Conor R Caffrey

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Characterization of proteinases from the midgut of Rhipicephalus (Boophilus) microplus involved in the generation of antimicrobial peptides
    Carlos E Cruz
    Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05508 900, Brazil
    Parasit Vectors 3:63. 2010
  2. pmc Rapid induction of IgE responses to a worm cysteine protease during murine pre-patent schistosome infection
    Lucia A de Oliveira Fraga
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    BMC Immunol 11:56. 2010
  3. doi request reprint Schistosomiasis: from drug deployment to drug development
    Conor R Caffrey
    Sandler Center for Drug Discovery, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California 94158, USA
    Curr Opin Infect Dis 24:410-7. 2011
  4. pmc A global comparison of the human and T. brucei degradomes gives insights about possible parasite drug targets
    Susan T Mashiyama
    Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biomedical Research QB3, University of California San Francisco, San Francisco, California, United States of America
    PLoS Negl Trop Dis 6:e1942. 2012
  5. pmc RNA interference in Schistosoma mansoni schistosomula: selectivity, sensitivity and operation for larger-scale screening
    Sasa Stefanic
    Sandler Center for Drug Discovery, California Institute for Quantitative Biosciences QB3, University of California San Francisco, San Francisco, California, United States of America
    PLoS Negl Trop Dis 4:e850. 2010
  6. pmc Structure-guided development of selective TbcatB inhibitors
    Jeremy P Mallari
    Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, California 94143 2280, USA
    J Med Chem 52:6489-93. 2009
  7. pmc SmCL3, a gastrodermal cysteine protease of the human blood fluke Schistosoma mansoni
    Jan Dvorak
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California, United States of America
    PLoS Negl Trop Dis 3:e449. 2009
  8. doi request reprint Biolistic transformation of Schistosoma mansoni: Studies with modified reporter-gene constructs containing regulatory regions of protease genes
    Jan Dvorak
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biosciences QB3, 1700 4th St, University of California, San Francisco, CA 94158 2550, USA
    Mol Biochem Parasitol 170:37-40. 2010
  9. pmc A parasite cysteine protease is key to host protein degradation and iron acquisition
    Theresa C O'Brien
    Department of Pathology and Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California 94158 2550, USA
    J Biol Chem 283:28934-43. 2008
  10. pmc Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB
    Jeremy P Mallari
    Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, CA 94143 2280, USA
    Bioorg Med Chem Lett 18:2883-5. 2008

