James McKerrow

Summary

Affiliation: University of California
Country: USA

Publications

  1. 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
  2. pmc Two approaches to discovering and developing new drugs for Chagas disease
    J H McKerrow
    Sandler Center at Mission Bay, University of California, San Francisco, CA 94158 2330, USA
    Mem Inst Oswaldo Cruz 104:263-9. 2009
  3. 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
  4. 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
  5. pmc Gene expression patterns during adaptation of a helminth parasite to different environmental niches
    Emmitt R Jolly
    California Institute for Quantitative Biomedical Research QB3 of the University of California, San Francisco, San Francisco, CA 94158 USA
    Genome Biol 8:R65. 2007
  6. ncbi request reprint Interview with James McKerrow
    James McKerrow
    Sandler Center for Drug Discovery, Department of Pharmaceutical Chemistry, University of California, 1700 4th Street, Suite 214, San Francisco, CA 94158, USA
    Future Med Chem 3:1243-6. 2011
  7. pmc Development of protease inhibitors for protozoan infections
    James H McKerrow
    Department of Pathology, University of California San Francisco, 1700 4th Street, San Francisco, CA 94158 2330, USA
    Curr Opin Infect Dis 21:668-72. 2008
  8. pmc A functional proteomics screen of proteases in colorectal carcinoma
    J H McKerrow
    Department of Pathology, University of California, San Francisco 94121, USA
    Mol Med 6:450-60. 2000
  9. ncbi request reprint Proteases in parasitic diseases
    James H McKerrow
    Department of Pathology, Sandler Center, University of California, San Francisco, California 94143, USA
    Annu Rev Pathol 1:497-536. 2006
  10. ncbi request reprint Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: insights on safety, target validation, and mechanism of action
    J H McKerrow
    Department of Pathology, UCSF VA Medical Center, San Francisco, CA 94121, USA
    Int J Parasitol 29:833-7. 1999

Detail Information

Publications86

  1. 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
  2. pmc Two approaches to discovering and developing new drugs for Chagas disease
    J H McKerrow
    Sandler Center at Mission Bay, University of California, San Francisco, CA 94158 2330, USA
    Mem Inst Oswaldo Cruz 104:263-9. 2009
    ..It is optimized for robotic liquid handling and has been validated through a screen of a library of FDA-approved drugs identifying 65 hits...
  3. 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...
  4. 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...
  5. pmc Gene expression patterns during adaptation of a helminth parasite to different environmental niches
    Emmitt R Jolly
    California Institute for Quantitative Biomedical Research QB3 of the University of California, San Francisco, San Francisco, CA 94158 USA
    Genome Biol 8:R65. 2007
    ..We report a global transcriptional analysis of how this parasite alters gene regulation to adapt to three distinct environments...
  6. ncbi request reprint Interview with James McKerrow
    James McKerrow
    Sandler Center for Drug Discovery, Department of Pharmaceutical Chemistry, University of California, 1700 4th Street, Suite 214, San Francisco, CA 94158, USA
    Future Med Chem 3:1243-6. 2011
    b>James McKerrow's research interests focus on the biology of the host-parasite relationship, from primitive single-cell protozoa to complex multicellular bloodflukes...
  7. pmc Development of protease inhibitors for protozoan infections
    James H McKerrow
    Department of Pathology, University of California San Francisco, 1700 4th Street, San Francisco, CA 94158 2330, USA
    Curr Opin Infect Dis 21:668-72. 2008
    ..These roles include processing of host or parasite surface proteins for invasion of host cells, digestion of host proteins for nutrition, and inactivation of host immune defense mediators...
  8. pmc A functional proteomics screen of proteases in colorectal carcinoma
    J H McKerrow
    Department of Pathology, University of California, San Francisco 94121, USA
    Mol Med 6:450-60. 2000
    ..Proteases facilitate several steps in cancer progression. To identify proteases most suitable for drug targeting, actual enzyme activity and not messenger RNA levels or immunoassay of protein is the ideal assay readout...
  9. ncbi request reprint Proteases in parasitic diseases
    James H McKerrow
    Department of Pathology, Sandler Center, University of California, San Francisco, California 94143, USA
    Annu Rev Pathol 1:497-536. 2006
    ....
