Jesus G. Valenzuela, Ph.D.
Chief, Vector Molecular Biology Unit
Dr. Valenzuela received his Ph.D. in Biochemistry from The University of Arizona in 1995. He joined the Laboratory of Parasitic Diseases in 1996, became a research fellow in 1999, and an Investigator in October, 2002.
Description of Research Program
The Vector Molecular Biology Unit focuses on the molecular aspects of salivary and midgut genes in vector/parasite interaction. We are interested in the use of salivary genes as vaccines to block parasite or pathogen transmission. We have identified and isolated a salivary gene from the sand fly Phlebotomus papatasi that confers protection against Leishmania major infection. We are currently using high-throughput approaches to isolate salivary proteins from different vectors of disease and DNA vaccination strategies to test these candidates. This novel approach to use vector salivary proteins or genes to block parasite infection may be applicable to other species of leishmania and also to other systems like in ixodid ticks to control Lyme disease. Future work on this area is directed to:
- The use of sand fly salivary genes on large animals, including dogs, to block leishmania infection,
- The use of sand fly salivary genes to block transmission to other species of leishmania, and
- The use of the tick Ixodes scapularis salivary genes to block borrelia infection.
 |
 |
Another interest of the unit is the identification of the leishmania attachment site on the sand fly midgut. The lipophosphoglycan (LPG) structure present in the surface of the leishmania parasite is important for the attachment of the parasite to the sand fly midgut. Classical biochemical attempts have failed to identify and isolate this attachment site in the vector midgut. We have isolated and sequenced a large set of full-length genes expressed on the midgut of different phlebotomines and identified candidate genes that may express the leishmania attachment site. Future work on this area is directed to: 1) Express these putative LPG receptors on heterologous systems (293 cells and cell-free expression systems) and test for parasite binding, 2) Identify the different LPG receptors on the different sand flies, and 3) Characterize novel genes present in the midgut of sand flies.
Research Group Members
Jesus G. Valenzuela, Amy Seitz, Fabiano Oliveira
Selected Recent Publications
To view a complete listing, visit PubMed.
Valenzuela, J.G., Charlab, R., Mather, T.N., and Ribeiro, J.M.C. (2000). Purification, cloning, and expression of a novel salivary anti-complement protein from the tick, Ixodes scapularis. J. Biol. Chem. 275:18717-23.
Valenzuela J.G., Belkaid, Y., Garfield, M., Mendez, S., Kamhawi, S., Rowton, E., Sacks D.L. and Ribeiro, J.M.C. (2001). Toward a defined anti-Leishmania vaccine targeting vector antigens: Characterization of a protective salivary protein. J. Exp. Med. 194:331-42.
Valenzuela J.G. (2002). High-throughput approaches to study salivary proteins and genes from vectors of diseases. Insect Biochem. Mol. Biol. 32:1199-209.
Valenzuela J.G., Francischetti, I.M., Garfield, M. and Ribeiro J.M.C. (2002). Exploring the sialome of the tick, Ixodes scapularis. J. Exp. Biol. 205:2843-64
Gomes R.B., Brodskyn, C., de Oliveira C.I., Costa, J., Miranda, J.C., Caldas, A, Valenzuela J.G., Barral-Neto, M and Barral, A. (2002). Seroconversion against Lutzomyia longipalpis saliva concurrent with the development of anti-Leishmania chagasi delayed-type hypersensitivity. J. Infect. Dis.186:1530-4
Ramalho-Ortigao, J.M., Kamhawi, S., Rowton, E.D., Ribeiro, J.M.C., and Valenzuela, J.G. (2003). Cloning and characterization of trypsin- and chymotrypsin-like proteases from the midgut of the sand fly vector Phlebotomus papatasi. Insect Biochem. Mol. Biol. 33:163-71
Aliberti, J., Valenzuela J.G., Carruters, V.B., Hieny, S., Andersen, J., Charest, H., Reis e Sousa, C., Fairlamb, A., Ribeiro, J.M.C., Sher, A. (2003). Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells. Nat. Immunol. 4:485-490
back to top