- Platt Laboratory | Lysosomal and Sphingolipid Disorders Research Group
As a doctoral student, my research focuses on interplay between lipids shed by pathogens, such as pathogenic Mycobacterium Tuberculosis (MTB), and their lysosomal targets for sustaining intracellular latency and preventing imminent destruction.
Previous work in our group revealed an unexpected yet stark similarity between tuberculosis infection and a rare lysosomal storage disorder, Neimann-Pick Disease, Type C.
According to this model, free lipids shed by pathogenic mycobacteria inhibit a lysosomal transmembrane protein, NPC1, to prevent phagosome: lysosome fusion which is required for clearance of the pathogens. In addition, inhibition of this protein leads to accumulation of myriads of lipids including cholesterol and sphingosine to be utilized as a carbon source by the invading pathogen, as well as leading to defects in calcium release from acidic organelles, which in turn is essential for cellular cargo sorting, including pathogen clearance.
Building on this newly emerging host-mediated paradigm which span lysosomal storage and infectious diseases research , my main aim is to elucidate the pathogen lipids which are most potent in NPC1 inhibition, that can later be exploited as therapeutic targets.
I also have an interest in stability of lysosomal membranes and its repercussions in normal physiology and pathological states.