The mechanism and function of cell competition in tumors

描述(由申请人提供)：我的长期职业目标是获得终身教职，并在癌细胞生物学领域建立一个独立的研究计划。我提出了一个为期三年的职业发展计划，使我能够成为一名成功的独立研究调查员。在这项拟议的研究中，我将通过实现三个具体目标来重点了解肿瘤中细胞竞争的机制和功能：(1)确定在NF2突变肿瘤细胞中差异表达的YAP是否可以诱导细胞竞争；(2)确定差异表达YAP诱导的克隆优势过程中的介体；(3)确定差异表达YAP的肿瘤细胞之间的相互作用对肿瘤发生的影响。本研究的主要方法是建立肿瘤细胞克隆优势模型。这项拟议的研究结果将为肿瘤细胞之间的竞争性相互作用提供机制和功能上的指示。此外，由于细胞竞争可以调节肿瘤的进展和治疗反应，竞争相互作用的已识别的分子介质和效应器可能被开发成诊断标记或治疗靶点。这份提出的职业发展计划是基于我过去独特的科学史，这使我成为从事这一主题的理想人选。由于该项目处于开发的早期阶段，对拟议工作的高风险方面的管理，如建立模型和研究工具，预计将是技术上的挑战。在寻求K22奖项的过程中，我的目标是获得更多学习手机的技能 癌症中的相互作用。这些技能将通过参加课程和咨询/与相关专家合作获得。Filippo Giancotti博士的实验室是研究癌症生物学中细胞黏附和信号传递的著名研究项目，MSKCC是一个拥有最先进核心设施和高度互动的科学社区的理想环境，为我的研究和其他职业发展活动提供了独特的资源，以加强我在以下方面的专业技能：助学金和手稿写作、演示、申请过程和终身教职跟踪职位的谈判、指导和实验室管理。K22奖将为我提供受保护的时间，这对加强新的研究主题至关重要，并将促进我与这个社区中不同的专业知识的互动，促进我作为一名独立研究人员的成熟，并使我能够顺利过渡到我的独立职业生涯。

DESCRIPTION (provided by applicant): My long-term career goal is to secure a tenure-track faculty position and establish an independent research program in the area of cancer cell biology. I propose a three-year career development plan that will enable me to become a successful independent research investigator. In this proposed research, I will focus on understanding the mechanism and function of cell competition in tumors by achieving three specific aims: (1) to determine if differential YAP expression in NF2 mutant tumor cells can induce cell competition; (2) to identify mediators in the clonal dominance process induced by differential YAP expression; and (3) to determine the impact of the interaction between tumor cells differentially expressing YAP on tumorigenesis. The main approach in this study will be tumor cell clonal dominance models. Results from this proposed research will provide mechanistic and functional indications of the competitive interaction between tumor cells. Moreover, identified molecular mediators and effectors of the competitive interaction might be developed into diagnostic markers or therapeutic targets since cell competition could modulate tumor progression and therapeutic response. This proposed career development plan is based on my past unique scientific history, which makes me an ideal person to pursue this subject. Because this project is in the early stages of development, management of high risk aspects of the proposed work, such as establishment of models and research tools, is anticipated to be technique-challenging. In seeking a K22 award, I aim to gain additional skills in studying cellular interactions in cancer. These skills will be obtained through attending courses and consulting/collaborating with related experts. Dr. Filippo Giancotti's lab, a well-known research program in studying cell adhesion and signaling in cancer biology, as well as MSKCC, an ideal environment with state-of- the-art core facilities and a highly interactive scientific community, provide me unique recourses for my research and other career development activities to strengthen my professional skills in: grant and manuscript writing, presentation, the application process and negotiations for tenure track positions, mentoring and lab management. The K22 award would provide me with protected time critical to strengthen the new research subject and would foster my interaction with the diverse expertise in this community, facilitate my maturation as an independent researcher, and enable a smooth transition toward my independent career.