ShEEP Request for Next Generation High Dimension Flow Cytometer

ShEEP 请求下一代高维流式细胞仪

• 批准号: 9796482
• 负责人: Louis J. Dell'Italia
• 金额: --
• 依托单位: BIRMINGHAM 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: 2019-01-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9796482
• 关键词: Abnormal Cell; Acute; Address; Advanced Development; Affect; Alabama; Animal Model; Animal Sources; Apoptosis; Area; Autoimmune Diseases; Award; B-Lymphocytes; Biomedical Research; Biopsy; Blood; Body Fluids; Bronchoalveolar Lavage Fluid; Cardiac; Caring; Cell Cycle; Cells; Chronic; Clinical; Clinical Research; Consultations; Country; Data; Data Analyses; Detection; Development; Diabetes Mellitus; Disease; Enrollment; Equipment; Experimental Designs; Flow Cytometry; Fostering; Funding; Future; Gastrointestinal tract structure; Genetic Transcription; Glioblastoma; Goals; Growth Factor; Heart Diseases; Heart Injuries; Heart failure; Human; Human body; Image; Immune; Immune System Diseases; Immunologics; Individual; Inflammation; Inflammatory; Institutes; Interdisciplinary Study; Kidney; Kidney Diseases; Lasers; Leadership; Learning; Link; Liquid substance; Lung; Lung diseases; Maintenance; Malignant Neoplasms; Mammalian Cell; Mammary gland; Medical; Medical center; Membrane; Microglia; Mission; Molecular Target; Nervous system structure; Neurodegenerative Disorders; One-Step dentin bonding system; Pathogenicity; Pathologic; Patients; Performance; Peripheral Blood Mononuclear Cell; Phenotype; Population; Population Heterogeneity; Positioning Attribute; Process; Production; Renal carcinoma; Research; Research Personnel; Sampling; Sheep; Site; Skeletal Muscle; Skin Cancer; Solid; Source; Specimen; Stains; Stem cells; Stream; Stromal Cells; Structure; Support System; System; Systemic Lupus Erythematosus; Systems Analysis; T-Lymphocyte; Technology; Thinking; Time; Tissues; Translating; Tube; Universities; Vesicle; Veterans; Work; analytical tool; autoreactive B cell; cancer stem cell; cell type; cellular targeting; common treatment; cytokine; design; effective therapy; exosome; experimental study; flexibility; health care delivery; high dimensionality; high end computer; human disease; human tissue; idiopathic pulmonary fibrosis; improved; insight; instrument; instrumentation; kidney vascular structure; lung injury; macrophage; microvesicles; mitochondrial membrane; muscle regeneration; new technology; next generation; novel; novel strategies; operation; peripheral blood; photomultiplier; precision medicine; prevent; programs; protein expression; recruit; symposium; transcriptome

Inflammation and immunological mechanisms are at the epicenter of all disease mechanisms. High-parameter flow cytometry is a powerful analytical tool that will enable the Birmingham VA Medical Center (BVAMC) researchers to identify and analyze distinct phenotypes in the very heterogeneous populations of cells derived from various sources of animal models and human specimens. There is no high dimensional flow cytometer at the BVAMC or the affiliate, the University of Alabama at Birmingham (UAB), yet there is an acute need for BVAMC investigators to have access to such an instrument. The BD FACSymphony features an ultra-quiet VPX (also known as VITA 46), which is the next generation of ruggedized compact embedded electronic systems that supports up to 50 high-performance photomultiplier tubes (PMTs) and improves detection sensitivity to enable the user to identify and analyze rare cell subtypes in advance. In order to understand the causes of diseases such as cancer, kidney disease, heart failure, diabetes, or degenerative diseases of the nervous system, it is important to define the cell population not at just one point in time but at multiple times in a disease process. Multiparameter analysis improves the efficiency by requiring smaller sample volume and by increasing sample throughput. This is critical for human samples available at limited amounts from human tissue and body fluids. Increased number of parameters facilitates improved simultaneous functional characterization of cells by intracellular staining of phosphorylated targets, cytokine and growth factor production, analysis of cell cycle, apoptosis, mitochondria membrane polarization, etc. These capacities are critical for understanding a broad spectrum of single cells or fluids derived from VA patients in active studies by the BVAMC investigators. For example, in Dr. Mountz's work in Systemic Lupus Erythematosis (SLE), the BD FACSymphony will be used to specifically and very individually determine the pathogenic phenotype of autoreactive B cells and other cells in SLE patients and enable tailored precision medical therapy approaches. The important precision medicine approaches can be best utilized and targeted when the abnormal cell subpopulation in a specific individual and disease can be identified, and specifically suppressed. This is of considerable importance to facilitate the development of effective therapies for VA patients who have developed inflammatory and autoimmune diseases presented in this proposal. In another novel approach, Drs. Dell'Italia and Gaggar will utilize the BD Symphony to track the secretion of exosomes in acute and chronic lung and heart injury. Exosomes are membrane-bound structures secreted by a wide range of mammalian cell types carrying and transporting cellular cargo in normal and pathologic states. The ability to utilize flow cytometry to directly interrogate individual exosomes and their content is tremendously valuable and offers insight to the pathogenic features of a given exosome population. In each of the projects presented in this proposal, there is a similar targeted cellular approach for cardiac, pulmonary, vascular kidney disease and cancer, as well as immunological disease of the gastrointestinal tract and nervous system. The application of this exciting new technology will enhance funding capabilities and most importantly our research goals and mission of Veteran-centric medical care.

