炎癌转化是肿瘤形成的重要机制，本研究聚焦胃炎转向胃癌的质变点，旨在实现早期胃癌的分子信息可视化。胃癌发生主要与幽门螺杆菌等介导的炎症反应诱发胃上皮细胞极性丧失及基因组不稳定等因素有关，但其分子调控机制及靶向干预策略仍不明确。我们发现，MST4-Ezrin-ACAP4（MEA）信号轴决定胃上皮细胞极性，并应答胃内环境刺激调控胃酸分泌，其异常活化与胃癌发生有关。故提出“慢性炎症诱发MEA信号轴异常调控，介导胃癌炎癌转化”的科学假说。为深入解析胃“炎癌转化”调控信号轴分子功能，拟建立整合临床来源胃类器官体系与高分辨层光共聚焦成像的集成式胃癌演进动态可视化平台，优化相分离激酶活性报告系统，以揭示炎症因子改变胃上皮细胞可塑性与命运抉择的动态特征、以及MEA信号轴调控胃癌发生的分子功能可视化，为胃癌预警与早期诊断提供新策略；同时筛选出MST4活性调控的小分子抑制剂，为胃癌预防与早期治疗提供潜在药物。

Inflammation-malignancy transition is the critical mechanism underlining tumor initiation. This study focuses on the key process of gastritis transition into gastric cancer, in order to visualize the molecular markers of early stage gastric cancer. The initiation of gastric cancer is related to the loss of polarity in gastric epithelial cell induced by H. pylori elicited inflammation and disturbance of genome stability, while the molecular regulation mechanism and target intervention strategy remain elusive. According to our previous studies, MST4-Ezrin-ACAP4 (MEA) pathway determines the polarity of gastric epithelial cells and acid secretion induced by gastric internal environment, while its abnormal activation is related to the initiation of gastric cancer. Therefore, we propose the hypothesis, “chronic inflammation induces the dysregulation of MEA signal pathway, which mediates the gastric inflammation malignancy transition”. To probe the molecular function of the regulating pathway, we will establish the integrated dynamic visualization platform of gastric cancer development, combining clinical gastric organoid models with high resolution light sheet confocal imaging system. We plan to optimize the optical kinase activity reporting system based on protein phase separation, to realize the dynamic characteristics visualization of gastric epithelium plasticity and destiny changes in response to inflammatory cytokines, and to realize the molecular function visualization of MEA signaling axis in mediating gastric cancer initiation, which will raise new strategy for gastric cancer prevention and early diagnosis. Meanwhile, we will elect small molecular that could inhibiting MST4 activity, in order to provide potential drugs for gastric cancer prevention and early treatment.