PSP Omics Center of Acute to Chronic Pain Signatures

PSP 组学中心急性至慢性疼痛特征

• 批准号: 10231045
• 负责人: Jon Jacobs
• 金额: $ 137.52万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10231045
• 关键词: Acute; Acute Pain; Address; Anti-Inflammatory Agents; Attenuated; Biochemical; Bioinformatics; Biological Assay; Cells; Clinical; Clinical Research; Collaborations; Communication; Complex; Data; Data Analyses; Data Set; Development; Event; Generations; Genome; Genomics; Goals; Healthcare; Human; Immune; Infiltration; Inflammatory Response; Informatics; Laboratories; Lipids; Mass Spectrum Analysis; Mediator of activation protein; Medical center; Metadata; MicroRNAs; Molecular; Molecular Profiling; Opioid; Pacific Northwest; Pain; Pathway interactions; Phase; Physical activity; Physiological; Proteins; Protocols documentation; RNA; Receptor Cell; Reproducibility of Results; Resources; Role; Sampling; Signaling Molecule; Standardization; Stream; Stress; Synaptic plasticity; Technology; Time; Transducers; Universities; Validation; Work; base; chronic pain; data streams; experience; extracellular; flexibility; genetic variant; glial activation; high throughput screening; multiple omics; multiplex assay; novel; predictive signature; prevent; programs; prospective; success; therapeutically effective

PROJECT SUMMARY Chronic pain is currently a substantial and growing health care issue worldwide, with its treatment directly associated with opioid and non-steroidal anti-inflammatory use/abuse. Such treatment efforts however are generally insufficient, hence efforts to understand how chronic pain evolves, specifically its conversion from an acute pain event, can help inform upon more effective therapeutic options. Moreover, identification of molecular signatures associated with or predictive of conversion from acute to chronic pain would provide new avenues to prevent or attenuate such conversion. Though poorly understood, we do recognize the role of certain pathways and physiological events in this conversion, including but not limited to neurogenic inflammatory responses, synaptic plasticity, glial activation, and immune cell infiltration, along with their associated mediators and cell receptor interactions. These associated signaling molecules and mediators represent a wide range of biochemical species, i.e., proteins, lipids, metabolites, and extracellular RNAs, and there is evidence that such molecules could provide a novel multi-molecular signature to chronic pain conversion. Thus, the overall objective of this PNNL-Stanford-Pittsburgh Omics Data Generation Center (PSP-ODGC) is to develop and implement high throughput omics-based assays for quantifying a broad and diverse set of molecular players associated with acute to chronic pain conversion with the goal to develop predictive signatures as well as inform upon relevant molecular mechanisms. To accomplish this objective, we are bringing together advanced mass spectrometry (MS) multi-omics capabilities (Pacific Northwest National Laboratory, PNNL), genomics (Stanford Genome Technology Center), and high throughput screening capabilities (Luminex Core at University of Pittsburgh Medical Center, UPMC) to accurately detect and quantify a broad spectrum of prospective targets. Based upon our extensive previous experience within similar consortium, i.e., the MoTrPAC (Molecular Transducers of Physical Activity Consortium), we recognize the importance of the initial planning phase and the required need for flexible assay proposals and development. Hence, we also strongly stress the flexibility in our strategy and capabilities to adapt and meet the needs of the program. Overall we will facilitate communication and interaction with the MCCs, CCC, and DIRC to streamline sample handling/control efforts for timely initiation of the study and subsequent analysis. Secondly, provide the core ODGC components for the identification and quantification of omics targets for the verification of molecular signatures of acute to chronic pain conversion using a two prong discovery and targeted strategy, where the valid candidates will transition to the high throughput assay platforms such as Luminex. Thirdly, integrate efforts with the DIRC in addressing the storage, flow, and format of the quantitative analysis data and sample metadata and downstream informatics analyses.

项目摘要 慢性疼痛目前是全球范围内的重大医疗保健问题，其治疗直接 与阿片类药物和非甾体类抗炎使用/滥用有关。但是，这种治疗工作是 通常不足，因此努力了解慢性疼痛如何发展，特别是从 急性疼痛事件可以帮助您提供更有效的治疗选择。此外，鉴定分子 与从急性到慢性疼痛转化相关或相关的签名将为新途径提供 预防或衰减这种转换。尽管理解不佳，但我们确实认识到某些途径的作用 和这种转化中的生理事件，包括但不限于神经发生炎症反应， 突触可塑性，神经胶质激活和免疫细胞浸润以及它们的相关介体和细胞 受体相互作用。这些相关的信号分子和介体代表了广泛的 生化物种，即蛋白质，脂质，代谢产物和细胞外RNA，并且有证据表明这样 分子可以为慢性疼痛转化提供一种新型的多分子签名。因此，总体目标 这个pnnl-stanford-pittsburgh omics数据生成中心（PSP-odgc）是开发和实施高的 基于吞吐量的OMICS测定法，以量化与之相关的广泛而多样的分子玩家 急性转化为慢性疼痛转化，以开发预测性特征并告知相关的目标 分子机制。为了实现这一目标，我们将高级质谱法汇总在一起 （MS）多媒体功能（太平洋西北国家实验室，PNNL），基因组学（斯坦福基因组 技术中心）和高通量筛查能力（匹兹堡大学的Luminex Core 医疗中心，UPMC）准确地检测和量化了广泛的前瞻性目标。基于 我们在类似联盟（即Motrpac（分子传感器的） 体育活动联盟），我们认识到初始计划阶段的重要性和所需的需求 用于灵活的测定建议和开发。因此，我们也强烈强调战略的灵活性和 适应和满足计划需求的能力。总体而言，我们将促进沟通和互动 使用MCC，CCC和DIRC，可以简化样本处理/控制工作，以及时启动研究和 随后的分析。其次，提供核心ODGC组件以识别和定量 使用两个插脚验证急性转化为慢性疼痛转化的分子特征的目标目标 发现和有针对性的策略，有效的候选人将过渡到高通量测定平台 例如Luminex。第三，将努力与DIRC整合到解决的存储，流量和格式方面 定量分析数据以及样品元数据和下游信息分析。