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
基本信息
- 批准号:10675651
- 负责人:
- 金额:$ 82.48万
- 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:2021-09-24 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:ArticulationBiologicalBrain NeoplasmsCancer ModelCancer PatientCellsClassificationClinical ResearchComputer AnalysisDependenceDevelopmentDissectionGenesGenomicsGlioblastomaGoalsHumanIndividualInvestigationLaboratoriesMalignant GliomaMalignant NeoplasmsModelingMolecularMotionOncogenesOncogenicOutcomePathogenesisPathway interactionsPatientsPhenotypeProteinsProteomicsResearchResistanceRouteSolid NeoplasmStratificationSubgroupTestingTherapeuticTissuesTreatment FailureUniversitiesValidationWorkcancer genomecancer heterogeneitycomputerized toolsdesigndrug sensitivityhigh throughput technologyin vitro Modelin vivoinnovationneoplastic cellnew technologynew therapeutic targetnoveloperationpersonalized therapeuticprogramstargeted treatmenttherapeutic targettooltranscriptomicstumor
项目摘要
Abstract
The work to be pursued in this application will continue and expand the program pioneered by Dr. Iavarone to
combine innovative computational tools and state-of-the-art experimental cancer models in vitro and in vivo to
identify homogeneous subgroups of cancer patients in order to dissect the pathogenesis of cancer and design
tailored and fully validated personalized therapeutic approaches. The application is focused on glioblastoma
multiforme, one of the most lethal forms of human cancer. The investigation of glioblastoma has represented a
long-standing effort of Dr. Iavarone’s laboratory, which in recent work has produced novel targeted therapeutic
opportunities currently being tested in clinical studies. The proposal will also benefit from the organizational
contexts recently set in motion by the large network operations coordinated by the PI. The research plan is
articulated around the development of a novel and integrated computational-experimental framework for: i) the
identification of homogeneous groups of tumors sharing activation of the same biological pathways; ii) the study
of cancer heterogeneity at the single cell level to accurately inform tumor classifications; iii) the therapeutic
prediction emerging from the identification of driver modules and synthetic lethal relationships of malignant
glioma. We will develop and apply novel technologies for high-throughput transcriptomic and proteomic analysis
of individual cells within malignant glioma tissues. These approaches, which we have pioneered in our laboratory
at Columbia University during the last few years, will serve as the basis for the multifaceted computational
analysis that will extract genes and proteins responsible for the phenotypic state of individual cells. Experimental
validations will be selectively applied to the novel and most exciting molecular pathways and will be performed
by our laboratory that has an array of experimental tools and sequence-annotated patient-derived models to
pursue each individual question. As for the selection of oncogene-dependent and independent vulnerabilities
identified by our previous work, the ability of our studies to identify novel driver phenotypes and master regulators
of individual tumor cells will be geared towards routing the new mechanisms into pathway-based synthetic
lethality that will inform specific drug sensitivities. The successful outcome of this proposal is an integrated
computational-experimental pipeline that will be able to mechanistically identify the determinants of tumor
genomes and phenotypes of solid tumors. This information will be of invaluable significance to decipher evolving
tumor dependencies and provide the most accurate therapeutic predictions.
