Regulatory Crosstalk Between Human Endogenous Retroviruses, HIV, and EBV, in Lymphoma
淋巴瘤中人内源性逆转录病毒、HIV 和 EBV 之间的监管串扰
基本信息
- 批准号:10616708
- 负责人:
- 金额:$ 117.81万
- 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:2021-05-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AIDS related cancerAIDS-Related Diffuse Large B-cell LymphomaAcquired Immunodeficiency SyndromeAffectB-Cell LymphomasB-LymphocytesBCL2 geneBCL6 geneBindingBiologyBrazilCD4 Positive T LymphocytesCell LineCell ProliferationCellsClear cell renal cell carcinomaCoculture TechniquesCommon NeoplasmComplexCytotoxic T-LymphocytesDNADNA Transposable ElementsDataDeveloped CountriesDevelopmentDiseaseElementsEndogenous RetrovirusesEnhancersEnvironmental Risk FactorEpitopesEpstein-Barr Virus InfectionsEvolutionFamilyGene ExpressionGenesGeneticGenomicsGrantHIVHIV InfectionsHIV SeronegativityHumanHuman CloningHuman GenomeHuman Herpesvirus 4Immune TargetingImmunologyImmunophenotypingImmunotherapyIn VitroIncidenceIndividualInfectionJunk DNAK-18 conjugateLinkLymphomaLymphoma cellLymphomagenesisMalignant NeoplasmsMediatingMedicineMolecularMorphologyNucleic AcidsOncogenicPathogenesisPathologicPatientsPatternPersonsPhysiologicalPhysiologyPlayProcessProspective cohortProteinsProto-OncogenesRegulationRepressionRetrospective cohortRetroviridaeRoleSamplingSpecialistStandardizationSystemT-LymphocyteT-Lymphocyte EpitopesTestingTherapeutic InterventionTissuesTonsilTranslatingTumor SubtypeTumor Suppressor GenesUnited StatesUntranslated RNAUp-RegulationViralViral GenomeViremiaVirusWorkcomputerized toolsexomein vitro Modelinfected B celllarge cell Diffuse non-Hodgkin&aposs lymphomalymph nodesneoplastic cellnew therapeutic targetperipheral bloodpromoterresponseribosome profilingsingle-cell RNA sequencingsynergismtargeted treatmenttranscriptome sequencingtranscriptomicstumortumor microenvironmenttumor progressiontumorigenesis
项目摘要
PROJECT SUMMARY/ABSTRACT
Approximately 8% of the human genome is composed of sequences directly derived from germline infections of
diverse retroviruses, which have accumulated over the past ~100 million years of mammalian evolution. None
of these human endogenous retroviruses (HERVs) are known to represent fully functional retroviruses, but most
have retained noncoding regulatory sequences that can control expression of cellular genes acting as promoters
or enhancers, and some still encode proteins with various functional activities. While HERV sequences are often
ignored as merely inconsequential ‘junk’ DNA, there is evidence that a subset of these elements play crucial
roles in human physiology and disease, including cancer. Our previous work, as well as that of others, have
shown that both HIV and EBV infections activate certain HERV families that have oncogenic activities, and our
preliminary data reveal an overlap between these elements. Given that diffuse large B cell lymphomas (DBCL)
are frequently associated with EBV infection in people living with HIV, we hypothesize that there is a complex
intercellular regulatory crosstalk between AIDS related (AR)-DLBCL, HIV-infected T cells and the tissue
microenvironment, that is in part mediated by a specific subset of HERVs and their derived products that are
synergistically activated and promote oncogenesis. We will study DLBCL obtained from patients with or without
EBV (and with or without HIV) from the USA and Brazil, which will be comprehensively characterized
pathologically and molecularly using single-cell genomics and spatial transcriptomics. We will analyze these data
using computational tools we have tailored to profile and link HERV and gene expression. Furthermore, we will
establish in vitro models to dissect with precision the functional impact of HERV on the crosstalk between T cells
infected by HIV and B cells with or without EBV. We will also determine if differential HERV expression creates
neoantigenic epitopes, a feature that can be exploited for immunotherapy. This will be accomplished through
three specific aims: 1) Characterize and profile HERV regulation and expression within single cells in DLBCL
and AR-DLBCL; 2) Establish in vitro models to dissect the interaction between cellular and endogenous and
exogenous viruses in AR-DLBCL; 3) Identification of neo-antigenic HERV epitopes in DLBCL and ascertain if
cloned HERV specific CTL can lyse lymphoma cells in vitro. Our team consists of specialists in lymphoma biology
and medicine, transposable elements and HERVs, HIV and EBV viral immunology. Together, we will generate
understandings of how HERVs contribute to the pathogenesis of AR-DLCBL, and identify new antigenic targets
for novel therapies.
