Science Leadership and Integration

科学领导力与整合

• 批准号: 7923790
• 负责人: ALLAN BALMAIN
• 金额: $ 73.66万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7923790
• 关键词: Animals; Area; Backcrossings; Cancer Biology; Cancer Detection; Cancer Family; Collaborations; Data; Databases; Diabetes Mellitus; Diagnosis; Early Detection Research Network; Event; Family-Based Registry; Funding; Gene Expression; Genetic; Genetic Polymorphism; Goals; Human; Human Genetics; Individual; Investigation; Joints; Lead; Leadership; Malignant Neoplasms; Medicine; Mouse Models of Human Cancer Consortium; Mouse Strains; Mus; Normal tissue morphology; Obesity; Pilot Projects; Predisposition; Proteins; Research; Resistance; Science; Signal Pathway; Signal Transduction; Single Nucleotide Polymorphism; Skin Cancer; Skin Neoplasms; Specialized Program of Research Excellence; Structure; System; Testing; Therapeutic; Tissue Banking; Tissue Banks; Tissues; base; cancer therapy; comparative; genetic analysis; insight; member; mouse model; novel; programs; response; therapeutic target; treatment response; tumor; working group

DESCRIPTION (provided by applicant): This project will exploit mouse genetics to test the concepts and approaches that will be required to implement personalized medicine for human cancer. This will require joint studies, both within the mouse models of human cancer consortium (MMHCC) and together with other NCI-funded organizations, of systems genetics analysis of genetic background and gene expression networks in cancer susceptibility, progression and therapeutic responses. The value of systems-based approaches has been demonstrated from mouse studies of susceptibility to obesity and diabetes, in which the gene expression networks in normal tissues have revealed signaling pathways that reflect underlying susceptibility, as well as signaling hubs that are viable therapeutic targets. Similar studies of mouse models of skin cancer have identified hierarchical networks that control tissue structure and function, and provided novel insights into mechanisms that lead to skin tumor susceptibility. The application of these integrative systems approaches to cancer has major implications for all of the areas of research being pursued by the MMHCC. This project will include a Core Project, the purpose of which is to construct a browsable database of combined single nucleotide polymorphisms (SNPs) and gene expression data from tissues from interspecific backcross mice and from the Rl lines of the Collaborative Cross. Such a data base would be invaluable both for groups in the Cancer Susceptibility and Resistance cluster, but also more generally within the MMHCC and in other NCI-funded bodies. A tissue bank from the same animals will be available to members of the MMHCC for investigations of the genetic control of gene expression at the protein level. Pilot projects will be set up within the cancer susceptibility and resistance theme to use the same genetic approaches to investigate tumor susceptibility using different mouse models that represent the major forms of human cancer. A further goal is to investigate the interplay between germline polymorphisms and somatic events in cancer detection, progression and treatment responses. These aims overlap substantially with the Roadmap initiative, and in particular with the goals of the Integrated Cancer Biology Program (ICBP), the Specialized Programs of Research Excellence (SPORE) program, the Early Detection Research Network (EDRN) and the Cancer Family Registry (CFR). Representatives of each of these programs have provided supporting materials for this comparative mouse-human genetic approach to analysis of multiple aspects of cancer susceptibility.

描述（由申请人提供）：该项目将利用小鼠遗传学来测试为人类癌症实施个性化医学所需的概念和方法。这将需要在人类癌联盟（MMHCC）的小鼠模型以及其他NCI资助的组织中进行联合研究，对癌症易感性，进展和治疗反应中遗传背景和基因表达网络的系统遗传学分析。从小鼠对肥胖和糖尿病的易感性的研究中证明了基于系统的方法的价值，在这种研究中，正常组织中的基因表达网络揭示了反映了基本易感性的信号传导途径，以及可行的治疗靶标的信号传导枢纽。对皮肤癌小鼠模型的类似研究已经确定了控制组织结构和功能的分层网络，并提供了对导致皮肤肿瘤敏感性的机制的新见解。这些综合系统在癌症中的应用对MMHCC追求的所有研究领域具有重大影响。该项目将包括一个核心项目，其目的是构建一个合并的单核苷酸多态性（SNP）的可浏览数据库，以及来自种间反向缩写小鼠的组织和协作杂交线的组织的基因表达数据。对于癌症易感性和耐药性集群中的组，这种数据库都是无价的，但更普遍地在MMHCC和其他NCI资助的身体中。 MMHCC成员将使用来自同一动物的组织库，以研究蛋白质水平上基因表达的遗传控制。试点项目将在癌症的敏感性和抗药性主题中建立，使用相同的遗传方法使用代表人类癌症的主要形式的不同小鼠模型来研究肿瘤敏感性。另一个目标是研究癌症检测，进展和治疗反应中种系多态性与体细胞事件之间的相互作用。这些目的与路线图计划重叠，尤其是综合癌症生物学计划（ICBP），研究卓越专业计划（SPORE）计划，早期检测研究网络（EDRN）和癌症家族注册表（CFR）的目标。这些程序中每个程序的代表为这种比较的小鼠人类遗传方法提供了支持材料，以分析癌症易感性的多个方面。