  10. ncbi request reprint Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: insights on safety, target validation, and mechanism of action
    J H McKerrow
    Department of Pathology, UCSF VA Medical Center, San Francisco, CA 94121, USA
    Int J Parasitol 29:833-7. 1999
    ..Differential uptake of proteases by parasitic organisms versus host cells, and relatively less redundancy in parasite protease gene families, may be two factors which contribute to the successful treatment of animal models of infection...
  11. ncbi request reprint Cysteine protease inhibitors as chemotherapy for parasitic infections
    J H McKerrow
    Department of Pathology, VA Medical Center, University of California, San Francisco 94121, USA
    Bioorg Med Chem 7:639-44. 1999
    ..This suggests that cysteine protease inhibitors may provide an alternative to traditional therapy in drug-resistant organisms...
  12. pmc Designing drugs for parasitic diseases of the developing world
    James H McKerrow
    Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, USA
    PLoS Med 2:e210. 2005
  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. pmc Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic model
    Samuel G Melendez-Lopez
    Department of Pathology, University of California, San Diego, San Diego, California 92103 8416, USA
    Eukaryot Cell 6:1130-6. 2007
    ..The resultant dramatic inhibition of invasion by both inhibitors in this human colonic model of amebiasis strongly suggests a significant role of secreted amebic proteinases, such as EhCP1, in the pathogenesis of amebiasis...
  15. pmc A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target
    Chen He
    Department of Pathology and Medicine, University of California, San Diego, California 92103 8416, USA
    J Biol Chem 285:18516-27. 2010
    ..The unique expression pattern, localization, and biochemical properties of EhCP4 could be exploited as a potential target for drug design...
  16. ncbi request reprint Leishmania major: molecular modeling of cysteine proteases and prediction of new nonpeptide inhibitors
    P M Selzer
    Department of Pathology, University of California, San Francisco 94143, USA
    Exp Parasitol 87:212-21. 1997
    ..Three inhibitors were identified which were not only effective against the L. major protease but also inhibited parasite growth at 5-50 microM...
  17. pmc WormAssay: a novel computer application for whole-plate motion-based screening of macroscopic parasites
    Chris Marcellino
    Sandler Center for Drug Discovery, University of California San Francisco, San Francisco, California, USA
    PLoS Negl Trop Dis 6:e1494. 2012
    ..This system can be applied to the study of many macroparasites as well as other macroscopic organisms...
  18. ncbi request reprint Patterns of protease production during prostate cancer progression: proteomic evidence for cascades in a transgenic model
    R A Bok
    Department of Medicine, University of California, San Francisco, California 94143, USA
    Prostate Cancer Prostatic Dis 6:272-80. 2003
    ..Our results implicate pericellular proteases as initiators of major proteolytic cascades during tumor progression and suggest targets for maximal therapeutic effect...
  19. ncbi request reprint Upregulation of the secretory pathway in cysteine protease inhibitor-resistant Trypanosoma cruzi
    J C Engel
    Department of Pathology, University of California, Veteran Administration Medical Center, San Francisco, USA
    J Cell Sci 113:1345-54. 2000
    ..Cumulatively, these results suggest that CPI-resistance induces upregulation of Golgi complex function and post-Golgi secretory pathway, and release of precursors before the enzyme reaches its site of biologic activity...
  20. ncbi request reprint [Trypanocidal effect of cysteine protease inhibitors in vitro and in vivo in experimental Chagas disease]
    J C Engel
    Department of Pathology, University of California, San Francisco, USA
    Medicina (B Aires) 59:171-5. 1999
    ..Protease inhibitors may soon become good chemotherapeutic alternatives for acute and chronic Chagas' disease...
  21. ncbi request reprint A target within the target: probing cruzain's P1' site to define structural determinants for the Chagas' disease protease
    L S Brinen
    Department of Pathology, University of California, San Francisco 94143, USA
    Structure 8:831-40. 2000
    ..Cruzain is the major cysteine protease of T cruzi and has been the target of extensive structure-based drug design...
  22. pmc Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection
    J C Engel
    Department of Pathology, University of California San Francisco, California 94143, USA
    J Exp Med 188:725-34. 1998
    ..No abnormalities were noted in the Golgi complex of host cells. This study provides proof of concept that cysteine protease inhibitors can be given at therapeutic doses to animals to selectively arrest a parasitic infection...
