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

2型炎症在胃上皮化生分化和肿瘤转化的起始和进展中的作用

• 批准号: 10598700
• 负责人: Zhibin Chen
• 金额: $ 6.4万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10598700
• 关键词: Address; Affect; Autoimmune; Autoimmunity; CTLA4 gene; Cancer Biology; Development; Development Plans; Doctor of Philosophy; Economics; Educational Curriculum; Epithelial; Face; Funding; Genetic Polymorphism; Genetic Predisposition to Disease; Grant; Helicobacter Infections; Helicobacter pylori; Human; IL4 gene; Immune; Immunology; Individual; Infection; Inflammation; Interdisciplinary Study; Interleukin-13; Intrinsic factor; Knowledge; Lead; Learning; Malignant Neoplasms; Mentors; Metaplasia; Microbiology; Modeling; Mutation; Neoplastic Cell Transformation; Parents; Pathway interactions; Play; Premalignant Cell; Process; Professional Competence; Request for Applications; Research; Research Project Grants; Research Support; Research Training; Role; Scientist; Societies; Stomach; Students; Technology; Training; Work; autoimmune gastritis; cancer prevention; cancer therapy; career; career development; cytokine; design; gastric tumorigenesis; germ free condition; graduate student; interest; novel strategies; pathogen; pre-doctoral; racial and ethnic; response; social; synergism; tool; tumorigenesis; underrepresented minority student

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.

该应用程序要求NCI多样性研究补充资金以主动NCI赠款以回应 到PA-21-071，以支持研究生的研究培训和职业发展 贫困种族/种族和社会/经济背景。在这种多样性补充建议中， 专业研究生将领导一个特定的项目，该项目立即相关且至关重要 到却显然与父母NCI赠款不同。多样性补充提案是为研究生量身定制的 学生了解遗传造成胃肿瘤中宿主 - 病原体相互作用的兴趣 自身免疫的易感性。有证据表明2型炎症，其特征是该途径 由2型细胞因子IL4和IL13发起的 自身免疫性或幽门螺杆菌。这种多样性补充建议的目的是调查潜在的协同作用 幽门螺杆菌和2型自身免疫性注射术和胃肿瘤发生的进展。在 CTLA4KD模型，肿瘤发生是由CTLA4不足引起的自身免疫开始的，这模仿了 人类中CTLA4多态性或杂合突变的影响。它是由宿主内在因素驱动的 无菌条件不影响肿瘤发生的自身免疫发展和主动性。因此， CTLA4模型提出了一种独特的工具，可以研究H幽门螺和宿主内在免疫的潜在协同作用 失调，自身免疫性胃炎及其发展为恶性和癌症。具体来说， 研究生接受研究培训和职业发展指导，将学会使用 严格的科学推理和尖端技术，以解决以下两个问题：1）H。 幽门螺杆菌感染会影响胃自身免疫性和宿主 - 内部失调引起的恶性肿瘤的发作 由于CTLA4不足？ 2）幽门螺杆菌如何与预抗性细胞相互作用并影响其谱系 进展？该学生将参加精心设计的课程，专为博士培训而设计，并参加 经过精心策划的职业技能活动。学生将与心理团队合作发展个人职业 发展计划（IDP）和个性化的心理计划（IMP），指导学生进行培训 在进行跨学科研究方面成为独立和创造性科学的过程 微生物学，免疫学和癌症生物学。通过研究和职业培训，可以预期学生 不仅能够良好地促进自己的科学职业，而且还准备好面对新兴的职业 通过创造性的解决方案，世界上具有全面的科学专业精神来为社会服务的挑战。