SchistosomeWormPairNaturalHistoryMuseumPictureLibrary033443 IA 300x230
Scanning electron micrograph of a pair of adult Schistosoma mansoni worms. The more robust male (about 1 cm long) carries the female in a ventral groove called the gynecophoric canal. Photo credit: Natural History Museum Photo Library.

Schistosomiasis research within CDIPD is focused on the development of a new generation of therapeutics for the treatment of this widespread neglected tropical disease. Our drug discovery and development program for schistosomiasis began in 2009 through collaboration with UC San Francisco SMDC. With Rahul Singh at San Francisco State University we have built a phenotypic screening platform that uses automated image-based analysis tools to measure the multi-parametric responses of live Schistosoma mansoni parasites to identify anti-schistosomal compounds. We are currently screening collections of drugs approved for use in humans as well as synthetic and natural products supplied by our industrial and academic partners. Another focus of our research is to identify proteases, kinases and mevalonate pathway enzymes critical to parasite survival in the human host with the aim that these molecules will serve as potential drug screening or vaccine targets. For example, we are developing genetic manipulation approaches to knockdown multiple isoforms of cercarial elastase to understand their roles in host skin invasion while our research on other parasite proteolytic enzymes has identified a number of small molecule protease inhibitors as drug leads that we continue to test and develop.

While we seek new molecular targets for the treatment of schistosomiasis we are also trying to understand the mechanism of action of the anthelmintic drug praziquantel (PZQ). Praziquantel has been the only widely available drug to treat all forms of schistosomiasis for 35 years even though it does not affect a complete cure due to its inability to kill sexually immature schistosomes. We are using PZQ probes to identify its molecular target and proteomics and transcriptomics to understand its mechanism of action. Understanding how PZQ works will inform the development of a new generation of more effective anthelmintics.

 

pipeline 720x38
  • Proteases
  • Kinases
  • Mevalonate pathway enzymes
  • Phosphodiesterase-4 (PDE-4)
  • Compound libraries from various sources
  • Protease inhibitors
  • Salicylanilides
  • Other novel anti-schistosomal classes
 

PUBLICATIONS

Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases rhodesain, cruzain, and Schistosoma mansoni cathepsin B1. Antimicrob Agents Chemother. 2015 May;59(5):2666-77. doi: 10.1128/AAC.04601-14. Epub 2015 Feb 23. Fonseca NC, da Cruz LF, da Silva Villela F, do Nascimento Pereira GA, de Siqueira-Neto JL, Kellar D, Suzuki BM, Ray D, de Souza TB, Alves RJ, Sales Júnior PA, Romanha AJ, Murta SM, McKerrow JH, Caffrey CR, de Oliveira RB, Ferreira RS.

The QDREC web server: determining dose-response characteristics of complex macroparasites in phenotypic drug screens. Bioinformatics. 2015 May 1;31(9):1515-8. doi: 10.1093/bioinformatics/btu831. Epub 2014 Dec 24. Asarnow D, Rojo-Arreola L, Suzuki BM, Caffrey CR, Singh R.

Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib. Int J Parasitol Drugs Drug Resist. 2014 Dec;4(3):287-95. doi: 10.1016/j.ijpddr.2014.07.005. Beckmann S, Long T, Scheld C, Geyer R, Caffrey CR, Grevelding CG.

Activation route of the Schistosoma mansoni cathepsin B1 drug target: structural map with a glycosaminoglycan switch. Structure. 2014 Dec 2;22(12):1786-98. doi: 10.1016/j.str.2014.09.015. Epub 2014 Nov 13. Jílková A, Horn M, Rezáčová P, Marešová L, Fajtová P, Brynda J, Vondrášek J, McKerrow JH, Caffrey CR, Mareš M.

Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway. PLoS Negl Trop Dis. 2014 Jun;8(6):e2949. doi: 10.1371/journal.pntd.0002949. Andrade LF, Mourão Mde M, Geraldo JA, Coelho FS, Silva LL, Neves RH, Volpini A, Machado-Silva JR, Araujo N, Nacif-Pimenta R, Caffrey CR, Oliveira G.

