Microvesicles, Intercellular Communication, and Disease
Microvesicles, satellites of information transfer within the cell, are shed by numerous cell types and have been linked to biological activities that span the evolutionary spectrum, from bacteria to viral infectivity to a diversity of physiological processes in higher organisms. These processes include the immune response and neuronal function, as well as diseases such as cancer and neurodegenerative disorders. Very little is known about the signaling cues that drive microvesicles’ genesis in different cellular contexts—how they are loaded with specific protein and RNA cargo and how their parent cells shed them to mediate a variety of physiological functions.
Richard A. Cerione, Molecular Medicine/Chemistry and Chemical Biology, is using biochemical, cell biological, and structural approaches as well as mouse models to uncover the mechanisms that trigger the making, loading, and releasing of microvesicles. Building on past discoveries, Cerione’s team is asking several questions: What are the signaling cues that dictate the specific loading of microvesicles with protein and RNA cargo? Are these signals distinct from those used by exosomes, the other major class of extracellular vesicles? How does the biogenesis of microvesicles differ depending on the source—for example whether cancer cell or embryonic stem cell?
In addition, Cerione’s group is looking at the signals that trigger the shedding of microvesicles from their parental (donor) cells and the mechanisms that enable microvesicles to transfer protein and RNA cargo to their target cells. The research will yield new insights into fundamentally important biological processes of intercellular communication, as well as the molecular basis of various diseases and pathological disorders. NIH Award Number: 1R35GM122575-01