Core A: Determining and targeting mechanisms controlling cancer cell division

核心 A：确定和靶向控制癌细胞分裂的机制

基本信息

批准号：
10597192
负责人：
JULIEN SAGE
金额：
$ 23.44万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-25 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10597192
关键词：
Advisory Committees Awareness Cancer Control Cell Cycle Progression Cell Cycle Regulation Cell division Collaborations Communication Communities Community Outreach Cyclin D1 Development Electronic Mail Epigenetic Process Family Feedback First Aid Funding Genes Genetic Genetic Transcription Goals Group Meetings Human Individual Joints Laboratories Malignant Neoplasms Mentorship Monitor Mutate Newsletter Oncogenes Oncoproteins Participant Pathway interactions Peer Review Phosphorylation Play Productivity Protein Family Proteins Protocols documentation Publications Research Research Personnel Research Project Grants Role Schedule Series Site Techniques Transcriptional Regulation Tumor Suppressor Genes Tumor Suppressor Proteins Work clinical application cohesion data exchange experience experimental study gain of function mutation interdisciplinary approach loss of function mutation meetings member novel novel therapeutics programs social media symposium transcription factor web site

项目摘要

PROJECT SUMMARY Gain-of-function mutations of oncogenes and loss-of-function mutations of tumor suppressor genes drive the initiation and progression of human cancer. These genes also play critical roles in normal development and cellular differentiation. Genetic or epigenetic alterations in the Rb pathway are required for the initiation and progression of most types of human cancer. The three inter-related projects in this program will address major outstanding fundamental questions about the functioning of key proteins in the Rb pathway: Cyclin D-Cdk4/6 oncoproteins that regulate Rb by phosphorylation, the Rb family of tumor suppressors that act as transcriptional regulators, and the E2F family of transcription factors that interact with and are directly regulated by the Rb family proteins and control the transcription of genes important for cell cycle progression. A major goal of this program project is to investigate the Rb pathway using an interdisciplinary approach. The major goal of this Core is to provide an administrative framework to help implement the scientific goals and disseminate the results of the proposed experiments. Specifically, the Administrative Core will have three goals. The first goal will be to promote scientific interactions among the Project Leaders and laboratory members involved in the three main Projects and two Scientific Cores. The second goal will be to provide scientific and financial guidance and oversight, including in conjunction with an Internal Advisory Committee and an External Scientific Advisory Board. The third goal will be to facilitate communication among the members of the Projects and Cores themselves and to the greater scientific community and the public. To achieve these goals, the Leader for this Administrative Core, will work closely with the Leaders of each of the Projects and Scientific Cores. Regular scientific interactions to exchange ideas and results, feedback from members of the internal advisory committee and the external scientific advisory board, and specific metrics to monitor progress, will all be critical to help uncover novel fundamental mechanisms underlying cell cycle progression.

项目摘要肿瘤基因的功能性突变和肿瘤抑制基因功能丧失突变驱动人类癌症的启动和进展。这些基因在正常发展中也起着关键作用，细胞分化。启动需要RB途径中的遗传或表观遗传改变，并且大多数类型的人类癌症的进展。该计划中的三个相互关联项目将解决专业关于关键蛋白在RB途径中的功能的杰出基本问题：Cyclin D-CDK4/6 通过磷酸化调节RB的癌蛋白，磷酸化，RB的肿瘤抑制剂家族作为转录调节器和与RB家族相互作用并直接调节的转录因子家族的E2F家族蛋白质并控制对细胞周期进程很重要的基因转录。该计划的主要目标项目是使用跨学科方法研究RB途径。该核心的主要目标是提供一个行政框架来帮助实施科学目标并传播提出的实验。具体来说，行政核心将有三个目标。第一个目标是促进科学互动在参与三个主要项目和两个科学核心的项目领导者和实验室成员中。第二个目标是提供科学和财务指导和监督，包括内部咨询委员会和外部科学顾问委员会。第三个目标是促进项目成员和核心本身以及更大科学的沟通社区和公众。为了实现这些目标，该行政核心的领导者将与每个项目和科学核心的领导者。定期进行科学互动来交换思想和结果，内部咨询委员会成员的反馈和外部科学咨询委员会，和监视进度的特定指标，对于帮助发现新颖的基本机制至关重要基础细胞周期进程。