Collaborators

Detail Information

Publications31

  1. pmc Characterization of proteinases from the midgut of Rhipicephalus (Boophilus) microplus involved in the generation of antimicrobial peptides
    Carlos E Cruz
    Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05508 900, Brazil
    Parasit Vectors 3:63. 2010
    ..abstract:..
  2. pmc Rapid induction of IgE responses to a worm cysteine protease during murine pre-patent schistosome infection
    Lucia A de Oliveira Fraga
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    BMC Immunol 11:56. 2010
    ....
  3. doi request reprint Schistosomiasis: from drug deployment to drug development
    Conor R Caffrey
    Sandler Center for Drug Discovery, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California 94158, USA
    Curr Opin Infect Dis 24:410-7. 2011
    ..Accordingly, and in spite of the challenges associated with developing new antischistosomals as discussed herein, alternatives to PZQ should be identified. Various strategies to do this are highlighted here...
  4. pmc A global comparison of the human and T. brucei degradomes gives insights about possible parasite drug targets
    Susan T Mashiyama
    Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biomedical Research QB3, University of California San Francisco, San Francisco, California, United States of America
    PLoS Negl Trop Dis 6:e1942. 2012
    ..These sequence and structure data, along with interactive versions of the protein similarity networks generated in this study, are available at http://babbittlab.ucsf.edu/resources.html...
  5. pmc RNA interference in Schistosoma mansoni schistosomula: selectivity, sensitivity and operation for larger-scale screening
    Sasa Stefanic
    Sandler Center for Drug Discovery, California Institute for Quantitative Biosciences QB3, University of California San Francisco, San Francisco, California, United States of America
    PLoS Negl Trop Dis 4:e850. 2010
    ..Therefore, in the context of standardizing larger RNAi screens, data are limited on the extent of possible off-targeting effects, gene-to-gene variability in RNAi efficiency and the operational capabilities and limits of RNAi...
  6. pmc Structure-guided development of selective TbcatB inhibitors
    Jeremy P Mallari
    Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, California 94143 2280, USA
    J Med Chem 52:6489-93. 2009
    ..These data chemically validate TbcatB as a drug target and demonstrate that it is possible to potently and selectively inhibit TbcatB relative to trypanosomal and human homologues...
  7. pmc SmCL3, a gastrodermal cysteine protease of the human blood fluke Schistosoma mansoni
    Jan Dvorak
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California, United States of America
    PLoS Negl Trop Dis 3:e449. 2009
    ..Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction. A network of proteolytic enzymes (proteases) facilitates hydrolysis of host hemoglobin and serum proteins...
  8. doi request reprint Biolistic transformation of Schistosoma mansoni: Studies with modified reporter-gene constructs containing regulatory regions of protease genes
    Jan Dvorak
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biosciences QB3, 1700 4th St, University of California, San Francisco, CA 94158 2550, USA
    Mol Biochem Parasitol 170:37-40. 2010
    ..Electroporation of the same constructs was also weakly efficient (1-10% positives per experiment). However, reporter signals were found in tissues other than the gut, which may represent dysregulated transcription...
  9. pmc A parasite cysteine protease is key to host protein degradation and iron acquisition
    Theresa C O'Brien
    Department of Pathology and Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California 94158 2550, USA
    J Biol Chem 283:28934-43. 2008
    ..Because even a modest deficiency in tbcatB is lethal for the parasite, tbcatB is a logical target for the development of new anti-trypanosomal chemotherapy...
  10. pmc Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB
    Jeremy P Mallari
    Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, CA 94143 2280, USA
    Bioorg Med Chem Lett 18:2883-5. 2008
    ..The activity of these compounds was determined against cultured T. brucei, and specificity was assessed with a panel of four mammalian cell lines...
  11. pmc Bis-acridines as lead antiparasitic agents: structure-activity analysis of a discrete compound library in vitro
    Conor R Caffrey
    Sandler Center for Basic Research in Parasitic Diseases, BH508, University of California, San Francisco, 1700 4th Street, San Francisco, CA 94158 2330, USA
    Antimicrob Agents Chemother 51:2164-72. 2007
    ..Our approach illustrates the usefulness of screening focused compound libraries against multiple parasite targets. Some of the bis-acridines identified here may represent useful starting points for further lead optimization...
  12. ncbi request reprint Blood 'n' guts: an update on schistosome digestive peptidases
    Conor R Caffrey
    Sandler Center for Basic Research in Parasitic Diseases, Box 0511, University of California San Francisco, San Francisco, CA 94143, USA
    Trends Parasitol 20:241-8. 2004
  13. ncbi request reprint A multienzyme network functions in intestinal protein digestion by a platyhelminth parasite
    Melaine Delcroix
    Department of Pathology, Tropical Disease Research Unit and Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California 94158, USA
    J Biol Chem 281:39316-29. 2006
    ..It also provides insights into which of these proteases are logical targets for development of chemotherapy for schistosomiasis, a major global health problem...
  14. ncbi request reprint Genomic and proteomic approaches for Chagas' disease: critical analysis of diagnostic methods
    Jorge A Huete-Pérez
    Sandler Center for Basic Research in Parasitic Diseases, University of California, QB3 Building, Box 2550, 1700 4 Street, San Francisco, CA 94143, USA
    Expert Rev Mol Diagn 5:521-30. 2005
    ..These advances will certainly bring about major developments not only in our understanding of Trypanosoma cruzi biology, but also in the application of new technologies to disease prevention and control...
  15. ncbi request reprint SmCB2, a novel tegumental cathepsin B from adult Schistosoma mansoni
    Conor R Caffrey
    Tropical Disease Research Unit, Department of Pathology, Box 0511, University of California San Francisco, San Francisco, CA 94143, USA
    Mol Biochem Parasitol 121:49-61. 2002
    ..By immunohistochemistry, SmCB2 was localized in the tegumental tubercles and parenchyma of males with less product being visualized in the parenchyma of females. The enzyme may be lysosomal and function at the host parasite-interface...
  16. ncbi request reprint Substrate specificity of schistosome versus human legumain determined by P1-P3 peptide libraries
