Alterations of the Human SWI/SNF Complex in Lung Cancer

描述(申请人提供)：应聘者：应聘者是肿瘤科医生 他的职业目标是成为一名专注于 肺癌分子生长抑制途径与肺癌的发生发展 在体外和体内检测这些途径中的肿瘤变异的方法。 研究计划：肺癌是美国癌症死亡的首要原因 各州。降低死亡率将需要发展 基于对生长抑制通路的理解的预后标记物。 SWI/SNF综合体是满足这一关键需求的候选方案，因为它是 可能是肿瘤抑制因子、视网膜母细胞瘤(Rb)和 P130(RB2)。了解SWI/SNF的改变如何影响Rb和p130 功能，这项提案将确定下调的机制 BRG和BRM(AIM 1)，以阐明BRG1在Rb介导的生长中的作用 抑制(AIM 2)，以确定BRG1和BRM是否丢失或突变 原发肺癌(AIM 3)，并确定BRG1和BRM是否重要 对于p130功能(AIM 4)。本培训期间的目标是提供 一种紧张的研究经验，分子生物学的专业知识 作为一名经过双重培训的独立研究人员，他获得了职业生涯。 环境：莱恩伯格大学优良的研究环境 综合性癌症中心将促进这些具体目标的实现 目标。候选人S的培训和发展将由 一位资深而有成就的科学家的全心全意的指导和指导。 伯纳德·魏斯曼。贝弗莉·米切尔博士，谁有多年的经验？有以下经验 指导成功的医生/科学家，将提供受保护的研究 时间和翻译研究指导。因此，这一K08资金期将 允许获得新的技能，从而产生了一系列出版物 导致了独立的癌症研究生涯。

DESCRIPTION (provided by applicant): Candidate: The candidate is an Oncology fellow whose career goal is to become a translational researcher focusing on the molecular growth inhibitory pathways in lung cancer and the development of assays to detect neoplastic aberrance in these pathways both in vitro and in vivo. Research Plan: Lung cancer is the leading cause of cancer deaths in the United States. A reduction in the mortality will require the development of prognostic markers based on the understanding of growth inhibitory pathways. The SWI/SNF complex is a candidate to fill this critical need since it is likely required for function of the tumor suppressors, retinoblastoma (RB) and p130 (RB2). To understand how alterations in SWI/SNF may affect RB and p130 function, this proposal will determine the mechanisms for the down-regulation of BRG and BRM (AIM 1), to clarify the role of BRG1 in RB mediated growth inhibition (AIM 2), to determine if BRG1 and BRM are lost or mutated in primary lung cancers (AIM 3), and to determine if BRG1 and BRM are important for p130 function (AIM 4). It is the goal of this training period to provide an intense research experience whereby expertise in molecular biology is gained leading to a career as a dually trained independent researcher. Environment: The excellent research environment at the Lineberger Comprehensive Cancer Center will promote the accomplishment of these specific aims. The candidate?s training and development will be directed by the dedicated mentorship and guidance of a senior and accomplished scientist, Dr. Bernard Weissman. Dr. Beverly Mitchell, who has many years? experience in mentoring successful physician/scientists, will provide protected research time and translational research guidance. Thus, this K08 funding period will allow the acquisition of new skills resulting in a series of publications leading to an independent cancer research career.