Research Test-Bed Unit
研究试验台装置
基本信息
- 批准号:10539329
- 负责人:
- 金额:$ 55.91万
- 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:2021-12-10 至 2026-11-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalATAC-seqAddressAutomobile DrivingBackBedsBiologicalCancer ModelCell Differentiation processCellsChIP-seqChemoresistanceChromatinChromatin StructureComplexComputer AnalysisComputer ModelsCoupledCouplingDataDiseaseEnvironmentEpigenetic ProcessEventFeedbackFrequenciesGene ExpressionGenetic TranscriptionGenome MappingsGenomicsGoalsHi-CImageImaging DeviceImaging TechniquesImaging technologyKnowledgeMalignant NeoplasmsMalignant neoplasm of ovaryMapsModalityModelingModificationMolecularMolecular AnalysisMolecular ComputationsMolecular ConformationOutcomePathway interactionsPatternPhenotypePlatinumPluripotent Stem CellsPopulationPropertyRecurrenceRelapseRepressionResearchResistanceResolutionResourcesScienceSourceTechnologyTestingTheoretical modelTissuesUniversitiesWorkcancer cellcancer stem cellchemotherapyconventional therapyepigenomeepigenomicsfrontiergenome-widegenomic profileshigh resolution imaginghistone modificationimaging modalityimaging platformin vivoinhibitorinnovationnanoimagingnanomaterialsnanoscalephysical propertypressureprogramsrefractory cancerself-renewalsingle cell mRNA sequencingstem cell therapystem cellsstemnessstressorsuperresolution imagingtargeted agenttechnology developmenttechnology research and developmenttranscription factortranscriptional reprogrammingtranscriptometranscriptomicstumortumor initiationtumor microenvironmenttumor progressiontumorigenic
项目摘要
Research Test-Bed Unit: PROJECT SUMMARY
The overall goal of the U54 Northwestern University Center for Chromatin Nanoimaging in Cancer (NU-CCNIC)
is to develop and deploy a multi-scale chromatin nanoimaging platform together with molecular analyses and
computational modeling to characterize chromatin structure and transcriptional patterns associated with the
cancer stem cell (CSC) and chemoresistance phenotype. The immediate application of the proposed studies will
be ovarian cancer, a malignancy of unmet need. It has been speculated that CSCs represent the reservoir from
which recurrent, chemotherapy-resistant tumors arise. The key biological question addressed by this Center is
whether reprogramming of the transcriptome through epigenetic and chromatin organization-regulated
mechanisms leads to significant transcriptional plasticity, which is critical for CSCs to withstand and survive
stressors in the tumor environment, driving tumor initiation and progression. As part of NU-CCNIC, the Research
Test-Bed Unit (RTB) will provide source materials for the nanoimaging technologies developed by the
Technology Development Unit (TECH). These resources include cells and tissues at various transition points
between stem cell and non-stem cell phenotypes and between chemotherapy-sensitive and resistant states. The
studies conducted by the RTB will test the applicability of the Nanoscale Chromatin Imaging and Analysis (nano-
ChIA) platform and provide feedback to optimize its use. In addition, the RTB will perform state-of-the-art
computational genomic analyses of CSCs and chemotherapy-resistant cells, including single-cell mRNA
sequencing and genome mapping (e.g., Hi-C, ATAC-sequencing and ChIP-sequencing). The specific
objectives of this unit are: 1) To identify CSC-specific epigenomic features and 3D chromatin packing
conformations by integrating genome-wide maps of chromatin accessibility, contact frequency and gene
expression networks with high resolution nano-scale chromatin imaging features. 2) To identify whether the
transition to a chemotherapy-resistant state promotes stemness-like chromatin packing and conformation. Locus
specific epigenetic manipulations will be coupled with high resolution imaging technologies to investigate
resistant-state specific 3D chromatin packing and its relation to the CSC state. 3) To discover how global
epigenome manipulations induced by small enzymatic inhibitors block stemness and chemo-resistance through
alterations of chromatin packing. In all, the integrated interrogation of cancer through chromatin nanoimaging
methods (TECH) and genome-wide mapping (RTB) will discover how transcriptional plasticity of CSCs and
chemo-resistant cancer cells is regulated. The project is at the forefront of the field by using highly innovative
molecular and nanometer-scale chromatin imaging technologies to better understand the relationship between
higher level chromatin structure and key drivers of stemness and chemo-resistance in a disease that remains
lethal and difficult to treat.
研究试验台单元:项目总结
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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Daniela E Matei其他文献
Daniela E Matei的其他文献
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{{ truncateString('Daniela E Matei', 18)}}的其他基金
Understanding Metabolic Reprogramming in Platinum Resistant Ovarian Cancer
了解铂类耐药卵巢癌的代谢重编程
- 批准号:
10485428 - 财政年份:2022
- 资助金额:
$ 55.91万 - 项目类别:
Project 02: Tumor Methylomics Analysis Link with Racial Disparities in Ovarian Cancer
项目02:肿瘤甲基组学分析与卵巢癌种族差异的联系
- 批准号:
10488640 - 财政年份:2020
- 资助金额:
$ 55.91万 - 项目类别:
Project 02: Tumor Methylomics Analysis Link with Racial Disparities in Ovarian Cancer
项目02:肿瘤甲基组学分析与卵巢癌种族差异的联系
- 批准号:
10265428 - 财政年份:2020
- 资助金额:
$ 55.91万 - 项目类别:
An Epigenetic Strategy for Restoring Carboplatin Sensitivity in Ovarian Cancer
恢复卵巢癌卡铂敏感性的表观遗传学策略
- 批准号:
8806535 - 财政年份:2014
- 资助金额:
$ 55.91万 - 项目类别:
An Epigenetic Strategy for Restoring Carboplatin Sensitivity in Ovarian Cancer
恢复卵巢癌卡铂敏感性的表观遗传学策略
- 批准号:
8627405 - 财政年份:2014
- 资助金额:
$ 55.91万 - 项目类别:
Tissue-dynamics Imaging for Therapeutic Efficacy in Ovarian Cancer
组织动力学成像对卵巢癌治疗效果的影响
- 批准号:
9085110 - 财政年份:2013
- 资助金额:
$ 55.91万 - 项目类别:
Tissue-dynamics Imaging for Therapeutic Efficacy in Ovarian Cancer
组织动力学成像对卵巢癌治疗效果的影响
- 批准号:
8656327 - 财政年份:2013
- 资助金额:
$ 55.91万 - 项目类别:
Tissue-dynamics Imaging for Therapeutic Efficacy in Ovarian Cancer
组织动力学成像对卵巢癌治疗效果的影响
- 批准号:
8471381 - 财政年份:2013
- 资助金额:
$ 55.91万 - 项目类别:
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