Our laboratory is interested in understanding the immune mechanisms that determine outcome of "New world" cutaneous and visceral leishmaniasis caused by L. mexicana and L. donovani respectively. We are particularly interested in studying the role of cytokines in regulation of immune responses during these two species of Leishmania and the use of cytokine and cytokine receptor gene deficient mice has been a very powerful tool in these studies. As cytokines can modulate functions of several cells of the immune system in vivo , we are now using cell-specific gene deficient mice lacking specific cytokine receptors on specific immune cells such as macrophages and T cells. These mice are generated using cre/lox technology that enables us to delete a gene in cell-specific manner. We believe that these studies will enable us to determine how cytokines regulate immune responses in vivo during leishmaniasis. With regards to L. donovani , our studies have focused on understanding the regulation of effector cell responses in murine visceral leishmaniasis caused by L. donovani . Of particular interest to our group is the determining the immune mechanisms that mediate protection and/or induce immunopathology during VL. More recently, in collaboration with the McGill University, we have initiated studies that focus on the development of amastigote-specific single candidate vaccine against visceral and "New world" cutaneous leishmaniasis that cause considerable morbidity and mortality in humans. Another area of research in our laboratory is understanding the immunological basis of gender-related differences in susceptibility to Leishmania. In these studies, we are interested in determining the roles of sex-hormones in modulation of immune response and determining the outcome of Leishmania infection. Our long-term goal is to identify the basic mechanisms by which cytokines regulate T cell responses and host immunity to cutaneous leishmaniasis caused by L. mexicana and visceral leishmaniasis caused by L. donovani and utilize this knowledge to develop a vaccine against these diseases.