Developmental Origins of Neural Tumors Using a Novel Genetic Inducible Analysis
使用新型遗传诱导分析研究神经肿瘤的发育起源
基本信息
- 批准号:7713166
- 负责人:
- 金额:$ 17.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-08-15 至 2014-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAnimal ModelBiologyBrain NeoplasmsCause of DeathCell CountCell LineageCell NucleusCellsCerebellumCharacteristicsChildClassificationClinicalCollagenCytoplasmic GranulesDependenceDesmoplasticDevelopmentDiagnostic Neoplasm StagingDorsalErinaceidaeFacultyFosteringFutureGene Expression ProfileGenesGeneticGenetic TechniquesGenomicsGlial Fibrillary Acidic ProteinGoalsGolgi ApparatusHumanInheritedInterneuronsK-Series Research Career ProgramsKnockout MiceLaboratoriesLip structureMalignant NeoplasmsMalignant neoplasm of brainMapsMentorsMentorshipMethodologyModalityMolecularMolecular ProfilingMusMutateMutationNeuroepithelial, Perineurial, and Schwann Cell NeoplasmNeuronsOncogenicOutcomePathway interactionsPlayPositioning AttributeProliferatingProteinsPurkinje CellsRadiationResearchResearch PersonnelResistanceRoleScientistSecondary toSignal PathwaySignal TransductionStagingSyndromeSystemTechniquesTestingTherapeuticTimeToxic effectTreatment outcomeTumor BiologyTumor stageVentricularage groupbasecareer developmentcell typegranule cellimprovedin vivoloss of function mutationmedulloblastomamortalitymouse modelmutantneoplastic cellnestin proteinneural precursor cellneurodevelopmentnovelpostnatalprecursor cellprogramspublic health relevanceresearch studysuccesstumortumor progression
项目摘要
DESCRIPTION (provided by applicant): Project Summary: Medulloblastoma is a malignant brain tumor in children with significant mortality and poor outcomes secondary to toxicity of cun-ent therapy. Evidence points to medulloblastoma originating from neural precursor cells located within the cerebelluni and roles for Sonic hedgehog and Wnt signaling pathways in this brain tumor have also been implicated. The long-term goals ofthis project are to better understand the developmental origins and molecular signatures of sporadic medulloblastomas by studying their characteristics in genetically and pathophysiologically relevant mouse models in order to improve treatment options. I hypothesize that each particular medulloblastoma subtype arises from distinct germinal zones of the cerebellum and consequentially have distinctive molecular signatures and dependence on signaling pathways related to their tumor cell of origin. I will use a novel genetic technique to generate mosaic mice where genes are conditionally mutated at endogenous loci and simultaneously marked with GFP in single cells under both temporal and cell type-specific control. This sophisticated approach will allow me to address fundamental questions in medulloblastoma biology such as tumor cell of origin, role of microenvironment in promoting or restricting tumor formation, unambiguously determine the molecular profiles of GFP+ marked tumor ceils during different tumor stages, as well as characterize treatment-resistant GFP+ tumor cells. These studies will be performed under the mentorship of Dr. Alexandra Joyner, an expert in neural development and mouse genetics, and the co-mentorship of Dr. Eric Holland, an expert in brain tumor biology. Both mentors and their laboratories provide the optimal setting for developing expertise in the techniques and methodologies required for future success in this field after my transition to an independent faculty position during the period of this K award. Weill Cornell's outstanding institutional commitment to fostering my career development is shown by limiting clinical responsibilities and administrative duties to allow at least 75% effort devoted to research, and providing independent research space and a tenure-track faculty position at the time of my transition to an independent research scientist.
Public Health Relevance: Medulloblastoma is the most common brain tumor in children and one of the leading causes of death in this age group. The goal ofthis application is to better understand the molecular basis of medulloblastoma using genetically relevant mouse models with the aim of identifying new target(s) for therapy for this devastating cancer.
