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The HIV-associated Opioid Micro-Environment (HOME) Project

HIV 相关阿片类药物微环境 (HOME) 项目

基本信息

批准号：
10056153
负责人：
Sara Gianella Weibel
金额：
$ 236.81万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10056153
关键词：
AIDS/HIV problem ATAC-seq Abdomen Address Adipose tissue Alcohol or Other Drugs use Alcohols Anatomy Area Atlases Autopsy Basal Ganglia Biological Assay Blood Brain CD4 Positive T Lymphocytes Categories Cell Nucleus Cells Cerebrospinal Fluid Cervix Uteri Cessation of life Chromatin Chronic Disease Clonal Expansion Clonality Cocaine Collection Colon Communities Cyclohexanes DNA DNA Integration Data Disease Environment Freezing Funding Gap Junctions Genetic Transcription Genital system Genome Gifts Goals HIV HIV Genome Heart Hour Human body Immune Immunologics Individual Inflammation Infrastructure Investments Laboratories Length Life Liquid substance Liver Lung Lymphoid Tissue Malignant Neoplasms Maps Marijuana Mass Fragmentography Measures Methamphetamine Methods Modernization Molecular Morphine Myocardial Infarction Opioid Outcome Ovary Parents Participant Pathway interactions Pattern Pericardial body location Persons Polymerase Chain Reaction Population Prostate Proviruses RNA Regimen Reporting Research Priority Resolution Sampling Site Source Spleen Stroke Substance abuse problem T cell clonality T-Cell Receptor T-Lymphocyte Techniques Technology Testis Time Tissue Sample Tissues Toxicology Transcript United States National Institutes of Health Urine Ursidae Family Viral antiretroviral therapy base cohort deep sequencing digital frontal lobe ileum innovation integration site kidney cortex lymph nodes mass spectrometer migration multiple omics opioid exposure opioid use outreach prescription opioid programs reproductive tract single-cell RNA sequencing therapy development transcriptome sequencing transcriptomics volunteer

项目摘要

Abstract The proposed `HOME' project is in the NIH/OAR high research priority area of eradicating HIV from persistent reservoirs and responsive to the parent RFA for highly innovative studies at the nexus of substance abuse and HIV/AIDS. Most HIV anatomical reservoirs are hard to reach but studying blood alone is not enough to fully characterize HIV reservoirs. Thus, we will leverage prior NIH investments in our unique `Last Gift Cohort'. No such cohort is available elsewhere. The cohort obtains blood (before death) and a uniquely large set of tissues (within 6 hours after death) comprehensively from persons with HIV (PWH) who die while on documented, suppressive antiretroviral therapy (ART). For our HOME project, we will collect the following 17 tissues/fluids: blood, gut (ileum and colon), lymph nodes, kidney cortex, spleen, lungs, liver, genital tract (prostate/testes or cervix/ovaries), adipose tissues (abdominal, subscapular and pericardial), heart, brain (basal ganglia, frontal cortex and cerebrospinal fluid). We will then use these samples for state-of-the-art `Single-Cell Multi-Omics' technologies to address the following Goals, which are directly responsive to the parent RFA: • Goal 1: To Deeply Characterize the HIV Reservoir (Size and Activity) in the Blood and Tissues at a Single Genome Level in Relation to Opioid Levels. • Goal 2: To Deeply Characterize the T Cell and HIV DNA Clonality in the Blood and Tissues to “Quantify the Distribution and Diversity of Clonal Expansion” in relation to opioid levels. • Goal 3: To identify HIV and Opioid-associated immunologic Mechanisms Associated with HIV Persistence and Increased HIV RNA Transcription at the Single Cell Level. By leveraging our unique source of tissues and data generated through state-of-art methods, we will for the first time deliver a map of HIV persistence, activity and clonality across the human body in relation to opioid use. We will also reveal comprehensive molecular details and define parameters of HIV persistence at single-cell resolution, which will uniquely advance HIV cure efforts.

摘要拟议的“HOME”项目属于NIH/OAR的高度优先研究领域，即从持续存在的艾滋病毒感染者中根除艾滋病毒。水库和响应父RFA高度创新的研究在药物滥用的关系，艾滋病毒/艾滋病的大多数艾滋病毒的解剖储存库很难达到，但仅研究血液不足以完全表征艾滋病病毒库。因此，我们将在我们独特的“最后的礼物队列”中利用NIH之前的投资。没有这样的群体其他地方可用。该队列获得血液（死亡前）和一组独特的大型组织（6小时内死亡后），全面从人与艾滋病毒（PWH谁死，而记录，抑制抗逆转录病毒疗法（ART）。对于我们的HOME项目，我们将收集以下17种组织/液体：血液、肠道（回肠和结肠）、淋巴结、肾皮质、脾、肺、肝、生殖道（前列腺/睾丸或子宫颈/卵巢）、脂肪组织（腹部、肩胛下和心包）、心脏、脑（基底节、额叶皮质和脑脊液）。然后，我们将使用这些样品进行最先进的“单细胞多组学” 技术，以实现以下目标，这是直接响应父RFA： ·目标1：在单个样本中深入表征血液和组织中的HIV储库（大小和活性）基因组水平与阿片类药物水平的关系。 ·目标2：深入表征血液和组织中的T细胞和HIV DNA克隆性，以“量化克隆扩增的分布和多样性”与阿片类药物水平的关系。目标3：确定与艾滋病毒持续存在有关的艾滋病毒和阿片类药物相关免疫机制并在单细胞水平上增加HIV RNA转录。通过利用我们独特的组织来源和通过最先进的方法生成的数据，我们将首先时间提供了一个地图的艾滋病毒的持久性，活动和克隆在人体内与阿片类药物的使用。我们还将揭示全面的分子细节，并确定艾滋病毒在单细胞中持续存在的参数。该决议将独特地推动艾滋病毒治疗工作。