p12CDK2AP1 Regulation of Normal and Neoplastic Growth

描述(由申请人提供)：NCI针对未被充分代表的少数族裔的指导式职业发展K01奖项的建议计划是两年指导阶段，然后是三年独立阶段。导师阶段将为少数族裔首席研究员提供高级培训，由加州大学洛杉矶分校头颈癌实验室/牙科研究所的David Wong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分子成像研究所的莉莉·吴博士共同指导。这一阶段将为候选人提供机会，将她的努力集中在研究和开发上，以独立科学家的学术生涯为目标。这项建议的总体目标是利用体内模型系统研究p12 CDK2AP11在调节正常和肿瘤生长中的作用。我们的理论基础是p12CDK2AP1，一种细胞周期调节蛋白和CDK2相关蛋白，在70%的头颈癌中普遍下调，在体内参与调节正常和肿瘤的生长。一些研究表明，在肿瘤细胞中重新表达p12 CDK2AP1会导致生长抑制和诱导凋亡，但对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，候选人将致力于研究Pi2 CDK2AP1在正常发育中的作用，并产生基于p12 CDK2AP1的头颈部癌症治疗的新基因疗法。除了研究性培训外，职业发展计划中还纳入了教学内容，以加强应聘者的整体职业发展。还将制定明确的里程碑，以评估候选人的科学进步，特别是在过渡到独立阶段期间。在独立阶段，候选人将致力于研究p12 CDK2AP1在肿瘤生长中的作用，方法是暂时消除p12 CDK2AP1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。对p12 CDK2AP1消融和治疗的细胞和分子反应的检测将有助于深入了解这种细胞周期调节因子在体内正常和肿瘤生长中的作用。这种K01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.