Characterizing single cell states of activated and transformed B cells in rhesus macaque models
恒河猴模型中活化和转化 B 细胞的单细胞状态特征
基本信息
- 批准号:10665491
- 负责人:
- 金额:$ 23.62万
- 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:2023-03-02 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAddressArchivesAreaB-Cell Acute Lymphoblastic LeukemiaB-Cell DevelopmentB-Cell LymphomasB-LymphocytesB-cell receptor repertoire sequencingBiologicalCRISPR screenCancer BurdenCancerousCell Culture TechniquesCell LineCell surfaceCellsCellular Indexing of Transcriptomes and Epitopes by SequencingDependenceDevelopmentDiagnosticDifferentiation AntigensDimensionsDiseaseEBV-associated diseaseEnvironmentEpstein Barr Nuclear Antigen 3Epstein-Barr Virus InfectionsEpstein-Barr Virus-Related Malignant NeoplasmEpstein-Barr pathogenesisGene ExpressionGenetic TranscriptionGoalsGrowthHeterogeneityHumanHuman Herpesvirus 4IRF4 geneImmuneImmunocompromised HostImmunophenotypingIn VitroIndividualInfectionInfectious AgentIntegration Host FactorsKnowledgeLMP1LinkLongitudinal StudiesLymph Node TissueLymphocryptovirusLymphoid TissueLymphomaLymphoproliferative DisordersMS4A1 geneMacaca mulattaMalignant NeoplasmsMapsMeasuresMediatingMethodsMicroRNAsModelingMolecularMolecular ProfilingNaturePathway interactionsPatientsPre-Clinical ModelPredispositionProcessProliferatingProliferation MarkerPropertyRefractoryResolutionResourcesRestRhesusSamplingSideTechniquesTherapeuticTumor AntigensTumor TissueViralViral CancerViral ProteinsVirusVirus Diseasescell transformationchronic infectionexperimental studygammaherpesvirusgene productgenetic manipulationgenetic signatureimmune checkpointimprovedin vivoinfected B cellinfectious disease modellatent infectionlymphoblastoid cell linemolecular dynamicsmolecular markermultiple omicsmutantpermissivenesspre-clinicalpremalignantprogramssingle-cell RNA sequencingtime usetranscription factortranscriptometranscriptome sequencingtranscriptomicstumortumor heterogeneity
项目摘要
Project Summary
Epstein-Barr virus (EBV) causes significant disease in patients with congenital or acquired immune deficiencies.
Elucidating markers of early cancer and understanding tumor composition are essential in improving diagnostics
and therapies for EBV diseases. In vitro, EBV infection of B cells induces formation of lymphoblastoid cell lines
(LCLs) which mimic properties of lymphoproliferative disease and serve as a model to investigate B cell
transformation processes. Multiple viral gene products dramatically reprogram the B cell environment, and
several host factors critical for maintaining LCL proliferation have been identified; however, host factors leading
to LCL outgrowth as well as the distinct cellular substages required for establishment of persistent infection and
B cell transformation are less understood. Deciphering the molecular mechanisms involved in these processes
is an ongoing challenge due to the refractory nature of primary B cells for genetic manipulation and the observed
heterogeneity in viral and cellular gene expression detected through standard bulk transcriptome analysis. To
address gaps in our current knowledge, we will use multi-omic single-cell approaches to define B cell molecular
signatures and cell markers that delineate early virus-mediated transformation. For these studies, we will
investigate a pre-clinical EBV model, rhesus macaque (RM) cells and tumor tissues infected with rhesus
lymphocryptovirus (rLCV). By simultaneously measuring immunophenotypes and gene expression, we aim to
identify B cell states that successfully navigate infection towards the LCL trajectory. Leveraging these
approaches to further analyze rLCV+ lymphoid tissues, we aim to define biological properties of pre-cancerous
and cancerous states at the single cell level.
