Project 1: Modeling tumor evolution in mouse and organoid models
项目 1:在小鼠和类器官模型中模拟肿瘤进化
基本信息
- 批准号:8866152
- 负责人:
- 金额:$ 36.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-05-19 至 2020-04-30
- 项目状态:已结题
- 来源:
- 关键词:AdenocarcinomaAffectAnabolismAndrogen ReceptorAndrogensAntiandrogen TherapyBiologicalBiological AssayBiological ModelsCellsClinicClinicalClonal EvolutionCollaborationsColorDataData AnalysesDrug TargetingEpithelialEpitheliumEventEvolutionGene Expression ProfileGenetically Engineered MouseGlioblastomaGrowthHematologic NeoplasmsHeterogeneityHomeostasisIndividualInvestigationLesionLongitudinal StudiesMalignant NeoplasmsMalignant neoplasm of prostateMapsMediatingMethodsModelingMolecularMusNatural regenerationOrganoidsPatientsPatternPharmaceutical PreparationsPhenotypePlayProstateProstatic NeoplasmsRecording of previous eventsReporterResistanceRoleSamplingSeverity of illnessSolid NeoplasmSourceStagingStem cellsTherapeuticTherapeutic AgentsTissuesTreatment FailureTumor-Associated ProcessVariantabirateronebasecancer initiationcastration resistant prostate cancerin vivoinnovationinsightmathematical methodsmathematical modelmouse modelnovelreceptor functionrecombinaseresponsetherapy resistanttranscriptomicstumortumor progression
项目摘要
Project 1: Modeling tumor evolution in mouse and organoid models
ABSTRACT
Clonal evolution and tumor heterogeneity are believed to play key roles in generating patient-specific
variations in tumor phenotype during cancer progression and in the emergence of treatment resistance.
Although clonal evolution has been well studied in hematological malignancies, it is less understood in solid
tumors, in part due to difficulties in performing longitudinal assessments. To overcome many of the challenges
of studying clonal evolution in solid tumors, we developed a reductionist model system for investigating clonal
histories and demonstrated its feasibility in prostate cancer. In preliminary studies, we show that multi-color
lineage-tracing can be employed to follow clonal fates in genetically-engineered mouse models of prostate
cancer, and that a novel organoid culture approach can be used for longitudinal assessments of clonal growth
and response to therapy. These approaches will be used together with single-cell transcriptome analyses of
tumor heterogeneity and sophisticated mathematical approaches that will allow us to investigate whether
prostate cancer follows a linear or branched evolutionary pattern.
We will now investigate clonal evolution in prostate cancer by pursuing three specific aims: 1) investigation
of clonal evolution during tissue homeostasis and regeneration by employing multi-color lineage-tracing and
organoid culture to follow clonal histories; 2) analysis of clonal evolution during cancer progression using multi-
color lineage-tracing in mouse models of prostate cancer together with organoid culture for longitudinal
analyses, with data analyzed by single-cell transcriptomics and mathematical modeling; and 3) investigation of
the clonal response to therapy by longitudinal analyses of clonal evolution in organoid culture after drug
treatments. These studies will be greatly facilitated by the analyses of evolutionary moduli spaces and
topological data analyses performed in collaboration with the Mathematical Core, as well as by interactions
with Projects 2 and 3. Taken together, our proposed studies will provide robust mathematical analyses of a
reductionist model of clonal evolution for solid tumors, providing insights into the emergence of resistance to
therapy.
项目 1:在小鼠和类器官模型中模拟肿瘤进化
抽象的
克隆进化和肿瘤异质性被认为在产生患者特异性方面发挥着关键作用
癌症进展过程中肿瘤表型的变化以及治疗耐药性的出现。
尽管克隆进化在血液恶性肿瘤中已得到充分研究,但在实体瘤中的了解却较少。
肿瘤,部分原因是进行纵向评估的困难。克服许多挑战
在研究实体瘤中的克隆进化过程中,我们开发了一个还原论模型系统来研究克隆
历史并证明了其在前列腺癌中的可行性。在初步研究中,我们表明多色
谱系追踪可用于追踪前列腺基因工程小鼠模型中的克隆命运
癌症,并且一种新的类器官培养方法可用于克隆生长的纵向评估
以及对治疗的反应。这些方法将与单细胞转录组分析一起使用
肿瘤异质性和复杂的数学方法将使我们能够研究是否
前列腺癌遵循线性或分支的进化模式。
我们现在将通过追求三个具体目标来研究前列腺癌的克隆进化:1)研究
通过采用多色谱系追踪和技术,研究组织稳态和再生过程中的克隆进化
类器官培养以追踪克隆历史; 2) 使用多因素分析癌症进展过程中的克隆进化
前列腺癌小鼠模型的颜色谱系追踪与纵向类器官培养相结合
分析,通过单细胞转录组学和数学模型分析数据; 3) 调查
通过药物治疗后类器官培养中克隆进化的纵向分析来评估克隆对治疗的反应
治疗。进化模空间的分析将极大地促进这些研究
与数学核心合作以及通过交互进行拓扑数据分析
与项目 2 和 3 一起。总之,我们提出的研究将为
实体瘤克隆进化的还原论模型,提供了对耐药性出现的见解
治疗。
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 }}
Raul Rabadan其他文献
Raul Rabadan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('Raul Rabadan', 18)}}的其他基金
Towards a quantitative understanding of tumor evolution
定量了解肿瘤进化
- 批准号:
10642835 - 财政年份:2021
- 资助金额:
$ 36.64万 - 项目类别:
Towards a quantitative understanding of tumor evolution
定量了解肿瘤进化
- 批准号:
10297157 - 财政年份:2021
- 资助金额:
$ 36.64万 - 项目类别:
A transdisciplinary approach for dissecting stem cell states in prostate cancer
剖析前列腺癌干细胞状态的跨学科方法
- 批准号:
10686186 - 财政年份:2021
- 资助金额:
$ 36.64万 - 项目类别:
A transdisciplinary approach for dissecting stem cell states in prostate cancer
剖析前列腺癌干细胞状态的跨学科方法
- 批准号:
10491218 - 财政年份:2021
- 资助金额:
$ 36.64万 - 项目类别:
Towards a quantitative understanding of tumor evolution
定量了解肿瘤进化
- 批准号:
10454356 - 财政年份:2021
- 资助金额:
$ 36.64万 - 项目类别:
A transdisciplinary approach for dissecting stem cell states in prostate cancer
剖析前列腺癌干细胞状态的跨学科方法
- 批准号:
10273639 - 财政年份:2021
- 资助金额:
$ 36.64万 - 项目类别:
Uncovering Evolutionary History using the Topology of Genomic Data with Applications to HIV
利用基因组数据拓扑揭示进化历史并应用于艾滋病毒
- 批准号:
9037791 - 财政年份:2015
- 资助金额:
$ 36.64万 - 项目类别:
Uncovering Evolutionary History using the Topology of Genomic Data with Applications to HIV
利用基因组数据拓扑揭示进化历史并应用于艾滋病毒
- 批准号:
9265491 - 财政年份:2015
- 资助金额:
$ 36.64万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 36.64万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 36.64万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 36.64万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 36.64万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 36.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 36.64万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 36.64万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 36.64万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 36.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 36.64万 - 项目类别:
Studentship