Elucidating single cell changes in neurogenic brain regions during HIV and cannabinoid exposure

阐明艾滋病毒和大麻素暴露期间神经源性大脑区域的单细胞变化

基本信息

  • 批准号:
    10686685
  • 负责人:
  • 金额:
    $ 253.11万
  • 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:
    2023-05-15 至 2028-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY (ABSTRACT) The use of cannabis for recreation and medicinal purposes is disproportionately high among people living with HIV (PLWH) and nearly half of cannabis using PLWH are estimated to be at risk for cannabis use disorder. Yet, whether cannabis is therapeutic or detrimental on the central nervous system (CNS) of PLWH remains controversial, highlighting the need for well-controlled studies generating reproducible data from specific cannabinoids, brain regions, and CNS cell types. Our research has shown that cell-type specific epigenetic patterns relate to HIV-associated cognitive impairment in PLWH, more frequent or recent cannabis use may reduce myeloid inflammation and impact brain structure in PLWH, and our recent single cell studies of the CNS in PLWH revealed distinct CSF microglia-like cells expressing CD204 in PLWH and ongoing HIV viral transcription in cerebrospinal fluid cells despite ART. Prior research has shown neurogenic brain regions including the subventricular zone of the lateral ventricles and hippocampus are of high relevance to persistent HIV infection and cannabinoid exposures. However, critical gaps in understanding neurogenic brain regions at single cell level in the setting of HIV and cannabinoid exposures remain. We are leveraging brain tissues from an established oral dosing model of cannabidiol and THC in a nonhuman primate (NHP) model of HIV, application of new single cell technologies permitting the simultaneous profiling of gene expression and open chromatin from the same cell (10X Genomics Multiome: RNA+ATAC) in brain tissues, a new single cell assay capable of measuring multiple histone modifications, and pharmacological profiling of current ART regimens and cannabinoid levels in brain tissues. Our central hypothesis is a therapeutic role of cannabinoids in ameliorating HIV neuropathogenesis in the CNS by enhancing the proliferation and survival of neural progenitor cells and immature neurons and reducing glial inflammation. To identify cell types, epigenetic cell states, and gene pathways relevant to neuropathogenesis, viral persistence, and cannabinoid exposures, we are harnessing 180 brain tissue samples from an established oral administration of either cannabidiol (CBD) or Δ9- tetrahydrocannabinol (THC) in NHP and single cell assays (10X Genomics single nucleus multiome and a new single cell assay developed at the NYGC capable of measuring the genome-wide presence of multiple histone modifications and protein-DNA binding sites). Moreover, accompanying single cell data will be generated from conserved neurogenic brain regions of human postmortem brain tissues from 40 donors based on HIV status (+/-) and cannabis exposure (+/-). We will also explore the frequency of single cells in neurogenic regions of the brain that are infected and impacted by cannabinoids by harnessing a bioinformatics pipeline that detects both viral transcripts and transposase accessible provirus. This project will generate comprehensive single cell datasets in NHP and humans to improve our understanding of the cross talk between HIV and cannabinoids in neurogenic regions of the brain and has high programmatic priority to goals of the SCORCH program expansion.
项目总结(摘要)

项目成果

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Michael Jay Corley其他文献

Michael Jay Corley的其他文献

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{{ truncateString('Michael Jay Corley', 18)}}的其他基金

Decoding epigenetic scars of smoldering neuroinflammation and CNS complications in people with HIV
解码艾滋病毒感染者闷烧性神经炎症和中枢神经系统并发症的表观遗传疤痕
  • 批准号:
    10748566
  • 财政年份:
    2023
  • 资助金额:
    $ 253.11万
  • 项目类别:
Determining the interplay of MAIT cells and the translocated microbiome in HIV-induced neuroinflammation
确定 MAIT 细胞和易位微生物组在 HIV 诱导的神经炎症中的相互作用
  • 批准号:
    10744475
  • 财政年份:
    2023
  • 资助金额:
    $ 253.11万
  • 项目类别:
Impact of Microbial Dysbiosis on MAIT Cell Tissue Repair Program after Acute HIV Infection
急性 HIV 感染后微生物失调对 MAIT 细胞组织修复程序的影响
  • 批准号:
    10661769
  • 财政年份:
    2022
  • 资助金额:
    $ 253.11万
  • 项目类别:
Epigenetic dysregulation of inflammation linked to longitudinal cardiac toxicity in perinatal HIV infection
炎症的表观遗传失调与围产期 HIV 感染的纵向心脏毒性有关
  • 批准号:
    10570883
  • 财政年份:
    2022
  • 资助金额:
    $ 253.11万
  • 项目类别:
Impact of Microbial Dysbiosis on MAIT Cell Tissue Repair Program after Acute HIV Infection
急性 HIV 感染后微生物失调对 MAIT 细胞组织修复程序的影响
  • 批准号:
    10481899
  • 财政年份:
    2022
  • 资助金额:
    $ 253.11万
  • 项目类别:
Epigenetic dysregulation of inflammation linked to longitudinal cardiac toxicity in perinatal HIV infection
炎症的表观遗传失调与围产期 HIV 感染的纵向心脏毒性有关
  • 批准号:
    10483606
  • 财政年份:
    2022
  • 资助金额:
    $ 253.11万
  • 项目类别:
Investigating Cellular Immunometabolic Mechanisms Underlying HIV-Related Cardiovascular Disease Risk
研究 HIV 相关心血管疾病风险背后的细胞免疫代谢机制
  • 批准号:
    10491277
  • 财政年份:
    2021
  • 资助金额:
    $ 253.11万
  • 项目类别:
Investigating Cellular Immunometabolic Mechanisms Underlying HIV-Related Cardiovascular Disease Risk
研究 HIV 相关心血管疾病风险背后的细胞免疫代谢机制
  • 批准号:
    10326950
  • 财政年份:
    2021
  • 资助金额:
    $ 253.11万
  • 项目类别:
Investigating Cellular Immunometabolic Mechanisms Underlying HIV-Related Cardiovascular Disease Risk
研究 HIV 相关心血管疾病风险背后的细胞免疫代谢机制
  • 批准号:
    10682551
  • 财政年份:
    2021
  • 资助金额:
    $ 253.11万
  • 项目类别:
The role of epigenetic transcriptional memory in monocyte-macrophage cells and cardiovascular disease risk
表观遗传转录记忆在单核巨噬细胞和心血管疾病风险中的作用
  • 批准号:
    10444925
  • 财政年份:
    2018
  • 资助金额:
    $ 253.11万
  • 项目类别:

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