Research Topics
| James McKerrowSummaryAffiliation: University of California Country: USA Publications
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Publications
Proteomic analysis of adult S. mansoni gut contentsMelaine 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
Two approaches to discovering and developing new drugs for Chagas diseaseJ 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...- Gene expression patterns during adaptation of a helminth parasite to different environmental nichesEmmitt 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... - Interview with James McKerrowJames 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. 2011b>James McKerrow's research interests focus on the biology of the host-parasite relationship, from primitive single-cell protozoa to complex multicellular bloodflukes... - Development of protease inhibitors for protozoan infectionsJames 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... - Proteases in parasitic diseasesJames H McKerrow
Department of Pathology, Sandler Center, University of California, San Francisco, California 94143, USA
Annu Rev Pathol 1:497-536. 2006.... - A functional proteomics screen of proteases in colorectal carcinomaJ 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... - A multienzyme network functions in intestinal protein digestion by a platyhelminth parasiteMelaine 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... - Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: insights on safety, target validation, and mechanism of actionJ 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... - Cysteine protease inhibitors as chemotherapy for parasitic infectionsJ 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... - Designing drugs for parasitic diseases of the developing worldJames H McKerrow
Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, USA
PLoS Med 2:e210. 2005 - A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic targetChen 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... - Leishmania major: molecular modeling of cysteine proteases and prediction of new nonpeptide inhibitorsP 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... - Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic modelSamuel 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... - WormAssay: a novel computer application for whole-plate motion-based screening of macroscopic parasitesChris 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... - Patterns of protease production during prostate cancer progression: proteomic evidence for cascades in a transgenic modelR 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... - Upregulation of the secretory pathway in cysteine protease inhibitor-resistant Trypanosoma cruziJ 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... - Cysteine proteases of parasitic organismsM 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... - Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruziJ 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... - Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infectionJ 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... - A target within the target: probing cruzain's P1' site to define structural determinants for the Chagas' disease proteaseL 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... - [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... - Proteomic analysis of human skin treated with larval schistosome peptidases reveals distinct invasion strategies among species of blood flukesJessica Ingram
Tetrad Graduate Program, University of California San Francisco, San Francisco, California, USA
PLoS Negl Trop Dis 5:e1337. 2011.... - Expression and alteration of the S2 subsite of the Leishmania major cathepsin B-like cysteine proteaseV 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... - Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesienseC 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... - Inhibitors of SARS-CoV entry--identification using an internally-controlled dual envelope pseudovirion assayYanchen 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... 
Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatBJeremy 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...- Bis-acridines as lead antiparasitic agents: structure-activity analysis of a discrete compound library in vitroConor 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... - IrAE: an asparaginyl endopeptidase (legumain) in the gut of the hard tick Ixodes ricinusDaniel 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... - Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitorMaha 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... - Drug discovery and development for neglected parasitic diseasesAdam 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... - The common gamma chain cytokines interleukin (IL)-2 and IL-7 indirectly modulate blood fluke development via effects on CD4+ T cellsRebecca 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... - Proteases from Schistosoma mansoni cercariae cleave IgE at solvent exposed interdomain regionsAkhmed 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... - A multi-enzyme cascade of hemoglobin proteolysis in the intestine of blood-feeding hookwormsAngela L Williamson
Department of Microbiology and Tropical Medicine, The George Washington University, Washington, DC 20037, USA
J Biol Chem 279:35950-7. 2004.... - A phagocytosis mutant of Entamoeba histolytica is less virulent due to deficient proteinase expression and releaseKen 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... - Identification and characterization of a cathepsin L-like cysteine protease from Gnathostoma spinigerumNatthawan 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... - The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor familyStephanie 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... - Identification of the major cysteine protease of Giardia and its role in encystationKelly 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... - Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepaticaColin 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... - Potency and selectivity of P2/P3-modified inhibitors of cysteine proteases from trypanosomesPriyadarshini 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... - Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogensMarion 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... - Dipeptidyl-alpha,beta-epoxyesters as potent irreversible inhibitors of the cysteine proteases cruzain and rhodesainFlorenci 