ShEEP Request for Next Generation High Dimension Flow Cytometer

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学中心(BVAMC) 研究人员在非常不同的细胞群体中识别和分析不同的表型 从各种来源的动物模型和人类标本中提取。没有高维的流式细胞仪在 BVAMC或附属机构，阿拉巴马大学伯明翰分校(UAB)，但迫切需要 BVAMC调查人员有权接触到这样的仪器。BD FAC交响乐采用超静音 VPX(也称为VITA 46)，它是下一代坚固紧凑的嵌入式电子产品 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。为了更好地理解 疾病的原因，如癌症、肾脏疾病、心力衰竭、糖尿病或退行性疾病 神经系统，重要的是不只在一个时间点上定义细胞数量，而是在 这是一个疾病的过程。多参数分析通过需要较小的样本量和 增加样品吞吐量。这对于从人类身上获得有限数量的人体样本至关重要。 组织和体液。增加参数数量有助于改进同步功能 细胞内磷酸化靶标、细胞因子和生长因子染色鉴定细胞 产生，细胞周期分析，细胞凋亡，线粒体膜极化等。这些能力是 在积极的研究中，对了解来自VA患者的广泛的单细胞或液体至关重要 BVAMC的调查人员。例如，在蒙茨博士对系统性红斑狼疮(SLE)的研究中，BD FAC SYMPHONY将被用来专门和非常个别地确定肺炎的致病表型 SLE患者的自身反应性B细胞和其他细胞，并使量身定做的精确药物治疗方法成为可能。 当细胞异常时，重要的精确医学手段可以得到最好的利用和靶向 特定个体和疾病中的亚群可以被识别，并被特别抑制。这是 对促进为患有以下疾病的VA患者开发有效治疗方法具有相当重要的意义 本提案中提出的已发展的炎症性和自身免疫性疾病。在另一种新方法中， Dell‘Italia博士和Gaggar博士将利用BD交响乐追踪急性和慢性疾病患者外显子的分泌情况。 慢性肺和心脏损伤。外切体是一种膜结合的结构，由多种 哺乳动物细胞类型在正常和病理状态下运载和运输细胞货物。有能力 利用流式细胞术直接询问单个外切体，其内容具有极大的价值和 提供对给定外体种群的致病特征的洞察。在提交的每个项目中 这项建议，有一个类似的靶向细胞方法，用于治疗心脏、肺、血管肾脏疾病和 癌症，以及胃肠道和神经系统的免疫性疾病。技术的应用 这项令人兴奋的新技术将增强资金能力，最重要的是，我们的研究目标和 以退伍军人为中心的医疗保健使命。

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.