Mechanisms of epidermal growth during development, homeostasis, and tumorigenesis

描述（由申请人提供）：在整个研究生和博士后阶段，我的目标是获得培训和经验，使我能够在发育和癌症生物学方面建立一个独立和成功的研究计划。具体来说，我感兴趣的是调节上皮组织发育和稳态的机制，以及在疾病状态（如癌症）中发生的变化。我的博士后培训计划的提醒是获得额外的技能和开发研究材料，我将能够进行到一个独立的立场在学术界。 洛克菲勒大学是我作为一名独立研究人员发展事业的理想场所。该大学是三机构计划的一部分，连同纪念斯隆-凯特琳癌症中心和威尔-康奈尔医学院，这是一个首要的环境进行研究，与同行的科学家互动，并参加讲座的领导人在各个领域。三机构小组还组织生物信息学和生物统计学的研讨会，以及致力于临床和癌症研究的讲座，这两者都是我培训的重点。此外，在这里，我将与计算和癌症生物学方面的专家合作。最后，福克斯实验室和洛克菲勒大学资源中心的资源将提供设备、培训和技术帮助，以确保拟议研究的成功完成。 为了满足我的研究和职业发展目标，我建议进行全基因组，RNAi介导的修饰剂筛选体内，以揭示调控机制，在发展过程中和癌基因诱导的增生表皮组织生长和稳态。我希望这项全面的工作将导致许多候选基因的识别，特别是在生理环境中运作。我所提出的方法的高通量性质和独创性将使我能够完成博士后培训，并在此过程中为未来的研究计划奠定坚实的基础。在独立阶段的开始，我将基于我的研究确定所选择的候选人使用的机制，以调节胚胎皮肤发育和表皮肿瘤发生模型中的组织生长。我将在随后向NIH（NIAMS和NCI）和其他可用资金来源申请资助时使用这些发现。 公共卫生相关性：在正常器官发育期间或在癌症等复杂疾病中，细胞的作用由其内在潜力和从生理环境中接收的指令决定。到目前为止，我们已经成功地确定了细胞自主行为的调节因子，但环境的影响却很难研究。该提案旨在利用最新的技术进步，对发育和癌症期间环境输入对组织生长的影响进行全面的全基因组调查。

DESCRIPTION (provided by applicant): Throughout the graduate and postdoctoral stages, my goal has been to get training and experience that will allow me to establish an independent and successful research program in developmental and cancer biology. Specifically, I am interest in the mechanisms that regulate epithelial tissue development and homeostasis, and to changes that occur in disease states such as cancer. My plan for the reminder of the postdoctoral training is to acquire additional skills and develop research material that I will be able to carry into an independent position in academia. The Rockefeller University is an ideal place for the development of my career as an independent researcher. The University is a part of the Tri-Institutional Program, together with Memorial Sloan-Kettering Cancer Center and Weill-Cornell Medical College, which is a premier environment to conduct research, interact with fellow scientists, and attend lectures by leaders in a variety of fields. The Tri-Institutional group also organizes workshops in bioinformatics and biostatistics, and lectures dedicated to clinical and cancer research, both of which are the focus of my training. Furthermore, here I will interact with collaborators that are experts in computational and cancer biology. Lastly, the resources within the Fuchs laboratory and the Resource Centers present at the Rockefeller University will provide equipment, training, and technical help that will ensure successful completion of the proposed research. In order to meet my research and career development goals I propose to conduct a genome-wide, RNAi- mediated modifier screen in vivo, to uncover regulatory mechanisms that govern epidermal tissue growth and homeostasis during development and in oncogene-induced hyperplasia. I expect that this comprehensive work will result in identification of many candidate genes that specifically operate within the physiological environment. The high-throughput nature and the originality of the approach that I propose, will allow me to complete postdoctoral training, and in the process set up a solid foundation for the future research program. At the start of the independent stage, I will base my research on identifying mechanisms used by selected candidates, to regulate tissue growth in the models of embryonic skin development and epidermal tumorigenesis. I will use these findings in subsequent grant support applications to the NIH (NIAMS and NCI), and other available sources of funding. PUBLIC HEALTH RELEVANCE: What a cell does, during normal organ development or in a complex disease like cancer, is defined by its intrinsic potential and by instructions that it receives from the physiological environment. To date, we have been successful in identifying regulators of cell autonomous behaviors, but the environmental influences have been harder to study. This proposal aims to take advantage of recent technical progress, and conduct a comprehensive, genome-wide investigation of the effect of environmental input on tissue growth during development and cancer.