Research Support Core B: Primary Cell, Biomimetic, and iPSC-derived Cell Models

研究支持核心 B:原代细胞、仿生和 iPSC 衍生细胞模型

基本信息

  • 批准号:
    10632094
  • 负责人:
  • 金额:
    $ 73.12万
  • 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:
    2021-09-15 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary - Primary Cell, Biomimetics, and iPSC-derived Cellular Models Core B Understanding the mechanism(s) by which cocaine, methamphetamine, cannabis, and opioids amplify the damage of HIV latency is a central goal of the CWRU Center for Excellence on the Impact of Substance Use on HIV. Our understanding of HIV latency and persistence has been complicated by the small numbers of latently infected cells found in the circulation, the difficulty of obtaining comprehensive sets of tissue samples from patients, the lack of known phenotypic markers that can distinguish latently infected cells from uninfected ones, and limited information about the behavior of tissue reservoirs in vivo. Core B will provide both ex vivo primary cell models (Aim 1) and highly sensitive nucleic acid-based assays to measure the impact of substance use on the HIV reservoir (Aim 2) in clinical samples. A key unresolved issue is how each individual drug modulates the latent HIV reservoir in multiple cell types and tissues. The Primary Cell, Biomimetic, and iPSC-derived Cell Models Core B team will provide and develop for Center investigators innovative and highly informative cellular and biomimetic models for the three main organ targets of drug use and HIV – the brain, gut, and the immune system. Organoids derived from tissue explants and induced pluripotent stem cells (iPSC) will be used to mimic the tissue microenvironment and extend the range of assays beyond what can be achieved using single cell ex vivo models. The models offered by Core B will be used throughout the Center of Excellence to evaluate the impact of drug use on HIV latency and will also be established ex vivo with samples derived from persons with Substance Use Disorder and HIV on anti-retroviral therapy. These models will each reflect the diversity of molecular mechanisms governing the response to drug use and HIV latency in CD4 T cells from the periphery, mucosal T cells from the gut, and microglial, neuronal, and microvascular endothelial cells from the CNS and will also provide unique opportunities to contrast the effects of substance use in vivo with direct cell biological analyses ex vivo. Importantly, the Core B team will continue to develop new assays and methods to study the impact of substance use on the mechanisms of HIV persistence and latency. In particular, this effort includes (a) developing single cell RNA induction assays, (b) modeling the TFH compartment, and (c) advancing iPSC-derived cerebral organoids to study drug use and HIV latency in the CNS. Thus, Core B, in collaboration with the molecular services in Core C, will provide access to novel technologies for evaluating the cellular, proteomic, microbiological, metabolomic, and transcriptomic changes associated with substance use and their impact on HIV reservoirs in patient samples available in Core D and to primary cell cultures and tools to manipulate cells that would not otherwise be available to Substance Use researchers at our institutions and nationwide.
原代细胞,仿生学和ipsc衍生的细胞模型

项目成果

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专利数量(0)

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JONATHAN KARN其他文献

JONATHAN KARN的其他文献

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{{ truncateString('JONATHAN KARN', 18)}}的其他基金

The role of RNA m6A modification in the regulation of HIV latency and reactivation
RNA m6A 修饰在调节 HIV 潜伏和再激活中的作用
  • 批准号:
    10600078
  • 财政年份:
    2022
  • 资助金额:
    $ 73.12万
  • 项目类别:
The role of RNA m6A modification in the regulation of HIV latency and reactivation
RNA m6A 修饰在调节 HIV 潜伏和再激活中的作用
  • 批准号:
    10461499
  • 财政年份:
    2022
  • 资助金额:
    $ 73.12万
  • 项目类别:
Research Support Core B: Primary Cell, Biomimetic, and iPSC-derived Cell Models
研究支持核心 B:原代细胞、仿生和 iPSC 衍生细胞模型
  • 批准号:
    10304584
  • 财政年份:
    2021
  • 资助金额:
    $ 73.12万
  • 项目类别:
New Inhibitors of HIV latency reactivation
HIV潜伏期再激活的新抑制剂
  • 批准号:
    10010720
  • 财政年份:
    2020
  • 资助金额:
    $ 73.12万
  • 项目类别:
New Inhibitors of HIV latency reactivation
HIV潜伏期再激活的新抑制剂
  • 批准号:
    10208701
  • 财政年份:
    2020
  • 资助金额:
    $ 73.12万
  • 项目类别:
Control of P-TEFb biogenesis and HIV transcription in primary T-cells
原代 T 细胞中 P-TEFb 生物发生和 HIV 转录的控制
  • 批准号:
    10158438
  • 财政年份:
    2019
  • 资助金额:
    $ 73.12万
  • 项目类别:
Regulation of HIV latency by microglial-neuronal interactions
小胶质细胞-神经元相互作用对 HIV 潜伏期的调节
  • 批准号:
    10220927
  • 财政年份:
    2019
  • 资助金额:
    $ 73.12万
  • 项目类别:
Regulation of HIV latency by microglial-neuronal interactions
小胶质细胞-神经元相互作用对 HIV 潜伏期的调节
  • 批准号:
    10674037
  • 财政年份:
    2019
  • 资助金额:
    $ 73.12万
  • 项目类别:
Control of P-TEFb biogenesis and HIV transcription in primary T-cells
原代 T 细胞中 P-TEFb 生物发生和 HIV 转录的控制
  • 批准号:
    10403547
  • 财政年份:
    2019
  • 资助金额:
    $ 73.12万
  • 项目类别:
Control of P-TEFb biogenesis and HIV transcription in primary T-cells
原代 T 细胞中 P-TEFb 生物发生和 HIV 转录的控制
  • 批准号:
    10629307
  • 财政年份:
    2019
  • 资助金额:
    $ 73.12万
  • 项目类别:

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