Molecular, Cellular, and Tissue Characterization Unit
分子、细胞和组织表征单元
基本信息
- 批准号:10246896
- 负责人:
- 金额:$ 74.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-19 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalATAC-seqAftercareAntibodiesAntigen PresentationArchitectureAtlasesBiopsyCDK4 geneCellsChemicalsChromatinCollectionCost ControlDetectionDisseminated Malignant NeoplasmDrug TargetingEventExtracellular MatrixFaceFluorescenceFluorescence MicroscopyFormalinFreezingGene Expression ProfileGenerationsGenomeGenomic InstabilityGenomicsGoalsHumanImageImage AnalysisImmuneImmune checkpoint inhibitorImmunofluorescence ImmunologicImmunohistochemistryImmunomodulatorsIndividualIonsLabelLesionMalignant NeoplasmsMalignant neoplasm of prostateMapsMechanicsMetastatic breast cancerMolecularMutationOligonucleotidesParaffin EmbeddingPathway interactionsPatientsPeriodicityPharmaceutical PreparationsPlant ResinsPrimary NeoplasmProductionRadiology SpecialtyResistanceResolutionSamplingScanning Electron MicroscopySignal TransductionSpecimenStainsStromal CellsTechnologyTherapeuticTimeTissuesWorkbasecancer cellcastration resistant prostate cancercohortcombinatorialcomparativedrug efficacyepigenomeepigenomicsexhaustionhigh dimensionalityhormone receptor-positivehormone therapyimmune checkpointimprovedindexingindividual patientinhibitor/antagonistinsertion/deletion mutationmalignant breast neoplasmmolecular imagingneoplastic cellnext generationparaformprospectiveresistance mechanismsingle cell sequencingtargeted treatmenttechnology developmenttriple-negative invasive breast carcinomatumortumor-immune system interactions
项目摘要
ABSTRACT – Characterization Unit
The Characterization Unit will be responsible for omic and multiscale image analyses of pairs of biopsies taken
pre- and on/post treatment from patients with metastatic breast and prostate cancer undergoing treatment with
current generation pathway and immune checkpoint targeted treatments. The paired biopsies represent sensitive
and resistant lesions and comparative analyses of these enable discovery of mechanisms of resistance. Twenty
pairs of samples each from three treatment cohorts will be analyzed. Specifically, (a) hormone-receptor positive
breast cancer (HRBC) undergoing treatment with a CDK4/6 inhibitor in combination with endocrine therapy, (b)
triple negative breast cancer (TNBC) undergoing treatment with a PARP inhibitor and an immunomodulatory
agent, and (c) castration resistant prostate cancer (CRPC) undergoing treatment with enzalutamide. Aim 1 will
analyze OCT frozen biopsies using Topographic Single Cell Sequencing (TSCS) to cells isolated from spatially
defined regions to enable analysis of genomic copy number changes, mutations, and indels and Single-cell
Combinatorial Indexing ATAC-seq (sci-ATAC-seq) to elucidate chromatin accessibility in single cells. The cells
analyzed using sci-ATAC-seq will be computationally mapped to cyclic immunofluorescence (cycIF) stained sec-
tions based on predicted gene expression patterns. Aim 2 will analyze formalin-fixed paraffin embedded (FFPE)
sections using multiplex immunohistochemistry (mIHC) and cycIF to assess the tumor and stromal cell compo-
sition and the molecular states thereof. In addition, next generation cycIF using oligonucleotide labeled antibod-
ies will be developed to enable high dimension cycIF staining and imaging using both conventional and super
resolution fluorescence microscopy. Aim 3 will analyze paraformaldehyde fixed, resin embedded (PFRE) speci-
mens using Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) to identify ultrastructural changes in
2D images and targeted 3D volumes with 4-nm resolution. In addition, work in this aim will assess the utility of
Serial Block Face Imaging SEM (SBFI) to define 3D ultrastructural changes in larger volumes, but at lower res-
olution.
摘要-表征单元
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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JOE W. GRAY其他文献
JOE W. GRAY的其他文献
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{{ truncateString('JOE W. GRAY', 18)}}的其他基金
Understanding the Impact of Microscale and Nanoscale Heterogeneity and Resistance
了解微米级和纳米级异质性和阻力的影响
- 批准号:
10166790 - 财政年份:2020
- 资助金额:
$ 74.64万 - 项目类别:
Omic and Multidimensional Spatial Atlas of Metastatic Breast and Prostate Cancers
转移性乳腺癌和前列腺癌的组学和多维空间图谱
- 批准号:
9788351 - 财政年份:2018
- 资助金额:
$ 74.64万 - 项目类别:
Omic and Multidimensional Spatial Atlas of Metastatic Breast and Prostate Cancers
转移性乳腺癌和前列腺癌的组学和多维空间图谱
- 批准号:
10005913 - 财政年份:2018
- 资助金额:
$ 74.64万 - 项目类别:
Omic and Multidimensional Spatial Atlas of Metastatic Breast and Prostate Cancers
转移性乳腺癌和前列腺癌的组学和多维空间图谱
- 批准号:
10471933 - 财政年份:2018
- 资助金额:
$ 74.64万 - 项目类别:
Molecular, Cellular, and Tissue Characterization Unit
分子、细胞和组织表征单元
- 批准号:
10471935 - 财政年份:2018
- 资助金额:
$ 74.64万 - 项目类别:
Molecular, Cellular, and Tissue Characterization Unit
分子、细胞和组织表征单元
- 批准号:
10005916 - 财政年份:2018
- 资助金额:
$ 74.64万 - 项目类别:
Omic and Multidimensional Spatial Atlas of Metastatic Breast and Prostate Cancers
转移性乳腺癌和前列腺癌的组学和多维空间图谱
- 批准号:
10246894 - 财政年份:2018
- 资助金额:
$ 74.64万 - 项目类别:
Omic and Multidimensional Spatial Atlas of Metastatic Breast and Prostate Cancers
转移性乳腺癌和前列腺癌的组学和多维空间图谱
- 批准号:
10005901 - 财政年份:2018
- 资助金额:
$ 74.64万 - 项目类别:
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