Project 2: Dissection of clonal architecture and evolution in solid tumors
项目 2:实体瘤克隆结构和进化的剖析
基本信息
- 批准号:8866153
- 负责人:
- 金额:$ 36.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-05-19 至 2020-04-30
- 项目状态:已结题
- 来源:
- 关键词:AftercareArchitectureAreaAtlasesAutomationBiopsyCellsClinicalCodeComplementary DNADNAData AnalysesData SetDependencyDevicesDiseaseDissectionDrug resistanceEpigenetic ProcessEvolutionExcisionFailureFrequenciesGene Expression ProfileGenesGeneticGenetic TranscriptionGenetic VariationGenomeGenomic DNAGenomicsGlioblastomaHeterogeneityHumanIn VitroIndividualLibrariesMalignant - descriptorMalignant NeoplasmsMapsMedicalMessenger RNAMethodsMicrofabricationMicrofluidicsModelingMusMutationNatural SelectionsOperative Surgical ProceduresOutcomePatientsPatternPharmaceutical PreparationsPhylogenetic AnalysisPopulationPopulation ControlPrimary NeoplasmReagentReceptor Protein-Tyrosine KinasesRelapseRelative (related person)ReportingResearchResistanceSamplingSolid NeoplasmSpecimenStagingStructureSystemThe Cancer Genome AtlasTherapeuticTimeTissuesTreatment FailureTumor TissueValidationWorkcancer genomecombinatorialcostdriving forcedrug sensitivityepigenetic variationexomein vivoinhibitor/antagonistinsightmedical specialtiesneglectnew technologyoncologypressureresearch studysmall moleculetooltreatment strategytumortumor progression
项目摘要
TITLE
Project 2: Dissection of clonal architecture and evolution in solid tumors
ABSTRACT
Increasing evidence in solid tumors suggests that drug resistance and therapeutic failure results from
natural selection of resistant subclones during the disease course. Intra-tumor heterogeneity and cancer
subclonal diversity is the key driving force of the high failure rate of oncology drugs relative to other medical
specialties where drugs are applied to stable somatic genomes rather than the unstable genomes found in
human cancer. In this proposal, we focus on one of the most incurable and genetically heterogeneous tumors
(human glioblastoma), to predict and validate the landscape of driver alterations that mark initiation, founder
evolution, and therapy adaptation within individual patients. We will develop and apply novel technologies for
high-throughput transcription and genomic analysis of individual cells within malignant glioma tissues. Our
current system is capable of single cell mRNA capture, cDNA barcoding, and on-chip amplification, generating
amplicons for direct conversion into a standard, pooled sequencing library. We will adapt the same device for
massively parallel, on-chip capture of genomic DNA from individual cells for whole genome amplification and
exome capture. Next, we will functionally validate the single-cell glioma models in orthotopic mouse and
human systems in vitro and in vivo. The successful outcome of this proposal will be to deliver an integrated
computational-experimental pipeline that will be able to predict the forthcoming evolutionary moves of any solid
tumor in the presence of a defined set of selective pressures. This information will be of invaluable significance
to decipher evolving tumor dependencies and provide the most accurate therapeutic predictions.
标题
项目2:实体肿瘤克隆结构和进化的解剖
摘要
越来越多的实体肿瘤证据表明,耐药性和治疗失败是由
病程中抗性亚克隆的自然选择。肿瘤内异质性与肿瘤
亚克隆多样性是肿瘤药物相对于其他医学药物失败率高的关键驱动力
将药物应用于稳定的体细胞基因组而不是在
人类癌症。在这项提案中,我们关注的是一种最无法治愈、基因异质性最强的肿瘤。
(人类胶质母细胞瘤),为了预测和验证标志着开始的司机改变的景观,方正
患者个体内的进化和治疗适应。我们将开发和应用新技术,以
恶性胶质瘤组织内单个细胞的高通量转录和基因组分析。我们的
目前的系统能够捕获单细胞mRNA,进行cDNA条形码编码,以及芯片上扩增,生成
将扩增产物直接转化为标准的混合测序文库。我们将对相同的设备进行改装
大规模并行、芯片上捕获单个细胞的基因组DNA,用于全基因组扩增和
外显子捕获。接下来,我们将从功能上验证单细胞胶质瘤模型在原位小鼠和
体外和体内的人体系统。这项提议的成功结果将是提供一个完整的
计算-实验流水线,将能够预测任何固体即将到来的进化运动
肿瘤在一组确定的选择压力下。这一信息将具有无价的意义。
以破译不断演变的肿瘤相关性,并提供最准确的治疗预测。
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 }}
Antonio Iavarone其他文献
Antonio Iavarone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('Antonio Iavarone', 18)}}的其他基金
Evolution and targeting of the functional states of glioblastoma
胶质母细胞瘤功能状态的进化和靶向
- 批准号:
10467181 - 财政年份:2022
- 资助金额:
$ 36.93万 - 项目类别:
Evolution and targeting of the functional states of glioblastoma
胶质母细胞瘤功能状态的进化和靶向
- 批准号:
10651751 - 财政年份:2022
- 资助金额:
$ 36.93万 - 项目类别:
Evolution and targeting of the functional states of glioblastoma
胶质母细胞瘤功能状态的进化和靶向
- 批准号:
10729932 - 财政年份:2022
- 资助金额:
$ 36.93万 - 项目类别:
Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors
脑肿瘤的致癌机制、分子分层和治疗靶点
- 批准号:
10493186 - 财政年份:2021
- 资助金额:
$ 36.93万 - 项目类别:
Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors
脑肿瘤的致癌机制、分子分层和治疗靶点
- 批准号:
10729917 - 财政年份:2021
- 资助金额:
$ 36.93万 - 项目类别:
Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors
脑肿瘤的致癌机制、分子分层和治疗靶点
- 批准号:
10299894 - 财政年份:2021
- 资助金额:
$ 36.93万 - 项目类别:
Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors
脑肿瘤的致癌机制、分子分层和治疗靶点
- 批准号:
10675651 - 财政年份:2021
- 资助金额:
$ 36.93万 - 项目类别:
The Huwe1 ubiquitin ligase regulates mitosis, genomic stability and oncogenesis.
