Our research is driven by the desire to understand how the organelles of the endomembrane system - the collection of intracellular, membrane-bounded organelles that compartmentalize the biochemical reactions that fuel life - are assembled and maintained. The endomembrane system is broadly divided into the secretory pathway, which is responsible for the production and distribution of newly synthesized molecules throughout the cell, and the endocytic system, which internalizes components of the extracellular milieu and the plasma membrane. Elucidating the mechanisms that sort molecules to various organelles is of fundamental importance for understanding cell growth, division, multi-cellular development and physiology, and it is also crucial for understanding a broad range of diseases and afflictions - cancer, neurodegenerative disease, infectious disease, and many others. Phosphoinositide and GTPase signaling modules constitute the master regulators of organelle biogenesis.
Phosphoinositides (“PIPs”) are generated by phosphorylation of distinct positions on the inositol ring of phosphatidylinositol, an abundant lipid of all cellular membranes. Importantly, the cytoplasmic leaflet of each organelle is enriched in a different PIP, constituting an organelle specific PIP code. Similarly, distinct GTPases of the Rab and Arf families associate with distinct organelles and the transport vesicles that ferry molecules between them. Specific recognition of PIPs and GTPases by sorting and transport factors regulate the composition and identity of each organelle by regulating inter-organelle transport. In our lab we harness yeast genetics/genomics, proteomics, biochemistry, and live cell fluorescence microscopy to elucidate the molecular mechanisms of these sorting and trafficking pathways.