Clonal analysis of cancer by mitochondrial DNA barcoding
通过线粒体 DNA 条形码对癌症进行克隆分析
基本信息
- 批准号:10612155
- 负责人:
- 金额:$ 46.3万
- 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:2023-05-11 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAcute Myelocytic LeukemiaArchitectureBar CodesBiological AssayBiological ProcessBlood CellsCancer BiologyCancer PatientCell LineageCell divisionCellsCessation of lifeChromatinChronic Lymphocytic LeukemiaClinicalClonal EvolutionClone CellsCommunitiesComplexDNADevelopmentDiagnosisDisease ProgressionDissectionEcosystemEpigenetic ProcessEvolutionFLT3 geneFundingGene ExpressionGene Expression ProfileGene Expression ProfilingGenerationsGeneticGenetic TranscriptionGoalsHead and Neck CancerHeterogeneityHumanIndividualKnowledgeLesionLiftingMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of pancreasMeasuresMessenger RNAMethodsMissionMitochondrial DNAModalityMolecularMutateMutation AnalysisMyeloproliferative diseaseNuclearOutcomeOutputPatientsPatternPerformancePopulationPositioning AttributeProceduresProductionPublic HealthRecurrenceRecurrent diseaseRelapseResearchResearch PersonnelResistanceResolutionSamplingShapesSolid NeoplasmStructureSystemTechnologyTumor BiologyUnited States National Institutes of HealthVariantWorkanticancer researchcancer cellcancer therapycell typecohortdriver mutationepigenomeepigenomicsexperienceheteroplasmyimprovedin vitro Assayin vitro ModelinnovationinsightleukemiamRNA Expressionmultiple omicsneoplastic cellnovel therapeutic interventionprogramssingle cell analysissingle cell sequencingtherapy resistanttooltranscriptometranscriptome sequencingtumortumor eradication
项目摘要
Project Summary/Abstract
All tumors contain a mixture of different cell types. Within the malignant cell population, clonal evolution
leads to the emergence of clones with different genetic lesions, and various biological processes shape
the co-occurrence of different cell states that are characterized by specific transcriptional/epigenetic
landscapes. This heterogeneity underlies the persistence of small populations of tumor cells through
treatment, leading to disease recurrence, which is a major clinical challenge. To better understand clonal
structures and transcriptional/epigenetic states in primary human tumors, there is an unmet need for
technologies that comprehensively profile these modalities at single-cell resolution. The PI/PDs Peter
van Galen and Vijay Sankaran have pioneered the use of mitochondrial DNA (mtDNA) variants as
naturally occurring cell barcodes to reconstruct clonal relationships between cells, and demonstrate
simultaneous profiling of transcriptional (scRNA-seq) and epigenetic (scATAC-seq) cell states. As such,
they are uniquely positioned to realize the potential of these technologies to illuminate the complex tumor
ecosystem and identify vulnerabilities of different malignant cell types. The long-term goal of this
research is to guide new therapeutic approaches that can effectively eradicate heterogeneous tumor
cells. The overall objective is to establish enabling technologies that can be used across a wide range of
tumors to transform our understanding of cancer biology. Drs. Van Galen and Sankaran, supported by a
strong network of collaborators, will jointly work towards this objective through two specific aims: 1)
Advance and validate experimental methods to simultaneously dissect the transcriptome, epigenome,
and clonal structures in cancer and 2) Proof-of-principle profiling of acute myeloid leukemia clones at
diagnosis that subsequently drive recurrence. In the first Aim, the investigators will build on their recent
accomplishments to establish optimized and validated procedures for multi-omic analysis of primary
human cancer cells with clear performance measures. In the second Aim, paired diagnosis-relapse
samples from a well-defined cohort of acute myeloid leukemia patients will be analyzed to demonstrate
the simultaneous dissection of longitudinal patterns of clonal evolution with transcriptional/epigenetic cell
states - a key proof-of-principle for this technology. The approach is innovative by leveraging naturally
occurring mtDNA variants to layer clonal relationships onto current state-of-the-art assays for single-cell
analysis. The proposed research is significant because the successful completion of the project would
equip the scientific community with new tools for the comprehensive molecular/cellular characterization
of cancer. The expected output is a repeatable, reliable approach for single-cell analysis of primary
human cancer cells at three core modalities, yielding transcriptional, epigenetic, and clonal resolution.
