The role of mTOR in Ras mediated gliomagenesis

描述（由申请人提供）：本提案描述了一个为期五年的计划，作为放射肿瘤学的医生科学家的学术生涯的发展。主要研究者在加州大学旧金山分校弗朗西斯科完成了放射肿瘤学的住院医师培训，目前在加州大学旧金山分校放射肿瘤学系担任临床讲师，并将于2005年7月晋升为助理教授。PI实践神经放射肿瘤学治疗患有恶性胶质瘤的成人，同时在Russell O.派珀 一项研究mTOR在Ras介导的胶质瘤发生中作用的实验计划与教学研究和与UCSF脑肿瘤研究中心的重点互动相结合。该研究计划测试了Ras介导的胶质瘤发生通过Ral信号传导臂，导致mTOR及其下游效应物eIF4E激活的假设。由eIF4E活性上调的翻译靶标可能代表恶性神经胶质瘤治疗中的重要治疗靶标，并将进行评估。概述的研究计划和职业发展活动将发生在UCSF综合癌症中心，指定的国家癌症研究所研究中心，和UCSF脑肿瘤研究中心（BTRC），一个NCI命名为研究卓越的专业计划（SPORE）。导师Russell O. Pieper博士，神经外科系教授，共同导师Mitchel Berger，医学博士，神经外科系教授和加州大学旧金山分校脑孢子项目的PI，将加入大卫A。Larson博士，医学博士，放射肿瘤学系的教授，在整个获奖期间成立了一个指导PI成就的咨询委员会。UCSF放射肿瘤学系强烈支持概述的职业发展活动，并承诺提供临床和实验室资源，以支持PI向独立过渡。

DESCRIPTION (provided by applicant): This proposal describes a five year program for the development of an academic career as a physician-scientist in Radiation Oncology. The principal investigator completed residency training in Radiation Oncology at the University of California, San Francisco, is serving as a Clinical Instructor in the Department of Radiation Oncology at UCSF, and will be promoted to Assistant Professor in July of 2005. The PI practices neuro-radiation oncology treating adults with malignant gliomas while pursuing laboratory studies in gliomagenesis under the mentorship of Dr. Russell O. Pieper. An experimental program examining the role of mTOR in Ras mediated gliomagenesis is combined with didactic studies and focused interactions with the UCSF Brain Tumor Research Center. The research plan tests the hypothesis that Ras mediated gliomagenesis occurs through the Ral signaling arm, resulting in activation of mTOR and its downstream effector elF4E. The translational targets upregulated by elF4E activity may represent important therapeutic targets in the treatment of malignant gliomas, and will be assessed. The outlined research plan and career development activities will occur at the UCSF Comprehensive Cancer Center, a designated National Cancer Institute research center, and the UCSF Brain Tumor Research Center (BTRC), an NCI named Specialized Program of Research Excellence (SPORE). Mentor Russell O. Pieper, Ph.D., Professor in the Department of Neurological Surgery, and co-mentor Mitchel Berger, M.D., Professor in the Department of Neurological Surgery and PI of UCSF's Brain SPORE program, will be joined by David A. Larson, Ph.D., M.D., Professor in the Department of Radiation Oncology, in forming an advisory committee guiding the PI's achievement throughout the award period. The UCSF Department of Radiation Oncology strongly supports the career development activities outlined and has committed clinical and laboratory resources to support the PI's transition to independence.