Revealing Endothelial Extracellular Vesicle Biology Using CRISPR-Engineered Human Systems

Understanding how endothelial cells communicate is key to unravelling mechanisms underlying cardiometabolic disease. This project will generate CRISPR/Cas9-edited human induced pluripotent stem cell (iPSC)-derived endothelial cells to fluorescently tag key extracellular vesicle (EV) markers, enabling for the first time live-cell imaging of EV biogenesis and release at physiological expression levels in response to cardiovascular stimuli.These tools will drive focused, high-impact studies on EV function in vascular health through new international collaborations in RNA profiling, proteomics, EV bioengineering, and fundamental EV biology, areas not covered by my current British Heart Foundation Intermediate Fellowship. The project will apply these technologies to define how EV production and cargo are modulated under defined vascular stress conditions, ultimately linking mechanistic insights with translational relevance.This award will support the retention of a skilled postdoctoral researcher, ensuring continuity and accelerating delivery of key publications and preliminary data needed to underpin future funding. It will also provide protected time and tailored leadership training, positioning me strongly to apply for a Wellcome Career Development Award.By combining genome editing, live imaging, and systems biology, this work will comprehensively map EV pathways and identify future targets for therapeutic intervention and bioengineering strategies to modulate cellular responses.