The role of type 2 inflammation in the initiation and progression of metaplastic differentiation and neoplastic transformation of gastric epithelia

此应用程序请求NCI多样性研究补充资金以激活NCI拨款作为回应 到PA-21-071，以支持研究生的研究培训和职业发展 贫困的种族/民族和社会/经济背景。在这项多样性补充建议中，一个 博士后研究生将领导一个直接相关并具有重要互补性的具体项目。 与母公司的NCI补助金有着明显的区别。多样性补充方案是为毕业生量身定做的 学生对基因诱发的胃肿瘤发生中宿主-病原体相互作用的兴趣 自身免疫性易感性。有证据表明，以2型炎症为特征的途径 由2型细胞因子IL4和IL13启动，在由任一种细胞因子启动的胃肿瘤发生中起关键作用 自身免疫性或幽门螺杆菌感染。这项多样性补充建议的目的是调查潜在的协同效应。 幽门螺杆菌和自身免疫2型炎症在胃肿瘤发生发展中的作用在 CTLA4KD模型中，肿瘤的发生是由CTLA4缺乏引起的自身免疫启动的，这模仿了 CTLA4基因多态或杂合突变对人类的影响。它是由宿主内在因素驱动的，如 无菌条件不影响自身免疫的发展和肿瘤的发生。因此， CTLA4模型为研究幽门螺杆菌与宿主内源性免疫的潜在协同作用提供了独特的工具 自身免疫性胃炎及其向癌前病变的进展中的调节失调。具体地说， 研究生在接受研究培训和职业发展指导的同时，将学习使用 严谨的科学推理和尖端技术解决了以下两个问题：1)H。 幽门螺杆菌感染影响胃自身免疫和宿主内源性调节失调所致的癌前病变 由于CTLA4不足？2)幽门螺杆菌如何与癌前细胞相互作用并影响其谱系 进展？学生将参加为博士培训而设计的精心设计的课程，并参与 精心策划的职业技能活动。学生将与导师团队合作，发展个人职业生涯 发展计划(IDP)和个性化指导计划(IMP)，指导学员完成培训 成为独立和富有创造力的学者的过程，擅长于在 微生物学、免疫学和癌症生物学。通过研究和职业培训，期望学生 不仅要做好充分的准备，推进自己的科学事业，而且要做好面对新兴市场的准备 以富有创意的解决方案应对世界挑战，以全面的科学专业精神服务社会。

This application requests the NCI diversity research supplement funding to active an NCI grant in response to PA-21-071, to support the research training and career development of a graduate student from an underprivileged racial/ethnic and social/economic background. In this diversity supplement proposal, a predoctoral graduate student will lead a specific project that is immediately relevant and critically complementary to and yet clearly distinct from the parent NCI grant. The diversity supplement proposal is tailored for the graduate student’s interest to understand host-pathogen interaction in gastric tumorigenesis prompted by genetic predisposition of autoimmunity. There is evidence that type 2 inflammation, characterized by the pathway initiated by type 2 cytokine IL4 and IL13, plays a critical role in gastric tumorigenesis initiated by either autoimmunity or H. pylori. The objective in this diversity supplement proposal is to investigate potential synergy of H pylori and autoimmune type 2 inflammation in the initiation and progression of gastric tumorigenesis. In the CTLA4KD model, tumorigenesis is initiated by autoimmunity caused by CTLA4 insufficiency, which mimics the effect of CTLA4 polymorphisms or heterozygous mutations in humans. It is driven by host-intrinsic factor as germ-free conditions did not affect the autoimmunity development and initiation of tumorigenesis. Therefore, the CTLA4 model presents a unique tool to study potential synergy of H pylori and host-intrinsic immune dysregulation, in autoimmune gastritis and its progression to pre-malignancy and cancer. Specifically, the graduate student, while undergoes research training and career development mentoring, will learn to use rigorous scientific reasoning and cutting-edge technology to address the follow two questions: 1) How does H. pylori infection affect gastric autoimmunity and onset of pre-malignancy caused by host-intrinsic dysregulation due to CTLA4 insufficiency? 2) How does H. pylori interact with pre-malignant cells and affect their lineage progression? The student will take a well-crafted curriculum designed for PhD training as well as participate in well-orchestrated career skill activities. The student will work with a mentor team to develop an individual career development plan (IDP) and individualized mentoring plan (IMP), to guide the student through the training process to become independent and creative scholar excelling in conducting interdisciplinary research in microbiology, immunology and cancer biology. Through the research and career training, the student is expected to be not only well-equipped to advance their own scientific careers but also well-prepared to face emerging challenges in the world with creative solutions, with well-rounded scientific professionalism to serve the society.