Major Areas of Research
- Functional transcriptomic approaches to characterizing vector salivary proteins
- Development of natural models of vector-transmitted cutaneous and visceral leishmaniases to study the impact of immune responses to sand fly salivary proteins in parasite transmission, early events of pathogenesis post-bite, and adaptive immunity to naturally acquired disease
- Studies of human cellular immune responses to sand fly salivary proteins in volunteers and individuals living in leishmaniasis-endemic areas
- Development of biomarkers for vector exposure using immunogenic salivary proteins
The Vector Molecular Biology Section focuses on the molecular aspects of vector salivary proteins, with emphasis on studying the impact of sand fly salivary proteins at the vector/host/parasite interface. Our section combines basic approaches with entomological, veterinary, and clinical research, broadening our understanding of the relationship between immune responses to vector salivary proteins and disease outcome. Our ultimate goal is to use this information to contribute to the development of an effective vaccine by incorporating a salivary protein in an anti-Leishmania vaccine formulation, to develop animal models that mimic the disease transmission in nature, and to develop biomarkers of vector exposure for epidemiological studies.
Our interest in these studies is based on the fact that every time an infective sand fly gets a blood meal, it delivers Leishmania parasites and at the same time injects saliva, which contains a variety of potent bioactive proteins that helps the insect to get a blood meal and consequently modifies the environment where the parasite is deposited. Current vaccines and animal models of leishmaniasis do not take this fact into account, and we hypothesize this may be one of the reason why an effective vaccine is not yet available even after years of research and a number of promising available candidates. In our section, we identified salivary immunogens that can drive a protective immune response against this neglected disease, and we recently established relevant animal models of disease using the natural route of transmission, the bite of infective sand flies. These approaches are permitting the section to ask basic and fundamental research questions regarding the transmission of this vector borne-disease, to study the impact of selected salivary recombinant proteins in disease, to translate these findings to field research work, and to create partnerships with companies, research institutions, and non-profit organizations to apply this information for veterinary and public health purposes.
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 became a tenure-track investigator in the Laboratory of Malaria and Vector Research in October 2002. Dr. Valenzuela became a senior investigator in October 2009.
Aslan H, Dey R, Meneses C, Castrovinci P, Jeronimo SM, Oliva G, Fischer L, Duncan RC, Nakhasi HL, Valenzuela JG, Kamhawi S. A new model of progressive visceral leishmaniasis in hamsters by natural transmission via bites of vector sand flies. J Infect Dis. 2013 Apr 15;207(8):1328-38.
Oliveira F, Traoré B, Gomes R, Faye O, Gilmore DC, Keita S, Traoré P, Teixeira C, Coulibaly CA, Samake S, Meneses C, Sissoko I, Fairhurst RM, Fay MP, Anderson JM, Doumbia S, Kamhawi S, Valenzuela JG. Delayed-type hypersensitivity to sand fly saliva in humans from a leishmaniasis-endemic area of Mali is Th1-mediated and persists to midlife. J Invest Dermatol. 2013 Feb;133(2):452-9.
Abdeladhim M, Jochim RC, Ben Ahmed M, Zhioua E, Chelbi I, Cherni S, Louzir H, Ribeiro JM, Valenzuela JG. Updating the salivary gland transcriptome of Phlebotomus papatasi (Tunisian strain): the search for sand fly-secreted immunogenic proteins for humans. PLoS One. 2012;7(11):e47347.
Gomes R, Oliveira F, Teixeira C, Meneses C, Gilmore DC, Elnaiem DE, Kamhawi S, Valenzuela JG. Immunity to sand fly salivary protein LJM11 modulates host response to vector-transmitted leishmania conferring ulcer-free protection. J Invest Dermatol. 2012 Dec;132(12):2735-43.
Collin N, Assumpção TC, Mizurini DM, Gilmore DC, Dutra-Oliveira A, Kotsyfakis M, Sá-Nunes A, Teixeira C, Ribeiro JM, Monteiro RQ, Valenzuela JG, Francischetti IM. Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in vivo. Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2185-98.
Teixeira C, Gomes R, Collin N, Reynoso D, Jochim R, Oliveira F, Seitz A, Elnaiem DE, Caldas A, de Souza AP, Brodskyn CI, de Oliveira CI, Mendonca I, Costa CH, Volf P, Barral A, Kamhawi S, Valenzuela JG. Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America. PLoS Negl Trop Dis. 2010 Mar 23;4(3):e638.
Valenzuela JG, Belkaid Y, Kamhawi S, Sacks D, Ribeiro JMC, inventors; The United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Anti-arthropod vector vaccines, methods of selecting and uses thereof. United States patent US 7,964,576. 21 Jun 2011.
Valenzuela JG, Ribeiro JMC, Kamhawi S, Belkaid Y, Fischer L, Audonnet JC, Milward F, inventors; The United States of America as represented by the Department of Health and Human Services, Merial Limited, assignees. P. ariasi polypeptides, p. perniciosuspolypeptides and methods of use. United States patent US 7,741,437. 22 Jun 2010.
Valenzuela JG, Ribeiro JMC, Barral A, Netto M, Brodskyn C, Gomes R, inventors; The United States of America as represented by the Secretary of the Department of Health and Human Services, Cruz, assignees. Lutzomyia longipalpis polypeptides and methods of use. United States patent US 7,485,306. 3 Feb 2009.
Valenzuela JG, Belkaid Y, Kamhawi S, Sacks D, Ribeiro JMC, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Anti-arthropod vector vaccines, methods of selecting and uses thereof. United States patent US 7,388,089. 17 Jun 2008.
Ribeiro JMC, Valenzuela JG, Charlab R, Mather TN, inventors; The United States of America as represented by the Department of Health and Human Services, University of Rhode Island, assignees. Ixodes salivary anticomplement protein. United States patent US 7,153,947. 26 Dec 2006.
Francischetti IMB, Valenzuela JG, Ribeiro JMC, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Ixodes scapularis tissue factor pathway inhibitor. United States patent US 7,078,508. 18 Jul 2006.