摘要
在这项应用中所追求的工作将继续并扩展Iavarone博士开创的计划,
联合收割机结合创新的计算工具和最先进的体外和体内实验癌症模型,
确定癌症患者的同质亚组,以剖析癌症的发病机制,并设计
定制和充分验证的个性化治疗方法。该申请主要针对胶质母细胞瘤
多型癌是人类最致命的癌症之一。胶质母细胞瘤的研究代表了一个
Iavarone博士实验室的长期努力,在最近的工作中,
目前正在临床研究中测试的机会。该提案还将受益于组织
由PI协调的大型网络操作最近启动的上下文。研究计划是
阐述了一个新的和综合的计算实验框架的发展:i)
鉴定共享相同生物学途径激活的同质肿瘤组; ii)研究
在单细胞水平上的癌症异质性,以准确地告知肿瘤分类; iii)治疗
预测出现的驱动程序模块和恶性肿瘤的合成致死关系的识别
胶质瘤我们将开发和应用高通量转录组学和蛋白质组学分析的新技术
恶性神经胶质瘤组织中的单个细胞。我们在实验室中率先采用的这些方法
在哥伦比亚大学在过去的几年里,将作为基础的多方面计算
分析,将提取基因和蛋白质负责个别细胞的表型状态。实验
验证将选择性地应用于新的和最令人兴奋的分子途径,并将进行
由我们的实验室开发,该实验室拥有一系列实验工具和序列注释的患者衍生模型,
追求每个人的问题。至于癌基因依赖性和独立性脆弱性的选择
通过我们以前的工作确定,我们的研究能够识别新的驱动表型和主调节器
个体肿瘤细胞的研究将致力于将新机制引入基于途径的合成
致命性,将告知特定的药物敏感性。这一建议的成功结果是一个综合的
计算实验管道,将能够机械地确定肿瘤的决定因素
实体瘤的基因组和表型。这些信息对于破解进化论具有非常重要的意义
肿瘤依赖性,并提供最准确的治疗预测。
项目成果
期刊论文数量(1)
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:
$ 82.48万 - 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:
$ 82.48万 - 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:
$ 82.48万 - 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:
$ 82.48万 - 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:
$ 82.48万 - 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:
$ 82.48万 - 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:
$ 82.48万 - 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:
$ 82.48万 - 项目类别:
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
- 批准号:
8866153 - 财政年份:2015
- 资助金额:
$ 82.48万 - 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:
$ 82.48万 - 项目类别:
相似海外基金
NSF/BIO-DFG: Biological Fe-S intermediates in the synthesis of nitrogenase metalloclusters
NSF/BIO-DFG:固氮酶金属簇合成中的生物 Fe-S 中间体
- 批准号:
2335999 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Standard Grant
Collaborative Research: Conference: Large Language Models for Biological Discoveries (LLMs4Bio)
合作研究:会议:生物发现的大型语言模型 (LLMs4Bio)
- 批准号:
2411529 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Standard Grant
Collaborative Research: Conference: Large Language Models for Biological Discoveries (LLMs4Bio)
合作研究:会议:生物发现的大型语言模型 (LLMs4Bio)
- 批准号:
2411530 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Standard Grant
Collaborative Research: NSF-ANR MCB/PHY: Probing Heterogeneity of Biological Systems by Force Spectroscopy
合作研究:NSF-ANR MCB/PHY:通过力谱探测生物系统的异质性
- 批准号:
2412551 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Standard Grant
Elucidating mechanisms of biological hydrogen conversion through model metalloenzymes
通过模型金属酶阐明生物氢转化机制
- 批准号:
2419343 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Standard Grant
Collaborative Research: The Interplay of Water Condensation and Fungal Growth on Biological Surfaces
合作研究:水凝结与生物表面真菌生长的相互作用
- 批准号:
2401507 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Standard Grant
DESIGN: Driving Culture Change in a Federation of Biological Societies via Cohort-Based Early-Career Leaders
设计:通过基于队列的早期职业领袖推动生物协会联盟的文化变革
- 批准号:
2334679 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Standard Grant
REU Site: Modeling the Dynamics of Biological Systems
REU 网站:生物系统动力学建模
- 批准号:
2243955 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Standard Grant
Defining the biological boundaries to sustain extant life on Mars
定义维持火星现存生命的生物边界
- 批准号:
DP240102658 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Discovery Projects
Advanced Multiscale Biological Imaging using European Infrastructures
利用欧洲基础设施进行先进的多尺度生物成像
- 批准号:
EP/Y036654/1 - 财政年份:2024
- 资助金额:
$ 82.48万 - 项目类别:
Research Grant