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

PDAC 启动中细胞身份决策的多尺度功能图谱 (P01)

• 批准号: 403594753
• 金额: --
• 依托单位: Klinik und Poliklinik für Innere Medizin I: Kardiologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/403594753?language=en
• 关键词: Multiscale; functional; mapping; cell; identity

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.

胰腺癌的进化特征是通过分子重编程连续改变细胞命运。然而，我们对这些过程的理解是支离破碎的。利用独特的人类细胞模型系统和小鼠的新筛选技术，该项目将绘制KRAS诱导的转录、表观遗传和拓扑变化的图表并使其发挥功能，以创建驱动早期致癌细胞状态转变的分子程序的全球图谱。综合分析将集中于核心转录因子网络的发现，随后是对关键角色的下游机制研究，例如新发现的腺泡样化生的驱动因素Foxp1。该项目对疾病预防和治疗具有潜在的影响。