Spatial phosphoproteomics and circulating EVs of pancreatic cancer tumours to study intercellular crosstalk in the tumour and the tumour cell environment

• Applicant: Luisa Schmidt
• Subject Area: Cell Biology ; Biochemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 575984138

Pancreatic ductal adenocarcinoma (PDAC) is a prevalent and aggressive cancer driven by mutations in oncogenes such as KRAS and EGFR, and tumour suppressors like TP53 and SMAD4, which regulate cell growth, survival, and metastasis. Often diagnosed at late stages, PDAC’s immune evasion mechanisms underscore the need for early detection biomarkers. Despite research, the complex interactions between tumour cells and the tumour microenvironment (TME) are not fully understood. The TME plays a critical role in immune escape, metastasis, and therapy resistance. Extracellular vesicles (EVs), small membrane-bound particles released by cells, facilitate inter-cellular communication and may serve as biomarkers for non-invasive liquid biopsies, carrying proteins, nucleic acids, lipids, and metabolites that reflect cancer characteristics. This project aims to leverage the spatial phosphoproteome of PDAC tumours to better understand cellular mechanisms and inter-cellular communication within the TME, as well as to investigate the functional dynamics of EVs in plasma from PDAC patients. The research will combine laser capture-microdissection (LCM)-assisted spatial isolation, proteome sample preparation, and sequential enrichment of phosphorylated peptides. Additionally, non-invasive patient liquid biopsies will be used for EV enrichment. Integrating these techniques with cell culture experiments and immuno histochemistry verification experiments will enhance understanding of immune escape mechanisms and help identify early biomarkers. By uncovering novel therapeutic targets and biomarkers, this research has the potential to advance precision medicine, leading to more effective, personalized treatments. It will also provide deeper insights into tumour biology, particularly the complex communication within the TME, paving the way for better therapeutic approaches in PDAC.

• DFG Programme: WBP Fellowship
• International Connection: Denmark
• Host: Professor Dr. Jesper Velgaard Olsen