Immunological Basis for H. Pylori-Related Malignancies

描述(由申请者提供)：该奖项的总体目标是提供一个有指导的研究环境，使候选人能够发展成为幽门螺杆菌感染引起的胃癌领域的独立研究员。候选人目前正在接受NIH针对少数族裔的研究补充资料下的博士后培训支持，致力于胃粘膜对幽门螺杆菌感染的炎症反应。这一奖项将允许候选人开发一个相关但独立的项目，研究幽门螺杆菌的免疫反应在胃癌发生中的作用。候选人在感染动物模型和炎症介质的分子分析方面接受了广泛的培训。目前的职业目标是启动拟议的工作，该工作建立在之前的培训和专业知识的基础上，但朝着与胃癌相关的新方向发展。长期的职业目标是为这个项目获得独立的资金，并确保获得教职员工级别的学术任命。这些目标将通过两名在研究、培训和拟议研究领域具有丰富经验的高级调查人员的指导来实现。通过与导师建立密切但逐渐独立的科学关系，职业发展将得到加强。加州大学圣迭戈分校癌症中心的全部资源将由候选人使用。提高独立性将通过在科学会议上发表报告、批判性审查、出版作品和在以后几年提交拨款来实现。制定该研究项目是为了在候选人以前和现在的工作基础上发展一条独立的调查路线。幽门螺杆菌感染胃粘膜，导致消化性溃疡和胃癌的高风险。这一建议的中心假设是，幽门螺杆菌诱导的免疫反应失调了胃上皮细胞的周转，导致癌症的发生。这位候选人已经建立了幽门螺杆菌感染的小鼠和细胞培养模型，并将利用这些模型来确定炎症介质在胃上皮细胞凋亡和细胞增殖调节中的作用。根据这一奖项，候选人将能够将这项工作发展为一个富有成效的项目，将获得独立的资金。

DESCRIPTION (provided by applicant): The overall goal of this award is to provide a mentored research environment so that the candidate can develop into an independent investigator in the field of gastric cancer induced by Helicobacter pylori infection. The candidate is currently receiving postdoctoral training support under an NIH Research Supplement for Underrepresented Minorities, working on the inflammatory response to H. pylori infection of the gastric mucosa. This award will allow the candidate to develop a related but independent project on the role of the immune response to H. pylori in the development of gastric cancer. The candidate has received extensive training in animal models of infection and the molecular analysis of inflammatory mediators. The immediate career goal is to initiate the proposed work that builds on previous training and expertise but that moves in a new direction relevant to gastric cancer. The long-term career goal is to obtain independent funding for this project and to secure a faculty-level academic appointment. These goals will be achieved by mentoring from two senior investigators with extensive experience in research training and in the proposed area of study. Career development will be enhanced by a close but progressively independent scientific relationship with the mentors. The full resources of the UCSD Cancer Center will be used by the candidate. Increasing independence will be achieved by presentations at scientific meetings, critical reviews, publication of work, and grant submissions in later years. The research project is formulated to develop an independent line of investigation that is based on the previous and current work of the candidate. H. pylori infects the gastric mucosa, leading to peptic ulcers and a high risk of gastric cancer. The central hypothesis of this proposal is that H. pylori-induced immune response dysregulates gastric epithelial cell turnover, resulting in carcinogenesis. The candidate has developed mouse and cell culture models of H. pylori infection and will use these to determine the roles of inflammatory mediators in gastric epithelial cell apoptosis and in the regulation of cell proliferation. Under this award, the candidate will be able to develop this work into a productive project that will gain independent funding.