Regulation of Cell Motility by the Oncogenic ERK-MAPK Pathway

描述（由申请人提供）：该提案概述了一个培训计划，使其能够过渡到癌症研究的独立职业。该候选人拥有生物医学博士学位，并接受过用于研究细胞运动和细胞信号传导的遗传和生化技术的培训。她目前的导师是哈佛医学院细胞生物学教授John Blenis博士。Blenis博士是Ras/ERK和PI3K/mTORC1致癌信号通路机械解剖的全球领导者之一。该培训项目包括来自哈佛医学院细胞生物学教授Gaudenz Danuser博士的新指导。Danuser博士是开发新的计算方法的创新者，以解决化学和机械信号中以前无法实现的问题。该候选人正在研究在未转化的模型细胞和转化的癌细胞中，ERK和RSK调节细胞运动的转录不依赖机制。在短期内，拟议的研究计划将为候选人提供动态肌动球蛋白动力学高级定量成像的培训，这是一项新技术，并将为她提供时间发表更多的手稿并转移她的研究癌细胞迁移和侵袭。她已经确定了肌动球蛋白机制的几个组成部分，如MYPT1，作为新的ERK/RSK底物，并将进一步研究它们在驱动癌细胞迁移和侵袭中的作用。因此，该培训计划将使候选人成为一名独立的科学家，并进行长期的研究计划，将生化研究与基于显微镜的细胞骨架动力学解剖相结合，以了解驱动癌细胞运动的信号机制。这项基础研究将揭示与多种癌症类型相关的癌细胞迁移的基本机制，并将为针对具有激活ERK/RSK信号的癌症的治疗策略提供信息。

DESCRIPTION (provided by applicant): This proposal outlines a training program that will enable the transition to an independent career in cancer research. The candidate has a Ph.D. in Biomedical Sciences and is trained in genetic and biochemical techniques used to study cell motility and cell signaling. She is currently mentored by Dr. John Blenis, Professor of Cell Biology at Harvard Medical School. Dr. Blenis is one of the world's leaders in mechanistic dissection of the Ras/ERK and PI3K/mTORC1 oncogenic signaling pathways. The training program includes new mentoring from Dr. Gaudenz Danuser, Professor of Cell Biology at Harvard Medical School. Dr. Danuser is an innovator in developing new computational methods to address previously un-attainable questions in chemical and mechanical signaling. The candidate is researching the transcription-independent mechanisms by which ERK and RSK regulate cell motility in untransformed model cells and transformed cancer cells. In the short term, the proposed research program will provide training in advanced quantitative imaging of actomyosin dynamics, a new technique for the candidate, and will provide time for her to publish additional manuscripts and transition her studies cancer cell migration and invasion. She has identified several components of the actomyosin machinery, such as MYPT1, as novel ERK/RSK substrates and will further investigate their role in driving cancer cell migration and invasion. Thus, this training program will prepare the candidate to become an independent scientist, with a long-term research program that integrates biochemical studies with microscopy-based dissection of cytoskeletal dynamics to understand the signaling mechanisms that drive cancer cell motility. This basic research will uncover fundamental mechanisms of cancer cell migration relevant to multiple cancer types and will inform upon therapeutic strategies targeting cancers with activated ERK/RSK signaling.