Core 2: Stanford Breast Metastasis Center Organoid Core
核心 2:斯坦福乳腺转移中心类器官核心
基本信息
- 批准号:10272393
- 负责人:
- 金额:$ 26.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-14 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAddressAirBackBreastBreast Cancer ModelBreast Cancer PatientBreast cancer metastasisCRISPR interferenceCRISPR/Cas technologyCancer BiologyCancer RelapseCarcinomaCell CommunicationCell LineCellsCharacteristicsClinicalClinical PathologyClustered Regularly Interspaced Short Palindromic RepeatsCollaborationsCommunicationConsentCryopreservationDevelopmentDiseaseDrug ModelingsDrug TargetingDrug resistanceEpithelialEpithelial CellsExperimental ModelsFeedbackGenesGeneticGenetic EngineeringGenomicsGoalsHeterogeneityHistologicHistologyHumanImmuneImmune EvasionImmunological ModelsImpairmentInformation DisseminationLiquid substanceMalignant Epithelial CellMalignant NeoplasmsMediatingMetastatic breast cancerMethodsModelingMusMycoplasmaNeoplasm MetastasisOccupational activity of managing financesOrganoidsPathologyPatientsPatternPhagocytosisPharmaceutical PreparationsPhysiologicalPopulationPositioning AttributePrimary NeoplasmProductionPropertyProteomicsProtocols documentationQuality ControlResearchResearch PersonnelResourcesServicesSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationStandardizationStudy modelsSystemTechnologyTestingTissuesTumor TissueTumor-DerivedWorkanticancer researchbiobankbreast cancer genomicscancer subtypescell typedigitalfunctional genomicsgenome sequencingglycosylationin vitro Modelmacrophagemalignant breast neoplasmmammarymolecular subtypesnano-stringnext generationnovelpatient derived xenograft modelreconstitutionresponsesingle-cell RNA sequencingsynergismtherapeutic targettherapy resistanttooltranscriptometumortumor microenvironmenttumor-immune system interactionswhole genome
项目摘要
Abstract/Project Summary
Breast cancer research is substantially hampered by lack of experimental models that efficiently reflect
physiological disease necessary to provide a comprehensive understanding of metastatic disease. Conventional
cell lines and PDX models have contributed greatly to our understanding of breast cancer biology, but are
inefficiently derived, do not fully capture the heterogeneity across breast cancer subtypes and rarely mimic
clinical observations. Advancements in 3D organoid models from our lab and others have shown that patient-
derived organoids (PDOs) can be generated efficiently, retain histologic and genetic features of originating tumor,
closely mimic patient drug response and are amendable to scale for genomic functional screens. Recently, the
Kuo lab developed next generation PDOs by developing an Air-Liquid Interface (ALI) culture system that enables
culture of tumor epithelium en bloc with endogenous immune stroma (Cell, 2018). The advent of ALI organoid
culture provides critical experimental models for studying the tumor microenvironment. Here, the Organoid Core
provides essential patient derived organoid models for identifying the evolutionary dynamics and
microenvironmental determinants of metastatic breast cancer for Stanford Breast Metastasis Center
investigators.
Co-led by breast cancer genomics expert Dr. Christina Curtis and organoid pioneer Dr. Calvin Kuo,
the Stanford Breast Metastasis Center Organoid Core is uniquely positioned and qualified to address the
unmet needs highlighted in this RFA: Metastasis Research Network, by providing novel experimental models to
study metastatic dissemination patterns, cellular microenvironment crosstalk, and drug response. Here, the
organoid core will provide patient-derived breast cancer submerged organoids from primary and metastatic
tissue to study targeted drug resistance and to define specific metastatic patterns of breast cancer sub-clones
in Project 1, along with genomic functional screens using CRISPR/CAS9 and macrophage-mediated
phagocytosis in Project 3. Novel human breast cancer ALI organoid models will be extensively characterized
as compared to originating tissue in collaboration with Projects 1 and 2. Further, ALI culture conditions will be
optimized for functional tumor-immune crosstalk studies with Project 3. Upon successful completion, novel
organoid models will provide critical experimental tools for defining metastatic driver genes and identifying
therapeutic targets to overcome drug resistance and immune evasion.