  23. ncbi request reprint Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi
    J C Engel
    Department of Pathology, University of California, San Francisco, California 94143, USA
    J Cell Sci 111:597-606. 1998
    ..Accumulation of cruzain may decrease mobility of Golgi membranes and result in peripheral distention of cisternae. These major alterations of the Golgi complex parallel the death of T. cruzi epimastigotes...
  24. ncbi request reprint Cysteine proteases of parasitic organisms
    M Sajid
    Tropical Disease Research Unit, University of California, San Francisco, CA 94122, USA
    Mol Biochem Parasitol 120:1-21. 2002
    ..Cysteine protease classification will be re-examined in light of the diversity uncovered within parasitic organisms...
  25. pmc Inhibitors of SARS-CoV entry--identification using an internally-controlled dual envelope pseudovirion assay
    Yanchen Zhou
    Blood Systems Research Institute, University of California, San Francisco, CA 94118, USA
    Antiviral Res 92:187-94. 2011
    ..This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes...
  26. pmc Proteomic analysis of human skin treated with larval schistosome peptidases reveals distinct invasion strategies among species of blood flukes
    Jessica Ingram
    Tetrad Graduate Program, University of California San Francisco, San Francisco, California, USA
    PLoS Negl Trop Dis 5:e1337. 2011
    ....
  27. pmc Expression and alteration of the S2 subsite of the Leishmania major cathepsin B-like cysteine protease
    V J Chan
    Department of Pathology, University of California, San Francisco, CA, USA
    Biochem J 340:113-7. 1999
    ..s-1], support the findings that this protozoan protease has the P2 specificity of cathepsin L-like enzymes while retaining structural homology to mammalian cathepsin B...
  28. ncbi request reprint Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesiense
    C R Caffrey
    Tropical Disease Research Unit, Department of Pathology, University of California San Francisco, VAMC, 4150 Clement Street-113B, San Francisco, CA 94121, USA
    Mol Biochem Parasitol 118:61-73. 2001
    ..S2 subsite mapping of rhodesain and cruzain with fluorogenic peptidyl substrates demonstrates that the presence of alanine rather than glutamate at S2 prevents rhodesain from cleaving substrates in which P2 is arginine...
  29. pmc TLTF in cerebrospinal fluid for detection and staging of T. b. gambiense infection
    Maha Hamadien Abdulla
    Department of Surgery, Colorectal Research Center, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia Department of Pathology, Center for Discovery and Innovation in Parasitic Diseases, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 8:e79281. 2013
    ..Trypanosome-derived lymphocyte triggering factor (TLTF) is a molecule released by African trypanosomes that interacts with the host immune system, resulting in increased levels of IFN-γ production...
  30. 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...
  31. 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...
  32. pmc IrAE: an asparaginyl endopeptidase (legumain) in the gut of the hard tick Ixodes ricinus
    Daniel Sojka
    Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic and Faculty of Biological Sciences, University of South Bohemia, Ceske Budejovice, Czech Republic
    Int J Parasitol 37:713-24. 2007
    ..The possible functions of IrAE in the gut digestive processes of I. ricinus are compared with those suggested for other hematophagous parasites...
  33. 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...
  34. ncbi request reprint Identification and characterization of a cathepsin L-like cysteine protease from Gnathostoma spinigerum
    Natthawan Kongkerd
    Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
    Mol Biochem Parasitol 160:129-37. 2008
    ..Mouse anti-GST-proGsCL1 serum showed reactivity with 35-, 38- and 45-kDa proteins in the aL3 extracts. These proteins were shown to localize inside the intestinal cells of aL3...
  35. ncbi request reprint Drug discovery and development for neglected parasitic diseases
    Adam R Renslo
    Department of Pharmaceutical Chemistry and the Small Molecule Discovery Center, University of California San Francisco, San Francisco, CA 94158, USA
    Nat Chem Biol 2:701-10. 2006
    ..These neglected diseases present unique challenges to drug development that are being addressed by new consortia of scientists from academia and industry...
  36. pmc The common gamma chain cytokines interleukin (IL)-2 and IL-7 indirectly modulate blood fluke development via effects on CD4+ T cells
    Rebecca B Blank
    Tropical Disease Research Unit, Department of Pathology, University of California, San Francisco, San Francisco, CA, USA
    J Infect Dis 194:1609-16. 2006
    ..Thus, cytokines critical for CD4(+) T cell survival and function can mediate indirect but potent effects on developing schistosomes and underscore the importance of CD4(+) T cells in facilitating schistosome development...
