The role of mTOR in Ras mediated gliomagenesis

描述(由申请人提供)：这份建议书描述了一个五年计划，旨在发展放射肿瘤学的内科医生-科学家的学术生涯。这位首席研究员在加州大学旧金山分校完成了放射肿瘤学住院医师培训，目前担任加州大学旧金山分校放射肿瘤学系的临床讲师，并将于2005年7月晋升为助理教授。PI从事神经放射肿瘤学治疗成人恶性胶质瘤，同时在Russell O.Pieper博士的指导下进行胶质瘤形成的实验室研究。 一项研究mTOR在RAS介导的胶质瘤形成中的作用的实验计划结合了说教研究和与加州大学旧金山分校脑肿瘤研究中心的重点互动。该研究计划验证了这样的假设，即RAS介导的胶质瘤发生在RAL信号臂上，导致mTOR及其下游效应器elF4E的激活。由elF4E活性上调的翻译靶点可能代表恶性胶质瘤治疗中的重要治疗靶点，并将得到评估。概述的研究计划和职业发展活动将在加州大学旧金山分校综合癌症中心和加州大学旧金山分校脑瘤研究中心(BTRC)进行，UCSF综合癌症中心是指定的国家癌症研究所研究中心，加州大学旧金山分校脑瘤研究中心(BTRC)是NCI的专业卓越研究计划(SPOPE)。导师、神经外科教授Russell O.Pieper博士、共同导师Mitchel Berger医学博士、神经外科教授兼加州大学旧金山分校脑孢子项目PI将与放射肿瘤系教授David A.Larson一起组成一个咨询委员会，指导PI在整个颁奖期间取得的成就。加州大学旧金山分校放射肿瘤科大力支持概述的职业发展活动，并投入临床和实验室资源支持PI向独立的过渡。

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.