host cells by Toxoplasma requires secretion of the MIC2-M2AP adhesive protein complex
    My Hang Huynh
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    EMBO J 22:2082-90. 2003
    ..M2AP knockout parasites were also unable to rapidly secrete MIC2, an event that normally accompanies parasite attachment to a target cell. These findings indicate a critical role for the MIC2-M2AP protein complex in parasite invasion...
  26. ncbi request reprint Mutation of an unusual mitochondrial targeting sequence of SODB2 produces multiple targeting fates in Toxoplasma gondii
    Susannah D Brydges
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
    J Cell Sci 116:4675-85. 2003
    ..In addition to having an unusual targeting sequence, TgSODB2 is only the second mitochondrially imported, iron-containing SOD to be described...
  27. ncbi request reprint Translocation of ribosomal protein P0 onto the Toxoplasma gondii tachyzoite surface
    Alfica Sehgal
    Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400 005, India
    Int J Parasitol 33:1589-94. 2003
    ..Surface translocation of transiently expressed TgP0 and blocking of tachyzoite invasion of human foreskin fibroblasts by anti-PfP0 antibodies suggest that P0 protein plays an important role in T. gondii invasion of human cells...
  28. ncbi request reprint Neospora caninum expresses an unusual single-domain Kazal protease inhibitor that is discharged into the parasitophorous vacuole
    Meredith Teilhet Morris
    W Harry Feinstein Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    Int J Parasitol 34:693-701. 2004
    ..caninum lysate, one with a molecular mass approximately 11 kDa and another at approximately 20 kDa. This, along with mass spectrometry analysis of recombinant NcPI-S, suggests that the inhibitor is expressed as a dimer in the parasite...
  29. ncbi request reprint The novel coccidian micronemal protein MIC11 undergoes proteolytic maturation by sequential cleavage to remove an internal propeptide
    Jill M Harper
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Int J Parasitol 34:1047-58. 2004
    ..This is the first microneme protein characterised to date in the phylum Apicomplexa that possesses this unique structure and undergoes maturation by removal of an internal propeptide...
  30. ncbi request reprint A new release on life: emerging concepts in proteolysis and parasite invasion
    Vern B Carruthers
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Mol Microbiol 55:1617-30. 2005
    ..The sequential proteolytic events associated with invasion by pathogenic protozoa may represent vulnerable pathways for the future development of synergistic anti-protozoal therapies...
  31. pmc The opportunistic pathogen Toxoplasma gondii deploys a diverse legion of invasion and survival proteins
    Xing W Zhou
    The W Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    J Biol Chem 280:34233-44. 2005
    ..gondii tachyzoites. These findings provided a uniquely broad view of Toxoplasma secretory proteins that participate in parasite survival and pathogenesis during infection...
  32. ncbi request reprint Preparing for an invasion: charting the pathway of adhesion proteins to Toxoplasma micronemes
    My Hang Huynh
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Parasitol Res 98:389-95. 2006
    ..gondii and at a deeper understanding of the precise roles of M2AP propeptide and MIC2 targeting motifs in MIC protein trafficking...
  33. ncbi request reprint Proteolysis and Toxoplasma invasion
    Vern B Carruthers
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Room E5136, Baltimore, MD 21205, USA
    Int J Parasitol 36:595-600. 2006
    ..The identification of highly selective inhibitors for these proteases has the potential to not only further dissect their roles in infection but also to ameliorate disease...
  34. ncbi request reprint Host cell invasion by the opportunistic pathogen Toxoplasma gondii
    Vern B Carruthers
    W Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD 21205, USA
    Acta Trop 81:111-22. 2002
    ..gondii...

Research Grants15

  1. Proteolytic modulation of toxoplasma invasion proteins
    VERNON BRUCE CARRUTHERS; Fiscal Year: 2010
    ..Toxoplasma proteases may be good targets for new anti-parasitic drugs;this work is designed to test the function and significance of two such proteases. ..
  2. MICRONEME FUNCTION IN TOXOPLASMA
    VERNON CARRUTHERS; Fiscal Year: 2009
    ..Because cell adhesion is an essential feature of the parasite, we anticipate these studies may lead to novel future opportunities to interrupt infection and potentially ameliorate disease. ..
  3. Proteolytic modulation of toxoplasma invasion proteins
    VERNON CARRUTHERS; Fiscal Year: 2009
    ..Toxoplasma proteases may be good targets for new anti-parasitic drugs; this work is designed to test the function and significance of two such proteases. ..
  4. Mediators of Toxoplasma surviral during infection
    VERNON CARRUTHERS; Fiscal Year: 2004
    ..abstract_text> ..
  5. MICRONEME FUNCTION IN TOXOPLASMA
    VERNON CARRUTHERS; Fiscal Year: 2004
    ..Specific Aim III will be to identify host cell receptors recognized by MIC2. These studies will directly lead to a better understanding of the molecular mechanisms underlying T. gondii invasion of host cells. ..
  6. Proteomics analysis Toxoplasma gene knockout phenotypes
    VERNON CARRUTHERS; Fiscal Year: 2003
    ..We anticipate that this "functional proteomics" project will reveal previously unknown protein interactions that will be pivotal in defining the functions of secretory proteins in parasite invasion. ..
  7. Proteolytic modulation of toxoplasma invasion proteins
    VERNON BRUCE CARRUTHERS; Fiscal Year: 2011
    ..Toxoplasma proteases may be good targets for new anti-parasitic drugs;this work is designed to test the function and significance of two such proteases. ..