p12CDK2AP1 Regulation of Normal and Neoplastic Growth

描述（由申请人提供）：这个NCI辅导的职业发展为代表性不足的少数民族K 01奖的拟议计划是一个为期两年的辅导阶段，然后是一个为期三年的独立阶段。导师阶段将为少数族裔主要研究者提供高级培训，导师包括头颈癌研究实验室/牙科研究所的大卫王博士和加州大学洛杉矶分校基于载体的基因治疗实验室/Crump分子成像研究所的Lily Wu博士。这一阶段将为候选人提供机会，使其能够专注于研究和发展，以作为独立科学家的学术生涯。本提案的总体目标是使用体内模型系统研究p12 CDK 2AP 11在调节正常和肿瘤生长中的作用。我们的基本原理是，p12 CDK 2AP 1，一种细胞周期调节因子和CDK 2相关蛋白，通常在约70%的头颈癌中下调，在体内重要地参与调节正常和肿瘤生长。一些研究表明，在肿瘤细胞中重新表达p12 CDK 2AP 1导致生长抑制和诱导凋亡，然而关于该分子在调节正常细胞生长中的作用知之甚少。在指导阶段，候选人将参与研究pi 2 CDK 2AP 1在正常发育中的作用，并产生用于头颈癌治疗的新型p12 CDK 2AP 1基因疗法。除了研究培训外，职业发展计划中还纳入了教学内容，以加强候选人的总体职业发展。还将制定明确的里程碑，以评估候选人的科学进展，特别是在向独立阶段过渡期间。在独立阶段，候选人将通过暂时消除p12 CDK 2AP 1在成人头颈部组织中的表达，并为未来的翻译应用开发新的肿瘤靶向基因治疗策略，来研究p12 CDK 2AP 1在肿瘤生长中的作用。对p12 CDK 2AP 1消融和治疗的细胞和分子反应的检查将提供对这种细胞周期调节剂在体内正常和肿瘤生长中的功能的了解。这种K 01机制对于确保候选人发展成为癌症生物学领域的独立研究科学家所需的时间和资源至关重要。

DESCRIPTION (provided by applicant): The proposed plan for this NCI Mentored Career Development for Underrepresented Minorities K01 award is a two-year Mentored Phase, followed by a three-year Independent Phase. The Mentored Phase will provide for advanced training for the minority principal investigator under the co-mentorship of Dr. David Wong at the Laboratory of Head and Neck Cancer Research/Dental Research Institute and Dr. Lily Wu at the Vector-based Gene Therapy Laboratory/Crump Institute for Molecular Imaging at UCLA. This phase will provide the candidate with the opportunity to focus her efforts on research and development towards an academic career as an independent scientist. The overall goal of this proposal is to examine the role of p12 CDK2AP11 in regulating normal and neoplastic growth using in vivo model systems. Our rationale is that p12CDK2AP1, a cell cycle regulator and CDK2-associating protein commonly downregulated in -70% of head and neck cancers, is importantly involved in regulating normal and neoplastic growth in vivo. Several studies have shown that reexpressing p12 CDK2AP1 in tumor cells results in growth inhibition and induction of apoptosis, however little is known regarding the role of this molecule in regulating normal cell growth. During the Mentored Phase, the candidate will engage in investigating the role of pi2 CDK2AP1in normal development, and generating novel p12 CDK2AP1-based gene therapies for head and neck cancer treatment. In addition to the research training, a didactic component has been incorporated in the career development plan to enhance the candidate's overall career development. Defined milestones also will be in place to assess the candidate's scientific progress, particularly during transition to the Independent Phase. During the Independent Phase, the candidate will engage in examining the role of p12 CDK2AP1 in neoplastic growth by temporally ablating p12 CDK2AP1 expression specifically in adult head and neck tissues and developing novel tumor-targeted gene therapy strategies for future translational applications. The examination of the cellular and molecular responses to p12 CDK2AP1 ablation and therapy will provide insights into the functions of this cell cycle regulator in normal and neoplastic growth in vivo. This K01 mechanism is critical in assuring the time and resources needed for the development of the candidate into an independent research scientist in the field of cancer biology.