The aim of this research program is to investigate the anti- hemostatic and anti-inflammatory compounds in vector saliva that allow efficient blood feeding and enhancement of pathogen transmission. Anti-hemostatic compounds of interest include anti- clotting, anti-platelet and vasodilators. Anti-inflammatory compounds include immunomodulatory compounds as well as compounds that modify effector arms of the immune response, such as anti-complement activity found in the saliva of some ticks. While the vector attempts to modify the feeding site to enhance success of blood feeding, such site becomes locally compromised in its ability to react to injury and becomes an easy site for pathogen invasion. Novel pharmaceuticals and novel targets for vaccine development will be ultimate benefits of this program. In the current year we have discovered a novel nitric oxide carrier protein that is homologous to inositol phosphatase, suggesting this later enzyme may be regulated by NO. We have also discovered a new gene encoding for an apyrase activity, that adenosine is the main vasodilator of Phelebotomus sand flies, and that saliva of this sand fly modifies transmission of Leishmania major, making possible to identify new targets for vaccine development. The vasodilator of Anopheles mosquitoes was also purified and cloned, being a member of the myeloperoxidase family, while that of the black fly was found to be a novel gene. Finally, the kininase of the tick Ixodes dammini was purified and characterized as a member of the angiotensin converting enzyme family.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000810-02
Application #
6099124
Study Section
Special Emphasis Panel (LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Santiago, Paula Beatriz; de Araújo, Carla Nunes; Charneau, Sébastien et al. (2018) Exploring the molecular complexity of Triatoma dimidiata sialome. J Proteomics 174:47-60
Fernández-Medina, R D; Granzotto, A; Ribeiro, J M et al. (2016) Transposition burst of mariner-like elements in the sequenced genome of Rhodnius prolixus. Insect Biochem Mol Biol 69:14-24
Ribeiro, José M C; Schwarz, Alexandra; Francischetti, Ivo M B (2015) A Deep Insight Into the Sialotranscriptome of the Chagas Disease Vector, Panstrongylus megistus (Hemiptera: Heteroptera). J Med Entomol 52:351-8
Ribeiro, José M C; Kazimirova, Maria; Takac, Peter et al. (2015) An insight into the sialome of the horse fly, Tabanus bromius. Insect Biochem Mol Biol 65:83-90
Francischetti, Ivo M B; Assumpção, Teresa C F; Ma, Dongying et al. (2013) The ""Vampirome"": Transcriptome and proteome analysis of the principal and accessory submaxillary glands of the vampire bat Desmodus rotundus, a vector of human rabies. J Proteomics 82:288-319
Ronca, Raffaele; Kotsyfakis, Michalis; Lombardo, Fabrizio et al. (2012) The Anopheles gambiae cE5, a tight- and fast-binding thrombin inhibitor with post-transcriptionally regulated salivary-restricted expression. Insect Biochem Mol Biol 42:610-20
Francischetti, Ivo M B; Oliveira, Carlo J; Ostera, Graciela R et al. (2012) Defibrotide interferes with several steps of the coagulation-inflammation cycle and exhibits therapeutic potential to treat severe malaria. Arterioscler Thromb Vasc Biol 32:786-98
Ribeiro, Jose M C; Mans, Ben J; Arca, Bruno (2010) An insight into the sialome of blood-feeding Nematocera. Insect Biochem Mol Biol :
Guo, Yongjian; Ribeiro, Jose M C; Anderson, Jennifer M et al. (2009) dCAS: a desktop application for cDNA sequence annotation. Bioinformatics 25:1195-6
Calvo, Eric; Mans, Ben J; Ribeiro, Jose M C et al. (2009) Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein. Proc Natl Acad Sci U S A 106:3728-33

Showing the most recent 10 out of 115 publications