Simpson - Cancer secretome, extracellular communication, exosome and extracellular vesicle biology
Professor Richard Simpson
Professor, College of Science, Health and Engineering
Cell-cell communication is a fundamental physiological process that relies on the sending and receiving of signals. This process may involve direct contact between adjoining cells, or the release of secreted molecules. Recently, extracellular vesicles (EVs) emanating from cells have been recognized to play a key role in cell-cell communication at both paracrine and systemic levels. EVs comprise shed microvesicles (sMVs), apoptotic bodies and exosomes which differ based on their mechanism of biogenesis and size; of these, exosomes have been most widely studied. Exosomes are ~40–100 nm EVs released from a multitude of cell types that perform pleiotropic extracellular functions within the extracellular microenvironment. These functions include intrinsic and extrinsic signaling, immunological modulation, and horizontal transfer of proteins, lipids and genetic material (miRNA/mRNA/DNA) to recipient cells. The focus of our research is to utilize an integrated proteomic/genomic strategy directed towards understanding the role of the extracellular environment (specifically, EVs) in cancer progression. We utilize various in vitro and in vivo cancer/EMT models, and techniques including lipophilic-cell/EV-labelling, cell sorting, state-of-the-art fluorescence microscopy, western immunoblotting, mass spectrometry-based protein profiling for discovery and targeted strategies, and miR/mRNA/lncRNA profiling and qRT-PCR validation. We are a well-established group comprising several PhD and post-doctoral fellows.
Research projects include understanding exosome biogenesis (sorting, trafficking); understanding distinct populations of extracellular vesicles (exosome, shed microvesicles) (cancer cells, biofluids); identifying mechanisms of recipient cell update/internalization; investigating functional contribution of extracellular vesicles in EMT and cancer progression (in vitro and in vivo); characterise secretome (soluble-secreted proteins) from metastatic human cancers to establish and identify molecular differences that contribute to cancer progression; identify molecular differences in cell surface proteins (including protein complexes) between extracellular vesicle subtypes; isolate, biochemically characterize, and functionally investigate EV protein complexes.