描述(由申请人提供):项目概述:髓母细胞瘤是一种儿童恶性脑肿瘤,具有显著的死亡率和继发于当前治疗毒性的不良结局。有证据表明髓母细胞瘤起源于位于小脑内的神经前体细胞,并且也涉及Sonic hedgehog和Wnt信号通路在这种脑肿瘤中的作用。该项目的长期目标是通过在遗传学和病理生理学相关的小鼠模型中研究散发性髓母细胞瘤的特征,以更好地了解其发育起源和分子特征,从而改善治疗方案。我推测,每一个特定的髓母细胞瘤亚型来自不同的生发区的小脑,因此有独特的分子特征和依赖信号通路相关的肿瘤细胞的起源。我将使用一种新的遗传技术来产生嵌合体小鼠,其中基因在内源性位点发生条件突变,并同时在时间和细胞类型特异性控制下在单细胞中用GFP标记。这种复杂的方法将使我能够解决髓母细胞瘤生物学中的基本问题,如肿瘤细胞的起源,微环境在促进或限制肿瘤形成中的作用,明确确定GFP+标记的肿瘤细胞在不同肿瘤阶段的分子特征,以及表征治疗抗性GFP+肿瘤细胞。这些研究将在神经发育和小鼠遗传学专家Alexandra Joyner博士和脑肿瘤生物学专家Eric Holland博士的指导下进行。导师和他们的实验室都提供了最佳的设置,为发展专业知识的技术和方法所需的未来在这一领域的成功后,我过渡到一个独立的教师职位在此期间的K奖。威尔康奈尔大学的杰出机构承诺,以促进我的职业发展是通过限制临床责任和行政职责,让至少75%的努力致力于研究,并提供独立的研究空间和终身教职的时候,我过渡到一个独立的研究科学家。
公共卫生相关性:髓母细胞瘤是儿童中最常见的脑肿瘤,也是该年龄组死亡的主要原因之一。本申请的目的是使用遗传相关的小鼠模型更好地了解髓母细胞瘤的分子基础,目的是确定治疗这种毁灭性癌症的新靶点。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Praveen B. Raju其他文献
Praveen B. Raju的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Praveen B. Raju', 18)}}的其他基金
Inducing neural maturation in medulloblastoma by targeting EZH2
通过靶向 EZH2 诱导髓母细胞瘤神经成熟
- 批准号:
10700897 - 财政年份:2022
- 资助金额:
$ 17.15万 - 项目类别:
Inducing neural maturation in medulloblastoma by targeting EZH2
通过靶向 EZH2 诱导髓母细胞瘤神经成熟
- 批准号:
10446714 - 财政年份:2022
- 资助金额:
$ 17.15万 - 项目类别:
Inducing neural maturation in medulloblastoma by targeting EZH2
通过靶向 EZH2 诱导髓母细胞瘤神经成熟
- 批准号:
10416148 - 财政年份:2021
- 资助金额:
$ 17.15万 - 项目类别:
Developmental Origins of Neural Tumors Using a Novel Genetic Inducible Analysis
使用新型遗传诱导分析研究神经肿瘤的发育起源
- 批准号:
8516603 - 财政年份:2009
- 资助金额:
$ 17.15万 - 项目类别:
Developmental Origins of Neural Tumors Using a Novel Genetic Inducible Analysis
使用新型遗传诱导分析研究神经肿瘤的发育起源
- 批准号:
7910489 - 财政年份:2009
- 资助金额:
$ 17.15万 - 项目类别:
Developmental Origins of Neural Tumors Using a Novel Genetic Inducible Analysis
使用新型遗传诱导分析研究神经肿瘤的发育起源
- 批准号:
8116695 - 财政年份:2009
- 资助金额:
$ 17.15万 - 项目类别:
Developmental Origins of Neural Tumors Using a Novel Genetic Inducible Analysis
使用新型遗传诱导分析研究神经肿瘤的发育起源
- 批准号:
8308642 - 财政年份:2009
- 资助金额:
$ 17.15万 - 项目类别:
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 17.15万 - 项目类别:
Grant-in-Aid for Early-Career Scientists