PL Growth

PL增长

基本信息

批准号：
8934261
负责人：
TONY R. HUNTER
金额：
$ 1.97万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-12-01 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8934261
关键词：
Adenoviruses Affect Amino Acids Antimitotic Agents Apoptotic Area BRCA1 gene Biology Budgets Cancer Biology Cancer Center Cancer Center Support Grant Cell Aging Cell Cycle Cell Cycle Checkpoint Cell Differentiation process Cell Nucleus Cell Proliferation Cell Size Cells Chromatin Chromosomes Clinical DNA Damage DNA damage checkpoint Development Direct Costs Ensure Functional disorder Funding Gene Expression Genome Genome Stability Genomic Instability Genomics Goals Grant Growth Heterogeneity Histones Homeostasis Human Resources Knock-in Mouse Laboratories Light Maintenance Malignant Neoplasms Mammary gland Mediating Methods Mitosis Mitotic Modification Molecular Mutation Nematoda Nuclear Pore Nuclear Pore Complex Proteins Nuclear Receptors Nucleic Acid Regulatory Sequences Oncogenic Oncolytic Pathway interactions Peer Review Pharmaceutical Preparations Play Process Protein p53 Proteins Publications Regulation Repression Research Research Project Grants Resistance Role Rupture Signal Pathway Signal Transduction Somatic Cell Stem cells Stress Suppressor Genes System Telomerase Therapeutic Trans-Activators Transcriptional Regulation Translations Tumor Suppressor Genes Tumor Suppressor Proteins United States National Institutes of Health Yeasts biological adaptation to stress cancer cell cancer stem cell cancer therapy cancer type cell growth cell type chemical genetics chemotherapy chromatin modification crosslink fetal gene induction histone modification in vivo interest malignant breast neoplasm member micronucleus mouse model mutant neoplastic cell programs repaired response stem telomere tumor tumor progression

项目摘要

The overall scientific goal of the Growth Control and Genomic Stability Program is to understand mechanisms of proliferation, transcriptional regulation of oncogenic signaling pathways, DNA damage response and checkpoint activation, maintenance of genomic integrity and telomere function, and how these processes are disrupted or altered in cancer cells. Genomic instability is one of the key contributors to cancer progression and the genesis of tumor heterogeneity, and can engender either sensitivity or resistance to targeted and dastogenic cancer therapies. The members of this program study diverse aspects of how normal somatic cells, stem cells, and cancer cells respond to DNA damage, maintain genomic integrity, and respond to traditional and targeted chemotherapies. The functions of p53 in cell cycle checkpoint control and in diverse stress responses, and the use of adenovirus early proteins to interrogate cell signaling pathways and p53 checkpoint signaling comprise areas of significant focus of the program with opportunities for clinical translation. Chemical genetics is being used to study cellular signaling pathways that drive cancer cell proliferation. Other important topics include molecular mechanisms of transcriptional regulation of oncogenic pathways and of tumor suppressor gene expression, how nuclear pore subunits regulate gene expression, and the relationship of fetal mammary stem cells to stem-like cells in breast cancer. The program includes nine members from five different Laboratories (Departments), see the following page for a list of personnel. The NCI and other peer-reviewed cancer related support (direct costs) for the last budget year was $3,049,383. The substantial NIH and other federal support for this program is outlined in the table of externally funded research projects. The total number of cancer-relevant publications by members of this program in the last grant period (2008- 2012) was 132. Of the total publications, 1% were intraprogrammatic and 13% were interprogrammatic.

增长控制和基因组稳定计划的总体科学目标是了解增殖机制，致癌信号通路的转录调控，DNA损伤响应和检查点激活，基因组完整性和端粒功能的维护以及这些如何癌细胞中的过程被破坏或改变。基因组不稳定性是造成的关键因素之一癌症的进展和肿瘤异质性的起源，可以引起灵敏度或抗性进行靶向和达斯特癌疗法。该计划的成员研究如何正常的体细胞，干细胞和癌细胞对DNA损伤做出反应，维持基因组完整性，并且应对传统和有针对性的化学疗法。 p53在细胞周期检查点控制中的功能和在各种应力反应中，以及使用腺病毒早期蛋白来询问细胞信号通路和p53检查点信号传导包括该计划的重点重点的领域以及临床的机会翻译。化学遗传学用于研究驱动癌细胞的细胞信号传导途径增殖。其他重要主题包括分子机制的转录调控致癌途径和肿瘤抑制基因表达，核孔亚基如何调节基因表达，以及胎儿乳腺干细胞与乳腺癌中干细胞的关系。该计划包括来自五个不同实验室（部门）的九名成员，请参见下一页对于人员名单。 NCI和其他同行评审的癌症相关支持（直接费用）是上一年 $ 3,049,383。在表中概述了大量的NIH和其他联邦对该计划的支持外部资助的研究项目。该计划成员在上一个赠款期（2008-- 2012年）是总出版物中的132。1％是脑内图表，而13％的分解为译员。