Regulation of Cell Motility by the Oncogenic ERK-MAPK Pathway

致癌 ERK-MAPK 途径对细胞运动的调节

基本信息

批准号：
8754917
负责人：
Michelle Christine Mendoza
金额：
$ 11.58万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8754917
关键词：
Actins Actomyosin Address Adhesions Antibodies Automobile Driving BRAF gene Basic Science Biochemical Cancer Etiology Cancer cell line Carcinoma Cell Line Cell model Cells Cellular biology Chemicals Complex Computer software Computing Methodologies Cytoskeleton Data Dissection Disseminated Malignant Neoplasm Distant Doctor of Philosophy Epithelial Epithelial Cells Exhibits Fluorescence Microscopy Future Genetic Genetic Transcription Goals Image In Vitro KRAS2 gene Label Location MAP Kinase Gene Malignant Neoplasms Malignant neoplasm of pancreas Manuscripts Mechanics Mentors Microscopy Mitogen-Activated Protein Kinases Modeling Molecular Morbidity - disease rate Morphology Movement Mutation Myosin Light Chains Neoplasm Metastasis Normal Cell Oncogenic Organ Pathway interactions Patients Phosphorylation Phosphotransferases Production Publishing RPS6KA gene Receptor Protein-Tyrosine Kinases Regulation Research Ribosomal Protein S6 Kinase Role Science Scientist Signal Pathway Signal Transduction Site Speed Stratification Techniques Testing Therapeutic Time Tissue Microarray Tissue Sample Tissues Training Training Programs ZYX gene anticancer research base cancer cell cancer type career cell motility cell transformation epithelial to mesenchymal transition improved malignant breast neoplasm medical schools melanoma migration mortality mutant myosin phosphatase neoplastic cell new therapeutic target novel particle paxillin polymerization prevent professor programs spatiotemporal treatment strategy

项目摘要

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.

描述（由申请人提供）：该提案概述了一项培训计划，该计划将使过渡到癌症研究的独立职业。候选人有博士学位。在生物医学科学中，接受了用于研究细胞运动和细胞信号传导的遗传和生化技术的训练。她目前由哈佛医学院细胞生物学教授约翰·布莱尼斯（John Blenis）博士指导。 Blenis博士是RAS/ERK和PI3K/MTORC1致癌信号通路的世界机械解剖领导者之一。该培训计划包括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。候选人正在研究与转录无关的机制，通过这些机制，ERK和RSK调节未转化的模型细胞和转化的癌细胞中的细胞运动。在短期内，拟议的研究计划将提供训练肌动蛋白动力学的高级定量成像，这是候选人的一种新技术，并将为她提供时间出版其他手稿并过渡她的研究癌细胞迁移和入侵。她已经将肌动蛋白机械的几个组成部分（例如MyPT1）确定为新型ERK/RSK底物，并将进一步研究其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科学家，并通过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的解剖整合在一起，以了解驱动癌细胞运动性的信号传导机制。这项基础研究将发现与多种癌症类型相关的癌细胞迁移的基本机制，并将告知针对激活的ERK/RSK信号的癌症的治疗策略。