Immunological Basis for H. Pylori-Related Malignancies

描述（由申请人提供）：本奖项的总体目标是提供一个受指导的研究环境，使候选人能够发展成为幽门螺杆菌感染诱发胃癌领域的独立研究者。该候选人目前正在接受NIH对未被充分代表的少数民族研究补充的博士后培训支持，研究胃粘膜幽门螺杆菌感染的炎症反应。该奖项将允许候选人开展一个相关但独立的项目，研究幽门螺杆菌免疫反应在胃癌发展中的作用。该候选人在感染动物模型和炎症介质分子分析方面接受了广泛的培训。近期的职业目标是在之前的培训和专业知识的基础上开展拟议的工作，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，并获得一个教员级别的学术任命。这些目标将通过两位在研究培训和拟议研究领域具有丰富经验的高级研究员的指导来实现。与导师建立密切但逐渐独立的科学关系将促进职业发展。候选人将使用UCSD癌症中心的全部资源。在以后的几年里，将通过在科学会议上的演讲、批评性审查、发表工作成果和提交赠款来增加独立性。该研究项目的制定是为了建立一个独立的调查线，这是基于候选人以前和现在的工作。幽门螺旋杆菌感染胃粘膜，导致消化性溃疡和胃癌的高风险。该建议的中心假设是幽门螺旋杆菌诱导的免疫反应失调胃上皮细胞的转换，导致癌变。该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。在此奖励下，候选人将能够将这项工作发展成一个富有成效的项目，并将获得独立资助。

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.