炎症和免疫机制是所有疾病机制的中心。高参数 流式细胞术是一种强大的分析工具，将使伯明翰退伍军人医疗中心 (BVAMC) 能够 研究人员识别和分析非常异质的细胞群体中的不同表型 来自各种来源的动物模型和人体标本。目前还没有高维流式细胞仪 BVAMC 或其附属机构阿拉巴马大学伯明翰分校 (UAB)，但迫切需要 BVAMC 调查人员有权使用此类仪器。 BD FACSymphony 具有超静音功能 VPX（也称为 VITA 46），是下一代坚固耐用的紧凑型嵌入式电子产品 支持多达 50 个高性能光电倍增管 (PMT) 并改进检测的系统 灵敏度使用户能够提前识别和分析稀有细胞亚型。为了了解 癌症、肾病、心力衰竭、糖尿病或退行性疾病等疾病的原因 神经系统中，重要的是不仅要定义一个时间点上的细胞群，还要定义多个时间点上的细胞群。 一个疾病的过程。多参数分析通过需要更小的样品体积来提高效率 提高样品通量。这对于从人体中获取的数量有限的人体样本至关重要 组织和体液。参数数量的增加有利于改进同步功能 通过磷酸化靶标、细胞因子和生长因子的细胞内染色来表征细胞 生产、细胞周期分析、细胞凋亡、线粒体膜极化等。这些能力是 对于在积极的研究中了解来自 VA 患者的广泛单细胞或液体至关重要 BVAMC 调查员。例如，Mountz 博士在系统性红斑狼疮 (SLE) 方面的研究中，BD FACSymphony 将用于专门且非常单独地确定以下疾病的致病表型： SLE 患者体内的自身反应性 B 细胞和其他细胞，使定制的精准医疗方法成为可能。 当异常细胞出现异常时，重要的精准医疗方法可以得到最好的利用和靶向治疗。 可以识别特定个体和疾病的亚群，并进行针对性抑制。这是属于 促进针对患有 VA 患者的有效疗法的开发非常重要 患有本提案中提出的炎症和自身免疫性疾病。在另一种新颖的方法中， 博士。 Dell'Italia 和 Gaggar 将利用 BD Symphony 来追踪急性和慢性疾病中外泌体的分泌。 慢性肺和心脏损伤。外泌体是由多种细胞分泌的膜结合结构 在正常和病理状态下携带和运输细胞货物的哺乳动物细胞类型。有能力 利用流式细胞术直接询问单个外泌体，其内容非常有价值 提供对特定外泌体群体致病特征的深入了解。在提出的每个项目中 根据该提案，针对心脏、肺、血管肾疾病和其他疾病有类似的靶向细胞方法 癌症以及胃肠道和神经系统的免疫疾病。应用 这项令人兴奋的新技术将增强资助能力，最重要的是我们的研究目标和 以退伍军人为中心的医疗服务的使命。