Characterizing glioma heterogeneity with novel multiplexed nanoscale imaging technologies
利用新型复合纳米级成像技术表征神经胶质瘤的异质性
基本信息
- 批准号:10247568
- 负责人:
- 金额:$ 44.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-08 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:Adult GlioblastomaArchitectureAtlasesAutomationBar CodesBiologicalBiological ProcessCell CommunicationCellsComplexComputer softwareDNADataData SetDiagnosticDiffuseFunctional disorderFutureGene ExpressionGenesGenetic TranscriptionGlioblastomaGliomaHeterogeneityHistologicHumanImageImaging technologyImmuneIn SituInvadedLibrariesMalignant NeoplasmsMalignant neoplasm of brainMapsMessenger RNAMethodsMicroscopyModalityMolecularMorphologyNatureNon-MalignantOperative Surgical ProceduresOutputPathologyPatientsPhenotypeProcessProteinsProteomicsPublishingRNARadiology SpecialtyResearchResolutionSamplingSpecimenSpeedStructureTechniquesTechnologyTherapeutic InterventionTimeTissue ExpansionTissue SampleTissue imagingTissuesTranscriptTumor Cell InvasionTumor TissueTumor-Derivedantibody librariesbasebrain tissuecancer cellcell typecomputer frameworkconventional therapydesignfeature extractioninnovationinsightmolecular phenotypemultimodalitynanoscaleneoplastic cellnew technologynovelnovel therapeuticsprogramssingle cell sequencingsingle-cell RNA sequencingsuccesstherapeutic developmenttherapy resistanttooltranscriptomicstumortumor heterogeneity
项目摘要
Abstract:
Gliomas, with glioblastomas (GBM) in particular, are one of the most lethal human
malignancies due to lack of success with current conventional treatments due to their invasive
nature and heterogeneity. We will leverage expansion microscopy, a novel super-resolution
microscopy method, as a platform to develop novel tools for highly multiplexed in situ analysis to
generate comprehensive maps of GBM spatial heterogeneity and structure. We will use these
tools to help understand the molecular and morphological phenotypes of GBM invasion and
pathology, which we hope will guide future therapeutic interventions.
The proposed research will consist of three aims which seeks to develop novel in situ
analysis tools driven by biological questions in GBM organization: (1) Comprehensively map cell
types and states within GBM tumor tissue with high spatial resolution. To enable this, we will
develop an innovative method for highly multiplexed readout of RNA in expanded tissues with
tailored in situ gene expression panels based on single-cell RNA sequencing signatures. (2)
Study the nanoscale interactions between tumor cells and their surrounding microenvironment
that are implicated GBM invasion. To accomplish this, we will develop an approach for multiplexed
protein imaging with nanoscale resolution using DNA barcoded antibody libraries. (3) Develop a
scalable analysis platform with automation and analysis software to integrate multiplexed RNA
and protein imaging in the same sample. We will apply this platform to patient derived tumor
samples to understand the molecular and morphological phenotypes of invading GBM tumor cells,
as well as build a map of the spatial heterogeneity of GBM. These novel technologies to spatially
map molecular information in complex tissues will not only be invaluable for understanding glioma
and cancer, they will be broadly applicable to many other spatially complex biological processes.
文摘:
项目成果
期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cell type-specific inference of differential expression in spatial transcriptomics.
- DOI:10.1038/s41592-022-01575-3
- 发表时间:2022-09
- 期刊:
- 影响因子:48
- 作者:Cable, Dylan M.;Murray, Evan;Shanmugam, Vignesh;Zhang, Simon;Zou, Luli S.;Diao, Michael;Chen, Haiqi;Macosko, Evan Z.;Irizarry, Rafael A.;Chen, Fei
- 通讯作者:Chen, Fei
Spatiotemporal transcriptomic maps of whole mouse embryos at the onset of organogenesis.
在器官发生时,整个小鼠胚胎的时空转录组图。
- DOI:10.1038/s41588-023-01435-6
- 发表时间:2023-07
- 期刊:
- 影响因子:30.8
- 作者:Kumar, Abhishek Sampath;Tian, Luyi;Bolondi, Adriano;Hernandez, Amelia Aragones;Stickels, Robert;Kretzmer, Helene;Murray, Evan;Wittler, Lars;Walther, Maria;Barakat, Gabriel;Haut, Leah;Elkabetz, Yechiel;Macosko, Evan Z.;Guignard, Leo;Chen, Fei;Meissner, Alexander
- 通讯作者:Meissner, Alexander
Dissecting mammalian spermatogenesis using spatial transcriptomics.
