申请人聚焦于内分泌肿瘤的临床和基础研究，带领团队建立了肿瘤样本和数据库、模式动物和转化研究平台，重点开展胰腺、肾上腺等神经内分泌肿瘤(NET)的遗传、分子机制和干预研究。发现了肾上腺库欣综合征关键基因PRKACA及精确致病机制；系统研究了NET重要基因MEN1 的功能、机制和靶向治疗方法；首次报道了胰腺神经内分泌肿瘤高频突变基因YY1。成果以第一或通讯作者发表Science, Nat Commun (X2), J Hepatol, Mol Cell Biol等论文 9 篇，申请专利6项，获授权1项。基于临床样本库、研究队列、已构建的转基因和基因敲除小鼠模型和成熟技术平台，申请人将深入开展转录因子YY1的功能、分子机制和YY1突变NET的靶向治疗研究，并将完善NET样本和基因组数据库，运用Pan-cancer 等方法对NET进行系统分析和分子分型，探索内分泌肿瘤新的诊治方法。

The applicant focuses on clinical and basic research of endocrine tumors. The applicant led the research team to establish endocrine tumor bank, mouse models and systematic translational research. The main studies include genetics, molecular mechanisms and therapeutic intervention of pancreatic and adrenal neuroendocrine tumors (NET). We identified the activating hotspot PRKACA mutations and elucidated the precise molecular mechanisms in adrenal Cushing's syndrome. Our systematic investigations of MEN1 functions revealed the key signaling pathway and effective targeted therapy for MEN1-mutated NETs. We identified the activating hotspot YY1 mutations in pancreatic neuroendocrine tumors. The applicant published 9 papers as the first author or corresponding author on high impact journals, including Science, Nat Commun (X 2), J Hepatol and Mol Cell Biol. The applicant applied for 6 patents and one has been authorized. Based on clinical cohorts, tumor bank and transgenic mouse models, the applicant will investigate the precise molecular mechanisms and targeted therapy for YY1 mutated NET. Moreover, The applicant will strengthen the endocrine tumor bank and genomic database and perform Pan-cancer analysis and clinical analysis for molecular classification and regroup of NET. Our work will contribute to novel clinical diagnostic markers and therapeutic targets.