Genetic evolution of pre-germinal center B cell lymphomas in transgenic mice with the focus on Mantle Cell Lymphoma (A13)

我们将分析MCL进化背后的细胞内在和外在过程。通过染色质和转录谱分析以及全基因组功能筛选，我们将在小鼠模型中确定驱动特定阶段淋巴瘤进化的细胞内在信号传导和调控网络。同时，我们将表征和功能化淋巴瘤生态位的细胞/细胞相互作用，以评估微环境对淋巴瘤发生的贡献。通过这些研究获得的对MCL生物学的见解，以及我们在人类MCL中的高通量组合CRISPR辍学筛选，将发现治疗靶向的脆弱性。

We will analyse cell intrinsic and extrinsic processes underlying MCL evolution. By chromatin- and transcriptional profiling as well as genome-wide functional screening we will identify cell-intrinsic signalling and regulatory networks driving stage-specific lymphoma evolution in mouse models. In parallel, we will characterize and functionalize cell/cell interactions of the lymphoma niche to evaluate the contribution of the microenvironment to lymphomagenesis. The insights gained into MCL biology through these studies will - together with our high-throughput combinatorial CRISPR dropout screens in human MCL - discover vulnerabilities for therapeutic targeting.