MOSAIC: Targeting the Tissue State
MOSAIC:针对组织状态
基本信息
- 批准号:10729422
- 负责人:
- 金额:$ 34.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-18 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAftercareAstrocytesBiologicalBiopsyBone MarrowBrainCell NucleusCell ProliferationCell physiologyCellsChemoresistanceConditioned Culture MediaDisease ProgressionEndothelial CellsExtracellular MatrixFemaleGenomicsGlioblastomaGliomaGoalsHeterogeneityImageImmuneImmunocompetentImmunotherapyIn VitroInfiltrationInflammatoryInterleukin-10Interleukin-6LigandsMacrophageMagnetic Resonance ImagingMalignant GliomaMathematicsMediatingMesenchymalMicrogliaModelingMolecularMutationMyeloid CellsNeuronsNon-MalignantOligodendrogliaOncologyPatientsPatternPericytesPhenotypePopulationReceptor InhibitionRegimenRoleSamplingSignal PathwaySignal TransductionSliceSystems AnalysisT-LymphocyteTNF geneTestingTherapeuticTissuesTranslationsTumor Necrosis Factor ReceptorTumor PromotionXenograft Modelanti-PD-L1cell behaviorcell communitycytokineeffective therapyimaging facilitiesin vivoinsightmalememberneoplastic cellnovel therapeutic interventionprogenitorradiological imagingreceptorreceptor expressionrecruittemozolomidetherapy resistanttranscriptome sequencingtreatment responsetumortumor growthtumor initiationtumor microenvironmenttumor progression
项目摘要
SUMMARY: PROJECT 1: TARGETING GLIOMA TISSUE STATES
Glioblastoma (GBM) displays extensive cellular heterogeneity which represents a major obstacle for effective
treatment. This cellular heterogeneity not only consists of multiple tumor cell mutation factors that drive distinct
tumor cell behavior, but also impacts various non-tumor cells, contributing to tumor initiation, progression, and
treatment response. In fact, GBM’s microenvironment is multifaceted and consists of soluble factors, extracellular
matrix components, tissue-resident cells (neuron, astrocytes, endothelial cells, pericytes, etc.) and resident (e.g.
microglia) or recruited (e.g. bone-marrow derived macrophages) immune cells. Importantly, changes in the
cellular composition and cellular phenotypes can alter GBM tissue states to drive tumor growth and therapeutic
resistance. Thus, identifying the unique cellular composition and deciphering the multifaceted bidirectional
network between tumor cells and tumor microenvironment signals in various GBM tissue states can lead to
identification of novel therapeutic strategies.
Our preliminary studies using single nucleus RNAseq of pre- and post-treatment GBM has identified 3 tissue
states, corresponding to patterns of cohabitation of tumor and non-tumoral cell subpopulations. These
correspond to infiltrated brain, highly cellular proliferating tumor, and astrocytic / inflamed reactive tissue, which
is observed in the post-treatment samples and enriched in specific populations of myeloid cells and
mesenchymal glioma cells. Co-habitation of specific non-tumor cellular phenotypes in the glioma
microenvironment may influence glioma states signatures (astrocyte-like/mesenchymal, progenitor, proliferative)
that associate with tumor progression and therapeutic response. The goal of this project is to define the patterns
of cellular cohabitation associated with the tissue states and the cross-talk signals that influence local tissue
state, phenotypic expression, transitions and disease progression. Because of its known role in cross-talk
between specific populations in GBM, we will initially test the effects of targeting TWEAK-Fn14 signaling to drive
changes in tissue state. We hypothesize that targeting this as well as other key cross-talk signaling pathways
will induce tissue state transitions with corresponding alterations in cellular populations that will render tumors
more sensitive to therapeutic vulnerabilities and can be leveraged to slow tumor growth/progression.
To investigate the potential impact of such key states and their cross-talk, we propose three aims. Aim 1 focuses
on refining our understanding of glioma tissue states in both the pre- and post- treatment setting. Aim 2
investigates cross talk between the glioma cells and their microenvironment and how it may influence
progression. Aim 3 looks more locally at how cross-talk perturbations may impact tissue state transition.
项目1:靶向胶质瘤组织状态
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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Nhan L Tran其他文献
Uncertainty Quantification in Radiogenomics: EGFR Amplification in Glioblastoma
放射基因组学中的不确定性定量:胶质母细胞瘤中的 EGFR 扩增
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
Leland S. Hu;Lujia Wang;A. Hawkins;Jenny M. Eschbacher;K. Singleton;P. Jackson;K. Clark;Christopher P. Sereduk;Sen Peng;Panwen Wang;Junwen Wang;L. Baxter;Kris A. Smith;Gina L. Mazza;Ashley M. Stokes;B. Bendok;Richard S. Zimmerman;C. Krishna;Alyx Porter;M. Mrugala;J. Hoxworth;Teresa Wu;Nhan L Tran;Kristin R Swanson;Jing Li - 通讯作者:
Jing Li
Inhibition of phosphatidylinositol 3-kinase by PX-866 suppresses temozolomide-induced autophagy and promotes apoptosis in glioblastoma cells
- DOI:
10.1186/s10020-019-0116-z - 发表时间:
2019-11-14 - 期刊:
- 影响因子:5.7
- 作者:
Harder, Bryan G.;Peng, Sen;Nhan L Tran - 通讯作者:
Nhan L Tran
Nhan L Tran的其他文献
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{{ truncateString('Nhan L Tran', 18)}}的其他基金
Chemosensitization of Glioblastoma by Propentofylline
丙茶碱对胶质母细胞瘤的化疗增敏作用
- 批准号:
10480470 - 财政年份:2022
- 资助金额:
$ 34.34万 - 项目类别:
Targeting the Fn14-Rac1 signaling pathway in invasive gliomas
靶向侵袭性胶质瘤中的 Fn14-Rac1 信号通路
- 批准号:
7874678 - 财政年份:2008
- 资助金额:
$ 34.34万 - 项目类别:
Targeting the Fn14-Rac1 signaling pathway in invasive gliomas
靶向侵袭性胶质瘤中的 Fn14-Rac1 信号通路
- 批准号:
8073615 - 财政年份:2008
- 资助金额:
$ 34.34万 - 项目类别:
Targeting the Fn14-Rac1 signaling pathway in invasive gliomas
靶向侵袭性胶质瘤中的 Fn14-Rac1 信号通路
- 批准号:
8260789 - 财政年份:2008
- 资助金额:
$ 34.34万 - 项目类别:
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