Major Areas of Research
- Impact of vector arthropod bites and vector-derived factors on innate and adaptive host skin immune responses
- Determinants of successful parasite infection and transmission in Leishmania-infected sand flies
- Translational research on vectors of disease with emphasis in sand flies, ticks and mosquitoes
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. In 2019, Dr. Valenzuela became deputy chief of the Laboratory of Malaria and Vector Research.
The Vector Molecular Biology Section (VMBS) focuses on understanding how molecules from arthropod vectors are critical for the success of pathogen transmission and translating this knowledge into disease control opportunities. The section has two main themes: dissecting the immune events following an arthropod bite, mainly the cellular interactions at the vector-host-pathogen interface, and their implication for disease pathogenesis; and elucidating the determinants of successful transmission to a mammalian host by a competent arthropod vector.
The VMBS uses immunology, biochemistry, bioinformatics and functional genomic approaches combined with field entomological and clinical studies to address our main research questions. The main vector arthropods we study are sand flies, ticks and mosquitoes. Our two main interests encompass basic and translational lines of research. Basic research focuses on understanding the initial events in host skin after infected vector bites and has revealed several new mediators leading to immune changes affecting pathogen establishment. Another line of basic research focuses on understanding how arthropod vectors become infectious and has led to the identification of a new developmental stage in Leishmania that is pertinent to efficacy of transmission in nature. Our translational research goals are the understanding of the innate and adaptive skin immune responses to arthropod vector bites in human volunteers, the development of an effective vaccine by incorporating vector salivary proteins, and the development of biomarkers of vector exposure for epidemiological studies in disease endemic countries.
Shaden Kamhawi, Ph.D., Associate Scientist
Fabiano Oliveira, M.D., Ph.D., Associate Scientist
Tiago Donatelli Serafim, Ph.D., Research Fellow
Daniel Sonenshine, Ph.D., Professor Emeritus, Guest Researcher
Joshua Lacsina, M.D., Ph.D., NIAID Clinical Fellow
Eva Iniguez, Ph.D., Post-doctoral Fellow (INRO)
Thiago Soares de Souza Vieira, Ph.D., Visiting Post-doctoral Fellow
Johannes Doehl, Ph.D., Visiting Post-doctoral Fellow
Mara Short, Post-baccalaureate Research Trainee
Elliot Lowe, Post-baccalaureate Research Trainee (UGSP Scholar)
Aiyana Ponce, Post-baccalaureate Research Trainee (INRO)
Yvonne Rangel Gonzalez, Post-baccalaureate Research Trainee (INRO)
Sand Fly Insectary Group
Claudio Meneses, Research Associate
Timothy Wilson, IRTA Student
Serena Doh, IRTA Student
Aku Diane Akueson, IRTA Student
- DeSouza-Vieira T, Iniguez E, Serafim TD, de Castro W, Karmakar S, Disotuar MM, Cecilio P, Lacsina JR, Meneses C, Nagata BM, Cardoso S, Sonenshine DE, Moore IN, Borges VM, Dey R, Soares MP, Nakhasi HL, Oliveira F, Valenzuela JG, Kamhawi S. Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance. Cell Rep. 2020 Oct;33(4):108317.
- Dey R, Joshi AB, Oliveira F, Pereira L, Guimarães-Costa AB, Serafim TD, de Castro W, Coutinho-Abreu IV, Bhattacharya P, Townsend S, Aslan H, Perkins A, Karmakar S, Ismail N, Karetnick M, Meneses C, Duncan R, Nakhasi HL, Valenzuela JG, Kamhawi S. Gut Microbes Egested during Bites of Infected Sand Flies Augment Severity of Leishmaniasis via Inflammasome-Derived IL-1β. Cell Host Microbe. 2018 Jan;23(1):134-143.e6.
- Anderson JM, Moore IN, Nagata BM, Ribeiro JMC, Valenzuela JG, Sonenshine DE. Ticks, Ixodes scapularis, Feed Repeatedly on White-Footed Mice despite Strong Inflammatory Response: An Expanding Paradigm for Understanding Tick-Host Interactions. Front Immunol. 2017 Dec;8:1784.
Vector-Pathogen Molecular Interactions
- Coutinho-Abreu IV, Serafim TD, Meneses C, Kamhawi S, Oliveira F, Valenzuela JG. Leishmania infection induces a limited differential gene expression in the sand fly midgut. BMC Genomics. 2020 Sep;21(1):608.
- Serafim TD, Coutinho-Abreu IV, Oliveira F, Meneses C, Kamhawi S, Valenzuela JG. Sequential blood meals promote Leishmania replication and reverse metacyclogenesis augmenting vector infectivity. Nat Microbiol. 2018 May;3(5):548-555. doi: 10.1038/s41564-018-0125-7. Epub 2018 Mar.
Translational Research on Vectors of Disease:
- Manning JE, Oliveira F, Coutinho-Abreu IV, Herbert S, Meneses C, Kamhawi S, Baus HA, Han A, Czajkowski L, Rosas LA, Cervantes-Medina A, Athota R, Reed S, Mateja A, Hunsberger S, James E, Pleguezuelos O, Stoloff G, Valenzuela JG, Memoli MJ. Safety and immunogenicity of a mosquito saliva peptide-based vaccine: a randomised, placebo-controlled, double-blind, phase 1 trial. Lancet. 2020 Jun;395(10242):1998-2007.
- Evaluating the Safety and Immunogenicity of AGS-v PLUS, a Universal Mosquito-Borne Disease and Mosquito Control Vaccine: NCT04009824
- Safety and Immunogenicity of a First-in-Human Mosquito Saliva Peptide Vaccine; ClinicalTrials.gov Identifier: NCT03055000
- Defining Skin Immunity of a Bite of Key Insect Vectors in Humans; ClinicalTrials.gov Identifier: NCT03641339
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.
Participating Research Networks:
- GHIT partnership with CBER, FDA; Ohio State University, McGill University, Gennova Biopharmaceuticals Limited and Nagasaki University
- Baylor College of Medicine
- Yale School of Medicine
- Yale School of Public Health
- University of Maryland School of Medicine
- Uniformed Services University of the Health Sciences
- ConserV Bioscience
- HIC-Vac network
- CPqGM – FIOCRUZ
- Federal University of Minas Gerais
- Federal University of Ouro Preto
- Liverpool School of Tropical Medicine
- Pasteur Institute of Tunis
- Charles University in Prague
- Centro de Inv. en Alimentación y Desarrollo, A.C. (CIAD)