Regulation of Cell Motility by the Oncogenic ERK-MAPK Pathway

描述(由申请人提供)：本提案概述了一项培训计划，将使其能够过渡到癌症研究的独立职业生涯。该候选人拥有生物医学博士学位，并接受过遗传和生化技术方面的培训，这些技术用于研究细胞运动和细胞信号。她目前的导师是哈佛医学院细胞生物学教授约翰·布莱尼斯博士。Blenis博士是RAS/ERK和PI3K/mTORC1癌基因信号通路的机械剖析领域的世界领导者之一。培训计划包括哈佛医学院细胞生物学教授高登兹·丹尼瑟博士的新指导。Danuser博士在开发新的计算方法以解决化学和机械信号中以前无法获得的问题方面是一位创新者。这位候选人正在研究ERK和RSK在未转化的模型细胞和转化的癌细胞中调节细胞运动的转录独立机制。在短期内，拟议的研究计划将为候选人提供先进的肌球蛋白动力学定量成像方面的培训，并将为她提供时间发表更多的手稿，并过渡她对癌细胞迁移和侵袭的研究。她已经确定了肌动球蛋白机制的几个成分，如MYPT1，作为新的ERK/RSK底物，并将进一步研究它们在推动癌细胞迁移和侵袭中的作用。因此，这一培训计划将使候选人为成为一名独立科学家做好准备，并拥有一项长期研究计划，该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，并将为针对激活的ERK/RSK信号通路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.