  37. 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...
  38. pmc Identification of the major cysteine protease of Giardia and its role in encystation
    Kelly N DuBois
    Department of Pathology, the Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, CA 94158, USA
    J Biol Chem 283:18024-31. 2008
    ..These data suggest that Giardia cysteine protease 2 is not only the major cysteine endoprotease expressed in Giardia, but is also central to the encystation process...
  39. ncbi request reprint The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family
    Stephanie X Wang
    Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA
    Structure 15:535-43. 2007
    ..Interactions of chagasin with a target protease are reminiscent of the cystatin family inhibitors. Protein inhibitors of cysteine proteases may have evolved more than once on nonhomologous scaffolds...
  40. pmc Identification of a new class of nonpeptidic inhibitors of cruzain
    Katrien Brak
    Department of Chemistry, University of California, Berkeley, California 94720, USA
    J Am Chem Soc 130:6404-10. 2008
    ..This inhibitor completely eradicated the T. cruzi parasite from mammalian cell cultures and consequently has the potential to lead to new chemotherapeutics for Chagas disease...
  41. pmc Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica
    Colin M Stack
    Institute for the Biotechnology of Infectious Diseases, University of Technology Sydney, Sydney, New South Wales 2007, Australia
    J Biol Chem 283:9896-908. 2008
    ..The emergence of a specialized collagenolytic function in Fasciola likely contributes to the success of this tissue-invasive parasite...
  42. ncbi request reprint Potency and selectivity of P2/P3-modified inhibitors of cysteine proteases from trypanosomes
    Priyadarshini Jaishankar
    Small Molecule Discovery Center, University of California, San Francisco, CA 94158, USA
    Bioorg Med Chem Lett 18:624-8. 2008
    ..Rhodesain selectivity could be enhanced further by combining these P2 modifications with certain P3 amide substituents...
  43. ncbi request reprint Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens
    Marion G Götz
    School of Chemistry and Biochemistry and the Petit Institute for Bioscience and Bioengineering, Georgia Institute of Technology, Atlanta, Georgia 30332 0400, USA
    J Med Chem 51:2816-32. 2008
    ..The preferred P1' residues have aromatic substituents. Aza-asparaginyl Michael acceptors react with thiols, which provides insight into the mechanism of their inhibition of asparaginyl endopeptidases...
  44. ncbi request reprint Dipeptidyl-alpha,beta-epoxyesters as potent irreversible inhibitors of the cysteine proteases cruzain and rhodesain
    Florenci V González
    Departament de Quimica Inorganica i Organica, Universitat Jaume I, 12071 Castello, Spain
    Bioorg Med Chem Lett 17:6697-700. 2007
    ..The dipeptidyl epoxyesters 3 and 4 are potent, irreversible inhibitors of cruzain and rhodesain...
  45. 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...
  46. ncbi request reprint Squamous cell carcinoma antigen 1 is an inhibitor of parasite-derived cysteine proteases
    Sachiko Kanaji
    Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, 5 1 1 Nabeshima, Saga 849 8501, Japan
    FEBS Lett 581:4260-4. 2007
    ..The inhibitory activities of SCCA1 were due to its resistance to cleavage by the cysteine proteases. The findings indicate that induction of cysteine protease inhibitors might be a novel defense mechanism against parasite development...
  47. pmc A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection
    Patricia S Doyle
    Department of Pathology, University of California San Francisco, CA 94121, USA
    Antimicrob Agents Chemother 51:3932-9. 2007
    ..The majority (60 to 100%) of inhibitor-treated Rag1(-/-) mice had increased survival, negative PCR, and normal tissues by histopathological examination...
  48. ncbi request reprint Proteases from Schistosoma mansoni cercariae cleave IgE at solvent exposed interdomain regions
    Akhmed Aslam
    Institute of Genetics, University of Nottingham, Queen s Medical Centre, Nottingham, UK
    Mol Immunol 45:567-74. 2008
    ..Indeed, the finding may raise new possibilities for treatment of IgE-mediated allergic reactions mediated through Fcepsilon-receptors...
  49. ncbi request reprint A phagocytosis mutant of Entamoeba histolytica is less virulent due to deficient proteinase expression and release
    Ken K Hirata
    Departments of Pathology and Medicine, University of California, San Diego, CA 92103 8416, USA
    Exp Parasitol 115:192-9. 2007
    ..These findings provide an important link between phagocytosis, passive release of multiple cysteine proteinases, and attenuated virulence of this E. histolytica mutant...
  50. ncbi request reprint Production and processing of a recombinant Fasciola hepatica cathepsin B-like enzyme (FhcatB1) reveals potential processing mechanisms in the parasite
    Simone A Beckham
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
    Biol Chem 387:1053-61. 2006
    ..Thus, there appear to be a number of ways in which this enzyme can be processed to its optimally active form prior to secretion by F. hepatica...
  51. pmc Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease
    Stephanie X Wang
    Department of Pathology and the Sandler Center, San Francisco General Hospital, University of California, CA 94143, USA
    Proc Natl Acad Sci U S A 103:11503-8. 2006
    ..Motifs similar to FP2(nose) and FP2(arm) are found only in related plasmodial proteases, suggesting that they confer malaria-specific functions...
  52. 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
  53. ncbi request reprint Aza-peptide Michael acceptors: a new class of inhibitors specific for caspases and other clan CD cysteine proteases
    Ozlem Dogan Ekici
    School of Chemistry and Biochemistry and the Parker H Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332 0400, USA
    J Med Chem 47:1889-92. 2004
    ..Aza-Lys and aza-Orn derivatives were potent inhibitors of gingipain K and clostripain. Aza-peptide Michael acceptors showed no cross reactivity toward papain, cathepsin B, and calpain...
  54. pmc Schistosoma mansoni: sex-specific modulation of parasite growth by host immune signals
    David C Hernandez
    Department of Pathology, University of California San Francisco, HSW 501, 513 Parnassus Avenue, San Francisco, California 94143, USA
    Exp Parasitol 106:59-61. 2004
    ..The male schistosome therefore appears to play a central role both in transducing signals from the adaptive immune system and in facilitating female development...
  55. ncbi request reprint Aza-peptide epoxides: potent and selective inhibitors of Schistosoma mansoni and pig kidney legumains (asparaginyl endopeptidases)
    Karen Ellis James
    School of Chemistry and Biochemistry, and the Petit Institute for Bioscience and Bioengineering, Georgia Institute of Technology, Atlanta, GA 30332 0400, USA
    Biol Chem 384:1613-8. 2003
    ..The inhibitors have little or no inhibitory activity with other proteases such as caspases, chymotrypsin, papain, cathepsin B, granzyme B, and various aspartyl proteases...
  56. pmc Involvement of TNF in limiting liver pathology and promoting parasite survival during schistosome infection
    Stephen J Davies
    Tropical Disease Research Unit, Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA
    Int J Parasitol 34:27-36. 2004
    ..Finally, we provide evidence that TNF plays an unexpected role in maintaining adult schistosome viability in the portal system...
  57. pmc Developmental plasticity in schistosomes and other helminths
    Stephen J Davies
    Tropical Disease Research Unit, Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA
    Int J Parasitol 33:1277-84. 2003
    ..Further work is needed to determine whether developmental plasticity plays any role in increasing the probability of schistosome transmission and life cycle propagation under adverse conditions, as it does in other helminth life cycles...
  58. 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...
  59. ncbi request reprint Improved trypanocidal activities of cathepsin L inhibitors
    Njinkeng Joseph Nkemgu
    Abteilung Parasitologie, Hygiene Institut der Ruprecht Karls Universität, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
    Int J Antimicrob Agents 22:155-9. 2003
    ..Also, all inhibitors blocked proteinolysis in the lysosome consistent with the inhibition of rhodesain/brucipain. In conclusion, the data support the potential of cathepsin L inhibitors for rational anti-trypanosomal drug development...
  60. pmc A surface amebic cysteine proteinase inactivates interleukin-18
    Xuchu Que
    Department of Pathology, University of California, San Diego, California 92103, USA
    Infect Immun 71:1274-80. 2003
    ..E. histolytica may block the host inflammatory response by a novel mechanism, inactivation of IL-18...
  61. 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...
  62. ncbi request reprint CoMFA and HQSAR of acylhydrazide cruzain inhibitors
    Carlos R Rodrigues
    LASSBio, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, 21944 970, Brazil
    Bioorg Med Chem Lett 12:1537-41. 2002
    ..689). Based upon the information derived from CoMFA and HQSAR, we have identified some key features that may be used to design new acylhydrazide derivatives that may be more potent cruzain inhibitors...
