Robert Spooner

Summary

Affiliation: University of Warwick School of Life Sciences
Location: Coventry, UK
URL: http://www2.warwick.ac.uk/fac/sci/lifesci/people/rspooner/

Publications

  1. pmc Retrograde transport pathways utilised by viruses and protein toxins
    Robert A Spooner
    Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, UK
    Virol J 3:26. 2006
  2. pmc Ricin trafficking in plant and mammalian cells
    J Michael Lord
    School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK
    Toxins (Basel) 3:787-801. 2011
  3. pmc Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways
    Evelyn Fuchs
    Department of Cell Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany
    J Cell Biol 177:1133-43. 2007
  4. ncbi Toxin entry and trafficking in mammalian cells
    Peter Watson
    Department of Biochemistry, University of Bristol, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK
    Adv Drug Deliv Rev 58:1581-96. 2006
  5. ncbi Internalized Pseudomonas exotoxin A can exploit multiple pathways to reach the endoplasmic reticulum
    Daniel C Smith
    Molecular Cell Biology Group, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
    Traffic 7:379-93. 2006
  6. pmc Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum
    Robert A Spooner
    Molecular Cell Biology, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
    Biochem J 383:285-93. 2004
  7. ncbi Methods to improve efficacy in suicide gene therapy approaches: targeting prodrug-activating enzymes carboxypeptidase G2 and nitroreductase to different subcellular compartments
    Silke Schepelmann
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, London, UK
    Methods Mol Med 90:279-301. 2004
  8. ncbi Retrograde transport of toxins across the endoplasmic reticulum membrane
    J M Lord
    Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, U K
    Biochem Soc Trans 31:1260-2. 2003
  9. ncbi Ricin. Mechanisms of cytotoxicity
    Michael J Lord
    Department of Biological Sciences, University of Warwick, Coventry, UK
    Toxicol Rev 22:53-64. 2003
  10. pmc A novel vascular endothelial growth factor-directed therapy that selectively activates cytotoxic prodrugs
    R A Spooner
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Br J Cancer 88:1622-30. 2003

