Proteomics subtyping and circadian dynamics of PDACs to develop novel therapeutic strategies (P11)

我们将全面研究基因定义的PDAC亚型随时间的蛋白质组和磷酸化蛋白质组，以实现对生物钟和不同致癌突变（如KrasG 12 D，KrasG 12 D/Trp 53 R172 H，BrafV 637 E和Pik 3caH 1047 R）驱动的细胞代谢和信号通路网络的机制性见解。从我们的蛋白质组学/磷酸蛋白质组学和昼夜节律研究中获得的PDAC亚型特异性候选靶点的功能表征将使我们能够确定癌症标志物和新型药物靶点，目的是为这种毁灭性疾病开发亚型特异性的慢性疾病治疗策略。

We will comprehensively study the proteome and phosphoproteome of genetically defined PDAC subtypes over time to achieve mechanistic insights into the cellular metabolism and signaling pathway networks driven by the circadian clock and different oncogenic mutations such as KrasG12D, KrasG12D/Trp53R172H, BrafV637E and Pik3caH1047R. The functional characterization of PDAC subtype specific candidate targets obtained from our proteomics/phosphoproteomics and circadian studies will allow us to pinpoint cancer markers and novel drug targets with the goal to develop subtype-specific chronotherapeutic treatment strategies for this devastating disease.