    Mary A Mathieu
    Department of Pathology, UCSF, San Francisco, CA 94143, USA
    Mol Biochem Parasitol 121:99-105. 2002
    ..Predictions of substrate specificity from the library screen were confirmed using single peptide substrates for kinetic assays...
  17. ncbi request reprint Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidase
    Mohammed Sajid
    Department of Pathology, Tropical Disease Research Unit and Sandler Centre for Basic Research in Parasitic Diseases, University of California San Francisco, Box 0511, San Francisco, CA 94143, USA
    Mol Biochem Parasitol 131:65-75. 2003
    ..This study characterizes the major digestive cysteine peptidase in schistosomes and defines novel trans-processing events required to activate the SmCB1 zymogen in vitro which may facilitate the digestive process in vivo...
  18. pmc Quantification and clustering of phenotypic screening data using time-series analysis for chemotherapy of schistosomiasis
    Hyokyeong Lee
    Department of Computer Science, San Francisco State University, San Francisco, CA 94132, USA
    BMC Genomics 13:S4. 2012
    ..Development of techniques for automated, high-throughput drug screening against these diseases, especially in whole-organism settings, constitutes one of the great challenges of modern drug discovery...
  19. doi request reprint Cysteine peptidases of kinetoplastid parasites
    Conor R Caffrey
    Sandler Center for Drug Discovery, California Institute for Quantitative Biosciences, Byers Hall, University of California San Francisco, San Francisco, USA
    Adv Exp Med Biol 712:84-99. 2011
    ..Their applications as vaccine candidates and diagnostic markers as well as their chemical and genetic validation as drug targets are also summarized...
  20. ncbi request reprint Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi
    Doron C Greenbaum
    Sandler Center for Basic Research in Parasitic Diseases, Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA
    J Med Chem 47:3212-9. 2004
    ..Our results suggest that thiosemicarbazones represent validated drug leads that kill several species of protozoan parasites through the inhibition of cysteine proteases as well as other novel targets...
  21. ncbi request reprint Differential use of protease families for invasion by schistosome cercariae
    Jan Dvorak
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biomedical Research QB3, 1700 4th Street, University of California, San Francisco, CA 94158 2550, USA
    Biochimie 90:345-58. 2008
    ..Computational analysis of serine protease phylogeny revealed an extraordinarily distant relationship between S. mansoni serine proteases and other members of the Clan PA family S1 proteases...
  22. pmc Vinyl sulfones as antiparasitic agents and a structural basis for drug design
    Iain D Kerr
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158 2550, USA
    J Biol Chem 284:25697-703. 2009
    ....
  23. doi request reprint Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatB
    Jeremy P Mallari
    Graduate Program in Chemistry and Chemical Biology and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143 2280, USA
    J Med Chem 51:545-52. 2008
    ..In addition, a predictive model of trypanocidal activity was developed on the basis of potency against TbcatB and various calculated physical property descriptors...
  24. pmc Proteomic analysis of adult S. mansoni gut contents
    Melaine Delcroix
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biomedical Research QB3, 1700 4th St, University of California, San Francisco, CA 94158 2330, USA
    Mol Biochem Parasitol 154:95-7. 2007
  25. ncbi request reprint Homology modeling and SAR analysis of Schistosoma japonicum cathepsin D (SjCD) with statin inhibitors identify a unique active site steric barrier with potential for the design of specific inhibitors
    Conor R Caffrey
    Sandler Center for Basic Research in Parasitic Diseases, University of California at San Francisco, Box 0511, San Francisco, CA 94143, USA
    Biol Chem 386:339-49. 2005
    ..The unique steric barrier identified here provides a structural focus for further development of more specific SjCD inhibitors...
  26. ncbi request reprint Synthesis and structure-activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzain
    Xiaohui Du
    Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94143, USA
    J Med Chem 45:2695-707. 2002
    ..The nonpeptide nature of this series, small size, and extremely low cost of production suggest this is a promising direction for the development of new antitrypanosome chemotherapy...
  27. doi request reprint Kinetoplastid papain-like cysteine peptidases
    Conor R Caffrey
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biosciences, Byers Hall, University of California San Francisco, 1700 4th Street, San Francisco, CA 94158, USA
    Mol Biochem Parasitol 167:12-9. 2009
    ..In addition, the applications of kinetoplastid CATB and CATL enzymes as vaccine candidates, diagnostic markers and drug targets are discussed...
  28. pmc A comparative chemogenomics strategy to predict potential drug targets in the metazoan pathogen, Schistosoma mansoni
    Conor R Caffrey
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 4:e4413. 2009
    ..The comparative chemogenomics strategy presented generates a tractable set of S. mansoni proteins for experimental validation as drug targets against this insidious human pathogen...
  29. ncbi request reprint Chemotherapy of schistosomiasis: present and future
    Conor R Caffrey
    Sandler Center for Basic Research in Parasitic Diseases, Byers Hall N508, University of California San Francisco, 1700 4th Street, San Francisco, CA 94158 2330, United States
    Curr Opin Chem Biol 11:433-9. 2007
    ..g. the trioxolanes), including those where knowledge of the parasite target (e.g. cysteine proteases and hemozoin formation) is more defined...
  30. pmc Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor
    Maha Hamadien Abdulla
    Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biomedical Research, University of California San Francisco, San Francisco, California, United States of America
    PLoS Med 4:e14. 2007
    ..Due to the lack of a vaccine, patient therapy is heavily reliant on chemotherapy with praziquantel as the World Health Organization-recommended drug, but concerns over drug resistance encourage the search for new drug leads...
  31. ncbi request reprint Screening of acyl hydrazide proteinase inhibitors for antiparasitic activity against Trypanosoma brucei
    Conor R Caffrey
    Department of Pathology, Tropical Disease Research Unit, University of California San Francisco, San Francisco, CA 94143, USA
    Int J Antimicrob Agents 19:227-31. 2002
    ..Nevertheless, the data support the potential of acyl hydrazides as antitrypanosomal chemotherapeutic agents for treatment of sleeping sickness...