Grant: Operating Grant

Leishmania is an important human pathogen that causes leishmaniasis, a vector-borne parasitic disease with a large spectrum of clinical manifestations, and infects more than 12 million people worldwide. In order to survive within its mammalian host, Leishmania has to differentiate from the extracellular promastigote form found in the insect vector into the amastigote stage inside the phagolysosomes of macrophages. The ability of Leishmania to survive within the acidic phagolysosome milieu depends upon the developmental regulation of a variety of genes which is controlled by complex RNA regulatory pathways. Genes preferentially expressed in response to various environmental stimuli in the macrophages should play a central role in the parasite's intracellular survival and pathogenesis. Very little is known, however on the mechanisms underlying their stage-specific expression and their putative function. In the past 10 years, we have made important contributions to our understanding of how differentially expressed genes throughout the developmental stages of Leishmania are regulated using global genomics and proteomics approaches. Our main research interest is to delineate the molecular mechanisms that control stage-specific regulation of gene expression in Leishmania and contribute to parasite pathogenesis. These studies would possibly depict novel mechanisms of gene regulation and pinpoint promising targets for the development of novel therapeutic strategies against these important but neglected human parasitic diseases.