Alterations of the Human SWI/SNF Complex in Lung Cancer

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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.