PATHOGENESIS OF HELICOBACTER HEPATICUS

肝螺杆菌的发病机制

• 批准号: 6700873
• 负责人: CATHERINE S BECKWITH
• 金额: $ 12.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6700873
• 关键词: Helicobacter; bacteria infection mechanism; bacterial genetics; disease /disorder model; gene expression; gene targeting; genetically modified animals; hepatitis; inflammatory bowel diseases; laboratory mouse; liver neoplasms; microarray technology; molecular pathology; virulence

DESCRIPTION (Provided by applicant): Catherine Beckwith, D.V.M, Ph.D., Diplomate, American College of Laboratory Animal Medicine, received her doctoral training with Dr. Lela Riley at the University of Missouri where her research focused on development of diagnostic assays, identification of virulence factors, and characterization of the pathogenesis of rodent Helicobacter infections. With the SERCA, Dr. Beckwith will build upon her background in research and obtain additional training that will allow her to develop into an independently funded research investigator. Dr. Beckwith will train in the rich intellectual environment of SU where Dr. Stanley Falkow, an internationally renowned leader in bacterial pathogenesis research, will mentor her. Dr. Beckwith is co-sponsored by Linda Cork, D.V.M., Ph.D., a veterinary pathologist and the Department Chair of Comparative Medicine, who will ensure that she has the resources and time to carry out her research. Clinical and teaching responsibilities will be only as sufficient to maintain her clinical skills. Dr. Beckwith will conduct an in-depth research project, present her research at national scientific meetings, participate in laboratory meetings, attend specialized courses at Cold Spring Harbor Laboratory, and attend seminars and journal clubs related to bacterial pathogenesis. Dr. Beckwith's research will use a molecular and genetic approach to identify and characterize virulence factors in H. hepaticus, the cause of IBD, chronic active hepatitis, and hepatocellular tumors in mice. The H. hepaticus-infected mouse is an animal model of chronic bacterial infection, which closely mimics human hepatobiliary and inflammatory bowel diseases. Dr. Beckwith will create a transposon library in H. hepaticus and identify virulence factors through negative selection in mice. Novel virulence factors and the host response will be characterized using traditional and cutting edge techniques including global gene expression analysis with microarrays. Characterization of virulence factors is essential to understanding the pathogenesis of IBD and hepatitis caused byH. hepaticus. Recent evidence suggests a link between helicobacters and chronic hepatobiliary diseases in humans. The long-term goal of the proposal is to develop new strategies for prevention and treatment of chronic liver and intestinal disease in humans.

描述（由申请人提供）：Catherine Beckwith，D.V.M，Ph.D.，美国实验动物医学学院文凭，在密苏里大学跟随 Lela Riley 博士接受博士培训，她的研究重点是诊断分析的开发、毒力因子的鉴定以及啮齿动物螺杆菌感染发病机制的表征。 通过 SERCA，贝克威斯博士将利用她的研究背景并获得额外的培训，使她能够发展成为一名独立资助的研究调查员。 Beckwith博士将在SU丰富的智力环境中接受培训，国际知名的细菌发病机制研究领军人物Stanley Falkow博士将指导她。 Beckwith 博士由兽医病理学家兼比较医学系主任 Linda Cork（D.V.M.、Ph.D.）共同赞助，她将确保她有资源和时间来开展研究。 临床和教学职责仅足以维持她的临床技能。 Beckwith博士将开展深入的研究项目，在国家科学会议上展示她的研究成果，参加实验室会议，参加冷泉港实验室的专业课程，并参加与细菌发病机制相关的研讨会和期刊俱乐部。 Beckwith 博士的研究将使用分子和遗传学方法来识别和表征肝螺杆菌的毒力因子，肝螺杆菌是小鼠 IBD、慢性活动性肝炎和肝细胞肿瘤的病因。 肝螺杆菌感染的小鼠是一种慢性细菌感染的动物模型，与人类肝胆疾病和炎症性肠病非常相似。 Beckwith 博士将在肝螺杆菌中创建转座子文库，并通过小鼠负选择来鉴定毒力因子。 新的毒力因子和宿主反应将使用传统和尖端技术来表征，包括使用微阵列进行全局基因表达分析。 毒力因子的表征对于了解幽门螺杆菌引起的 IBD 和肝炎的发病机制至关重要。肝丝。 最近的证据表明螺杆菌与人类慢性肝胆疾病之间存在联系。 该提案的长期目标是制定预防和治疗人类慢性肝脏和肠道疾病的新策略。