项目总结/文摘
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Ribosomal profiling of human endogenous retroviruses in healthy tissues.
- DOI:10.1186/s12864-023-09909-x
- 发表时间:2024-01-02
- 期刊:
- 影响因子:4.4
- 作者:Dopkins, Nicholas;Singh, Bhavya;Michael, Stephanie;Zhang, Panpan;Marston, Jez L.;Fei, Tongyi;Singh, Manvendra;Feschotte, Cedric;Collins, Nicholas;Bendall, Matthew L.;Nixon, Douglas F.
- 通讯作者:Nixon, Douglas F.
3D chromosomal architecture in germinal center B cells and its alterations in lymphomagenesis.
- DOI:10.1016/j.gde.2022.101915
- 发表时间:2022-06
- 期刊:
- 影响因子:4
- 作者:Papin, Antonin;Cesarman, Ethel;Melnick, Ari
- 通讯作者:Melnick, Ari
Endogenous Reverse Transcriptase Inhibition Attenuates TLR5-Mediated Inflammation.
- DOI:10.1128/mbio.03280-22
- 发表时间:2023-02-28
- 期刊:
- 影响因子:6.4
- 作者:
- 通讯作者:
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ETHEL CESARMAN其他文献
ETHEL CESARMAN的其他文献
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{{ truncateString('ETHEL CESARMAN', 18)}}的其他基金
Tri-I Stimulating Access to Research in Residency program (Tri-I StARR - NIAID)
Tri-I 促进住院医师研究项目 (Tri-I StARR - NIAID)
- 批准号:
10592130 - 财政年份:2023
- 资助金额:
$ 117.81万 - 项目类别:
Rapid Sample-to-Answer Diagnosis of Kaposi's Sarcoma Across Sub-Saharan Africa using KS-COMPLETE
使用 KS-COMPLETE 对撒哈拉以南非洲地区的卡波西肉瘤进行快速样本到答案诊断
- 批准号:
10416778 - 财政年份:2022
- 资助金额:
$ 117.81万 - 项目类别:
Rapid Sample-to-Answer Diagnosis of Kaposi's Sarcoma Across Sub-Saharan Africa using KS-COMPLETE
使用 KS-COMPLETE 对撒哈拉以南非洲地区的卡波西肉瘤进行快速样本到答案诊断
- 批准号:
10642906 - 财政年份:2022
- 资助金额:
$ 117.81万 - 项目类别:
Regulatory Crosstalk Between Human Endogenous Retroviruses, HIV, and EBV, in Lymphoma
淋巴瘤中人内源性逆转录病毒、HIV 和 EBV 之间的监管串扰
- 批准号:
10228431 - 财政年份:2021
- 资助金额:
$ 117.81万 - 项目类别:
Regulatory Crosstalk Between Human Endogenous Retroviruses, HIV, and EBV, in Lymphoma
淋巴瘤中人内源性逆转录病毒、HIV 和 EBV 之间的监管串扰
- 批准号:
10398963 - 财政年份:2021
- 资助金额:
$ 117.81万 - 项目类别:
(PQ 6) New Models of KSHV Oncogenesis and KS Immune Environment
(PQ 6) KSHV 肿瘤发生和 KS 免疫环境的新模型
- 批准号:
10737765 - 财政年份:2020
- 资助金额:
$ 117.81万 - 项目类别:
(PQ 6) New Models of KSHV Oncogenesis and KS Immune Environment
(PQ 6) KSHV 肿瘤发生和 KS 免疫环境的新模型
- 批准号:
10397107 - 财政年份:2020
- 资助金额:
$ 117.81万 - 项目类别: