J M Kelly

Summary

Affiliation: London School of Hygiene and Tropical Medicine
Country: UK

Publications

  1. pmc Benznidazole-resistance in Trypanosoma cruzi: evidence that distinct mechanisms can act in concert
    Monica C O Campos
    Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, IOC, Avenida Brasil 4365, Manguinhos, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil Electronic address
    Mol Biochem Parasitol 193:17-9. 2014
  2. pmc Highly sensitive in vivo imaging of Trypanosoma brucei expressing "red-shifted" luciferase
    Alex P McLatchie
    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    PLoS Negl Trop Dis 7:e2571. 2013
  3. pmc Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population
    Ana Maria Mejía
    Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, University of London, United Kingdom
    J Infect Dis 206:220-8. 2012
  4. pmc Centromere-associated topoisomerase activity in bloodstream form Trypanosoma brucei
    Samson O Obado
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Nucleic Acids Res 39:1023-33. 2011
  5. pmc Centromere-associated repeat arrays on Trypanosoma brucei chromosomes are much more extensive than predicted
    Maria C Echeverry
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
    BMC Genomics 13:29. 2012
  6. pmc The Trypanosoma cruzi metacyclic-specific protein Met-III associates with the nucleolus and contains independent amino and carboxyl terminal targeting elements
    Eva Gluenz
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Int J Parasitol 37:617-25. 2007
  7. pmc Repetitive DNA is associated with centromeric domains in Trypanosoma brucei but not Trypanosoma cruzi
    Samson O Obado
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
    Genome Biol 8:R37. 2007
  8. pmc pTcINDEX: a stable tetracycline-regulated expression vector for Trypanosoma cruzi
    Martin C Taylor
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    BMC Biotechnol 6:32. 2006
  9. pmc Evidence on the chromosomal location of centromeric DNA in Plasmodium falciparum from etoposide-mediated topoisomerase-II cleavage
    John M Kelly
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom
    Proc Natl Acad Sci U S A 103:6706-11. 2006
  10. pmc In vitro and in vivo activities of aminoadamantane and aminoalkylcyclohexane derivatives against Trypanosoma brucei
    J M Kelly
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Antimicrob Agents Chemother 45:1360-6. 2001

Collaborators

Detail Information

Publications41

  1. pmc Benznidazole-resistance in Trypanosoma cruzi: evidence that distinct mechanisms can act in concert
    Monica C O Campos
    Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, IOC, Avenida Brasil 4365, Manguinhos, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil Electronic address
    Mol Biochem Parasitol 193:17-9. 2014
    ..cruzi has an intrinsic ability to develop drug-resistance by independent sequential steps, even within a single population. This has important implications for drug development strategies. ..
  2. pmc Highly sensitive in vivo imaging of Trypanosoma brucei expressing "red-shifted" luciferase
    Alex P McLatchie
    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    PLoS Negl Trop Dis 7:e2571. 2013
    ..However, lack of sensitivity in detecting deep tissue bioluminescence at wavelengths below 600 nm has restricted the wide-spread use of in vivo imaging to investigate infections with T. brucei and other trypanosomatids...
  3. pmc Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population
    Ana Maria Mejía
    Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, University of London, United Kingdom
    J Infect Dis 206:220-8. 2012
    ..They also demonstrate that T. cruzi has a propensity to undergo genetic changes that can lead to drug resistance, a finding that has implications for future therapeutic strategies...
  4. pmc Centromere-associated topoisomerase activity in bloodstream form Trypanosoma brucei
    Samson O Obado
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Nucleic Acids Res 39:1023-33. 2011
    ..Evidence that we present here suggests that sumoylation of the T. brucei enzyme is not required for centromere-specific cleavage activity...
  5. pmc Centromere-associated repeat arrays on Trypanosoma brucei chromosomes are much more extensive than predicted
    Maria C Echeverry
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
    BMC Genomics 13:29. 2012
    ..Initial estimates from the genome sequencing project suggested that these arrays ranged from 2 - 8 kb. In this paper, we show that the centromeric repeat regions are much more extensive...
  6. pmc The Trypanosoma cruzi metacyclic-specific protein Met-III associates with the nucleolus and contains independent amino and carboxyl terminal targeting elements
    Eva Gluenz
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Int J Parasitol 37:617-25. 2007
    ..To investigate the function of Met-III, we used gene deletion. This showed that Met-III is not required for the development of metacyclic trypomastigotes and that null mutants can complete the life-cycle in vitro...
  7. pmc Repetitive DNA is associated with centromeric domains in Trypanosoma brucei but not Trypanosoma cruzi
    Samson O Obado
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
    Genome Biol 8:R37. 2007
    ..Their genomes display several unusual characteristics and, despite completion of the trypanosome genome projects, the location of centromeric DNA has not been identified...
  8. pmc pTcINDEX: a stable tetracycline-regulated expression vector for Trypanosoma cruzi
    Martin C Taylor
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    BMC Biotechnol 6:32. 2006
    ..To this end we report the development of a stable tetracycline-dependent expression vector applicable to this parasite and describe in detail the parameters of the system...
  9. pmc Evidence on the chromosomal location of centromeric DNA in Plasmodium falciparum from etoposide-mediated topoisomerase-II cleavage
    John M Kelly
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom
    Proc Natl Acad Sci U S A 103:6706-11. 2006
    ..These unusual properties suggest that P. falciparum chromosomes contain a class of "regional" centromere distinct from those described in other eukaryotes, including the human host...
  10. pmc In vitro and in vivo activities of aminoadamantane and aminoalkylcyclohexane derivatives against Trypanosoma brucei
    J M Kelly
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Antimicrob Agents Chemother 45:1360-6. 2001
    ..These results suggest that aminoadamantane derivatives could have potential as a new class of trypanocidal agents...
  11. ncbi request reprint Distinct mitochondrial and cytosolic enzymes mediate trypanothione-dependent peroxide metabolism in Trypanosoma cruzi
    S R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT United Kingdom
    J Biol Chem 275:8220-5. 2000
    ..The parasite-specific features of T. cruzi cytoplasmic peroxiredoxin and T. cruzi mitochondrial peroxiredoxin may be exploitable in terms of drug development...
  12. ncbi request reprint The gametocyte-activating factor xanthurenic acid stimulates an increase in membrane-associated guanylyl cyclase activity in the human malaria parasite Plasmodium falciparum
    D K Muhia
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Microbiol 42:553-60. 2001
    ..These results therefore suggest that xanthurenic acid-induced exflagellation may be mediated by activation of the parasite cGMP signalling pathway...
  13. pmc The anti-influenza virus drug rimantadine has trypanocidal activity
    J M Kelly
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom
    Antimicrob Agents Chemother 43:985-7. 1999
    ..4). The activity is pH dependent and is consistent with a mechanism involving inhibition of the ability to regulate internal pH. Rimantadine is also toxic to the trypanosomatid parasites Trypanosoma cruzi and Leishmania major...
  14. pmc Biochemical characterization of a trypanosome enzyme with glutathione-dependent peroxidase activity
    S R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Biochem J 352:755-61. 2000
    ..With lower-affinity substrates such as t-butyl hydroperoxide, the rate-limiting step is the reduction of the oxidant. The data presented here identify a new arm of the T. cruzi oxidative defence system...
  15. doi request reprint Iron metabolism in trypanosomatids, and its crucial role in infection
    M C Taylor
    Pathogen Molecular Biology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Parasitology 137:899-917. 2010
    ..The central role of iron in both parasite metabolism and the host response is attracting interest as a possible point of therapeutic intervention...
  16. ncbi request reprint Trypanosoma cruzi adenylyl cyclase is encoded by a complex multigene family
    M C Taylor
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK
    Mol Biochem Parasitol 104:205-17. 1999
    ..This constitutively active recombinant protein will be a useful tool for dissecting the catalytic mechanism of adenylyl cyclase...
  17. ncbi request reprint Guanylyl cyclase activity associated with putative bifunctional integral membrane proteins in Plasmodium falciparum
    D J Carucci
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom
    J Biol Chem 275:22147-56. 2000
    ..The profound structural differences identified between mammalian and parasite guanylyl cyclases suggest that aspects of this signaling pathway may be mechanistically distinct...
  18. ncbi request reprint The amino terminal domain of a novel WD repeat protein from Trypanosoma cruzi contains a non-canonical mitochondrial targeting signal
    Elizabeth V Bromley
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Int J Parasitol 34:63-71. 2004
    ..Interestingly this region lacks a typical amino terminal presequence suggesting that mitochondrial import is mediated by an alternative targeting signal...
  19. pmc The terminal step in vitamin C biosynthesis in Trypanosoma cruzi is mediated by a FMN-dependent galactonolactone oxidase
    Flora J Logan
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Biochem J 407:419-26. 2007
    ..The conserved lysine residue within this motif (Lys-450) is not required for cofactor binding, but its replacement by glycine renders the protein completely inactive...
  20. pmc TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate specificity restricted to fatty acid and phospholipid hydroperoxides, is localized to the endoplasmic reticulum
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Biochem J 364:787-94. 2002
    ..cruzi oxidative defence system by protecting newly synthesized lipids from peroxidation...
  21. pmc Peroxiredoxins play a major role in protecting Trypanosoma cruzi against macrophage- and endogenously-derived peroxynitrite
    Lucia Piacenza
    Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
    Biochem J 410:359-68. 2008
    ..Together with recent reports of up-regulation of antioxidant enzymes during metacyclogenesis, our results identify components of the antioxidant enzyme network of T. cruzi as virulence factors of emerging importance...
  22. pmc A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes
    Shane R Wilkinson
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Proc Natl Acad Sci U S A 105:5022-7. 2008
    ..This potential for drug resistance by a simple mechanism has important implications, because nifurtimox is currently undergoing phase III clinical trials against African trypanosomiasis...
  23. ncbi request reprint Functional characterisation of the iron superoxide dismutase gene repertoire in Trypanosoma brucei
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Free Radic Biol Med 40:198-209. 2006
    ..These experiments therefore identify essential components of the superoxide metabolising arm of the T. brucei oxidative defence system and validate these enzymes as parasite-specific targets for drug design...
  24. ncbi request reprint Femtosecond electron-transfer reactions in mono- and polynucleotides and in DNA
    Gavin D Reid
    School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK
    J Am Chem Soc 124:5518-27. 2002
    ..We conclude that long-range electron transfer in DNA is not exceptionally fast as would be expected if DNA behaved as a "molecular wire" but nor is it as slow as is seen in proteins, which do not benefit from pi-stacking...
  25. ncbi request reprint The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    J Biol Chem 277:17062-71. 2002
    ..The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites...
  26. pmc Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Proc Natl Acad Sci U S A 99:13453-8. 2002
    ..These findings identify an arm of the oxidative defense system of this medically important parasite. The absence of this redox pathway in the human host may be therapeutically exploitable...
  27. pmc Validation of spermidine synthase as a drug target in African trypanosomes
    Martin C Taylor
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Biochem J 409:563-9. 2008
