Our research is focused on understanding the determinants of immunity and molecular mechanisms related to the immunopathogenesis in leishmaniasis. We have characterized a program of Leishmania-induced alternative macrophage activation in progressive visceral leishmaniasis, defining the regulation of inducible nitric oxide synthase and arginase in macrophages and fibroblasts, and identifying the key role of STAT6 signaling. We have also investigated the impact of malnutrition on innate immunity and visceral leishmaniasis, and ongoing work is focused on characterizing the mechanisms of impairment of lymph node function during polynutrient deficiency. We have used several approaches to identify vaccine candidates for leishmaniasis, and have defined vaccine efficacy in experimental infection models. We are particularly interested in the use of vaccination to interrupt transmission from the reservoir host (dogs) to the insect vector (sand flies) in regions endemic for visceral leishmaniasis.