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

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建立肿瘤进化模型

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)

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Raul Rabadan其他文献

Raul Rabadan的其他文献

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{{ 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:
Administrative Core
行政核心
  • 批准号:
    8866150
  • 财政年份:
    2015
  • 资助金额:
    $ 36.64万
  • 项目类别:
CORE C Rabadan
核心C拉巴丹
  • 批准号:
    10614999
  • 财政年份:
    2014
  • 资助金额:
    $ 36.64万
  • 项目类别:

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