Lysosomes are cell's recycling and waste disposal system. It contains a battery of enzymes (acid hydrolases) that degrade a wide variety of macromolecules and cellular debris into reusable forms. In so doing lysosomes play a vital role in maintaining cellular homeostasis. The broad goal of our research is to understand the role of this fascinating organelle in human health and diseases. We use various methods ranging from molecular biology, cell biology, protein biochemistry to genomic and proteomic tools to address our research problems. Current research in our laboratory is focused on two major areas: 1. To investigate the pathogenesis of mucopolysaccharidoses, a group of genetic disorders caused by deficiency of one of the eleven lysosomal enzymes required for stepwise degradation of glycosaminoglycans (GAGs). Widespread lysosomal accumulation of undegraded or partially degraded GAGs results in cellular and multiple organ dysfunctions leading to premature death in most cases. The genetic causes of these diseases despite being known for years, actual pathways leading from lysosomal storage to cellular damage or death are still unclear. We address these unresolved issues by using well-characterized cell culture and mouse models of these diseases. We are also trying to develop a drosophila model of these diseases. 2. To understanding how certain intracellular pathogens utilize lysosome as their replicating niche. Phagocytes normally use acidic and proteolytic environment of the lysosome to destroy engulfed pathogens. But, some pathogens are smart enough to be able to survive and even replicate in such harsh conditions. Using a macrophage infection model of the protozoan parasite Leishmania sp. we ask: a) how the pathogens tolerate such harsh lysosomal conditions and b) how replicating parasites compete with the host for acquisition of essential nutrients (e.g. iron).