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。阿片类药物是治疗 治疗疼痛，但它们在慢性疼痛条件下的使用缺乏证据基础，而且固有的风险 上瘾。目前与阿片类药物相关的死亡危机突显了与广泛使用阿片类药物相关的风险。 精密人类疼痛网络是NIH Hear倡议的一部分，旨在提供有关 构成痛觉神经轴的细胞类型的多样性。在这里，我们提出了一个U19项目，名为 《人类疼痛组织综合研究中心》(Intercept Pain)。我们将在过去成功的基础上，在 我们的人体组织研究计划，并扩大工作范围，直接解决 精确的人类痛苦网络。我们的计划利用世界一流的基因组学和计算资产 和华盛顿大学麦克唐纳基因组研究所的强大机构实力 疼痛、轴突退变和再生的神经生物学，以及协调发展的遗传学 关于所涉及的组织和细胞的转录和功能特性的基础性新知识 在人类的疼痛传导、传递和调制中起重要作用。我们将提供一份全面的手机地图集 应用单核RNAseq、空间转录和多重技术研究人外周神经基因表达 蛋白质组学，并利用这一点来了解与创伤性(神经瘤)和 特发性(遗传性)痛性神经病。我们还将提供扩展的单核测序图谱 背根节，包括无痛史和近期有痛史的供者的背根节。我们将生成一个 使用成像质量细胞术绘制hDRG的空间图谱，并优化集成IMC的计算方法 HDRG的单细胞转录分析。最后，我们将结合电生理的分析， HDRG和人脊髓背角神经元的转录和形态数据。我们会工作的 与其他中心一起优化协议和数据收集，以允许跨多个中心进行集成分析， 与U24 DCIC和Hear Data生态系统合作。这些目标将通过 三个科学项目的协调活动，由疼痛神经生物学、遗传学、 以及轴突退化和再生的机制。项目名称如下： 项目1：多组学周围神经图谱使疼痛分子表型的精细图谱成为可能。 项目2：通过整合转录组学在单细胞水平上表征人背根神经节 和空间蛋白质组学 项目3：单细胞分辨率下人背根神经节和脊髓的功能和遗传学特征 这些项目由经验丰富的项目领导团队和管理核心人员提供支持 组织采购和处理核心，以及数据核心。