At EV-iTEC, we study extracellular vesicles as biological systems rather than solely as analytical readouts. Our research investigates the mechanisms underlying vesicle release, cargo composition, and functional activity, utilizing quantitative measurements, rigorous quality control, and methodologically informed experimental design. The following projects demonstrate the application of these principles to address fundamental questions in extracellular vesicle biology.
PhD projects are partly funded by the Deutsche Forschungsgemeinschaft (DFG) through the Research Training Group GRK25 „The Inflammatory Tumor Secretome – From Understanding to Novel Therapies“.
Quantitative Characterization of the Core Extracellular Vesicle Proteome
Transitioning from qualitative marker lists to quantitative and comparable extracellular vesicle core proteomes.
Traditionally, the protein content of extracellular vesicles is reported as a list of markers indicating presence or absence. In contrast, this project adopts a quantitative approach to protein content, enabling objective comparisons across different isolation methods, sample types, and experimental conditions. Given that the isolation technique substantially affects the proteins recovered, this research advances extracellular vesicle proteomics as a method-aware analytical framework. This approach enables the differentiation of true biological variation from artifacts introduced during sample preparation and thereby allows for sophisticated analysis of EV biogenesis pathways and sorting mechanisms. The project is conducted in collaboration with the Institute of Translational Proteomics and the associated Core Facility.
Regulated EV Release Under Stress Conditions
How does a stress alarmin find its way onto extracellular vesicles, and is the cell purposefully directing it there?
IL-33 functions as an alarm signal that may be retained in the nucleus, degraded, or released extracellularly via association with vesicles. Previous studies have demonstrated that vesicle-bound IL-33 is biologically active and can influence the microenvironment of pancreatic tumors. However, the mechanisms determining the cellular routing of IL-33, and whether its incorporation into vesicles is a regulated sorting event or a consequence of cytoplasmic abundance, remain unclear.
This project aims to elucidate the regulatory mechanisms governing the packaging of IL-33 onto vesicles and to determine whether vesicle-bound IL-33 exhibits distinct functional properties compared to its soluble counterpart.
BAG6-Dependent EV Biogenesis and Membrane Organization
How does BAG6 regulate EV biogenesis under physiological and stress conditions?
The chaperone BAG6 contributes to protein homeostasis, autophagy, membrane integrity, and protein trafficking within cells. BAG6-deficient cells release extracellular vesicles (EVs) with altered molecular and functional characteristics, suggesting that BAG6 may influence EV biogenesis.
This project aims to define the role of BAG6 in EV biogenesis under physiological and stress conditions. By comparing BAG6-deficient cells with matched stress models and rescue experiments, the project will determine whether BAG6 directly contributes to EV formation, cargo loading and release, or whether altered EV profiles arise indirectly from BAG6-dependent cellular stress responses.