INTERCEPT: Integrated Research Center for human Pain Tissues

截取：人类疼痛组织综合研究中心

• 批准号: 10707405
• 负责人: Robert W Gereau
• 金额: $ 233.02万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707405
• 关键词: Address; American; Anatomy; Animal Model; Atlases; Catalogs; Cell Nucleus; Cells; Central Nervous System; Chromatin; Chromosome Mapping; Collaborations; Cytometry; Data; Data Collection; Development; Doctor of Philosophy; Electrophysiology (science); Epidemic; Failure; Gene Expression; Genes; Genetic; Genetic Transcription; Genome; Genomics; Goals; Helping to End Addiction Long-term; Human; Human Biology; Image; Inherited; Institute of Medicine (U.S.); Institution; International; Knowledge; Leadership; Learning; Location; Maps; Morphology; Neurobiology; Neuroma; Neurons; Opioid; Pain; Pain Clinics; Pain Map; Patient Care; Peripheral Nerves; Peripheral Nervous System Diseases; Physiological; Posterior Horn Cells; Preparation; Price; Property; Proteomics; Protocols documentation; Recording of previous events; Reporting; Research; Research Personnel; Resolution; Risk; Scientist; Site; Spinal Cord; Spinal Ganglia; Spinal cord posterior horn; Testing; Tissue Procurements; Tissues; Translating; United States National Institutes of Health; Universities; Washington; Work; addiction; axon regeneration; axonal degeneration; cell type; chronic pain; chronic painful condition; data ecosystem; evidence base; experience; human tissue; improved; insight; molecular phenotype; multiple omics; novel therapeutics; opioid epidemic; opioid mortality; opioid use; overdose death; pain model; painful neuropathy; patch sequencing; pre-clinical; programs; searchable database; single nucleus RNA-sequencing; species difference; success; tissue processing; tool; transcriptome sequencing; transcriptomics; transmission process

Abstract: Tens of millions of Americans suffer from chronic pain. Opioids represent the main tool for treating pain, but their use in chronic pain conditions suffers from a poor evidence base and the inherent risk of addiction. The current crisis of opioid-related deaths highlights the risk associated with widespread opioid use. The PRECISION Human Pain Network, part of the NIH HEAL Initiative, seeks to provide foundational data on the diversity among cell types that comprise the pain neuraxis. Here, we propose a U19 program entitled “Integrated Research Center for Human Pain Tissues” (INTERCEPT Pain). We will build on prior successes in our human tissue research program, and expand the scope of work to directly address the goals of the PRECISION Human Pain Network. Our program leverages the world-class genomics and computational assets of the McDonnell Genome Institute here at Washington University and substantial institutional strengths in neurobiology of pain, axon degeneration and regeneration, and genetics in a coordinated program to develop foundational new knowledge regarding the transcriptional and functional properties of tissues and cells involved in pain transduction, transmission and modulation in humans. We will provide a comprehensive atlas of cellular gene expression in human peripheral nerve using single nuclei RNAseq, spatial transcriptomics and multiplex proteomics, and leverage this to understand the distribution of genes involved in traumatic (neuromas) and idiopathic (hereditary) painful neuropathies. We will also provide expanded single-nucleus sequencing atlases of dorsal root ganglia, including DRG from donors without and with a recent history of pain. We will generate a spatial atlas of hDRG using imaging mass cytometry, and optimize computational approaches for integrated IMC and single cell transcriptomic analysis of hDRG. Finally, we will combine analysis of electrophysiological, transcriptional, and morphological data from hDRG and human spinal cord dorsal horn neurons. We will work with other centers to optimize protocols and data collection to allow integrated analysis across multiple centers, in collaboration with the U24 DCIC and HEAL data ecosystem. These goals will be accomplished through the coordinated activity of 3 scientific projects, led by international leaders in the fields of pain neurobiology, genetics, and mechanisms of axon degeneration and regeneration. The project titles are as follows: Project 1: Multi-omics peripheral nerve atlas enables fine-mapping of pain molecular phenotypes. Project 2: Characterization of the human dorsal root ganglia at the single cell level via integrated transcriptomics and spatial proteomics Project 3: Functional and genetic characterization of human DRG and spinal cord at single cell resolution The projects are supported by an experienced program leadership team and an administration core, a human tissue procurement and processing core, and a data core.

摘要：数以千万计的美国人患有慢性疼痛。阿片类药物是主要工具 治疗疼痛，但它们在慢性疼痛中的使用缺乏证据基础，并且存在固有的风险 瘾。当前与阿片类药物相关的死亡危机凸显了广泛使用阿片类药物带来的风险。 PRECISION 人类疼痛网络是 NIH HEAL Initiative 的一部分，旨在提供以下方面的基础数据： 构成疼痛神经轴的细胞类型的多样性。在这里，我们提出一个名为“U19”的计划 “人类疼痛组织综合研究中心”（INTERCEPT Pain）。我们将在之前的成功基础上再接再厉 我们的人体组织研究计划，并扩大工作范围以直接实现该目标 精确人类疼痛网络。我们的计划利用世界一流的基因组学和计算资产 华盛顿大学麦克唐纳基因组研究所的优势以及在 疼痛的神经生物学、轴突变性和再生以及遗传学在协调计划中的发展 有关所涉及组织和细胞的转录和功能特性的基础新知识 在人类疼痛转导、传递和调节中。我们将提供全面的蜂窝图谱 使用单核 RNAseq、空间转录组学和多重分析在人周围神经中进行基因表达 蛋白质组学，并利用它来了解与创伤（神经瘤）和 特发性（遗传性）疼痛性神经病。我们还将提供扩展的单核测序图谱 背根神经节，包括来自没有或有近期疼痛史的捐赠者的 DRG。我们将生成一个 使用成像质量细胞术绘制 hDRG 空间图谱，并优化集成 IMC 的计算方法 hDRG 的单细胞转录组分析。最后，我们将结合电生理分析， 来自 hDRG 和人类脊髓背角神经元的转录和形态学数据。我们将工作 与其他中心合作优化协议和数据收集，以便跨多个中心进行综合分析， 与 U24 DCIC 和 HEAL 数据生态系统合作。这些目标将通过 由疼痛神经生物学、遗传学、 以及轴突变性和再生的机制。项目名称如下： 项目 1：多组学周围神经图谱能够精细绘制疼痛分子表型。 项目 2：通过整合转录组学在单细胞水平表征人类背根神经节 和空间蛋白质组学 项目 3：单细胞分辨率下人类 DRG 和脊髓的功能和遗传表征 这些项目得到了经验丰富的项目领导团队和管理核心、人员的支持 组织采购和处理核心，以及数据核心。