ShEEP Request for Imaging Mass Cytometry

ShEEP 成像质量细胞计数请求

• 批准号: 9905867
• 负责人: AMANDA C. LARUE
• 金额: --
• 依托单位: RALPH H JOHNSON VA MEDICAL CENTER
• 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 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905867
• 关键词: Ablation; Address; Alzheimer' s Disease; Animal Model; Animals; Antibodies; Architecture; Behavioral; Bioinformatics; Biomedical Research; Cardiovascular Diseases; Cell Separation; Cells; Cellular Morphology; Clinical; Clinical Trials; Complement; Complex; Consultations; Core Facility; Cytometry; Data Analyses; Detection; Development; Disease; Disease Progression; Evaluation; Event; Extracellular Matrix; Feedback; Fees; Flow Cytometry; Genomics; Goals; Health; Histology; Human; Image; Immunology; In Situ; Injury; Isotopes; Label; Laboratories; Lasers; Logistics; Maintenance; Medical; Medical center; Mental disorders; Metals; Methodology; Methods; Molecular; Orthopedics; Pathologic; Pathologic Processes; Pathology; Patients; Physiological; Physiological Processes; Population Analysis; Positioning Attribute; Precision therapeutics; Proteins; Protocols documentation; Research; Research Personnel; Resolution; Resource Sharing; Sampling; Schedule; Services; Sheep; South Carolina; Spinal cord injury; Stem cells; Strategic Planning; Stroke; Structure; System; Technology; Time; Tissue Sample; Tissues; Training; Translations; Traumatic Brain Injury; Universities; Veterans; base; cell type; conflict resolution; design; dimensional analysis; experience; health care quality; high dimensionality; human disease; imaging capabilities; imaging modality; improved; innovative technologies; instrumentation; interest; next generation; novel; novel marker; novel therapeutics; oncology; operation; preservation; respiratory; tool; transcriptomics; translational medicine; treatment response

The goal of this proposal is to install and integrate the Fluidigm Hyperion Imaging Mass Cytometer (IMC) system in the Cellular and Molecular Evaluation Core (CMEC) Facility within Research Service at the Ralph H. Johnson (RHJ) VA Medical Center. The overarching objective of this core facility is to provide tools and services, including immunohistochemical, flow cytometry, and cell sorting applications, necessary to support and advance research that directly impacts the health of our Veterans. Conventional immunohistochemical (IHC) approaches have been historically limited to the simultaneous detection of only a few markers (~8). Traditional flow cytometry, while allowing for multiparameter analysis, does not allow for spatial analysis of cellular or subcellular marker expression within a tissue. In contrast, time of flight mass cytometry (CyTOF) allows for the simultaneous detection of 40+ markers on one single cell. By combining the existing high dimensional Helios mass cytometer CyTOF platform with the Hyperion laser ablation system, we are able to bring this powerful detection method, termed imaging mass cytometry (IMC), into tissues. The central hypothesis addressed by this core is that the high dimensional analysis Hyperion IMC system will allow VA researchers to use small fixed tissue samples to examine complex subcellular, cellular, and cell-matrix interactions in the intact tissue microenvironment and provide a technology bridge to existing transcriptomic and imaging methods to understand pathologies impacting our Veterans. Our investigators have identified four primary aims that will be accomplished through this groundbreaking technology that provides high throughput, high-dimensional quantitative analyses in situ of complex cellular samples: 1) Identify novel cell types and their cellular and sub-cellular proteins that contribute to the pathology of disease; 2) Uncover new intracellular, cell- cell, and cell-ECM interactions important for disease progression; 3) Examine rare events (including stem cells) in physiological and pathological conditions; and 4) Discover novel biomarkers of disease and/or clinical response to treatment, enhancing the development of targeted, personalized, precision therapies. The state-of-the-art technology afforded by the Hyperion IMC System is broadly applicable across the diverse animal- and human-based research efforts of our local VAMC investigators including studies in traumatic brain injury, stroke, spinal cord injury, respiratory illness, cardiovascular disease, immunology, oncology, orthopedic injury, Alzheimer’s disease, and mental health disorders. This technology does not currently exist at RHJ VAMC, the Affiliate (Medical University of South Carolina, MUSC), or in the state. Based on the number of interested investigators and diverse disease-related applications, we believe that this upgrade will meet demands of investigators for cutting edge technologies to advance translational medicine and allow the VA CMEC to provide the next generation of mass cytometry capabilities. This expansion will position VA as a leader in integration of mass cytometry into clinical trials, personalized disease treatments, and development of novel therapies. Incorporating the Hyperion Imaging Mass Cytometer System into the established CMEC will greatly strengthen the research capabilities of our station (and those in the VISN), facilitating basic scientific discovery of mechanisms underlying physiological and pathological processes and translation of these findings to support the rapid implementation of cutting-edge personalized medical treatment to improve quality healthcare for our Nation’s Veterans.

