Targeting of Genes in the Mammalian Genome
哺乳动物基因组中的基因靶向
基本信息
- 批准号:8310167
- 负责人:
- 金额:$ 42.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1976
- 资助国家:美国
- 起止时间:1976-12-01 至 2015-07-31
- 项目状态:已结题
- 来源:
- 关键词:A MouseAffectAlveolar RhabdomyosarcomaAnteriorApplications GrantsAreaBehaviorBrainCell TherapyCell divisionCellsChildChildhoodChromosomal translocationDevelopmentDiseaseEmbryoEpitheliumEtiologyEventEwings sarcomaFingerprintFrequenciesGaliumGene TargetingGenerationsGenesGeneticGenetic MarkersGenetic RecombinationGoalsGrantHomeostasisHumanIn VitroInstitutesIntestinesLabelLaboratoriesLengthMaintenanceMalignant Bone NeoplasmMalignant NeoplasmsModelingMolecularMolecular ProfilingMusMutagenesisNatureNeuronsOutputPaperPediatric OncologistPopulationPositioning AttributePostdoctoral FellowProcessProteinsProtocols documentationPublishingRadiosurgeryRecruitment ActivityReportingRoleScientistSimulateSourceStem cellsSystemTherapeuticTissuesTraumaWorkadult stem cellbasechemotherapycomplex biological systemsdesignfusion genehuman cancer mouse modelhuman diseaseimprovedin vivoinduced pluripotent stem cellinsightintestinal cryptintestinal epitheliumleukemia/lymphomamammalian genomemouse modelnew technologyprogramsresponsesarcomastemstem cell biologystem cell populationsuccesssynovial sarcomatherapeutic developmenttooltumor progressionyoung adult
项目摘要
DESCRIPTION (provided by applicant): Sarcomas primarily affect children and young adults. For pediatric oncologists, sarcomas are a major problem. Most are extremely aggressive and current protocols of surgery, radiation and chemotherapy are not adequate. Significant improvement for many sarcomas will require a detailed understanding of the genetic factors responsible for its progression, so that a gene targeted-based therapy can be developed to manage the cancer. Each sarcoma is likely to require its own specific molecular-based therapies for its management. To achieve these goals the information based for each sarcoma will likely require generating a mouse model of the human cancer that accurately simulates the human condition. The criterion to establish a "good" mouse model for the human cancer is now very rigorous. Each human cancer is being classified with a genetic fingerprint involving the expression profile of thousands of genes. Having established authenticity of the mouse model, it can be used to identify the secondary genetic events responsible for its progression. Having in turn identified the genetic players, their identity can be used as a platform to generate a rational approach to therapeutic development. We have successfully modeled alveolar rhabdomyosarcoma and synovial sarcoma and are in the process of modeling Ewing's sarcoma. We will use these mouse models to determine the secondary genetic events responsible for their progression. We also propose to generate improved third generation mouse models that will initiate the cancers by inducing the appropriate chromosomal translocation in their cell of origin. The therapeutic potential of iPS cells for cell-base therapy of many major human diseases is enormous. However, attaining this potential will require a much deeper understanding of adult stem cell biology, which is nature's normal means for maintaining tissue homeostasis and response to modest trauma. We propose to continue our functional studies of two adult stem cell systems, intestinal stem cells and neuronal stem cells. These two stem cell systems are at opposite ends of the spectrum in terms of the frequency of tissue turnover that they maintain. By comparing these two systems we may gain insights into how adult stem cell systems can be modulated to alter their output.
描述(由申请人提供):肉瘤主要影响儿童和年轻人。对于儿科肿瘤学家,肉瘤是一个主要问题。大多数是极具侵略性的手术,放射线和化学疗法不足的手术方案。许多肉瘤的显着改善将需要详细了解导致其进展的遗传因素,以便可以开发出基于基因的基于基因的疗法来管理癌症。每个肉瘤都可能需要其自己的特定基于分子的疗法来进行管理。 为了实现这些目标,每个肉瘤的信息可能需要产生人类癌症的小鼠模型,以准确模拟人类状况。现在,为人类癌症建立“良好”小鼠模型的标准现在非常严格。每个人类癌症都被遗传指纹分类,涉及数千种基因的表达谱。建立了小鼠模型的真实性后,它可用于识别导致其进展的次要遗传事件。反过来,他们确定了遗传参与者,它们的身份可以用作平台,以生成一种理性的治疗性开发方法。我们已经成功地对肺泡横纹肌肉瘤和滑膜肉瘤进行了建模,并正在对Ewing的肉瘤进行建模。 我们将使用这些小鼠模型来确定负责其进展的次要遗传事件。我们还建议生成改进的第三代小鼠模型,该模型将通过在其原始细胞中诱导适当的染色体易位来启动癌症。 IPS细胞在许多主要人类疾病的细胞碱基疗法中的治疗潜力是巨大的。但是,达到这种潜力将需要对成年干细胞生物学有更深入的了解,这是维持组织稳态和对适度创伤的反应的正常手段。我们建议继续对两个成年干细胞系统,肠道干细胞和神经元干细胞的功能研究。就其维持的组织周转频率而言,这两个干细胞系统处于频谱的相对端。通过比较这两个系统,我们可以深入了解如何调节成年干细胞系统以改变其输出。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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MARIO R CAPECCHI其他文献
MARIO R CAPECCHI的其他文献
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{{ truncateString('MARIO R CAPECCHI', 18)}}的其他基金
TCF/LEF function during intestinal maintenance and colon tumorigenesis
TCF/LEF 在肠道维持和结肠肿瘤发生过程中的功能
- 批准号:
8449513 - 财政年份:2013
- 资助金额:
$ 42.6万 - 项目类别:
From Defective Microglia to Cortical Activity and Pathological Behavior
从有缺陷的小胶质细胞到皮质活动和病理行为
- 批准号:
8444493 - 财政年份:2011
- 资助金额:
$ 42.6万 - 项目类别:
From Defective Microglia to Cortical Activity and Pathological Behavior
从有缺陷的小胶质细胞到皮质活动和病理行为
- 批准号:
8267617 - 财政年份:2011
- 资助金额:
$ 42.6万 - 项目类别:
From Defective Microglia to Cortical Activity and Pathological Behavior
从有缺陷的小胶质细胞到皮质活动和病理行为
- 批准号:
8826810 - 财政年份:2011
- 资助金额:
$ 42.6万 - 项目类别:
From Defective Microglia to Cortical Activity and Pathological Behavior
从有缺陷的小胶质细胞到皮质活动和病理行为
- 批准号:
8645751 - 财政年份:2011
- 资助金额:
$ 42.6万 - 项目类别:
From Defective Microglia to Cortical Activity and Pathological Behavior
从有缺陷的小胶质细胞到皮质活动和病理行为
- 批准号:
8472381 - 财政年份:2011
- 资助金额:
$ 42.6万 - 项目类别:
TCF/LEF function during intestinal maintenance and colon tumorigenesis
TCF/LEF 在肠道维持和结肠肿瘤发生过程中的功能
- 批准号:
8234099 - 财政年份:2011
- 资助金额:
$ 42.6万 - 项目类别:
From Defective Microglia to Cortical Activity and Pathological Behavior
从有缺陷的小胶质细胞到皮质活动和病理行为
- 批准号:
8085590 - 财政年份:2011
- 资助金额:
$ 42.6万 - 项目类别:
TCF/LEF function during intestinal maintenance and colon tumorigenesis
TCF/LEF 在肠道维持和结肠肿瘤发生过程中的功能
- 批准号:
7786716 - 财政年份:2010
- 资助金额:
$ 42.6万 - 项目类别:
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