Collaborators

Detail Information

Publications47

  1. pmc Retrograde transport pathways utilised by viruses and protein toxins
    Robert A Spooner
    Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, UK
    Virol J 3:26. 2006
    ..Emerging data suggests instead that there is no common pathway utilised for retrograde transport by all of these pathogens, the choice of route being determined by the particular receptor utilised...
  2. pmc Ricin trafficking in plant and mammalian cells
    J Michael Lord
    School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK
    Toxins (Basel) 3:787-801. 2011
    ..In this review we will consider both of these trafficking routes...
  3. pmc Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways
    Evelyn Fuchs
    Department of Cell Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany
    J Cell Biol 177:1133-43. 2007
    ..These results suggest that Shiga toxin trafficking to the Golgi is a multistep process controlled by several Rab GAPs and their target Rabs and that this process is discrete from ligand-induced EGF receptor trafficking...
  4. ncbi Toxin entry and trafficking in mammalian cells
    Peter Watson
    Department of Biochemistry, University of Bristol, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK
    Adv Drug Deliv Rev 58:1581-96. 2006
    ..Studying the trafficking of toxins has led to a greater understanding of retrograde transport, a process which has key relevance to the correct intracellular delivery of pharmacological agents...
  5. ncbi Internalized Pseudomonas exotoxin A can exploit multiple pathways to reach the endoplasmic reticulum
    Daniel C Smith
    Molecular Cell Biology Group, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
    Traffic 7:379-93. 2006
    ..Thus, unexpectedly, an ER-directed toxin with a proteinaceous receptor shows promiscuity in its intracellular trafficking pathways, exploiting routes controlled by both lipid- and protein-sorting signals...
  6. pmc Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum
    Robert A Spooner
    Molecular Cell Biology, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
    Biochem J 383:285-93. 2004
    ..In contrast with other toxins, ricin does not appear to require either proteolytic cleavage or unfolding for PDI-catalysed reduction...
  7. ncbi Methods to improve efficacy in suicide gene therapy approaches: targeting prodrug-activating enzymes carboxypeptidase G2 and nitroreductase to different subcellular compartments
    Silke Schepelmann
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, London, UK
    Methods Mol Med 90:279-301. 2004
  8. ncbi Retrograde transport of toxins across the endoplasmic reticulum membrane
    J M Lord
    Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, U K
    Biochem Soc Trans 31:1260-2. 2003
    ..Treatment with the proteasomal inhibitor lactacystin increased the cytotoxicity of the lysine-enriched RTA to a level approaching that of wild-type RTA...
  9. ncbi Ricin. Mechanisms of cytotoxicity
    Michael J Lord
    Department of Biological Sciences, University of Warwick, Coventry, UK
    Toxicol Rev 22:53-64. 2003
    ....
  10. pmc A novel vascular endothelial growth factor-directed therapy that selectively activates cytotoxic prodrugs
    R A Spooner
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Br J Cancer 88:1622-30. 2003
    ..We conclude that enzyme prodrug therapy using VEGF as a targeting moiety represents a promising novel antitumour therapy, with VEGF(115)-CPG2(Q)3-H(6) being a lead candidate...
  11. pmc The secretion inhibitor Exo2 perturbs trafficking of Shiga toxin between endosomes and the trans-Golgi network
    Robert A Spooner
    Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK
    Biochem J 414:471-84. 2008
    ....
  12. pmc Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum
    Robert A Spooner
    Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom
    Proc Natl Acad Sci U S A 105:17408-13. 2008
    ....
  13. pmc A human embryonic kidney 293T cell line mutated at the Golgi alpha-mannosidase II locus
    Max Crispin
    Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, United Kingdom
    J Biol Chem 284:21684-95. 2009
    ..The Lec36 cell line will be useful for expressing therapeutic glycoproteins with hybrid-type glycans and as a sensitive host for detecting mutations in human MAN2A1 causing type II congenital dyserythropoietic anemia...
  14. doi An Exo2 derivative affects ER and Golgi morphology and vacuolar sorting in a tissue-specific manner in arabidopsis
    Mathias Sorieul
    School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom
    Traffic 12:1552-62. 2011
    ..Up to concentrations of 50 µm, the effects of LG8 are reversible...
  15. pmc Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways
    Mina Olga Aletrari
    School of Life Sciences, University of Warwick, Coventry, United Kingdom
    PLoS ONE 6:e22713. 2011
    ..We therefore investigated ESI as a potential inhibitor of toxin dislocation...
  16. doi How ricin and Shiga toxin reach the cytosol of target cells: retrotranslocation from the endoplasmic reticulum
    Robert A Spooner
    School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK
    Curr Top Microbiol Immunol 357:19-40. 2012
    ..Recent studies not only describe how these proteins breach the ER membrane, but also reveal aspects of a fundamental cell biological process, that of ER-cytosol dislocation...
  17. pmc RNAi screening of Drosophila (Sophophora) melanogaster S2 cells for ricin sensitivity and resistance
