Unravelling the biology of exosomes and their associates to combat disease

Cell communication involving exosomes and other extracellular vesicles is now recognized as a process of significant clinical relevance to a wide range of human disease, including cancer, diabetes, preeclampsia, endometriosis, cardiovascular and neurological disorders. Progress has, however, been hindered by our poor understanding of extracellular vesicle heterogeneity and the underlying biology, making it difficult to identify the specific content and functions of individual exosomes. A major stumbling block has been the lack of either genetic or pharmacological tools to block production of specific vesicle populations.
In my talk I will discuss our use of complementary fly and cancer cell line models to identify a new stress-induced exosome subtype, termed Rab11a-exosomes, which is formed and loaded via specific mechanisms that we can selectively inhibit. These vesicles carry key signalling cargos that can act at low concentrations to change target cell fate. Rab11a-exosomes are only a small fraction of secreted vesicles, but they are particularly potent, with critical molecular payloads and activities relevant to both physiological and pathological signalling, including therapy resistance. They also promote the formation of secreted protein aggregates, which are related to new disease-relevant extracellular signalling particles, called supermeres.
By characterising specific exosome subtypes and their links to extracellular protein aggregates, our findings offer new opportunities to identify combinations of disease biomarkers on individual extracellular signalling structures, particularly vesicles, thereby increasing the specificity of diagnostic tests for a wide range of human diseases. As our understanding of these fundamental mechanisms expands, new potential therapeutic pathways are emerging for the targeting of exosome-linked diseases, which warrant further investigation.

Dr Deborah Goberdhan is an Associate Professor of Cell Signalling linked to the Department of Physiology, Anatomy and Genetics at the University of Oxford. Deborah joined the department in 2001 and established an independent group in 2005. She led a CRUK Programme from 2015, which has uncovered a fundamental new mechanism by which exosomes are made and revealed new disease-relevant functions for these vesicles. Her work has a strong focus on taking findings from discovery science through to the clinic. Deborah has been a member of the Board of the International Society for Extracellular Vesicles since 2020 and is currently a co-ordinating author of MISEV2023, the third iteration of the extracellular vesicle field guidelines.