ACTIVATION OF THE JAK-STAT PATHWAY BY OXIDATIVE STRESS

氧化应激激活 JAK-STAT 通路

• 批准号: 2750271
• 负责人: AMY Rebecca SIMON
• 金额: $ 8.08万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2750271
• 关键词: biological signal transduction; cytokine; free radical oxygen; gene induction /repression; genetic promoter element; growth factor; molecular pathology; oxidative stress; tissue /cell culture; transcription factor

DESCRIPTION (Adapted from the applicant's abstract) This is an application for a Mentored Clinical Scientist Development Award for Dr. Amy Simon to pursue research on the influence of reactive oxygen species (ROS) on the novel JAK/STAT transcription pathways of mammalian cells which are involved in cell signaling of most growth factors and cytokines. Her preliminary studies provide the first information that these pathways may also respond to oxidants and be involved in pulmonary injury such as that of respiratory distress syndrome or pulmonary fibrosis. Further exploration of these observations may provide new insights into understanding pathogenesis and therapy of these conditions. Dr. Simon will work in the laboratory of Dr. Brent Cochran (a recognized national leader in transcription factor regulation) at the Tufts University School of Medicine which is adjacent to the New England Medical Center and will have as a co-sponsor Dr. Barry Fanburg, who is an authority on oxidant injury to the lung. She will have available to her all facilities, courses and conferences of the Department of Cellular and Molecular Physiology as well as those which Dr. Fanburg organizes and will interact almost daily with Dr. Cochran and periodically with Dr. Fanburg and an Advisory Committee. Preliminary results from work already done by Dr. Simon show that oxidant stress activates the DNA-binding of transcription factors from the STAT family of proteins. Her continued research will focus on the following specific aims: 1) To define the different redox regulatory factors that mediate STAT activation, 2) To determine the mechanism of STAT activation by ROS, 3) To identify the elements in the c-fos promoter required for the response to ROS and 4) To identify other downstream target genes for this pathway. These studies should allow Dr. Simon to extend her research credentials and to be competitive for a future independent research award while she assumes a staff position at this institution.

描述 （改编自申请人的摘要）这是 艾米·西蒙（Amy Simon）博士的指导临床科学家发展奖 关于活性氧（ROS）对新颖的影响的研究 哺乳动物细胞的JAK/STAT转录途径参与 大多数生长因子和细胞因子的细胞信号传导。 她的初步 研究提供了这些途径也可能做出回应的第一个信息 氧化剂并参与肺部损伤，例如呼吸道损伤 遇险综合征或肺纤维化。 进一步探索这些 观察可能为理解发病机理和 这些疾病的治疗。 西蒙博士将在博士的实验室工作。 布伦特·科克伦（Brent Cochran）（公认的转录因子国家领导者 塔夫茨大学医学院的法规） 新英格兰医疗中心，将担任巴里博士的共同赞助者 范堡（Fanburg）是肺部氧化损伤的权威。 她会的 该部门的所有设施，课程和会议都可以 细胞和分子生理以及范堡博士 组织并几乎每天都会与Cochran博士进行互动，并定期 与范堡博士和咨询委员会。 工作的初步结果 西蒙博士已经完成了氧化剂应力激活DNA结合 来自蛋白质统计系列的转录因子。 她继续 研究将侧重于以下特定目的：1）定义 介导统计激活的不同氧化还原调节因素，2） 确定ROS统计激活的机理，3）确定 响应ROS所需的C-FOS启动子中的元素和4） 确定该途径的其他下游靶基因。 这些研究 应该允许西蒙博士扩展她的研究证书并成为 竞争未来独立研究奖的竞争 该机构的员工职位。