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.

抽象的拟议的“家庭”项目位于NIH/OAR高的研究优先领域，从持久性地消除HIV 水库和对父母RFA的反应艾滋病毒/艾滋病。大多数HIV解剖学水库很难达到艾滋病毒水库。这，我们将利用在我们独特的“上次礼物队列”中进行先前的NIH投资。没有这样的队列是在其他地方可用。该队列获得血液（死亡前）和一组独特的组织（在6小时内死后）全面地来自患有艾滋病毒（PWH）的人，他们在有记录的抑制性情况下死亡抗逆转录病毒疗法（ART）。对于我们的家庭项目，我们将收集以下17个组织/流体：血液，肠道（回肠和结肠），淋巴结，肾皮质，脾脏，肺，肝，生殖道（前列腺/睾丸或睾丸或睾丸子宫颈/卵巢），脂肪组织（腹部，局部和心包），心脏，大脑（基底神经节，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“单细胞多词” 解决以下目标的技术，这些目标直接响应父级RFA： •目标1：深层表征单个血液和组织中的HIV储量（尺寸和活动）与阿片类药物水平有关的基因组水平。 •目标2：深层表征血液和组织中的T细胞和HIV DNA克隆性以“量化克隆扩张的分布和多样性相对于阿片类药物水平。 •目标3：确定与HIV持续性相关的艾滋病毒和阿片类药物相关的免疫机制并增加了单细胞水平的HIV RNA转录。通过利用我们通过最先进方法生成的独特的组织和数据来源，我们将首先时间提供与阿片类药物使用相关的人体艾滋病毒持久性，活性和克隆性的地图。我们还将揭示全面的分子细节并定义单细胞的HIV持久性参数解决方案，这将独特地促进艾滋病毒治愈的努力。