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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“家”项目是在NIH/OAR高度优先的研究领域，即从持久性疾病中根除艾滋病毒为药物滥用和药物滥用之间的联系进行高度创新的研究艾滋病毒/艾滋病。大多数HIV病毒的解剖储存库很难到达，但仅研究血液并不足以完全确定其特征艾滋病病毒的蓄水池。因此，我们将利用NIH之前在我们独特的“最后一份礼物队列”中的投资。没有这样的群体是在其他地方可用。队列获得血液(生前)和一组独特的大型组织(在6小时内死后)全面来自艾滋病毒携带者(PWH)，他们在有记录的、受抑制的情况下死亡抗逆转录病毒疗法(ART)。在我们的家庭项目中，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本来制作最先进的‘单细胞多欧姆IC’。解决以下目标的技术，这些目标直接响应父RFA： ·目标1：深入了解血液和组织中艾滋病毒储存库的特征(大小和活性) 基因组水平与阿片类药物水平的关系。 ·目标2：深入描述血液和组织中T细胞和艾滋病毒DNA的克隆性，以“量化克隆扩张的分布和多样性“与阿片类药物水平有关。 ·目标3：确定与艾滋病毒持久性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的转录。通过利用我们独特的组织来源和通过最先进的方法产生的数据，我们将第一次时间提供了一张与阿片类药物使用有关的艾滋病毒持久性、活动性和整个人体克隆的地图。我们还将揭示全面的分子细节并定义HIV在单细胞中的持久性参数决议，这将独一无二地推进艾滋病毒治疗工作。