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.

PUBLIC HEALTH RELEVANCE: Interactions between tumor cells in cancers were implied to be able to significantly modulate tumor progression and response to therapies. The proposed study will focus on understanding the mechanism and function of cell competition, a major type of such tumor cell interactions. Results from this study may pave the way to develop novel diagnostic markers as well as therapeutic methods, therefore contributing to the goal of NIH to improve public health.