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） 研究人员在非常异质的细胞群体中鉴定和分析不同的表型， 从各种来源的动物模型和人类标本。没有高维度的流式细胞仪， BVAMC或其附属机构，亚拉巴马大学伯明翰分校（UAB），但迫切需要 BVAMC调查人员有权使用这种仪器。BD FACSymphony具有超静音功能， VPX（也称为VITA 46），这是下一代坚固紧凑的嵌入式电子 支持多达50个高性能光电倍增管（PMT）并提高检测性能的系统 灵敏度，使用户能够提前识别和分析稀有细胞亚型。为了解 疾病的原因，如癌症、肾病、心力衰竭、糖尿病或退行性疾病， 在神经系统中，重要的是不仅要在一个时间点，而且要在多个时间点定义细胞群。 一种疾病的过程。多参数分析通过需要更小的样品体积和 增加样品吞吐量。这对于可从人类获得的有限量的人类样本至关重要 组织和体液参数数量的增加有助于改善同时功能 通过磷酸化靶标、细胞因子和生长因子的细胞内染色表征细胞 生产、细胞周期分析、细胞凋亡、线粒体膜极化等。这些能力是 对于了解活动性研究中VA患者来源的广谱单细胞或液体至关重要， BVAMC的调查人员例如，在Mountz博士的系统性红斑狼疮（SLE）研究中，BD FACSymphony将用于特异性和非常单独地确定 自身反应性B细胞和其他细胞在SLE患者中，并使定制的精确的医学治疗方法。 重要的精准医学方法可以最好地利用和靶向时，异常细胞 可以识别特定个体和疾病中的亚群，并特异性抑制。这一点 对于促进VA患者有效治疗的发展具有相当重要的意义， 发展中国家的炎症和自身免疫性疾病提出了这一建议。在另一种新颖的方法中， Drs. Dell'Italia和Gaggar将利用BD Symphony来跟踪急性和慢性炎症患者中外泌体的分泌， 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。的能力 利用流式细胞术直接询问单个外泌体及其内容物是非常有价值的， 提供了对给定外泌体群体的致病特征的洞察。在每一个项目中， 根据这项提议，对于心脏、肺、血管性肾病， 癌症以及胃肠道和神经系统的免疫性疾病。的应用 这项令人兴奋的新技术将提高资金能力，最重要的是我们的研究目标， 以退伍军人为中心的医疗护理的使命。