  63. ncbi request reprint Cercarial elastase is encoded by a functionally conserved gene family across multiple species of schistosomes
    Jason P Salter
    University of California San Francisco Graduate Program in Biomedical Sciences and the Department of Pathology, University of California, San Francisco, California 94143, USA
    J Biol Chem 277:24618-24. 2002
    ....
  64. 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...
  65. 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...
  66. ncbi request reprint Invasion of skin by Schistosoma cercariae
    James H McKerrow
    Trends Parasitol 18:193-5. 2002
    ..The mechanisms of host finding and invasion represent fascinating and complex biological phenomenon, which are discussed here...
  67. 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...
  68. 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...
  69. ncbi request reprint A multi-enzyme cascade of hemoglobin proteolysis in the intestine of blood-feeding hookworms
    Angela L Williamson
    Department of Microbiology and Tropical Medicine, The George Washington University, Washington, DC 20037, USA
    J Biol Chem 279:35950-7. 2004
    ....
  70. ncbi request reprint Discovery of trypanocidal compounds by whole cell HTS of Trypanosoma brucei
    Zachary B Mackey
    Department of Pathology and the Sandler Center for Basic Research in Parasitic Diseases, University of California, QB3 1700 4th St, San Francisco, CA 94158, USA
    Chem Biol Drug Des 67:355-63. 2006
    ..These included the two approved trypanocidal drugs, suramin and pentamidine, several other drugs suspected but never validated as trypanocidal, and 17 novel trypanocidal drugs...
  71. ncbi request reprint Giardia lamblia cysteine proteases
    Kelly N DuBois
    Department of Pathology and the Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, CA 94158 2550, USA
    Parasitol Res 99:313-6. 2006
  72. ncbi request reprint Antitrypanosomal activity of 5'-deoxy-5'-(iodomethylene)adenosine and related 6-N-cyclopropyladenosine analogues
    Magdalena Rapp
    Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, USA
    J Med Chem 49:2096-102. 2006
    ..In contrast to some other adenosine analogues modified at C5', the 6-N-cyclopropyladenosine analogues described here do not exhibit an inhibitory effect on AdoHcy hydrolase and displayed only marginal antiviral activity...
  73. ncbi request reprint Proteomic analysis of Schistosoma mansoni cercarial secretions
    Giselle M Knudsen
    Department of Pathology and the Sandler Center, University of California, San Francisco, California 94143 0446, USA
    Mol Cell Proteomics 4:1862-75. 2005
    ..Identification of proteins secreted by invasive larvae provides important new information for validation of models of skin invasion and immune evasion and aids in rational development of an anti-schistosome vaccine...
  74. pmc The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif
    Kailash C Pandey
    Department of Medicine, San Francisco General Hospital, P O Box 0811, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 102:9138-43. 2005
    ..Our results indicate that FP2 utilizes an unusual motif for two specific functions, interaction with hemoglobin, its natural substrate, and interaction with the prodomain, its natural inhibitor...
  75. ncbi request reprint Multiple cathepsin B isoforms in schistosomula of Trichobilharzia regenti: identification, characterisation and putative role in migration and nutrition
    Jan Dvorak
    Department of Parasitology, Faculty of Science, Charles University, Vinicna 7, CZ 12844 Prague, Czech Republic
    Int J Parasitol 35:895-910. 2005
    ..Also, both isoforms degraded myelin basic protein, the major protein component of nervous tissue, but were inefficient against hemoglobin, thus supporting the adaptation of T. regenti gut peptidases to parasitism of host nervous tissue...
  76. pmc In vivo imaging of tissue eosinophilia and eosinopoietic responses to schistosome worms and eggs
    Stephen J Davies
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Room B4104, Bethesda, MD 20814 4799, USA
    Int J Parasitol 35:851-9. 2005
    ..Contrary to expectations, we also demonstrate that schistosome parasites themselves induce significant intestinal eosinophilia and eosinopoiesis in the bone marrow at very early stages during prepatent infection...
  77. 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...
  78. ncbi request reprint Biolistic transformation of Schistosoma mansoni with 5' flanking regions of two peptidase genes promotes tissue-specific expression
    Volker Wippersteg
    Insitute for Genetics, Heinrich Heine University, Dusseldorf, Germany
    Int J Parasitol 35:583-9. 2005
    ..Promoter-deletion of the SmCF gene indicated the importance of one or more transcription factor binding sites in the first 169 bp for both GFP-expression and its tissue specificity...
