幽门螺杆菌（Hp）感染易引起慢性胃炎，导致胃溃疡和胃癌。广泛使用抗生素令Hp耐药成为普遍现象，深入阐释Hp感染致病机制对寻找新型抗菌药物至关重要。我们前期研究显示：Hp感染激活PIN1：PIN1一方面结合CagA，促进CagA和SHP2的相互作用；另一方面PIN1结合BRD4，增强肿瘤干细胞标记物CD44的转录水平；阻断PIN1和BRD4相互作用的BRD4多肽下调CD44的表达。敲低BRD4抑制Hp诱导的胃癌肿瘤干细胞成球率。这些结果提示：CagA/PIN1/BRD4轴可能参与调控Hp感染致癌。我们从Hp激活PIN1的分子机制入手，在细胞水平及小鼠体内阐释CagA/PIN1/BRD4轴对Hp感染致病的调控作用，并初步探讨BRD4多肽干预Hp感染的效果。本研究不仅揭示Hp感染致病的新机制，也为将PIN1和BRD4结合位点作为治疗Hp感染的潜在药物靶点提供理论依据。

Helicobacter pylori infection causes chronic gastritis and eventually leads to gastric ulcers and cancer. The prevalence of Hp resistance to multiple antibiotics has increased significantly due to the widespread use of antibiotics. It is crucial to understand pathogenic mechanisms of Hp infection for developing new antibacterial drugs. We found that Hp infection enhances PIN1 activity. On one hand, PIN1 binds to CagA to promote its interaction with SHP2, on the other hand, PIN1 interacts with BRD4, which increases the transcription of cancer stem cell marker CD44. An inhibitory peptide which dissociates Brd4 from Pin1 suppresses the transcription of CD44. Furthermore, we found that BRD4 knockdown impairs tumorsphere formation of gastric cancer stem cells induced by Hp. Together, these data suggest that CagA/PIN1/BRD4 axis might affect Hp infection-induced gastric cancer. In this proposal, we will elucidate the molecular mechanism of increased PIN1 activity caused by Hp infection. We will also determine the pathogenic mechanism of CagA/PIN1/BRD4 axis on Hp infection from the cellular level and in vivo. Finally, we will investigate the effect of the inhibitory peptide on Hp infection. This study will unveil the pivotal roles of CagA/PIN1/BRD4 axis during Hp infection and shed lights on the pathogenic mechanism of Hp infection-induced gastric ulcers and cancer. This study will also provide new therapeutic approaches for the treatment of Hp-mediated gastric diseases by targeting the binding site between BRD4 and PIN1.