Conor Caffrey

Position and Department:
Assistant Research Scientist and
Director of Biochemistry and Molecular Parasitology,
Sandler Center for Basic Research in Parasitic Diseases
Department of Pathology, Byers Hall 501E
University of California, San Francisco
San Francisco, CA 94158

Voice: (415) 476-6611
FAX: (415) 502-8193
Email: caffrey@cgl.ucsf.edu

Education:
1984 - 1988 University College Dublin, Ireland. B.Sc. (Hons.),Zoology
1988 - 1994 University College Dublin, Ireland. Ph.D., Mol. Biochem. Parasitology
Research Interests:
1) Characterization of proteolytic enzymes (proteases) of protozoan and helminth parasites
2) The network of proteases involved in nutrition of metazoan, endo- and ecto-hematophagous parasites
3) Proteases as targets for chemotherapy of parasitic diseases
4) Development of small-molecule inhibitors of proteases aschemotherapeutic agents
5) Proteases as molecular vaccine candidates
6) Targeted transcriptomics and proteomics: modulation of protease expression by parasites
7) Recombinant expression methodologies for proteases
Background:
Proteases (proteolytic enzymes) are fundamental tools with which cells, tissues and organisms grow, re-organize themselves, and indeed, invade each other. These enzymes mediate such diverse biological processes as apoptosis and tissue remodeling, and are intimately associated with many disease conditions such as arthritis, osteoporosis, invasive cancers and bacterial pathogenesis. Intense research over the last two decades has demonstrated that many proteases are considered or validated as ÒdruggableÓ targets for small-molecule-based therapies. My research at the Sandler Center and with collaborators has shown that the same is true for many protozoan and metazoan parasites. In particular, disruption of cysteine protease function in Schistosoma mansoni and Trypanosoma brucei, the etiological agents of the Òneglected tropical diseasesÓ, schistosomiasis and African Sleeping Sickness, respectively, severely limits parasite-survival and -reproduction. Our research employs both chemical and reverse genetic approaches to understand both the functional context of a given protease and whether it represents a potential drug target. Thus, our research focus merges with the continuing mission of the Sandler Center (http://www.ucsf.edu/mckerrow/slide.html) to develop low-cost, orally bioavailable drugs for human parasitic diseases. I gratefully acknowledge the manifold and fruitful collaborations with research groups in the US, UK, Germany and the Czech Republic and welcome future opportunities to collaborate with anyone interested.
Recent Publications:
1. Abdulla Hamadien M-, Sajid M, Lim KC, McKerrow, JH, Caffrey CR. 2007. Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor, PLoS Medicine, in press.

2.A multiple enzyme network functions in the intestinal protein digestion by a platyhelminth parasite. 2006. Delcroix M, Sajid M, Caffrey CR, Lim KC, Dvovak J, Hsieh I, Bahgat M, Dissous C, McKerrow JH. Journal of Biological Chemistry, in press. PMID: 17028179

3.McKerrow JH, Caffrey CR, Kelly B, Loke P, Sajid M. 2006. Proteases in Parasitic Diseases. In: Annual Review of Pathology: Mechanisms of Disease. Annual Reviews Publishing, Palo Alto, CA, USA.

4.Dalton, JP, Caffrey CR, Sajid, M, Stack C, Donnelly S, Loukas A, Don T, McKerrow J, Halton, DW, Brindley PJ. 2006. Proteases in trematode biology. In: Parasitic Flatworms: Molecular Biology, Biochemistry, Immunology and Physiology (Eds: Maule A, Marks NJ) CABI Publishing, Oxford, UK.

5.Steverding D, Caffrey CR, Sajid, M. 2006. Cysteine proteinase inhibitors as therapy for parasitic diseases: advances in inhibitor design. Mini Reviews in Medicinal Chemistry, 6, 1025-1032. PMID: 17018001

6.Huete-Perez JA, Flores-Obando RE, Ghedin E, Caffrey CR. 2005. Genomic and proteomic approaches for Chagas' disease: critical analysis of diagnostic methods. Expert Reviews in Molecular Diagnosis, 5, 521-530. PMID: 16013970

7.Caffrey CR, Placha L, Barinka C, Hradilek M, Dostal J, Sajid M, McKerrow JH, Majer P, Konvalinka J, Vondrasek J. 2005. 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. Biological Chemistry, 386, 339-49. PMID: 15899696

8.Dvorak J, Delcroix M, Rossi A, Vopalensky V, Posp’sek M, Sedinova M, Mikes L, Sajid M, Sali A, McKerrow JH, Horak P, Caffrey CR. 2005. Multiple cathepsin B isoforms in schistosomula of Trichobilharzia regenti: identification, characterisation and putative role in migration and nutrition. International Journal for Parasitology, 35, 895-910. PMID: 15950230

9.Wippersteg V, Sajid M, Walshe D, Khiem D, Salter JP, McKerrow JH, Grevelding CG, Caffrey CR. 2005. Biolistic transformation of Schistosoma mansoni with 5' flanking regions of two peptidase genes promotes tissue-specific expression. International Journal for Parasitology, 35, 583-589. PMID: 15862572

10. Caffrey CR, McKerrow JH, Salter JP, Sajid M. 2004. Blood ÔnÕ guts: an update on schistosome digestive peptidases. Trends Parasitol, 20, 241-248. PMID: 15105025