Extracellular vesicles of the kidney cortex – Mediators of pathologic signalling and untapped diagnostic resource

• Applicant: Dr. Fabian Braun
• Subject Area: Nephrology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 528262584

Extracellular vesicles (EVs) have been identified to be critical contributors to cancer cell biology, immune mediation and metabolic signaling. EVs are small membrane bound packages that contain specific proteins, nucleic acids and lipid cargo, facilitating intercellular signaling across great distances. Because of this, the use of EVs as a source for biomarkers has drawn significant attention. Yet, in nephrology, we currently lack 1) a concise understanding of cellspecific vesicle release and content, 2) how renal cells communicate through vesicles and 3) what effect different diseases exert on these parameters. This proposal aims to characterize the release and cargo of small and medium-sized extracellular vesicles of podocytes and proximal tubular cells to identify alterations upon cellular damage in glomerulosclerosis and acute kidney injury. Using dual reporter mice, we will separate and purify podocyte or proximal tubular cell-specific vesicles for single vesicle analysis and ultrasensitive proteomic profiling in health and disease. The proteome signatures will be used to identify putative markers in podocyte-specific vesicles and translate these to urine samples of patients. In parallel, we will characterize the cellular response to cell-specific vesicles upon podocyte / proximal tubular damage by deep multi-omic investigation of vesicle-treated podocytes and proximal tubular cells and analysis of patient biopsies. The proposed project has the potential to delineate the importance of intercellular signaling through extracellular vesicles in the kidney, uncover novel disease pathways and could guide the field of nephrology towards non-invasive diagnostic strategies that can serve as the foundation for redefining patient stratification and personalized therapies.

• DFG Programme: Research Grants