  79. ncbi request reprint Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain
    Naoaki Fujii
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94143, USA
    Bioorg Med Chem Lett 15:121-3. 2005
    ..Among the active inhibitors, several potently inhibited proliferation of cultures of T. brucei. However, only modest activity was observed in inhibition of proliferation of T. cruzi or P. falciparum...
  80. ncbi request reprint A gene family of cathepsin L-like proteases of filarial nematodes are associated with larval molting and cuticle and eggshell remodeling
    David B Guiliano
    Department of Biological Sciences, Imperial College of Science and Technology, London SW7 2AY, UK
    Mol Biochem Parasitol 136:227-42. 2004
    ....
  81. ncbi request reprint IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent
    Mallika Kaviratne
    Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 173:4020-9. 2004
    ..Together, these studies provide unequivocal evidence of a pathway of fibrogenesis that is IL-13 dependent but TGF-beta1 independent, illustrating the importance of targeting IL-13 directly in the treatment of infection-induced fibrosis...
  82. ncbi request reprint Peptidyl allyl sulfones: a new class of inhibitors for clan CA cysteine proteases
    Marion G Götz
    School of Chemistry and Biochemistry and the Petit Institute of Bioscience and Bioengineering, Georgia Institute of Technology, Atlanta, GA 30332 0400, USA
    Bioorg Med Chem 12:5203-11. 2004
    ..It was observed that the stereochemistry of the vinyl sulfone precursor played a role in the potency of the dipeptidyl allyl sulfone inhibitor...
  83. ncbi request reprint A cathepsin B-like protease is required for host protein degradation in Trypanosoma brucei
    Zachary B Mackey
    Department of Pathology Tropical Disease Research Unit, University of California, San Francisco, California 94143, USA
    J Biol Chem 279:48426-33. 2004
    ..Therefore, tbcatB, but not rhodesain, is essential for T. brucei survival in culture and is the most likely target of the diazomethane protease inhibitor Z-Phe-Ala-CHN(2) in T. brucei...
  84. ncbi request reprint Identification of genomic responses to collagen binding by trophozoites of Entamoeba histolytica
    Anjan Debnath
    National Institute of Cholera and Enteric Diseases, Kolkata, India
    J Infect Dis 190:448-57. 2004
    ..These results provide important new clues about how a pathogen orchestrates responses to the host environment as well as a new tool for the analysis of other aspects of Entamoeba species infection and pathogenicity...
  85. ncbi request reprint Cysteine proteinases from distinct cellular compartments are recruited to phagocytic vesicles by Entamoeba histolytica
    Xuchu Que
    Department of Pathology, University of California, San Diego, UCSD Medical Center, 200 West Arbor Drive, San Diego, CA 92103 8416, USA
    Mol Biochem Parasitol 119:23-32. 2002
    ..The production of active proteinases in baculovirus and large scale recombinant enzymes in bacteria should further our understanding of the role of different cysteine proteinase gene products in virulence...
  86. ncbi request reprint Transcriptional and secretory responses of Entamoeba histolytica to mucins, epithelial cells and bacteria
    Anjan Debnath
    Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, San Francisco, CA 94158, USA
    Int J Parasitol 37:897-906. 2007
    ..The enhanced expression of this gene cluster is consistent with enhanced phagocytosis of E. histolytica during interaction with bacteria...

Research Grants8

  1. Host Protein Degradation by Schistosome Parasites
    James McKerrow; Fiscal Year: 2003
    ..abstract_text> ..
  2. Host Protein Degradation by Schistosome Parasites
    James McKerrow; Fiscal Year: 2006
    ..abstract_text> ..
  3. High Throughput Assay for Screening Compounds(RMI)
    James McKerrow; Fiscal Year: 2005
    ..Computational and informatics capability is in place to acquire, store and cross-reference this data, and provide access to the scientific community through an open-source website. ..
  4. Host Protein Degradation by Schistosome Parasites
    James McKerrow; Fiscal Year: 2007
    ..abstract_text> ..
  5. Lead Identification to Clinical Candidate Selection: Drugs for Chagas Disease
    James H McKerrow; Fiscal Year: 2010
    ....