Trypsin- and chymotrypsin-like serine proteases in schistosoma mansoni-- 'the undiscovered country'. PLoS Negl Trop Dis. 2014 Mar;8(3):e2766. doi: 10.1371/journal.pntd.0002766. Horn M, Fajtová P, Rojo Arreola L, Ulrychová L, Bartošová-Sojková P, Franta Z, Protasio AV, Opavský D, Vondrášek J, McKerrow JH, Mareš M, Caffrey CR, Dvořák J.

Chemical and genetic validation of the statin drug target to treat the helminth disease, schistosomiasis. PLoS One. 2014;9(1):e87594. doi: 10.1371/journal.pone.0087594. Rojo-Arreola L, Long T, Asarnow D, Suzuki BM, Singh R, Caffrey CR.

Upregulation of retinal dehydrogenase 2 in alternatively activated macrophages during retinoid-dependent type-2 immunity to helminth infection in mice. PLoS Pathog. 2012;8(8):e1002883. doi: 10.1371/journal.ppat.1002883. Epub 2012 Aug 23. Broadhurst MJ, Leung JM, Lim KC, Girgis NM, Gundra UM, Fallon PG, Premenko-Lanier M, McKerrow JH, McCune JM, Loke P.

Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni. PLoS Negl Trop Dis. 2012;6(4):e1589. doi: 10.1371/journal.pntd.0001589. Epub 2012 Apr 3. Ingram JR, Rafi SB, Eroy-Reveles AA, Ray M, Lambeth L, Hsieh I, Ruelas D, Lim KC, Sakanari J, Craik CS, Jacobson MP, McKerrow JH.

Quantification and clustering of phenotypic screening data using time-series analysis for chemotherapy of schistosomiasis. BMC Genomics. 2012;13 Suppl 1:S4. doi: 10.1186/1471-2164-13-S1-S4. Epub 2012 Jan 17. Lee H, Moody-Davis A, Saha U, Suzuki BM, Asarnow D, Chen S, Arkin M, Caffrey CR, Singh R.

A blood fluke serine protease inhibitor regulates an endogenous larval elastase. J Biol Chem. 2012 Mar 2;287(10):7074-83. doi: 10.1074/jbc.M111.313304. Epub 2011 Dec 15. Quezada LA, Sajid M, Lim KC, McKerrow JH.

Proteomic identification of IPSE/alpha-1 as a major hepatotoxin secreted by Schistosoma mansoni eggs. PLoS Negl Trop Dis. 2011 Oct;5(10):e1368. doi: 10.1371/journal.pntd.0001368. Epub 2011 Oct 25. Abdulla MH, Lim KC, McKerrow JH, Caffrey CR.

Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discovery. Trends Parasitol. 2011 Dec;27(12):555-64. doi: 10.1016/j.pt.2011.09.003. Epub 2011 Oct 23. Review. Swain MT, Larkin DM, Caffrey CR, Davies SJ, Loukas A, Skelly PJ, Hoffmann KF.

Structural basis for inhibition of cathepsin B drug target from the human blood fluke, Schistosoma mansoni. J Biol Chem. 2011 Oct 14;286(41):35770-81. doi: 10.1074/jbc.M111.271304. Epub 2011 Aug 10. Jílková A, Rezácová P, Lepsík M, Horn M, Váchová J, Fanfrlík J, Brynda J, McKerrow JH, Caffrey CR, Mares M.

Schistosomiasis: from drug deployment to drug development. Curr Opin Infect Dis. 2011 Oct;24(5):410-7. doi: 10.1097/QCO.0b013e328349156f. Review. Caffrey CR, Secor WE.

Schistosome serine protease inhibitors: parasite defense or homeostasis? An Acad Bras Cienc. 2011 Jun;83(2):663-72. Quezada LA, McKerrow JH.

Schistosoma mansoni Polo-like kinases and their function in control of mitosis and parasite reproduction. An Acad Bras Cienc. 2011 Jun;83(2):627-35. Dissous C, Grevelding CG, Long T.

Mapping the pro-peptide of the Schistosoma mansoni cathepsin B1 drug target: modulation of inhibition by heparin and design of mimetic inhibitors. ACS Chem Biol. 2011 Jun 17;6(6):609-17. doi: 10.1021/cb100411v. Epub 2011 Mar 17. Horn M, Jílková A, Vondrásek J, Maresová L, Caffrey CR, Mares M.

