Targeting oncogene-induced DNA repair pathway switches (A09)

靶向癌基因诱导的 DNA 修复途径开关 (A09)

• 批准号: 460672213
• 金额: --
• 依托单位: Klinik für Hämatologie und Stammzelltransplantation
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/460672213?language=en
• 关键词: Targeting; oncogene; induced; DNA; repair

Reinhardt has identified a cell state transition in KRAS-driven non-small cell lung cancer cells that features a critical change in DNA damage repair competence accompanied with increased mutational burden and altered cancer drug sensitivities. He will unravel the molecular role of proteins of the ubiquilin family that mediate this transition, identify the gene regulatory elements that trigger ubiquilin overexpression and dissect the mechanism and additional targets of the ubiquilins using proteomics. In addition to these mechanistic studies, he will determine thera-peutic vulnerabilities in vitro and in mouse models.

Reinhardt已经确定了kras驱动的非小细胞肺癌细胞的细胞状态转变，其特征是DNA损伤修复能力的关键变化，伴随着突变负担的增加和癌症药物敏感性的改变。他将揭示介导这种转变的泛素家族蛋白质的分子作用，确定触发泛素过表达的基因调控元件，并利用蛋白质组学分析泛素的机制和其他靶点。除了这些机制研究外，他还将在体外和小鼠模型中确定治疗脆弱性。