The Role of NOTCH1 in the Pathogenesis of CLL.
NOTCH1 在 CLL 发病机制中的作用。
基本信息
- 批准号:8539207
- 负责人:
- 金额:$ 35.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-04-01 至 2018-03-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAntibodiesB-Cell DevelopmentB-LymphocytesBIRC3 geneCell ProliferationCell membraneCell physiologyCellsChronic Lymphocytic LeukemiaClonal ExpansionCodeDLEU2 geneDevelopmentDiagnosisDiseaseDisease ProgressionEventFrequenciesGenesGenomeGenomicsGoalsHematologic NeoplasmsKnockout MiceMature B-LymphocyteMediatingModelingMolecularMultivariate AnalysisMusMutationNOTCH1 geneNatureOncogenicPathogenesisPathway interactionsPatientsProcessProteinsProto-OncogenesRNA SplicingRegulationResearch ProposalsResistanceRichter&aposs SyndromeRoleSignal TransductionSurface AntigensTestingToll-like receptorsTransgenic MiceWestern Worldadult leukemiabasecancer therapychemotherapyclinically significantefficacy testinggamma secretaseimprovedin vivoinhibitor/antagonistlarge cell Diffuse non-Hodgkin&aposs lymphomamutantoutcome forecastprogramspublic health relevanceresearch studyresponsesmall moleculetherapeutic targettherapy developmenttumortumor progression
项目摘要
DESCRIPTION (provided by applicant: Chronic lymphocytic leukemia (CLL) is the most prevalent hematologic cancer in the US. Importantly, and in contrast with other hematologic malignancies, CLL responds only transiently to chemotherapy and there is no available curative therapy. Activating mutations in NOTCH1 have been recently found in 10-15% of CLL cases and are associated with poor prognosis, disease progression, chemotherapy resistance and transformation to diffuse large B cell lymphoma (DLBCL) (Fabbri et al., J Exp Med 2011; Puente et al, Nature 2011). Notably, NOTCH1 signaling can be effectively blocked with inhibitory antibodies and gamma-secretase inhibitors, currently under development as anti-NOTCH therapies for the treatment of cancer. Our central hypothesis is that NOTCH1 mutations may contribute to the pathogenesis of CLL by disrupting specific transcriptional programs that regulate cell proliferation, differentiation and survival in CLL cells. The goals of this research proposal are to define the molecular and cellular functions of NOTCH1 in CLL transformation, to analyze the oncogenic effects of mutant NOTCH1 in vivo, and to test the effects of NOTCH inhibition alone and in combination with chemotherapy in the treatment of CLL.
描述(申请人提供:慢性淋巴细胞白血病(CLL)是美国最常见的血液病。重要的是,与其他血液系统恶性肿瘤不同的是,CLL对化疗只有短暂的反应,并且没有可用的治疗方法。最近在10-15%的CLL病例中发现了NOTCH1的激活突变,并与不良预后、疾病进展、化疗耐药和向弥漫性大B细胞淋巴瘤(DLBCL)的转化有关(Fabbri等人,J Exp Med 2011;Puente等人,自然2011)。值得注意的是,NOTCH1信号可以被抑制性抗体和伽马分泌酶抑制剂有效地阻断,这两种药物目前正在开发中,作为癌症治疗的抗缺口疗法。我们的中心假设是,NOTCH1突变可能通过扰乱调节CLL细胞增殖、分化和生存的特定转录程序而参与CLL的发病。本研究的目标是明确NOTCH1在CLL转化中的分子和细胞功能,分析突变型NOTCH1在体内的致癌作用,并测试缺口抑制单独和联合化疗治疗CLL的效果。
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 }}
Riccardo Dalla-Favera其他文献
Riccardo Dalla-Favera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('Riccardo Dalla-Favera', 18)}}的其他基金
From pathogenesis to new therapeutic targets in diffuse large B cell lymphoma
弥漫性大B细胞淋巴瘤从发病机制到新的治疗靶点
- 批准号:
10737214 - 财政年份:2023
- 资助金额:
$ 35.83万 - 项目类别:
From pathogenesis to new therapeutic targets in Diffuse Large B cell Lymphoma
弥漫性大 B 细胞淋巴瘤从发病机制到新的治疗靶点
- 批准号:
10453790 - 财政年份:2016
- 资助金额:
$ 35.83万 - 项目类别:
From pathogenesis to new therapeutic targets in Diffuse Large B cell Lymphoma
弥漫性大 B 细胞淋巴瘤从发病机制到新的治疗靶点
- 批准号:
9528531 - 财政年份:2016
- 资助金额:
$ 35.83万 - 项目类别:
From pathogenesis to new therapeutic targets in Diffuse Large B cell Lymphoma
弥漫性大 B 细胞淋巴瘤从发病机制到新的治疗靶点
- 批准号:
9186876 - 财政年份:2016
- 资助金额:
$ 35.83万 - 项目类别:
From pathogenesis to new therapeutic targets in Diffuse Large B cell Lymphoma
弥漫性大 B 细胞淋巴瘤从发病机制到新的治疗靶点
- 批准号:
9977975 - 财政年份:2016
- 资助金额:
$ 35.83万 - 项目类别:
From pathogenesis to new therapeutic targets in Diffuse Large B cell Lymphoma
弥漫性大 B 细胞淋巴瘤从发病机制到新的治疗靶点
- 批准号:
10224858 - 财政年份:2016
- 资助金额:
$ 35.83万 - 项目类别:
From pathogenesis to new therapeutic targets in Diffuse Large B cell Lymphoma
弥漫性大 B 细胞淋巴瘤从发病机制到新的治疗靶点
- 批准号:
9326271 - 财政年份:2016
- 资助金额:
$ 35.83万 - 项目类别:
Role of MEF2B mutations in lymphomagenesis
MEF2B 突变在淋巴瘤发生中的作用
- 批准号:
8697703 - 财政年份:2014
- 资助金额:
$ 35.83万 - 项目类别:
Role of MEF2B mutations in lymphomagenesis
MEF2B 突变在淋巴瘤发生中的作用
- 批准号:
8849397 - 财政年份:2014
- 资助金额:
$ 35.83万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 35.83万 - 项目类别:
Research Grant