项目摘要
爱泼斯坦-巴尔病毒(EBV)会导致先天性或获得性免疫缺陷患者的重大疾病。
阐明早期癌症的标志物和了解肿瘤成分是提高诊断水平的关键
以及EBV疾病的治疗方法。EB病毒感染B细胞体外诱导淋巴母细胞系的形成
(LCLS)模拟淋巴增生性疾病的特性并作为研究B细胞的模型
转型过程。多种病毒基因产品极大地改变了B细胞环境,
已经确定了几个对维持LCL增殖至关重要的宿主因素;然而,宿主因素导致
至LCL生长以及建立持续感染所需的不同细胞亚阶段和
人们对B细胞转化知之甚少。破译这些过程中涉及的分子机制
是一个持续的挑战,因为原始B细胞对基因操作的难治性,以及观察到的
通过标准批量转录组分析检测到病毒和细胞基因表达的异质性。至
解决我们目前知识中的空白,我们将使用多组单细胞方法来定义B细胞分子
描述早期病毒介导性转化的签名和细胞标记。对于这些研究,我们将
研究临床前EB病毒模型、恒河猴(RM)细胞和肿瘤组织感染恒河猴
淋巴腺病毒(RLCV)。通过同时测量免疫表型和基因表达,我们的目标是
识别B细胞状态,成功地将感染引导至LCL轨迹。利用这些优势
为了进一步分析rLCV+淋巴组织,我们的目标是定义癌前病变的生物学特性
以及单细胞水平上的癌变状态。
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 }}
Rebecca L Skalsky其他文献
Analysis of the miRNA targetome in EBV-infected B cells
- DOI:
10.1186/1750-9378-7-s1-o2 - 发表时间:
2012-04-19 - 期刊:
- 影响因子:2.800
- 作者:
Rebecca L Skalsky;David L Corcoran;Eva Gottwein;Christopher L Frank;Markus Hafner;Jeffrey D Nusbaum;Regina Feederle;Henri-Jacques Delecluse;Micah Luftig;Thomas Tuschl;Uwe Ohler;Bryan R Cullen - 通讯作者:
Bryan R Cullen
Rebecca L Skalsky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('Rebecca L Skalsky', 18)}}的其他基金
Regulation of host miRNA activity by Epstein-Barr virus BHRF1
Epstein-Barr 病毒 BHRF1 对宿主 miRNA 活性的调节
- 批准号:
10170258 - 财政年份:2020
- 资助金额:
$ 23.62万 - 项目类别:
Regulation of host miRNA activity by Epstein-Barr virus BHRF1
Epstein-Barr 病毒 BHRF1 对宿主 miRNA 活性的调节
- 批准号:
10039435 - 财政年份:2020
- 资助金额:
$ 23.62万 - 项目类别:
microRNA Regulation of Gamma-herpesvirus Latency and Reactivation
microRNA 对 γ-疱疹病毒潜伏期和再激活的调节
- 批准号:
10532215 - 财政年份:2019
- 资助金额:
$ 23.62万 - 项目类别:
microRNA Regulation of Gamma-herpesvirus Latency and Reactivation
microRNA 对 γ-疱疹病毒潜伏期和再激活的调节
- 批准号:
10084264 - 财政年份:2019
- 资助金额:
$ 23.62万 - 项目类别:
microRNA Regulation of Gamma-herpesvirus Latency and Reactivation
microRNA 对 γ-疱疹病毒潜伏期和再激活的调节
- 批准号:
10319587 - 财政年份:2019
- 资助金额:
$ 23.62万 - 项目类别:
The role of viral and cellular miRNAs in B-cell lymphomagenesis
病毒和细胞 miRNA 在 B 细胞淋巴瘤发生中的作用
- 批准号:
8634961 - 财政年份:2014
- 资助金额:
$ 23.62万 - 项目类别:
The Role of Viral and Cellular miRNAs in B-cell Lymphomagenesis
病毒和细胞 miRNA 在 B 细胞淋巴瘤发生中的作用
- 批准号:
9334358 - 财政年份:2014
- 资助金额:
$ 23.62万 - 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:
$ 23.62万 - 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:
$ 23.62万 - 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:
$ 23.62万 - 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:
$ 23.62万 - 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:
$ 23.62万 - 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:
$ 23.62万 - 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:
$ 23.62万 - 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:
$ 23.62万 - 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:
$ 23.62万 - 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:
$ 23.62万 - 项目类别:
Research Grant