Rapid induction of IgE responses to a worm cysteine protease during murine pre-patent schistosome infection. BMC Immunol. 2010 Nov 15;11:56. doi: 10.1186/1471-2172-11-56. de Oliveira Fraga LA, Lamb EW, Moreno EC, Chatterjee M, Dvořák J, Delcroix M, Sajid M, Caffrey CR, Davies SJ.

RNA interference in Schistosoma mansoni schistosomula: selectivity, sensitivity and operation for larger-scale screening. PLoS Negl Trop Dis. 2010 Oct 19;4(10):e850. doi: 10.1371/journal.pntd.0000850. Stefanić S, Dvořák J, Horn M, Braschi S, Sojka D, Ruelas DS, Suzuki B, Lim KC, Hopkins SD, McKerrow JH, Caffrey CR.

Biolistic transformation of Schistosoma mansoni: Studies with modified reporter-gene constructs containing regulatory regions of protease genes. Mol Biochem Parasitol. 2010 Mar;170(1):37-40. doi: 10.1016/j.molbiopara.2009.11.001. Epub 2009 Nov 13. Dvorák J, Beckmann S, Lim KC, Engel JC, Grevelding CG, McKerrow JH, Caffrey CR.

Aza-peptidyl Michael acceptor and epoxide inhibitors--potent and selective inhibitors of Schistosoma mansoni and Ixodes ricinus legumains (asparaginyl endopeptidases). J Med Chem. 2009 Nov 26;52(22):7192-210. doi: 10.1021/jm900849h. Ovat A, Muindi F, Fagan C, Brouner M, Hansell E, Dvorák J, Sojka D, Kopácek P, McKerrow JH, Caffrey CR, Powers JC.

Chapter 4. Peptidases of trematodes. Adv Parasitol. 2009;69:205-97. doi: 10.1016/S0065-308X(09)69004-7. Review. Kasný M, Mikes L, Hampl V, Dvorák J, Caffrey CR, Dalton JP, Horák P.

The genome of the blood fluke Schistosoma mansoni. Nature. 2009 Jul 16;460(7253):352-8. doi: 10.1038/nature08160. Berriman M, Haas BJ, LoVerde PT, Wilson RA, Dillon GP, Cerqueira GC, Mashiyama ST, Al-Lazikani B, Andrade LF, Ashton PD, Aslett MA, Bartholomeu DC, Blandin G, Caffrey CR, Coghlan A, Coulson R, Day TA, Delcher A, DeMarco R, Djikeng A, Eyre T, Gamble JA, et

Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening. PLoS Negl Trop Dis. 2009 Jul 14;3(7):e478. doi: 10.1371/journal.pntd.0000478. Abdulla MH, Ruelas DS, Wolff B, Snedecor J, Lim KC, Xu F, Renslo AR, Williams J, McKerrow JH, Caffrey CR.

SmCL3, a gastrodermal cysteine protease of the human blood fluke Schistosoma mansoni. PLoS Negl Trop Dis. 2009 Jun 2;3(6):e449. doi: 10.1371/journal.pntd.0000449. Dvorák J, Mashiyama ST, Sajid M, Braschi S, Delcroix M, Schneider EL, McKerrow WH, Bahgat M, Hansell E, Babbitt PC, Craik CS, McKerrow JH, Caffrey CR.

A comparative chemogenomics strategy to predict potential drug targets in the metazoan pathogen, Schistosoma mansoni. PLoS One. 2009;4(2):e4413. doi: 10.1371/journal.pone.0004413. Epub 2009 Feb 9. Caffrey CR, Rohwer A, Oellien F, Marhöfer RJ, Braschi S, Oliveira G, McKerrow JH, Selzer PM.

Towards an understanding of the mechanism of action of praziquantel. Mol Biochem Parasitol. 2009 Mar;164(1):57-65. doi: 10.1016/j.molbiopara.2008.11.007. Epub 2008 Nov 28. Aragon AD, Imani RA, Blackburn VR, Cupit PM, Melman SD, Goronga T, Webb T, Loker ES, Cunningham C.

Proteomic analysis of skin invasion by blood fluke larvae. PLoS Negl Trop Dis. 2008 Jul 16;2(7):e262. doi: 10.1371/journal.pntd.0000262. Hansell E, Braschi S, Medzihradszky KF, Sajid M, Debnath M, Ingram J, Lim KC, McKerrow JH.

Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica. J Biol Chem. 2008 Apr 11;283(15):9896-908. Epub 2007 Dec 26. Stack CM, Caffrey CR, Donnelly SM, Seshaadri A, Lowther J, Tort JF, Collins PR, Robinson MW, Xu W, McKerrow JH, Craik CS, Geiger SR, Marion R, Brinen LS, Dalton JP.

Proteases in parasitic diseases. Annu Rev Pathol. 2006;1:497-536. Review. McKerrow JH, Caffrey C, Kelly B, Loke P, Sajid M.

Differential use of protease families for invasion by schistosome cercariae. Biochimie. 2008 Feb;90(2):345-58. Epub 2007 Sep 8. Dvorák J, Mashiyama ST, Braschi S, Sajid M, Knudsen GM, Hansell E, Lim KC, Hsieh I, Bahgat M, Mackenzie B, Medzihradszky KF, Babbitt PC, Caffrey CR, McKerrow JH.

Chemotherapy of schistosomiasis: present and future. Curr Opin Chem Biol. 2007 Aug;11(4):433-9. Epub 2007 Jul 24. Review. Caffrey CR.

Gene expression patterns during adaptation of a helminth parasite to different environmental niches. Genome Biol. 2007;8(4):R65. Jolly ER, Chin CS, Miller S, Bahgat MM, Lim KC, DeRisi J, McKerrow JH.

Proteomic analysis of adult S. mansoni gut contents. Mol Biochem Parasitol. 2007 Jul;154(1):95-7. Epub 2007 Mar 20. No abstract available. Delcroix M, Medzihradsky K, Caffrey CR, Fetter RD, McKerrow JH.

Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor. PLoS Med. 2007 Jan;4(1):e14. Abdulla MH, Lim KC, Sajid M, McKerrow JH, Caffrey CR.

The common gamma chain cytokines interleukin (IL)-2 and IL-7 indirectly modulate blood fluke development via effects on CD4+ T cells. J Infect Dis. 2006 Dec 1;194(11):1609-16. Epub 2006 Oct 23. Blank RB, Lamb EW, Tocheva AS, Crow ET, Lim KC, McKerrow JH, Davies SJ.

A multienzyme network functions in intestinal protein digestion by a platyhelminth parasite. J Biol Chem. 2006 Dec 22;281(51):39316-29. Epub 2006 Oct 6. Delcroix M, Sajid M, Caffrey CR, Lim KC, Dvorák J, Hsieh I, Bahgat M, Dissous C, McKerrow JH.

Characterization of immunoglobulin binding by schistosomes. Parasite Immunol. 2006 Sep;28(9):407-19. McIntosh RS, Jones FM, Dunne DW, McKerrow JH, Pleass RJ.

Proteomic analysis of Schistosoma mansoni cercarial secretions. Mol Cell Proteomics. 2005 Dec;4(12):1862-75. Epub 2005 Aug 18. Knudsen GM, Medzihradszky KF, Lim KC, Hansell E, McKerrow JH.

Multiple cathepsin B isoforms in schistosomula of Trichobilharzia regenti: identification, characterisation and putative role in migration and nutrition. Int J Parasitol. 2005 Jul;35(8):895-910. Dvorák J, Delcroix M, Rossi A, Vopálenský V, Pospísek M, Sedinová M, Mikes L, Sajid M, Sali A, McKerrow JH, Horák P, Caffrey CR.

In vivo imaging of tissue eosinophilia and eosinopoietic responses to schistosome worms and eggs. Int J Parasitol. 2005 Jul;35(8):851-9. Davies SJ, Smith SJ, Lim KC, Zhang H, Purchio AF, McKerrow JH, West DB.

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. Biol Chem. 2005 Apr;386(4):339-49. Caffrey CR, Placha L, Barinka C, Hradilek M, Dostál J, Sajid M, McKerrow JH, Majer P, Konvalinka J, Vondrásek J.

Biolistic transformation of Schistosoma mansoni with 5' flanking regions of two peptidase genes promotes tissue-specific expression. Int J Parasitol. 2005 May;35(6):583-9. Epub 2005 Mar 8. Wippersteg V, Sajid M, Walshe D, Khiem D, Salter JP, McKerrow JH, Grevelding CG, Caffrey CR.

Blood 'n' guts: an update on schistosome digestive peptidases. Trends Parasitol. 2004 May;20(5):241-8. Review. No abstract available. Caffrey CR, McKerrow JH, Salter JP, Sajid M.

Schistosoma mansoni: sex-specific modulation of parasite growth by host immune signals. Exp Parasitol. 2004 Jan-Feb;106(1-2):59-61. Hernandez DC, Lim KC, McKerrow JH, Davies SJ.

Aza-peptide epoxides: potent and selective inhibitors of Schistosoma mansoni and pig kidney legumains (asparaginyl endopeptidases). Biol Chem. 2003 Dec;384(12):1613-8. James KE, Götz MG, Caffrey CR, Hansell E, Carter W, Barrett AJ, McKerrow JH, Powers JC.

Involvement of TNF in limiting liver pathology and promoting parasite survival during schistosome infection. Int J Parasitol. 2004 Jan;34(1):27-36. Davies SJ, Lim KC, Blank RB, Kim JH, Lucas KD, Hernandez DC, Sedgwick JD, McKerrow JH.

Developmental plasticity in schistosomes and other helminths. Int J Parasitol. 2003 Sep 30;33(11):1277-84. Review. Davies SJ, McKerrow JH.

Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidase. Mol Biochem Parasitol. 2003 Sep;131(1):65-75. Sajid M, McKerrow JH, Hansell E, Mathieu MA, Lucas KD, Hsieh I, Greenbaum D, Bogyo M, Salter JP, Lim KC, Franklin C, Kim JH, Caffrey CR.

Cercarial elastase is encoded by a functionally conserved gene family across multiple species of schistosomes. J Biol Chem. 2002 Jul 5;277(27):24618-24. Epub 2002 May 1. Salter JP, Choe Y, Albrecht H, Franklin C, Lim KC, Craik CS, McKerrow JH.

Substrate specificity of schistosome versus human legumain determined by P1-P3 peptide libraries. Mol Biochem Parasitol. 2002 Apr 30;121(1):99-105. Mathieu MA, Bogyo M, Caffrey CR, Choe Y, Lee J, Chapman H, Sajid M, Craik CS, McKerrow JH.

SmCB2, a novel tegumental cathepsin B from adult Schistosoma mansoni. Mol Biochem Parasitol. 2002 Apr 30;121(1):49-61. Caffrey CR, Salter JP, Lucas KD, Khiem D, Hsieh I, Lim KC, Ruppel A, McKerrow JH, Sajid M.

Invasion of skin by Schistosoma cercariae. Trends Parasitol. 2002 May;18(5):193-5. McKerrow JH, Salter J.

Cysteine proteases of parasitic organisms. Mol Biochem Parasitol. 2002 Mar;120(1):1-21. Review. Erratum in: Mol Biochem Parasitol 2002 Apr 30;121(1):159. Sajid M, McKerrow JH.

Modulation of blood fluke development in the liver by hepatic CD4+ lymphocytes. Science. 2001 Nov 9;294(5545):1358-61. Davies SJ, Grogan JL, Blank RB, Lim KC, Locksley RM, McKerrow JH.

Schistosome invasion of human skin and degradation of dermal elastin are mediated by a single serine protease. J Biol Chem. 2000 Dec 8;275(49):38667-73. Salter JP, Lim KC, Hansell E, Hsieh I, McKerrow JH.

Identification of a cDNA encoding an active asparaginyl endopeptidase of Schistosoma mansoni and its expression in Pichia pastoris. FEBS Lett. 2000 Jan 28;466(2-3):244-8. Caffrey CR, Mathieu MA, Gaffney AM, Salter JP, Sajid M, Lucas KD, Franklin C, Bogyo M, McKerrow JH.

Blockage of skin invasion by schistosome cercariae by serine protease inhibitors. Am J Trop Med Hyg. 1999 Mar;60(3):487-92. Lim KC, Sun E, Bahgat M, Bucks D, Guy R, Hinz RS, Cullander C, McKerrow JH.

Schistosoma japonicum is less sensitive to cyclosporin A in vivo than Schistosoma mansoni. J Parasitol. 1999 Aug;85(4):736-9. Caffrey CR, Gsell C, Ruppel A.

Schistosoma haematobium, S. intercalatum, S. japonicum, S. mansoni, and S. rodhaini in mice: relationship between patterns of lung migration by schistosomula and perfusion recovery of adult worms. Parasitol Res. 1998;84(4):338-42. Rheinberg CE, Moné H, Caffrey CR, Imbert-Establet D, Jourdane J, Ruppel A.