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... - Differential use of protease families for invasion by schistosome cercariaeJan 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... - Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatBJeremy 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... - Squamous cell carcinoma antigen 1 is an inhibitor of parasite-derived cysteine proteasesSachiko 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... - A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infectionPatricia 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... - Identification of a new class of nonpeptidic inhibitors of cruzainKatrien 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... - Production and processing of a recombinant Fasciola hepatica cathepsin B-like enzyme (FhcatB1) reveals potential processing mechanisms in the parasiteSimone 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... - Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial proteaseStephanie 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... - Discovery of trypanocidal compounds by whole cell HTS of Trypanosoma bruceiZachary 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... - Aza-peptide Michael acceptors: a new class of inhibitors specific for caspases and other clan CD cysteine proteasesOzlem 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... - Schistosoma mansoni: sex-specific modulation of parasite growth by host immune signalsDavid 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... - 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... - Involvement of TNF in limiting liver pathology and promoting parasite survival during schistosome infectionStephen 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... - Developmental plasticity in schistosomes and other helminthsStephen 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... - Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidaseMohammed 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... - Improved trypanocidal activities of cathepsin L inhibitorsNjinkeng Joseph Nkemgu
Abteilung Parasitologie, , 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... - A surface amebic cysteine proteinase inactivates interleukin-18Xuchu 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... - Synthesis and structure-activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzainXiaohui 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... - CoMFA and HQSAR of acylhydrazide cruzain inhibitorsCarlos 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... - Cercarial elastase is encoded by a functionally conserved gene family across multiple species of schistosomesJason 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.... - Substrate specificity of schistosome versus human legumain determined by P1-P3 peptide librariesMary 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... - SmCB2, a novel tegumental cathepsin B from adult Schistosoma mansoniConor 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... - Invasion of skin by Schistosoma cercariaeJames 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... - Screening of acyl hydrazide proteinase inhibitors for antiparasitic activity against Trypanosoma bruceiConor 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... - Blood 'n' guts: an update on schistosome digestive peptidasesConor 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 - Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruziDoron 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... - Giardia lamblia cysteine proteasesKelly 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 - Antitrypanosomal activity of 5'-deoxy-5'-(iodomethylene)adenosine and related 6-N-cyclopropyladenosine analoguesMagdalena 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... - Proteomic analysis of Schistosoma mansoni cercarial secretionsGiselle 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... - The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motifKailash 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... - Multiple cathepsin B isoforms in schistosomula of Trichobilharzia regenti: identification, characterisation and putative role in migration and nutritionJan 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... - In vivo imaging of tissue eosinophilia and eosinopoietic responses to schistosome worms and eggsStephen 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... - 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 inhibitorsConor 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... - Biolistic transformation of Schistosoma mansoni with 5' flanking regions of two peptidase genes promotes tissue-specific expressionVolker Wippersteg
Insitute for Genetics, Heinrich-Heine-University, , 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... - Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzainNaoaki 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... - A gene family of cathepsin L-like proteases of filarial nematodes are associated with larval molting and cuticle and eggshell remodelingDavid B Guiliano
Department of Biological Sciences, Imperial College of Science and Technology, London SW7 2AY, UK
Mol Biochem Parasitol 136:227-42. 2004.... - IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independentMallika 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... - Peptidyl allyl sulfones: a new class of inhibitors for clan CA cysteine proteasesMarion 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... - A cathepsin B-like protease is required for host protein degradation in Trypanosoma bruceiZachary 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... - Identification of genomic responses to collagen binding by trophozoites of Entamoeba histolyticaAnjan 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... - Cysteine proteinases from distinct cellular compartments are recruited to phagocytic vesicles by Entamoeba histolyticaXuchu 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... - Transcriptional and secretory responses of Entamoeba histolytica to mucins, epithelial cells and bacteriaAnjan 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 Grants
- Host Protein Degradation by Schistosome ParasitesJames McKerrow; Fiscal Year: 2006..abstract_text> ..
- 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. ..
- Host Protein Degradation by Schistosome ParasitesJames McKerrow; Fiscal Year: 2007..abstract_text> ..
- Lead Identification to Clinical Candidate Selection: Drugs for Chagas DiseaseJames H McKerrow; Fiscal Year: 2010....