Huwe1 泛素连接酶调节有丝分裂、基因组稳定性和肿瘤发生。
- 批准号:
10188467 - 财政年份:2019
- 资助金额:
$ 36.93万 - 项目类别:
The role of the LZTR1 ubiquitin ligase in stem cells and cancer
LZTR1 泛素连接酶在干细胞和癌症中的作用
- 批准号:
9262886 - 财政年份:2015
- 资助金额:
$ 36.93万 - 项目类别:
The role of the LZTR1 ubiquitin ligase in stem cells and cancer
LZTR1 泛素连接酶在干细胞和癌症中的作用
- 批准号:
9067257 - 财政年份:2015
- 资助金额:
$ 36.93万 - 项目类别:
相似海外基金
Practical Study on Disaster Countermeasure Architecture Model by Sustainable Design in Asian Flood Area
亚洲洪泛区可持续设计防灾建筑模型实践研究
- 批准号:
17K00727 - 财政年份:2017
- 资助金额:
$ 36.93万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Functional architecture of a face processing area in the common marmoset
普通狨猴面部处理区域的功能架构
- 批准号:
9764503 - 财政年份:2016
- 资助金额:
$ 36.93万 - 项目类别:
Heating and airconditioning by hypocausts in residential and representative architecture in Rome and Latium studies of a phenomenon of luxury in a favoured climatic area of the Roman Empire on the basis of selected examples.
罗马和拉齐奥的住宅和代表性建筑中的火烧供暖和空调根据选定的例子,研究了罗马帝国有利的气候地区的奢华现象。
- 批准号:
317469425 - 财政年份:2016
- 资助金额:
$ 36.93万 - 项目类别:
Research Grants
SBIR Phase II: Area and Energy Efficient Error Floor Free Low-Density Parity-Check Codes Decoder Architecture for Flash Based Storage
SBIR 第二阶段:用于基于闪存的存储的面积和能源效率高、无错误层的低密度奇偶校验码解码器架构
- 批准号:
1632562 - 财政年份:2016
- 资助金额:
$ 36.93万 - 项目类别:
Standard Grant
SBIR Phase I: Area and Energy Efficient Error Floor Free Low-Density Parity-Check Codes Decoder Architecture for Flash Based Storage
SBIR 第一阶段:用于基于闪存的存储的面积和能源效率高、无错误层低密度奇偶校验码解码器架构
- 批准号:
1520137 - 财政年份:2015
- 资助金额:
$ 36.93万 - 项目类别:
Standard Grant
A Study on The Spatial Setting and The Inhavitant's of The Flood Prevention Architecture in The Flood Area
洪泛区防洪建筑空间设置及居民生活研究
- 批准号:
26420620 - 财政年份:2014
- 资助金额:
$ 36.93万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Area and power efficient interconnect architecture for multi-bit processing on FPGAs
用于 FPGA 上多位处理的面积和功率高效互连架构
- 批准号:
327691-2007 - 财政年份:2011
- 资助金额:
$ 36.93万 - 项目类别:
Discovery Grants Program - Individual
A FUNDAMENTAL STUDY ON UTILIZATION OF THE POST-WAR ARCHITECTURE AS URBAN REGENERATION METHOD, A case of the central area of Osaka city
战后建筑作为城市更新方法的基础研究——以大阪市中心区为例
- 批准号:
22760469 - 财政年份:2010
- 资助金额:
$ 36.93万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Area and power efficient interconnect architecture for multi-bit processing on FPGAs
用于 FPGA 上多位处理的面积和功率高效互连架构
- 批准号:
327691-2007 - 财政年份:2010
- 资助金额:
$ 36.93万 - 项目类别:
Discovery Grants Program - Individual
Area and power efficient interconnect architecture for multi-bit processing on FPGAs
用于 FPGA 上多位处理的面积和功率高效互连架构
- 批准号:
327691-2007 - 财政年份:2009
- 资助金额:
$ 36.93万 - 项目类别:
Discovery Grants Program - Individual