Associate Professor, UCSD

Skaggs School of Pharmacy & Pharmaceutical Sciences

Nematode and Trematode Core Director, CDIPD

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Follow me: https://pharmacy.ucsd.edu/faculty/bios/caffrey.shtml

Our group works in basic research, and in the pre-clinical and translational development of drugs and diagnostics for a number of tropical diseases, in particular, Human African Trypanosomiasis (Sleeping Sickness), hookworm infection and schistosomiasis. Our interests focus on (i) proteolytic enzymes in parasite biology and disease, (ii) small molecule protease inhibitors as drug leads, (iii) identifying new chemical entities (synthetic and natural products) or repurposing existing drugs for anti-parasite therapy and (iv) the development of simple diagnostics for disease surveillance and diagnosis. We collaborate with academic groups in Brazil, Germany, Ghana, the Czech Republic, the UK and the USA. We also work with industry (e.g., Anacor, AstraZeneca, and Merck) on a number of different drug discovery projects.

We have advanced a number of technologies to accelerate the discovery of new drug targets and drugs. For example, with collaborators at the UC San Francisco SMDC, we have built and refined a state-of-the-art phenotypic (whole organism) screening platform to identify anti-schistosomal compounds. The platform interfaces the schistosome parasite with various robotic systems to screen in-house and third-party compounds. With collaborators at San Francisco State University led by Rahul Singh, we have also developed a number of automated image-based analysis tools which the multi-parametric responses of the complex organisms like the schistosome can be measured. Finally, we possess small animal models of schistosome and hookworm infection to evaluate efficacy and pharmacokinetics of lead molecules of interest.
Our group has received support from the NIH-NIAID, NATO, the WHO, and the UBS Optimus Foundation among others, and we present frequent updates on our research at national and international meetings. We welcome enquiries from academia and industry alike on any of our activities.

PUBLICATIONS

High Throughput and Computational Repurposing for Neglected Diseases. Pharm Res. 2018 Dec 17;36(2):27. doi: 10.1007/s11095-018-2558-3. Review. Hernandez HW, Soeung M, Zorn KM, Ashoura N, Mottin M, Andrade CH, Caffrey CR, de Siqueira-Neto JL, Ekins S.

Cysteine proteases as digestive enzymes in parasitic helminths. PLoS Negl Trop Dis. 2018 Aug 23;12(8):e0005840. doi: 10.1371/journal.pntd.0005840. eCollection 2018 Aug. Review. Caffrey CR, Goupil L, Rebello KM, Dalton JP, Smith D.

Brain-Penetrant Triazolopyrimidine and Phenylpyrimidine Microtubule Stabilizers as Potential Leads to Treat Human African Trypanosomiasis. ChemMedChem. 2018 Sep 6;13(17):1751-1754. doi: 10.1002/cmdc.201800404. Epub 2018 Aug 7. Monti L, Wang SC, Oukoloff K, Smith AB 3rd, Brunden KR, Caffrey CR, Ballatore C.

Octopamine signaling in the metazoan pathogen Schistosoma mansoni: localization, small-molecule screening and opportunities for drug development. Dis Model Mech. 2018 Jul 30;11(7). pii: dmm033563. doi: 10.1242/dmm.033563. El-Sakkary N, Chen S, Arkin MR, Caffrey CR, Ribeiro P.

Phenotypic, chemical and functional characterization of cyclic nucleotide phosphodiesterase 4 (PDE4) as a potential anthelmintic drug target. PLoS Negl Trop Dis. 2017 Jul 13;11(7):e0005680. doi: 10.1371/journal.pntd.0005680. eCollection 2017 Jul. Long T, Rojo-Arreola L, Shi D, El-Sakkary N, Jarnagin K, Rock F, Meewan M, Rascón AA Jr, Lin L, Cunningham KA, Lemieux GA, Podust L, Abagyan R, Ashrafi K, McKerrow JH, Caffrey CR.

Odanacatib, a Cathepsin K Cysteine Protease Inhibitor, Kills Hookworm In Vivo. Pharmaceuticals (Basel). 2016 Jul 4;9(3). pii: E39. doi: 10.3390/ph9030039. Vermeire JJ, Suzuki BM, Caffrey CR.

Algorithmic Mapping and Characterization of the Drug-Induced Phenotypic-Response Space of Parasites Causing Schistosomiasis. IEEE/ACM Trans Comput Biol Bioinform. 2018 Mar-Apr;15(2):469-481. doi: 10.1109/TCBB.2016.2550444. Epub 2016 Apr 7. Singh R, Beasley R, Long T, Caffrey CR.

Structure-Bioactivity Relationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase 1 (PLK1), a Potential Drug Target in Schistosoma mansoni. PLoS Negl Trop Dis. 2016 Jan;10(1):e0004356. doi: 10.1371/journal.pntd.0004356. Long T, Neitz RJ, Beasley R, Kalyanaraman C, Suzuki BM, Jacobson MP, Dissous C, McKerrow JH, Drewry DH, Zuercher WJ, Singh R, Caffrey CR.

Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles. Biochimie. 2016 Mar;122:99-109. doi: 10.1016/j.biochi.2015.09.025. Epub 2015 Sep 26. Dvořák J, Fajtová P, Ulrychová L, Leontovyč A, Rojo-Arreola L, Suzuki BM, Horn M, Mareš M, Craik CS, Caffrey CR, O'Donoghue AJ.

Caenorhabditis elegans is a useful model for anthelmintic discovery. Nat Commun. 2015 Jun 25;6:7485. doi: 10.1038/ncomms8485. Burns AR, Luciani GM, Musso G, Bagg R, Yeo M, Zhang Y, Rajendran L, Glavin J, Hunter R, Redman E, Stasiuk S, Schertzberg M, Angus McQuibban G, Caffrey CR, Cutler SR, Tyers M, Giaever G, Nislow C, Fraser AG, MacRae CA, Gilleard J, Roy PJ.

Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors. PLoS Negl Trop Dis. 2015;9(6):e0003827. doi: 10.1371/journal.pntd.0003827. Fajtová P, Štefanić S, Hradilek M, Dvořák J, Vondrášek J, Jílková A, Ulrychová L, McKerrow JH, Caffrey CR, Mareš M, Horn M.

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.

Anthelmintic drug discovery: into the future. J Parasitol. 2015 Apr;101(2):125-33. doi: 10.1645/14-703.1. Epub 2015 Jan 13. Geary TG, Sakanari JA, Caffrey CR.

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.

A cysteine protease inhibitor rescues mice from a lethal Cryptosporidium parvum infection. Antimicrob Agents Chemother. 2013 Dec;57(12):6063-73. doi: 10.1128/AAC.00734-13. Epub 2013 Sep 23. Ndao M, Nath-Chowdhury M, Sajid M, Marcus V, Mashiyama ST, Sakanari J, Chow E, Mackey Z, Land KM, Jacobson MP, Kalyanaraman C, McKerrow JH, Arrowood MJ, Caffrey CR.

Dissecting the active site of the collagenolytic cathepsin L3 protease of the invasive stage of Fasciola hepatica. PLoS Negl Trop Dis. 2013 Jul 11;7(7):e2269. doi: 10.1371/journal.pntd.0002269. Print 2013. Corvo I, O'Donoghue AJ, Pastro L, Pi-Denis N, Eroy-Reveles A, Roche L, McKerrow JH, Dalton JP, Craik CS, Caffrey CR, Tort JF.

New insights into the machinery of blood digestion by ticks. Trends Parasitol. 2013 Jun;29(6):276-85. doi: 10.1016/j.pt.2013.04.002. Epub 2013 May 7. Review. Sojka D, Franta Z, Horn M, Caffrey CR, Mareš M, Kopáček P.

A global comparison of the human and T. brucei degradomes gives insights about possible parasite drug targets. PLoS Negl Trop Dis. 2012;6(12):e1942. doi: 10.1371/journal.pntd.0001942. Epub 2012 Dec 6. Mashiyama ST, Koupparis K, Caffrey CR, McKerrow JH, Babbitt PC.

Cure of hookworm infection with a cysteine protease inhibitor. PLoS Negl Trop Dis. 2012;6(7):e1680. doi: 10.1371/journal.pntd.0001680. Epub 2012 Jul 3. Vermeire JJ, Lantz LD, Caffrey CR.

Trypanosoma brucei: chemical evidence that cathepsin L is essential for survival and a relevant drug target. Int J Parasitol. 2012 May 1;42(5):481-8. doi: 10.1016/j.ijpara.2012.03.009. Epub 2012 Apr 24. Steverding D, Sexton DW, Wang X, Gehrke SS, Wagner GK, Caffrey CR.

Characterization of gut-associated cathepsin D hemoglobinase from tick Ixodes ricinus (IrCD1). J Biol Chem. 2012 Jun 15;287(25):21152-63. doi: 10.1074/jbc.M112.347922. Epub 2012 Apr 26. Sojka D, Franta Z, Frantová H, Bartosová P, Horn M, Váchová J, O'Donoghue AJ, Eroy-Reveles AA, Craik CS, Knudsen GM, Caffrey CR, McKerrow JH, Mares M, Kopácek P.

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.

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.

IrCL1 - the haemoglobinolytic cathepsin L of the hard tick, Ixodes ricinus. Int J Parasitol. 2011 Oct;41(12):1253-62. doi: 10.1016/j.ijpara.2011.06.006. Epub 2011 Jul 23. Franta Z, Sojka D, Frantova H, Dvorak J, Horn M, Srba J, Talacko P, Mares M, Schneider E, Craik CS, McKerrow JH, Caffrey CR, Kopacek P.

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.

Cysteine peptidases of kinetoplastid parasites. Adv Exp Med Biol. 2011;712:84-99. doi: 10.1007/978-1-4419-8414-2_6. Review. Caffrey CR, Lima AP, Steverding D.

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.

From innovation to application: social-ecological context, diagnostics, drugs and integrated control of schistosomiasis. Acta Trop. 2011 Sep;120 Suppl 1:S121-37. doi: 10.1016/j.actatropica.2010.08.020. Epub 2010 Sep 8. Review. Utzinger J, N'goran EK, Caffrey CR, Keiser J.

Characterization of proteinases from the midgut of Rhipicephalus (Boophilus) microplus involved in the generation of antimicrobial peptides. Parasit Vectors. 2010 Jul 27;3:63. doi: 10.1186/1756-3305-3-63. Cruz CE, Fogaça AC, Nakayasu ES, Angeli CB, Belmonte R, Almeida IC, Miranda A, Miranda MT, Tanaka AS, Braz GR, Craik CS, Schneider E, Caffrey CR, Daffre S.

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.

Hemoglobin digestion in blood-feeding ticks: mapping a multipeptidase pathway by functional proteomics. Chem Biol. 2009 Oct 30;16(10):1053-63. doi: 10.1016/j.chembiol.2009.09.009. Horn M, Nussbaumerová M, Sanda M, Kovárová Z, Srba J, Franta Z, Sojka D, Bogyo M, Caffrey CR, Kopácek P, Mares M.

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.

Structure-guided development of selective TbcatB inhibitors. J Med Chem. 2009 Oct 22;52(20):6489-93. doi: 10.1021/jm900908p. Mallari JP, Shelat AA, Kosinski A, Caffrey CR, Connelly M, Zhu F, McKerrow JH, Guy RK.

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.

Vinyl sulfones as antiparasitic agents and a structural basis for drug design. J Biol Chem. 2009 Sep 18;284(38):25697-703. doi: 10.1074/jbc.M109.014340. Epub 2009 Jul 20. Kerr ID, Lee JH, Farady CJ, Marion R, Rickert M, Sajid M, Pandey KC, Caffrey CR, Legac J, Hansell E, McKerrow JH, Craik CS, Rosenthal PJ, Brinen LS.

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.

Kinetoplastid papain-like cysteine peptidases. Mol Biochem Parasitol. 2009 Sep;167(1):12-9. doi: 10.1016/j.molbiopara.2009.04.009. Epub 2009 May 3. Review. Caffrey CR, Steverding D.

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.

A parasite cysteine protease is key to host protein degradation and iron acquisition. J Biol Chem. 2008 Oct 24;283(43):28934-43. doi: 10.1074/jbc.M805824200. Epub 2008 Aug 13. O'Brien TC, Mackey ZB, Fetter RD, Choe Y, O'Donoghue AJ, Zhou M, Craik CS, Caffrey CR, McKerrow JH.

Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB. Bioorg Med Chem Lett. 2008 May 1;18(9):2883-5. doi: 10.1016/j.bmcl.2008.03.083. Epub 2008 Apr 8. Mallari JP, Shelat A, Kosinski A, Caffrey CR, Connelly M, Zhu F, McKerrow JH, Guy RK.

Aza-peptidyl Michael acceptors. A new class of potent and selective inhibitors of asparaginyl endopeptidases (legumains) from evolutionarily diverse pathogens. J Med Chem. 2008 May 8;51(9):2816-32. doi: 10.1021/jm701311r. Epub 2008 Apr 17. Götz MG, James KE, Hansell E, Dvorák J, Seshaadri A, Sojka D, Kopácek P, McKerrow JH, Caffrey CR, Powers JC.

Profiling of proteolytic enzymes in the gut of the tick Ixodes ricinus reveals an evolutionarily conserved network of aspartic and cysteine peptidases. Parasit Vectors. 2008 Mar 18;1(1):7. doi: 10.1186/1756-3305-1-7. Sojka D, Franta Z, Horn M, Hajdusek O, Caffrey CR, Mares M, Kopácek P.

Recent initiatives and strategies to developing new drugs for tropical parasitic diseases. Expert Opin Drug Discov. 2008 Feb;3(2):173-86. doi: 10.1517/17460441.3.2.173. Caffrey CR, Steverding D.

Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatB. J Med Chem. 2008 Feb 14;51(3):545-52. doi: 10.1021/jm070760l. Epub 2008 Jan 4. Mallari JP, Shelat AA, Obrien T, Caffrey CR, Kosinski A, Connelly M, Harbut M, Greenbaum D, McKerrow JH, Guy RK.

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.

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.

Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic model. Eukaryot Cell. 2007 Jul;6(7):1130-6. Epub 2007 May 18. Meléndez-López SG, Herdman S, Hirata K, Choi MH, Choe Y, Craik C, Caffrey CR, Hansell E, Chávez-Munguía B, Chen YT, Roush WR, McKerrow J, Eckmann L, Guo J, Stanley SL Jr, Reed SL.

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.

Bis-acridines as lead antiparasitic agents: structure-activity analysis of a discrete compound library in vitro. Antimicrob Agents Chemother. 2007 Jun;51(6):2164-72. Epub 2007 Mar 19. Caffrey CR, Steverding D, Swenerton RK, Kelly B, Walshe D, Debnath A, Zhou YM, Doyle PS, Fafarman AT, Zorn JA, Land KM, Beauchene J, Schreiber K, Moll H, Ponte-Sucre A, Schirmeister T, Saravanamuthu A, Fairlamb AH, Cohen FE, McKerrow JH, Weisman JL, May B

IrAE: an asparaginyl endopeptidase (legumain) in the gut of the hard tick Ixodes ricinus. Int J Parasitol. 2007 Jun;37(7):713-24. Epub 2007 Jan 30. Sojka D, Hajdusek O, Dvorák J, Sajid M, Franta Z, Schneider EL, Craik CS, Vancová M, Buresová V, Bogyo M, Sexton KB, McKerrow JH, Caffrey CR, Kopácek P.

The cysteine proteinase inhibitor Z-Phe-Ala-CHN2 alters cell morphology and cell division activity of Trypanosoma brucei bloodstream forms in vivo. Kinetoplastid Biol Dis. 2007 Feb 28;6:2. Scory S, Stierhof YD, Caffrey CR, Steverding D.

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.

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.

Cysteine proteinase inhibitors as therapy for parasitic diseases: advances in inhibitor design. Mini Rev Med Chem. 2006 Sep;6(9):1025-32. Review. Steverding D, Caffrey CR, Sajid M.

Production and processing of a recombinant Fasciola hepatica cathepsin B-like enzyme (FhcatB1) reveals potential processing mechanisms in the parasite. Biol Chem. 2006 Aug;387(8):1053-61. Beckham SA, Law RH, Smooker PM, Quinsey NS, Caffrey CR, McKerrow JH, Pike RN, Spithill TW.

Aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of Trypanosoma brucei as lead trypanocidal agents. Bioorg Med Chem Lett. 2006 May 15;16(10):2753-7. Epub 2006 Mar 3. Vicik R, Hoerr V, Glaser M, Schultheis M, Hansell E, McKerrow JH, Holzgrabe U, Caffrey CR, Ponte-Sucre A, Moll H, Stich A, Schirmeister T.

Genomic and proteomic approaches for Chagas' disease: critical analysis of diagnostic methods. Expert Rev Mol Diagn. 2005 Jul;5(4):521-30. Review. Huete-Pérez JA, Flores-Obando RE, Ghedin E, Caffrey CR.

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.

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.

Peptidyl allyl sulfones: a new class of inhibitors for clan CA cysteine proteases. Bioorg Med Chem. 2004 Oct 1;12(19):5203-11. Götz MG, Caffrey CR, Hansell E, McKerrow JH, Powers JC.

Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi. J Med Chem. 2004 Jun 3;47(12):3212-9. Greenbaum DC, Mackey Z, Hansell E, Doyle P, Gut J, Caffrey CR, Lehrman J, Rosenthal PJ, McKerrow JH, Chibale K.

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.

Aza-peptide Michael acceptors: a new class of inhibitors specific for caspases and other clan CD cysteine proteases. J Med Chem. 2004 Apr 8;47(8):1889-92. Ekici OD, Götz MG, James KE, Li ZZ, Rukamp BJ, Asgian JL, Caffrey CR, Hansell E, Dvorák J, McKerrow JH, Potempa J, Travis J, Mikolajczyk J, Salvesen GS, Powers JC.

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.

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.

Improved trypanocidal activities of cathepsin L inhibitors. Int J Antimicrob Agents. 2003 Aug;22(2):155-9. Nkemgu NJ, Grande R, Hansell E, McKerrow JH, Caffrey CR, Steverding D.

Synthesis and structure-activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzain. J Med Chem. 2002 Jun 20;45(13):2695-707. Du X, Guo C, Hansell E, Doyle PS, Caffrey CR, Holler TP, McKerrow JH, Cohen FE.

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.

Screening of acyl hydrazide proteinase inhibitors for antiparasitic activity against Trypanosoma brucei. Int J Antimicrob Agents. 2002 Mar;19(3):227-31. Erratum in: Int J Antimicrob Agents. 2005 Jul;26(1):100. Nkemgu-Njinkeng, Joseph [corrected to Nkemngu, Njinkeng Joseph]. Int J Antimicrob Agents. 2005 Nov;26(5):424. Caffrey CR, Schanz M, Nkemngu NJ, Brush M, Hansell E, Cohen FE, Flaherty TM, McKerrow JH, Steverding D.

Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesiense. Mol Biochem Parasitol. 2001 Nov;118(1):61-73. Caffrey CR, Hansell E, Lucas KD, Brinen LS, Alvarez Hernandez A, Cheng J, Gwaltney SL 2nd, Roush WR, Stierhof YD, Bogyo M, Steverding D, McKerrow JH.

Cysteine proteinases of trypanosome parasites: novel targets for chemotherapy. Curr Drug Targets. 2000 Sep;1(2):155-62. Review. Caffrey CR, Scory S, Steverding D.

Aryl ureas represent a new class of anti-trypanosomal agents. Chem Biol. 2000 Sep;7(9):733-42. Du X, Hansell E, Engel JC, Caffrey CR, Cohen FE, 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.

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.

Cysteine protease inhibitors as chemotherapy for parasitic infections. Bioorg Med Chem. 1999 Apr;7(4):639-44. Review. McKerrow JH, Engel JC, Caffrey CR.

Trypanosoma brucei: killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-phe-ala-CHN2. Exp Parasitol. 1999 Apr;91(4):327-33. Scory S, Caffrey CR, Stierhof YD, Ruppel A, Steverding D.

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.

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.

Characterisation of proteolytic activity of excretory-secretory products from adult Strongylus vulgaris. Vet Parasitol. 1994 Apr;52(3-4):285-96. Caffrey CR, Ryan MF.