摘要/项目摘要
乳腺癌研究因缺乏有效反映乳腺癌的实验模型而受到严重阻碍。
生理性疾病,提供转移性疾病的全面了解所必需的。常规
细胞系和PDX模型极大地促进了我们对乳腺癌生物学的理解,但
推导效率低下,无法完全捕捉乳腺癌亚型之间的异质性,并且很少模仿
临床观察。我们实验室和其他实验室的3D类器官模型的进展表明,患者-
衍生的类器官(PDO)可以有效地产生,保留原始肿瘤的组织学和遗传学特征,
密切模拟患者药物反应,并可根据基因组功能筛选的规模进行修改。近日
Kuo实验室通过开发气液界面(ALI)培养系统开发了下一代PDO,
肿瘤上皮与内源性免疫基质的整体培养(Cell,2018)。ALI类器官的出现
培养为研究肿瘤微环境提供了关键的实验模型。这里,类器官核心
提供了用于鉴定进化动力学的基本的患者来源的类器官模型,
斯坦福大学乳腺转移中心转移性乳腺癌的微环境决定因素
investigators.
由乳腺癌基因组学专家克里斯蒂娜·柯蒂斯博士和类器官先驱卡尔文·郭博士共同领导,
斯坦福大学乳腺转移中心类器官核心是唯一定位和资格,以解决
本RFA中强调了未满足的需求:转移研究网络,通过提供新颖的实验模型,
研究转移性播散模式、细胞微环境串扰和药物反应。这里
类器官核心将提供来自原发性和转移性乳腺癌的患者来源的浸没类器官,
研究靶向耐药性并确定乳腺癌亚克隆的特定转移模式
在项目1中,沿着使用CRISPR/CAS 9和巨噬细胞介导的基因组功能筛选,
项目3中的吞噬作用。新型人乳腺癌ALI类器官模型将被广泛表征
与与项目1和2合作的原始组织相比。此外,ALI培养条件将是
针对项目3的功能性肿瘤免疫串扰研究进行了优化。成功完成后,小说
类器官模型将为定义转移驱动基因和识别
治疗靶点,以克服耐药性和免疫逃避。
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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CALVIN J KUO其他文献
CALVIN J KUO的其他文献
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{{ truncateString('CALVIN J KUO', 18)}}的其他基金
Intestinal organoid modeling of SARS-CoV-2-stimulated innate and adaptive immunity
SARS-CoV-2 刺激的先天性和适应性免疫的肠道类器官模型
- 批准号:
10319858 - 财政年份:2021
- 资助金额:
$ 26.33万 - 项目类别:
Core 2: Stanford Breast Metastasis Center Organoid Core
核心 2:斯坦福乳腺转移中心类器官核心
- 批准号:
10704695 - 财政年份:2021
- 资助金额:
$ 26.33万 - 项目类别:
Immunotherapy Modeling in Organoids Co-preserving Tumor and Infiltrating Immune Compartments
共保存肿瘤和浸润免疫区室的类器官的免疫治疗模型
- 批准号:
10212018 - 财政年份:2021
- 资助金额:
$ 26.33万 - 项目类别:
Intestinal organoid modeling of SARS-CoV-2-stimulated innate and adaptive immunity
SARS-CoV-2 刺激的先天性和适应性免疫的肠道类器官模型
- 批准号:
10654752 - 财政年份:2021
- 资助金额:
$ 26.33万 - 项目类别:
Immunotherapy Modeling in Organoids Co-preserving Tumor and Infiltrating Immune Compartments
共保存肿瘤和浸润免疫区室的类器官的免疫治疗模型
- 批准号:
10586140 - 财政年份:2021
- 资助金额:
$ 26.33万 - 项目类别:
Immunotherapy Modeling in Organoids Co-preserving Tumor and Infiltrating Immune Compartments
共保存肿瘤和浸润免疫区室的类器官的免疫治疗模型
- 批准号:
10374163 - 财政年份:2021
- 资助金额:
$ 26.33万 - 项目类别:
Intestinal organoid modeling of SARS-CoV-2-stimulated innate and adaptive immunity
SARS-CoV-2 刺激的先天性和适应性免疫的肠道类器官模型
- 批准号:
10450851 - 财政年份:2021
- 资助金额:
$ 26.33万 - 项目类别:
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