Affinity isolation and characterization of the cathepsin B-like proteinase Sj31 from Schistosoma japonicum. J Parasitol. 1997 Dec;83(6):1112-8. Caffrey CR, Ruppel A.

Evaluation of a stage-specific proteolytic enzyme of Schistosoma mansoni as a marker of exposure. Am J Trop Med Hyg. 1997 Jun;56(6):668-73. Ramzy RM, Faris R, Bahgat M, Helmy H, Franklin C, McKerrow JH.

Cytokine induction and exploitation in schistosome infections. Parasitology. 1997;115 Suppl:S107-12. Review. McKerrow JH.

Schistosome egg granulomas and hepatic expression of TNF-alpha are dependent on immune priming during parasite maturation. J Immunol. 1997 Jan 1;158(1):301-7. Leptak CL, McKerrow JH.

Schistosoma japonicum, S. mansoni, S. haematobium, S. intercalatum, and S. rodhaini: cysteine-class cathepsin activities in the vomitus of adult worms. Parasitol Res. 1997;83(1):37-41. Caffrey CR, Rheinberg CE, Moné H, Jourdane J, Li YL, Ruppel A.

Cathepsin B-like activity predominates over cathepsin L-like activity in adult Schistosoma mansoni and S. japonicum. Parasitol Res. 1997;83(6):632-5. Caffrey CR, Ruppel A.

Intercellular adhesion molecule 1 is the major adhesion molecule expressed during schistosome granuloma formation. Infect Immun. 1996 Nov;64(11):4706-13. Ritter DM, McKerrow JH.

Cysteine protease inhibitors block schistosome hemoglobin degradation in vitro and decrease worm burden and egg production in vivo. Mol Biochem Parasitol. 1996 Oct 30;81(2):179-89. Wasilewski MM, Lim KC, Phillips J, McKerrow JH.

Schistosoma mansoni: evidence for a 28-kDa membrane-anchored protease on schistosomula. Exp Parasitol. 1996 Jun;83(1):73-82. Ghendler Y, Parizade M, Arnon R, McKerrow JH, Fishelson Z.

Anti-immunoglobulin E treatment decreases worm burden and egg production in Schistosoma mansoni-infected normal and interferon gamma knockout mice. J Exp Med. 1994 Jul 1;180(1):43-51. Amiri P, Haak-Frendscho M, Robbins K, McKerrow JH, Stewart T, Jardieu P.

Hepatic schistosomiasis. Prog Liver Dis. 1994;12:121-35. Review. No abstract available. McKerrow JH, Sun E.

Schistosomes and host TNF. Parasitol Today. 1992 Dec;8(12):411-2. No abstract available. McKerrow JH, Ritter D.

Schistosoma mansoni: cell-specific expression and secretion of a serine protease during development of cercariae. Exp Parasitol. 1992 Aug;75(1):87-98. Fishelson Z, Amiri P, Friend DS, Marikovsky M, Petitt M, Newport G, McKerrow JH.

Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature. 1992 Apr 16;356(6370):604-7. Amiri P, Locksley RM, Parslow TG, Sadick M, Rector E, Ritter D, McKerrow JH.

The hemoglobinase of Schistosoma mansoni. R I Med. 1992 Apr;75(4):208-11. Review. No abstract available. McKerrow JH.

Steady-state kinetics of the schistosomal hypoxanthine-guanine phosphoribosyltransferase. Biochemistry. 1992 Jan 28;31(3):806-10. Yuan L, Craig SP 3rd, McKerrow JH, Wang CC.

Arresting tissue invasion of a parasite by protease inhibitors chosen with the aid of computer modeling. Biochemistry. 1991 Nov 26;30(47):11221-9. Cohen FE, Gregoret LM, Amiri P, Aldape K, Railey J, McKerrow JH.

Recent insights into the structure and function of a larval proteinase involved in host infection by a multicellular parasite. Proc Soc Exp Biol Med. 1991 Jun;197(2):119-24. Review. No abstract available. McKerrow JH, Newport G, Fishelson Z.

High level expression in Escherichia coli of soluble, enzymatically active schistosomal hypoxanthine/guanine phosphoribosyltransferase and trypanosomal ornithine decarboxylase. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2500-4. Craig SP 3rd, Yuan L, Kuntz DA, McKerrow JH, Wang CC. Craig

The hypoxanthine-guanine phosphoribosyltransferase of Schistosoma mansoni. Further characterization and gene expression in Escherichia coli. J Biol Chem. 1990 Aug 15;265(23):13528-32. Yuan L, Craig SP, McKerrow JH, Wang CC.

Molecular and biochemical studies of the cercarial proteinase of Schistosoma mansoni. Mem Inst Oswaldo Cruz. 1989 Oct;84 Suppl 1:209-10. No abstract available. McKerrow JH.

Evidence for a class of very small introns in the gene for hypoxanthine-guanine phosphoribosyltransferase in Schistosoma mansoni. Nucleic Acids Res. 1989 Feb 25;17(4):1635-47. Craig SP 3rd, Muralidhar MG, McKerrow JH, Wang CC.

Schistosome proteases. Parasitol Today. 1988 Dec;4(12):334-40. McKerrow JH, Doenhoff MJ.

Analysis of cDNA encoding the hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) of Schistosoma mansoni; a putative target for chemotherapy. Nucleic Acids Res. 1988 Jul 25;16(14B):7087-101. Craig SP 3rd, McKerrow JH, Newport GR, Wang CC.

The Schistosomatium douthitti cercarial elastase is biochemically and structurally distinct from that of Schistosoma mansoni. Mol Biochem Parasitol. 1988 Mar;28(2):113-20. Amiri P, Sakanari J, Basch P, Newport G, McKerrow JH.

Preparation of mouse monoclonal anticbodies and evidence for a host immune response to the preacetabular gland proteinase of Schistosoma mansoni cerariae. Am J Trop Med Hyg. 1986 May;35(3):536-43. Pino-Heiss S, Petitt M, Beckstead JH, McKerrow JH.

Purification and characterization of hypoxanthine-guanine phosphoribosyltransferase from Schistosoma mansoni. A potential target for chemotherapy. J Biol Chem. 1986 Jan 15;261(2):944-8. Dovey HF, McKerrow JH, Aldritt SM, Wang CC.

Proteinases from invasive larvae of the trematode parasite Schistosoma mansoni degrade connective-tissue and basement-membrane macromolecules. Biochem J. 1985 Oct 1;231(1):47-51. McKerrow JH, Jones P, Sage H, Pino-Heiss S.

Action of tubercidin and other adenosine analogs on Schistosoma mansoni schistosomules. Mol Biochem Parasitol. 1985 Aug;16(2):185-98. Dovey HF, McKerrow JH, Wang CC.

Schistosoma mansoni: degradation of host extracellular matrix by eggs and miracidia. Exp Parasitol. 1985 Apr;59(2):217-21. Pino-Heiss S, Brown M, McKerrow JH.

Purification and characterization of an elastinolytic proteinase secreted by cercariae of Schistosoma mansoni. J Biol Chem. 1985 Mar 25;260(6):3703-7. McKerrow JH, Pino-Heiss S, Lindquist R, Werb Z.

Purine salvage in Schistosoma mansoni schistosomules. Mol Biochem Parasitol. 1984 Apr;11:157-67. Dovey HF, McKerrow JH, Wang CC.

Degradation of purified skin keratin by a proteinase secreted from Schistosoma mansoni cercariae. J Parasitol. 1983 Oct;69(5):992-4. No abstract available. Tzeng S, McKerrow JH, Fukuyama K, Jeong K, Epstein WL.

Degradation of extracellular matrix by larvae of Schistosoma mansoni. I. Degradation by cercariae as a model for initial parasite invasion of host. Lab Invest. 1983 Aug;49(2):195-200. McKerrow JH, Keene WE, Jeong KH, Werb Z.

Partial purification and characterization of an inhibitor from newborn-rat epidermis with activity against the proteinase of Schistosoma mansoni cercariae. Biochem J. 1982 Dec 1;207(3):479-84. Tzeng S, McKerrow JH, Jeong K, Fukuyama K, Epstein WL.

Schistosoma mansoni: cercarial degradation of a radioactively labeled collagen gel. Exp Parasitol. 1982 Apr;53(2):249-54. No abstract available. McKerrow JH, Jeong KH.