- DOI:10.1016/j.celrep.2021.109915
- 发表时间:2021-11-02
- 期刊:
- 影响因子:8.8
- 作者:Chen H;Murray E;Sinha A;Laumas A;Li J;Lesman D;Nie X;Hotaling J;Guo J;Cairns BR;Macosko EZ;Cheng CY;Chen F
- 通讯作者:Chen F
Photoselective sequencing: microscopically guided genomic measurements with subcellular resolution.
光选择性测序:具有亚细胞分辨率的显微镜引导基因组测量。
- DOI:10.1038/s41592-023-01845-8
- 发表时间:2023
- 期刊:
- 影响因子:48
- 作者:Mangiameli,SarahM;Chen,Haiqi;Earl,AndrewS;Dobkin,JulieA;Lesman,Daniel;Buenrostro,JasonD;Chen,Fei
- 通讯作者:Chen,Fei
Highly sensitive spatial transcriptomics at near-cellular resolution with Slide-seqV2.
- DOI:10.1038/s41587-020-0739-1
- 发表时间:2021-03
- 期刊:
- 影响因子:46.9
- 作者:Stickels RR;Murray E;Kumar P;Li J;Marshall JL;Di Bella DJ;Arlotta P;Macosko EZ;Chen F
- 通讯作者:Chen F
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{{ truncateString('Fei Chen', 18)}}的其他基金
Spatial genomic tools to interrogate T cell clonotypes, tumor clones and the microenvironment
用于询问 T 细胞克隆型、肿瘤克隆和微环境的空间基因组工具
- 批准号:
10565141 - 财政年份:2023
- 资助金额:
$ 44.5万 - 项目类别:
Dissecting Nrf2-dependent HIF1a activation mechanism in arsenic-induced cancer stem-like cells
剖析砷诱导的癌症干细胞样细胞中 Nrf2 依赖性 HIF1a 激活机制
- 批准号:
10435281 - 财政年份:2021
- 资助金额:
$ 44.5万 - 项目类别:
Arsenic-Induced miRNA-199 and mriRNA-214 Deplete Mitochondrial DNA for the Generation of Cancer Stem-Like Cells
砷诱导的 miRNA-199 和 mRNA-214 消耗线粒体 DNA 以生成癌症干细胞样细胞
- 批准号:
10489836 - 财政年份:2021
- 资助金额:
$ 44.5万 - 项目类别:
Dissecting Nrf2-dependent HIF1a activation mechanism in arsenic-induced cancer stem-like cells
剖析砷诱导的癌症干细胞样细胞中 Nrf2 依赖性 HIF1a 激活机制
- 批准号:
10316248 - 财政年份:2021
- 资助金额:
$ 44.5万 - 项目类别:
Arsenic-Induced miRNA-199 and mriRNA-214 Deplete Mitochondrial DNA for the Generation of Cancer Stem-Like Cells
砷诱导的 miRNA-199 和 mRNA-214 消耗线粒体 DNA 以生成癌症干细胞样细胞
- 批准号:
10463263 - 财政年份:2021
- 资助金额:
$ 44.5万 - 项目类别:
Reduced Reactive Oxygen Species and Oxidative Phosphorylation in Arsenic-Induced Cancer Stem Cells
砷诱导的癌症干细胞中活性氧的减少和氧化磷酸化
- 批准号:
10441939 - 财政年份:2021
- 资助金额:
$ 44.5万 - 项目类别:
Dissecting Nrf2-dependent HIF1a activation mechanism in arsenic-induced cancer stem-like cells
剖析砷诱导的癌症干细胞样细胞中 Nrf2 依赖性 HIF1a 激活机制
- 批准号:
10515655 - 财政年份:2021
- 资助金额:
$ 44.5万 - 项目类别:
A high-resolution molecular and lineage atlas of the mouse brain using Slide-seq
使用 Slide-seq 绘制小鼠大脑的高分辨率分子和谱系图谱
- 批准号:
10088261 - 财政年份:2020
- 资助金额:
$ 44.5万 - 项目类别:
A cellular atlas of the primate and human basal ganglia
灵长类动物和人类基底神经节的细胞图谱
- 批准号:
10527335 - 财政年份:2020
- 资助金额:
$ 44.5万 - 项目类别:
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