Multiscale functional mapping of cell identity decisions in PDAC initiation (P01)

点击翻译按钮获取中文摘要

Pancreatic cancer evolution is characterized by consecutive cellular fate changes through molecular reprogramming. Our understanding of these processes is, however, fragmented. Utilizing unique human cellular model systems and novel screening technologies in mice, this project will chart and functionalize KRAS induced transcriptional, epigenetic and topological changes to create global maps of molecular programs driving early oncogenic cell state transitions. Integrative analyses will focus on the discovery of core transcription factor networks, followed downstream mechanistic studies on critical players, such as Foxp1, a newly identified driver of acinar to ductal metaplasia. The project has potential implications for disease prevention and therapy.