    Vidya Pawar
    Department of Biological Sciences, University of Warwick, Coventry, UK
    J Biomol Screen 16:436-42. 2011
    ....
  18. doi LG186: An inhibitor of GBF1 function that causes Golgi disassembly in human and canine cells
    Frédéric Boal
    Cell Biology Laboratories, School of Biochemistry, Medical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK
    Traffic 11:1537-51. 2010
    ..Unlike other Arf-GEF and reported GBF1 inhibitors including BFA, Exo2 and Golgicide A, LG186 induces disassembly of the Golgi stack in both human and canine cells...
  19. doi Fine tuning Exo2, a small molecule inhibitor of secretion and retrograde trafficking pathways in mammalian cells
    Lucie J Guetzoyan
    Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
    Mol Biosyst 6:2030-8. 2010
    ..Our results provide unique compounds with low toxicity and enhanced specificity to unpick the complexity of membrane trafficking networks...
  20. pmc Folding-competent and folding-defective forms of ricin A chain have different fates after retrotranslocation from the endoplasmic reticulum
    Shuyu Li
    Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom
    Mol Biol Cell 21:2543-54. 2010
    ..We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate...
  21. ncbi Drug targeting: learning from toxin entry and trafficking in mammalian cells
    Robert A Spooner
    Cardiff University, School of Biosciences, Museum Avenue, Cardiff, CF10 3AX, UK
    Curr Opin Drug Discov Devel 13:86-95. 2010
    ....
  22. doi Simple oxidation of pyrimidinylhydrazones to triazolopyrimidines and their inhibition of Shiga toxin trafficking
    Lucie J Guetzoyan
    Department of Chemistry, University of Warwick, CV4 7AL, UK
    Eur J Med Chem 45:275-83. 2010
    ..The effect of these compounds on Shiga toxin (STx) trafficking in HeLa cells and comparison to the previously reported Exo2 is also detailed...
  23. ncbi Three new prodrugs for suicide gene therapy using carboxypeptidase G2 elicit bystander efficacy in two xenograft models
    Frank Friedlos
    Cancer Research Campaign Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, SM2 5NG United Kingdom
    Cancer Res 62:1724-9. 2002
    ....
  24. ncbi Appropriate subcellular localisation of prodrug-activating enzymes has important consequences for suicide gene therapy
    R A Spooner
    CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, United Kingdom
    Int J Cancer 93:123-30. 2001
    ..These data demonstrate that the site of enzyme expression and prodrug activation is an important variable that requires consideration in suicide gene therapy approaches...
  25. ncbi In suicide gene therapy, the site of subcellular localization of the activating enzyme is more important than the rate at which it activates prodrug
    R A Spooner
    Cancer Research Campaign Centre for Cancer Therapeutics at the Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Cancer Gene Ther 7:1348-56. 2000
    ..These data demonstrate that the location of the enzyme in the cell is more important than the enzyme activity as the determinant in mediating cytotoxicity...
  26. ncbi A recombinant single-chain antibody interleukin-2 fusion protein
    P Savage
    Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London
    Cell Biophys 22:61-77. 1993
    ..In vivo administration of tumor-binding SCA-IL-2 should result in a localized high concentration of rIL-2 in the tumor tissues, maximizing the anti-tumor response while keeping systemic side effects to a minimum...
  27. ncbi A universal antibody-derived targeting agent
    R A Spooner
    Royal Postgraduate Medical School, Department of Clinical Oncology, Hammersmith Hospital, London
    Cell Biophys 22:225-42. 1993
    ..The ScFv described here can therefore be considered as a universal agent for delivery of drugs, toxins, or radionuclides to any cell type for which a previously characterized antibody exists...
  28. ncbi Applications of monoclonal antibodies in clinical oncology
    A J George
    Dept of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
    Immunol Today 15:559-61. 1994
    ..However, a recent conference provided evidence that the field is coming of age, and that antibodies, and their recombinant derivatives, will continue to find a role in the clinic...
  29. ncbi Deoxyribonuclease I (DNAse I). A novel approach for targeted cancer therapy
    H Linardou
    Tumour Targeting Laboratory, Imperial Cancer Research Fund, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
    Cell Biophys 24:243-8. 1994
    ..The use of a mammalian enzyme should be much less toxic and less immunogenic than current immunotoxins and may expand the current limits of immunotoxin therapy...
  30. ncbi DNA vaccination for cancer treatment
    R A Spooner
    Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
    Gene Ther 2:173-80. 1995
    ..Expression of DNA encoding fragments of tumour-specific proteins as neo-antigens or surrogate antigens in a novel context may be a means of breaking immunological tolerance and lead to the generation of tumour-specific immune responses...
  31. ncbi Genetic delivery of enzymes for cancer therapy
    M P Deonarain
    Tumour Targeting Laboratory, ICRF Oncology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
    Gene Ther 2:235-44. 1995
    ..However, more research is still needed to enable full exploitation of the transcriptional differences between tumour and normal cells so that more existing cancers can be treated in this way...
