Hypoxia inducible transcription in antitumor strategies

描述（由申请人提供）：候选人：我的职业目标是成为 一个独立的物理学家，科学家，主要专注于研究，旨在 了解肿瘤发生的机制基础和 这些知识对癌症合理疗法的发展有重要意义。 的 希望这样的研究不仅能增进对人类的理解， 治疗小儿恶性肿瘤，我已经完成了我的 临床奖学金，而且在一般肿瘤学中也有用。 为 不久的将来，霍华德·特明奖将大大有助于我过渡到 作为一名分子癌症科学家， 在大卫博士的指导下继续研究1-2年 利文斯顿。 在这一点上，我将计划进行全面过渡， 独立的立场。 工作环境： 丹娜-法伯癌症研究所和哈佛医学院 提供良好的协作环境， 本建议中概述的研究和培训目标， 指导和不指导阶段的赠款。 有现成的进入国家的途径- DFCI和HMS的最先进的设备、设施和核心服务。 利文斯顿博士被广泛认为是一位优秀的科学导师， 实验室提供了一个完全支持和刺激的知识和 科学环境。 研究：本建议的具体目标是：1。确定机制 由此缺氧诱导型转录的破坏导致抗肿瘤 效果 2. 寻找专门干扰缺氧的小分子- 响应式转录 3. 尝试创建基于机制的映像 研究缺氧反应抑制剂在动物中的作用的方法 肿瘤的

DESCRIPTION (provided by applicant): Candidate: My career goal is to become an independent physician-scientist with a primary focus on research aimed at understanding the mechanistic bases for tumorigenesis and the application of such knowledge to the development of rational therapeutics for cancer. The hope would be that such research would not only advance the understanding and treatment of pediatric malignancies, where I have already completed my clinical fellowship, but also be of utility in oncology in general. For the immediate future, the Howard Temin Award would greatly assist my transition to full independence as a molecular cancer scientist by providing support for the next 1-2 years of continued research under the mentorship of Dr. David Livingston. At that point, I would plan to undertake a transition to a fully independent position. Environment: The Dana-Farber Cancer Institute and Harvard Medical School provide excellent collaborative environments for the completion of the research and training goals outlined in this proposal, both during the mentored and unmentored phases of the grant. There is ready access to state- of-the-art equipment, facilities, and core services both at the DFCI and HMS. Dr. Livingston is widely regarded as an excellent scientific mentor, and his laboratory provides a wholly supportive and stimulating intellectual and scientific environment. Research: The specific aims of this proposal are: 1. Determine the mechanism whereby disruption of hypoxia-inducible transcription leads to an anti-tumor effect. 2. Search for small molecules that specifically perturb hypoxia- responsive transcription. 3. Attempt to create a mechanism-based imaging method for studying the effect of hypoxia-response inhibitors in animal tumors.