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

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.
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:
{{ 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 }}

ETHEL CESARMAN其他文献

ETHEL CESARMAN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('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:
Next-Gen Oncopathology Program
下一代肿瘤病理学计划
  • 批准号:
    10676213
  • 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:
    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:
B cell determinants of EBV latency
EBV 潜伏期的 B 细胞决定因素
  • 批准号:
    10541734
  • 财政年份:
    2022
  • 资助金额:
    $ 117.81万
  • 项目类别:
B cell determinants of EBV latency
EBV 潜伏期的 B 细胞决定因素
  • 批准号:
    10701826
  • 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:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了