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Professor Peter J Hotez
Department of Microbiology and Tropical Medicine
The George Washington University
2300 Eye St., NW, Washington DC 20037, USA
Email: mtmpjh@gwumc.edu
Tel: 202-994-3532
Fax: 202-994-2913
Homepage: http://www.gwumc.edu/microbiology

Research
Our major interest is in vaccine development for human hookworm infection with a focus on a strategy that targets parasite enzymes, especially proteases. Work is in progress to study proteases from the infective larval stages of the parasite, which are used in skin invasion. These include a novel astacin like metalloprotease (MTP-1), as well as a member of the pathogenesis related protein (PRP) superfamily (ASP-2), which bears a resemblance to the Cone Snail Protease. In addition, we are developing the adult hookworm hemoglobin-degrading proteases including aspartic (APR-1 and APR-2), cysteine- (CP-2), and metalloproteases (MEP-1), which are also major vaccine candidates. Our approach relies on developing a multi-antigen vaccine comprised of both a larval and an adult hookworm antigen. Phase 1 human vaccine trials for ASP-2 are being planned for early 2005.
Collaborations
Alex Loukas
Olutoyin Asojo
Jeff Bethony
Paul Brindley
Publications
Jones BF, Hotez PJ. Molecular cloning and characterization of Ac-MEP-1 a developmentally regulated gut luminal metalloendopeptidase from adult Ancylostoma caninum hookworm. MOLECULAR AND BIOCHEMICAL PARASITOLOGY 2002; 119 (1): 107-116.

Zhan B, Hotez PJ, Wang Y, Hawdon JM. A developmentally regulated metalloprotease secreted by host-stimulated Ancylostoma caninum third-stage infective larvae is a member of the astacin family of proteases. MOLECULAR AND BIOCHEMICAL PARASITOLOGY 2002; 120: 291-6 .

Hotez PJ, Zhan B, Bethony JM, Loukas A, Williamson A, Goud G, Hawdon JM, Dobardzic A, Dobardzic R, Ghosh K, Bottazzi ME, Mendez S, Zook B, Wang Y, Liu S, Essiet-Gibson I, Chung-Debose S, Xiao SH, Knox D, Meagher M, Inan M, Correa-Oliveira R, Vilk P, Shepherd HR, Brandt W, Russell PK. Progress in the development of a recombinant vaccine for human hookworm disease: the human hookworm vaccine initiative. INTERNATIONAL JOURNAL FOR PARASITOLOGY 2003; 33: 1245-58.

Zhan B, Liu Y, Badamchian M, Williamson A, Feng JJ, Loukas A, Hawdon JM, Hotez PJ. Molecular characterization of the Ancylostoma-secreted protein (ASP) family from the adult stage of Ancylostoma caninum. INTERNATIONAL JOURNAL FOR PARASITOLOGY 2003; 33: 897-907.
Goud GN, Zhan B, Ghosh K, Loukas A, Hawdon J, Dobardzic A, Deumic V, Liu S, Dobardzic R, Zook BC, Qun J, Liu YY, Hoffman L, Chung-Debose S, Patel R, Mendez S, Hotez PJ. Cloning, yeast expression, isolation and vaccine testing of recombinant Ancylostoma secreted protein 1 (ASP-1) and ASP-2 from Ancylostoma ceylanicum. JOURNAL OF INFECTIOUS DISEASES 2004; 189: 919-29.

Loukas A, Bethony JM, Williamson AL, Goud GN, Mendez S, Zhan B, Hawdon JM, Bottazzi ME, Brindley PJ, Hotez PJ. Vaccination of dogs with recombinant cysteine protease from the intestine of canine hookworms diminishes fecundity and growth of worms. JOURNAL OF INFECTIOUS DISEASES 2004; 189: 1952-61.





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