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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：
8534066
负责人：
Michelle Christine Mendoza
金额：
$ 0.64万
依托单位：
HARVARD MEDICAL SCHOOL
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 2014-01-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8534066
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）：本提案概述了一个培训计划，将使过渡到一个独立的职业生涯在癌症研究。候选人拥有博士学位。他在生物医学科学领域接受过遗传和生物化学技术方面的培训，这些技术用于研究细胞运动和细胞信号。她目前由哈佛医学院细胞生物学教授John Blenis博士指导。Blenis博士是Ras/ERK和PI 3 K/mTORC 1致癌信号通路机制研究的世界领导者之一。培训计划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ERK和RSK调节未转化模型细胞和转化癌细胞中细胞运动的转录非依赖性机制。在短期内，拟议的研究计划将提供先进的肌动球蛋白动力学定量成像的培训，这是候选人的一项新技术，并将为她提供时间发表更多的手稿，并将她的研究转移到癌细胞迁移和入侵。她已经确定了肌动球蛋白机制的几种组分，如MYPT 1，作为新型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，这个培训计划将准备候选人成为一个独立的科学家，与一个长期的研究计划，将生化研究与细胞骨架动力学的显微镜解剖相结合，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，并将为靶向具有活化ERK/RSK信号传导的癌症的治疗策略提供信息。