  32. pmc Activation of the xylDLEGF promoter of the TOL toluene-xylene degradation pathway by overproduction of the xylS regulatory gene product
    R A Spooner
    J Bacteriol 169:3581-6. 1987
    ..The operator sequences required for xylS interactions lay upstream of the OP2 transcriptional start, and the xylS gene product recognized this region even in the absence of known coinducers...
  33. ncbi Immunotoxins: monoclonal antibody-toxin conjugates--a new approach to cancer therapy
    J M Lord
    Department of Biological Sciences, University of Warwick, Coventry, England
    Adv Biotechnol Processes 11:193-211. 1989
  34. ncbi Genetic, functional and sequence analysis of the xylR and xylS regulatory genes of the TOL plasmid pWW0
    R A Spooner
    J Gen Microbiol 132:1347-58. 1986
    ..The ORF designated xylS appears capable of encoding a polypeptide of approximately 37 kDa...
  35. ncbi Genetically engineered antibodies for diagnostic pathology
    R A Spooner
    Tumour Targeting Laboratory, ICRF Oncology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
    Hum Pathol 25:606-14. 1994
    ..Detection could be by recognition of a genetically fused flag or tag epitope, by the fusion of an enzyme whose activity can be assayed, or by fusion with a protein that can interact with pre-existing histopathological reagents...
  36. ncbi Expression of immunoglobulin heavy chain-ricin A chain fusions in mammalian cells
    R A Spooner
    Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, U K
    Mol Immunol 31:117-25. 1994
    ..We conclude that the ricin A chain moiety retains biological activity precluding the expression of biologically active antibody-ricin A chain fusion proteins in mammalian cells...
  37. pmc Construction, characterisation and kinetics of a single chain antibody recognising the tumour associated antigen placental alkaline phosphatase
    P Savage
    Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
    Br J Cancer 68:738-42. 1993
    ..Additionally, the SCA can also be used for the construction of antibody based fusion proteins to target other effector functions to tumour cells...
  38. ncbi Regressions of established breast carcinoma xenografts by carboxypeptidase G2 suicide gene therapy and the prodrug CMDA are due to a bystander effect
    S M Stribbling
    CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Hum Gene Ther 11:285-92. 2000
    ..These results suggest that a bystander effect plays a major role in suicide gene therapy regimens with stCPG2(Q)3 and CMDA...
  39. ncbi Self-immolative anthracycline prodrugs for suicide gene therapy
    I Niculescu-Duvaz
    CRC Centre for Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    J Med Chem 42:2485-9. 1999
    ..Prodrug 12 underwent an 11-fold activation when assayed in the cell line expressing externally surface-tethered CPG2...
  40. ncbi Self-immolative nitrogen mustard prodrugs for suicide gene therapy
    D Niculescu-Duvaz
    CRC Centre for Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, U K
    J Med Chem 41:5297-309. 1998
    ..These data demonstrate the viability of this strategy and indicate that self-immolative prodrugs can be synthesized to release potent mustard drugs selectively by cells expressing CPG2 tethered to the cell surface in GDEPT...
  41. ncbi Gene-directed enzyme prodrug therapy
    I Niculescu-Duvaz
    CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Bioconjug Chem 9:4-22. 1998
  42. ncbi A cell surface tethered enzyme improves efficiency in gene-directed enzyme prodrug therapy
    R Marais
    CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK
    Nat Biotechnol 15:1373-7. 1997
    ..Systemic administration of CMDA to mice bearing established xenografts of the transfected cells led to sustained tumor regressions or cures...
  43. ncbi Gene-directed enzyme prodrug therapy with a mustard prodrug/carboxypeptidase G2 combination
    R Marais
    CRC Centre for Cancer Therapeutics at the Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Cancer Res 56:4735-42. 1996
    ..These results establish this CPG2 enzyme/CMDA prodrug system as an effective combination for the gene-directed enzyme prodrug therapy approach...
  44. ncbi A single-chain Fv reactive with the Goodpasture antigen
    C N Ross
    Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom
    Lab Invest 74:1051-9. 1996
    ..The potential of HBR-3 as a diagnostic reagent in Alport's syndrome has been demonstrated. The development of this recombinant molecule should permit new approaches to the investigation of Goodpasture's disease...
  45. ncbi Construction, expression and characterisation of a single chain anti-tumour antibody (scFv)-IL-2 fusion protein
    E Boleti
    Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
    Ann Oncol 6:945-7. 1995
    ..This molecule could be used to target interleukin-2 to PLAP-expressing tumours...
  46. pmc A recombinant single chain antibody interleukin-2 fusion protein
    P Savage
    Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
    Br J Cancer 67:304-10. 1993
    ..In vivo administration of a tumour binding SCA-IL-2 should result in a localised high concentration of IL-2 in tumour tissues, maximising the anti-tumour immune response, whilst keeping systemic side effects to a minimum...
  47. ncbi Immunotoxins: status and prospects
    R A Spooner
    Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, UK
    Trends Biotechnol 8:189-93. 1990
    ..Genetic engineering is increasingly being used to refine and modify these conjugates, and it is now possible to design, express and purify completely recombinant therapeutic molecules...