该建议的目的是安装和集成流体成像质量细胞仪（IMC）系统 在Ralph H. Johnson的研究服务中的细胞和分子评估核心（CMEC）中 （RHJ）VA医疗中心。该核心设施的总体目标是提供工具和服务，包括 免疫组织化学，流式细胞仪和细胞分选应用，以支持和提高研究所必需 这直接影响了我们退伍军人的健康。常规免疫组织化学（IHC）方法具有 从历史上看，仅限于几个标记（〜8）的简单发现。传统的流式细胞仪， 在允许多参数分析的同时，不允许对细胞或亚细胞标记的空间分析 在组织中的表达。相比之下，飞行质量细胞仪（CYTOF）的时间允许同时进行 在一个单元格上检测40多个标记。通过组合现有的高维Helios质量细胞仪 通过Hyperion激光消融系统的Cytof平台，我们能够带来这种强大的检测方法， 被称为成像质量细胞仪（IMC），进入组织。 该核心解决的中心假设是高维分析Hyperion IMC系统将 允许VA研究人员使用小的固定组织样品检查复杂的亚细胞，细胞和细胞 - 矩阵 完整组织微环境中的相互作用，并为现有转录组和 理解影响我们退伍军人的病理的成像方法。我们的调查人员已经确定了四个 通过这项提供高通量的开创性技术将实现的主要目标 复杂细胞样品的原位高维定量分析：1）识别新型细胞类型及其 细胞和亚细胞蛋白有助于疾病的病理； 2）发现新的细胞内细胞 - 细胞和细胞ECM相互作用对于疾病进展很重要； 3）检查罕见事件（包括干细胞） 在身体和病理条件下； 4）发现疾病和/或临床的新型生物标志物 对治疗的反应，增强目标，个性化的精确疗法的发展。 Hyperion IMC系统提供的最先进的技术广泛适用于潜水员 我们当地VAMC研究人员的动物和人类研究工作，包括创伤性大脑的研究 损伤，中风，脊髓损伤，呼吸道疾病，心血管疾病，免疫学，肿瘤学，骨科 受伤，阿尔茨海默氏病和心理健康疾病。该技术目前不存在于RHJ VAMC， 会员（南卡罗来纳州医科大学，MUSC）或该州。基于兴趣数量 调查人员和与疾病有关的应用程序的应用，我们认为此升级将满足 尖端技术的研究人员可以推进转化医学并允许VA CMEC提供 下一代的质量细胞术能力。这种扩展将把VA定位为整合的领导者 大规模细胞仪进入临床试验，个性化疾病治疗和新疗法的发展。 将Hyperion成像质量细胞仪系统纳入已建立的CMEC将大大增强 我们的电台（以及VISN中的人员）的研究能力，支持基本科学发现 物理和病理过程的基础机制以及这些发现的翻译以支持 快速实施最先进的个性化医疗，以改善我们的质量医疗保健 国家的退伍军人。