    ..brucei cannot scavenge sufficient spermidine from their environment to meet growth requirements...
  28. ncbi request reprint Purine nucleotide cyclases in the malaria parasite
    David A Baker
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Trends Parasitol 20:227-32. 2004
  29. ncbi request reprint Structure, function and evolution of microbial adenylyl and guanylyl cyclases
    David A Baker
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Microbiol 52:1229-42. 2004
    ..A review is timely because the explosion of data from the various genome projects is providing new and exciting insights into protein function and evolution...
  30. pmc Functional mapping of a trypanosome centromere by chromosome fragmentation identifies a 16-kb GC-rich transcriptional "strand-switch" domain as a major feature
    Samson O Obado
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Genome Res 15:36-43. 2005
    ..This unusual type of organization may represent a paradigm for centromeres in T. cruzi and other primitive eukaryotes...
  31. pmc Vitamin C biosynthesis in trypanosomes: a role for the glycosome
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Proc Natl Acad Sci U S A 102:11645-50. 2005
    ..It is implicit, therefore, that bloodstream-form trypanosomes also possess a capacity for ascorbate transport...
  32. ncbi request reprint RNA interference identifies two hydroperoxide metabolizing enzymes that are essential to the bloodstream form of the african trypanosome
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    J Biol Chem 278:31640-6. 2003
    ..These experiments therefore identify redox pathways that are essential for oxidative defense in T. brucei and validate the corresponding peroxidases as targets for drug design...
  33. ncbi request reprint The suppression of galactose metabolism in Trypanosoma cruzi epimastigotes causes changes in cell surface molecular architecture and cell morphology
    James I Macrae
    Division of Biological Chemistry and Molecular Microbiology, The School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Mol Biochem Parasitol 147:126-36. 2006
    ..The apparent haploid deficiency suggests that epimerase levels are close to limiting, at least in the epimastigote form, and might be exploited as a potential drug target...
  34. ncbi request reprint Multiple splice variants encode a novel adenylyl cyclase of possible plastid origin expressed in the sexual stage of the malaria parasite Plasmodium falciparum
    David K Muhia
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom
    J Biol Chem 278:22014-22. 2003
    ....
  35. pmc Deletion of the Trypanosoma brucei superoxide dismutase gene sodb1 increases sensitivity to nifurtimox and benznidazole
    S Radhika Prathalingham
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Antimicrob Agents Chemother 51:755-8. 2007
    ..Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide...
  36. pmc Mitochondrial superoxide radicals mediate programmed cell death in Trypanosoma cruzi: cytoprotective action of mitochondrial iron superoxide dismutase overexpression
    Lucia Piacenza
    Departamento de Bioquimica, Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
    Biochem J 403:323-34. 2007
    ....
  37. pmc Design, synthesis, and trypanocidal activity of new aminoadamantane derivatives
    Ioannis Papanastasiou
    Department of Pharmaceutical Chemistry, University of Athens, Athens, Greece
    J Med Chem 51:1496-500. 2008
    ..The most active analogues, 1c, 1d, 2c, 2g, and 3b, illustrate the synergistic effect of the lipophilic character of the C1 side chain and the C2 functionality on trypanocidal activity...
  38. doi request reprint Design and synthesis of bioactive 1,2-annulated adamantane derivatives
    Grigoris Zoidis
    Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli Zografou, GR 15771, Athens, Greece
    Org Biomol Chem 6:3177-85. 2008
    ..Oxazolone 20 showed significant trypanocidal activity against bloodstream forms of the African trypanosome, Trypanosoma brucei, being approximately 3 times more potent than rimantadine and almost 50-fold more active than amantadine...
  39. ncbi request reprint The role of glutathione peroxidases in trypanosomatids
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Biol Chem 384:517-25. 2003
    ....
  40. ncbi request reprint Photooxidation of guanine by a ruthenium dipyridophenazine complex intercalated in a double-stranded polynucleotide monitored directly by picosecond visible and infrared transient absorption spectroscopy
    Benjamin Elias
    Service de Chimie Organique et Photochimie, CP 160 08, Universite Libre de Bruxelles, 50 Avenue F D Roosevelt, 1050 Bruxelles, Belgium
    Chemistry 14:369-75. 2008
    ....
  41. ncbi request reprint Targeting of photooxidative damage on single-stranded DNA representing the bcr-abl chimeric gene using oligonucleotide-conjugates containing [Ru(phen)3](2+)-like photosensitiser groups
    Conor W Cream
    Chemistry Department, Trinity College, University of Dublin, Dublin 2, Ireland
    Photochem Photobiol Sci 1:1024-33. 2002
    ..These results are therefore consistent with the photooxidative damage being induced by a reaction close to the photosensitiser rather than by a diffusible species such as 1O2...