My laboratory has been developing tools to help understanding the cell biology of signaling networks. Our techniques permit the visualization as well as the non-invasive manipulation of intact cells. We have a long-standing interest in cell-based assays to study the impact of mutations in cystic fibrosis. Our expertise in lipid and especially phosphoinositide synthesis and cell biology connected us to growth factor and cannabinoid receptor signaling and receptor internalization. The use of photo-activatable (“caged”) lipid derivatives led to several discoveries including the finding that sphingosine releases calcium from lysosomes. Since our move to OHSU, we increased our efforts for better understanding pancreatic islet biology and especially the extracellular factors that govern insulin and glucagon secretion. 

Our newest toolset comprises of multifunctional lipid derivatives that are photo-crosslinkable, can perform click chemistry for labeling, and feature a “caged” group to control probe metabolism inside cells. These tools became especially useful during the COVID pandemic when it became important to study the lipid interactomes in healthy and virus-infected cells. This topic is part of an extensive collaboration with the Pacific Northwest National Laboratory (PNNL) and Dr. Fikadu Tafesse, a virologist from the OHSU Department of Microbiology and Molecular Immunology.   In addition, using our lipid tools, we identified essential proteins that regulate lipid transport in cells. We are currently learning to perform cryo-electron microscopy for performing structural analysis of lipid binding proteins.