Exosome Biogenesis & Function
Exosomes are small secreted vesicles that have the same topology as the cell, are ~30-150 nm in diameter, and are enriched in exosome cargo proteins. Exosomes are made by all cells, are abundant in all biofluids, and transmit signals, proteins, and RNAs to other cells. Using cell and animal models, our laboratory investigates the molecular mechanisms of exosome biogenesis in vitro and in vivo.
Cell and Exosome Engineering
Our laboratory invents new cell and exosome engineering technologies and applies them to the design, production, and testing of exosome-based vaccines and therapeutics. These projects include the invention of high-efficiency tools and methods for rapidly creating high-expressing transgenic cell lines, generating new ‘exosome producer’ cell lines with increased exosome yield and reduced sheddase activity, and the combination of these and other advances for producing exosomes of defined content and function.
Cell Biology of SARS-CoV-2 Spike
Our team discovered that SARS-CoV-2 Spike is a lysosomal protein, that Spike reprograms host lysosomes to serve as virus storage and egress compartments, and that the Spike D614G mutation that triggered the first wave of the pandemic does so by restoring Spike structure and trafficking to lysosomes. Our current Spike studies are to identify its lysosome sorting receptor and to discover how Spike induces lysosome clustering and blocks lysosome fusion with endosomes.
Synthetic Control of Cell Signaling
Together with the lab of Dr. Mike Caterina, we have invented synthetic negative feedback systems that couple hyperactive cell signaling pathways to their own downregulation. Current efforts are aimed at developing these systems into clinical therapeutics for treating chronic pain and other signaling diseases, while also applying them as tools for cell signaling research.