This will be enabling for NCI-funded projects in a range of tumor systems.
项目总结/文摘
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Vijay Ganesh Sankaran其他文献
Vijay Ganesh Sankaran的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Vijay Ganesh Sankaran', 18)}}的其他基金
Selective pressures from inherited variation impacting myeloproliferative neoplasm initiation
遗传变异的选择性压力影响骨髓增生性肿瘤的发生
- 批准号:
10651876 - 财政年份:2022
- 资助金额:
$ 46.3万 - 项目类别:
Selective pressures from inherited variation impacting myeloproliferative neoplasm initiation
遗传变异的选择性压力影响骨髓增生性肿瘤的发生
- 批准号:
10513391 - 财政年份:2022
- 资助金额:
$ 46.3万 - 项目类别:
Identifying Genome-wide Association Study-Nominated Regulators of Erythropoiesis
确定全基因组关联研究提名的红细胞生成调节因子
- 批准号:
8607354 - 财政年份:2014
- 资助金额:
$ 46.3万 - 项目类别:
Identifying Genome-wide Association Study-Nominated Regulators of Erythropoiesis
确定全基因组关联研究提名的红细胞生成调节因子
- 批准号:
8811154 - 财政年份:2014
- 资助金额:
$ 46.3万 - 项目类别:
Systematic Genetic Dissection of Human Erythropoiesis
人类红细胞生成的系统遗传解剖
- 批准号:
10403556 - 财政年份:2014
- 资助金额:
$ 46.3万 - 项目类别:
Systematic Genetic Dissection of Human Erythropoiesis
人类红细胞生成的系统遗传解剖
- 批准号:
8797944 - 财政年份:2014
- 资助金额:
$ 46.3万 - 项目类别:
Systematic Genetic Dissection of Human Erythropoiesis
人类红细胞生成的系统遗传解剖
- 批准号:
9544704 - 财政年份:2014
- 资助金额:
$ 46.3万 - 项目类别:
Identifying Genome-wide Association Study-Nominated Regulators of Erythropoiesis
确定全基因组关联研究提名的红细胞生成调节因子
- 批准号:
9025971 - 财政年份:2014
- 资助金额:
$ 46.3万 - 项目类别:
Systematic Genetic Dissection of Human Erythropoiesis
人类红细胞生成的系统遗传解剖
- 批准号:
10629304 - 财政年份:2014
- 资助金额:
$ 46.3万 - 项目类别:
Systematic Genetic Dissection of Human Erythropoiesis
人类红细胞生成的系统遗传解剖
- 批准号:
9325007 - 财政年份:2014
- 资助金额:
$ 46.3万 - 项目类别:
相似海外基金
Computing analysis of leukemic stem cell dynamics in acute myelocytic leukemia
急性粒细胞白血病白血病干细胞动力学的计算分析
- 批准号:
19K08356 - 财政年份:2019
- 资助金额:
$ 46.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Generation of immunotoxins with super-targeting mAb in the acute myelocytic leukemia
在急性髓细胞白血病中使用超靶向单克隆抗体产生免疫毒素
- 批准号:
23501309 - 财政年份:2011
- 资助金额:
$ 46.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
DETERMINANTS OF RESPONSE OF ACUTE MYELOCYTIC LEUKEMIA
急性粒细胞白血病反应的决定因素
- 批准号:
3556971 - 财政年份:1980
- 资助金额:
$ 46.3万 - 项目类别:
DETERMINANTS OF RESPONSE OF ACUTE MYELOCYTIC LEUKEMIA
急性粒细胞白血病反应的决定因素
- 批准号:
3556968 - 财政年份:1980
- 资助金额:
$ 46.3万 - 项目类别:
ERADICATION OF ACUTE MYELOCYTIC LEUKEMIA CELLS BY MAB THERAPY
通过 MAB 疗法根除急性粒细胞白血病细胞
- 批准号:
3889304 - 财政年份:
- 资助金额:
$ 46.3万 - 项目类别: