Leishmaniasis Research in NIAID Labs
NIAID scientists conduct collaborative research on leishmaniasis to advance the understanding of all aspects of the disease, including the different species of disease-causing Leishmania parasites, the varieties of sand flies that transmit the parasites to animals and humans, and how human and animal immune systems respond to the infection. Scientists in NIAID’s Division of Intramural Research and Vaccine Research Center use lab discoveries to develop experimental vaccines and treatments for mild and severe forms of leishmaniasis, experimental medical tools that are then evaluated for efficacy in animals before advancing to studies in humans.
Laboratory of Parasitic Diseases
Division of Intramural Research
Cell Biology Section
Dennis M. Dwyer, Ph.D., leads a research program that aims to identify the unique physiological properties of Leishmania parasites, with the ultimate goal of finding logical targets for new therapeutic, diagnostic, and preventive strategies.
Lab studies focus on identifying and characterizing, in biochemical and molecular terms, the basic properties of enzymes secreted by Leishmania parasites and defining the functional roles of these enzymes in the survival of the parasites within their sand fly vectors and mammalian hosts.
Read more about the Cell Biology Section.
Intracellular Parasite Biology Section
David L. Sacks, Ph.D., oversees research projects that address the immunology and cell biology of leishmanial infections and the biology of Leishmania parasites within their mammalian hosts and sand fly vectors. The ultimate goal is to develop new strategies to treat and prevent leishmanial infections and to potentially apply these insights to diseases caused by other intracellular pathogens, such as tuberculosis, or to other vector-borne diseases, such as malaria.
Dr. Sacks and his collaborators seek to define the role of sand fly saliva in modulating the host response to Leishmania parasites. The lab uses experimental mouse models to define how the host acquires resistance to Leishmania infection, as well as to uncover the immunoregulatory mechanisms that control persistent infection after treatment, which is a hallmark of the infection in humans.
Read more about the Intracellular Parasite Biology Section.
Mucosal Immunology Unit
Yasmine Belkaid, Ph.D., heads a research program investigating the immunologic mechanisms induced by parasites to promote their survival within their human and animal hosts. Her studies and others like them have found that natural regulatory T (Treg) cells help limit collateral tissue damage caused by vigorous immune responses, but these cells also can limit the magnitude of the immune response, resulting in a failure to adequately contain infection.
These findings have led Dr. Belkaid and her colleagues to explore how natural Treg cells mediate the immune response during infection by single-cell parasites, such as Leishmania. By focusing their attention on immune regulatory mechanisms within mammalian hosts, scientists in her lab hope to uncover and unleash potent immune responses against such parasites, potentially leading to new treatments against diseases such as leishmaniasis and toxoplasmosis.
Read more about the Mucosal Immunology Unit.
Laboratory of Malaria and Vector Research
Division of Intramural Research
Vector Biology Section
José M.C. Ribeiro, M.D., Ph.D., directs a research program that explores the biochemical and pharmacological properties found in the salivary glands of blood-feeding insects and ticks. Dr. Ribeiro and his team have deciphered the genetic makeup of substances found in sand fly saliva and discovered several novel anti-clotting, anti-platelet, and vasodilatory agents that help the sand fly evade the mammalian host’s immune system when feeding.
Scientists in his lab seek to improve the understanding of how blood-feeding behavior in insects and ticks evolved and, at the same time, identify new compounds in the saliva of these insects and ticks that can be used to help develop treatments or vaccines.
Read more about the Vector Biology Section.
Vector Molecular Biology Unit
Jesus G. Valenzuela, Ph.D., leads a research program that studies the molecular aspects of salivary and midgut proteins in disease-transmitting vectors such as sand flies. Dr. Valenzuela and his team aim to improve understanding of the molecular interactions between vector, parasite, and mammalian host, and to identify targets for transmission-blocking vaccines and vector-based salivary vaccines for leishmaniasis and other vector-borne diseases.
The lab develops tools to study the immune responses to proteins in sand fly saliva and to understand how cellular immune responses to these proteins can protect against Leishmania infection. It investigates how Leishmania parasites interact with midgut proteins in the sand fly to survive and multiply and how the parasites can influence expression of certain midgut proteins. The lab also conducts epidemiologic studies of leishmaniasis in Mali, Africa, to advance scientific understanding of Leishmania infection and of cellular immune responses to sand fly salivary proteins in humans.
Read more about the Vector Molecular Biology Unit.
Cellular Immunology Laboratory
Vaccine Research Center
Robert Seder, M.D., directs a research program focused on designing vaccines that confer long-term protection from diseases that require cell-mediated immunity in humans, such as tuberculosis and leishmaniasis.
Studies by Dr. Seder and his research team seek to define the requirements for generating long-term cellular immune responses and to identify the cellular and molecular mechanisms by which different vaccine formulations induce long-term cellular immunity. The lab has recently developed a potential immune correlate of protection (a measurable sign of immunity) for an infection requiring a cell-mediated response; this correlate could be used in future clinical studies to evaluate vaccines against Leishmania infection.
Read more about the Cellular Immunology Laboratory.
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