Recent work from the lab and others indicates that FLASH-RT spares healthy tissue by preserving the stem/progenitor cells that allow a complete recovery after radiation injury. However, the molecular mechanisms underlying the FLASH sparing effect remains unknown. In this project, we propose, using cutting-edge technologies, to investigate the molecular and cellular consequences of FLASH compared to conventional (CONV) radiation therapy on healthy tissue.
This project will define the molecular and cellular characteristics that underlie the FLASH sparing effect using single cell RNA sequencing and spatial transcriptomic (sequential smFISH). The results will be validated in 3D cultures derived from patients and will shed some light on the inter-individual responses to FLASH radiation therapy across patients. This aspect will be of utmost importance for future FLASH clinical trials in order to recruit the patients that will benefit from FLASH radiation therapy.