Lysosome biogenesis and amino acid signaling in cancer

It has become increasingly clear that lysosome-governed processes support cancer progression, for example by reprogramming anabolic metabolism and by facilitating cancer cell survival through the recycling of macromolecules.

Lysosome abundance is frequently increased in cancers, however, although this arguably increases the potential of tumor cells to execute lysosomal-processes, the molecular pathways that control lysosome biogenesis and turnover have remained remarkably poorly characterized, so has the role of these pathways in cancer.During my postdoctoral studies in John Blenis’s lab at Weill Cornell Medicine/Harvard Medical School, I have uncovered the molecular basis for how lysosomes coordinate their abundance to changes in the cellular availability of amino acids.

Strikingly, dysregulation of this novel amino acid signaling pathway leads to aberrant production of lysosomes and hyper-activation of mTORC1, a central promoter of cell growth and cancer.

Advancing from my unique discoveries, I will map the components of the elusive biological machinery that controls lysosome abundance in mammalian cells and characterize its role in cancer, using state-of-the-art screening methods as well as in vitro and in vivo methods.

My findings may open up completely new possibilities for pharmacological manipulation of lysosome biogenesis and turnover to combat cancer.