Mutations in epigenetic modifiers and their impact on tumorigenesis and drug response in SCLC (B03+)

在这个项目中，M。Schweiger将剖析SCLC发展和药物反应的表观遗传手段。主要重点将放在染色质修饰剂的频繁突变上，其中细胞系和小鼠模型将用于蛋白质组学分析，并剖析对翻译后组蛋白修饰的影响。基于先前的数据，热应激反应将被用作蛋白毒性应激的替代物和用于评价治疗效果的模型。B03将与B04密切合作，开发针对突变染色质修饰剂的化合物，并建立化学药物筛选以优化表观遗传药物。结果将被转移到人类组织样本和小鼠模型的SCLC将被用来评估产生的新的治疗方案。

In this project M. Schweiger will dissect epigenetic means of SCLC development and drug response. The main focus will be on frequent mutations in chromatin modifiers, where cell lines and mouse models will be used for proteomic analyses and to dissect the effect on post-translational histone modifications. Based on previous data, the heat stress response will be utilized as surrogate for proteotoxic stress and model for evaluation of the therapeutic effect. B03 will collaborate closely with B04 for chemical compounds targeting mutated chromatin modifiers and to set up a chemical drug screen to optimize epigenetic drugs. Results will be transferred to human tissue samples and mouse models of SCLC will be employed to evaluate resulting new treatment options.