Hippo通路是进化过程中一条非常保守的信号通路，其下游关键蛋白Yap1在细胞增殖、器官大小、干细胞自我更新、肿瘤发生及组织再生等过程中发挥重要调控作用。在前期研究中，我们发现在肺神经内分泌细胞（pulmonary neuroendocrine cells，PNECs）中特异型敲除Yap1导致PNECs发育异常，此外在PNECs中过表达激活型的Yap1蛋白，在肺损伤和小细胞肺癌发生时可分别促进PNECs和小细胞肺癌细胞转分化，调控肺损伤修复和小细胞肺癌的发生发展。但是，Yap1蛋白如何调控PNECs发育过程及其介导的肺损伤修复、小细胞肺癌的发生等调控作用的分子机理尚不明确。因此，为解决这些问题，我们将通过运用多种基因敲除及转基因小鼠模型、转录组测序、蛋白组学分析等实验技术系统研究并揭示Yap1在肺神经内分泌细胞中的功能及作用机制，并为小细胞肺癌等相关疾病的治疗研究提供理论基础和治疗策略。

Hippo pathway is a conserved signaling pathway, which plays multiple function in cell proliferation, organ size control, stemness maintenance, carcinogenesis and tissue regeneration. In previous study, we found that conditional knockout of Yap1 in pulmonary neuroendocrine cells (PNECs) leads to defects of formation of neuroepithelial body. Besides, activation of Yap1 expression in PNECs promotes transdifferentiation of PNESc and cancer cells during lung injury and small cell lung cancer pathogenesis respectively. However, the molecular mechanism of Yap1 in PNECs development and PNECs mediated lung injury repair and carcinogenesis remains to be elucidated. Thus，we plan to explore the role of Yap1 in PNECs using multiple genetic modified animal model, transcriptome sequencing and proteomics analysis. This work will help us to understand a more thorough molecular mechanism in the PNECs development and provides a potential therapeutic target for treatment of lung related disease.