Pathophysiology Core

病理生理学核心

• 批准号: 10686928
• 负责人: Rubin M. Tuder
• 金额: $ 17.88万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686928
• 关键词: Animal Model; Animals; Blood Vessels; Cells; Collection; Complement; Complement Activation; Data; Disease; Functional disorder; Genomics; Goals; Histologic; Human; Image; Immune Targeting; Immune system; Immunofluorescence Immunologic; Immunohistochemistry; Inflammation; Inflammatory; Investigation; Label; Leadership; Lesion; Lung; Malignant Neoplasms; Mass Spectrum Analysis; Mediating; Messenger RNA; Methodology; Methods; Modeling; Morphology; Mus; Newborn Infant; Pathologist; Pathology; Pattern; Phenotype; Preparation; Proteins; Proteome; Proteomics; Pulmonary Hypertension; RNA; Rattus; Research Personnel; Resources; Role; Sampling; Services; Structure; System; Translating; Translations; experience; experimental study; high throughput analysis; human tissue; imaging approach; immune imaging; inflammatory marker; innovation; laser capture microdissection; member; pulmonary vascular disorder; pulmonary vascular remodeling; tissue processing; transcriptomics

The primary objective of the Pathology and Imaging Core is to provide accurate phenotypic characterization of pulmonary vascular remodeling, document activation of complement, assess inflammation, and isolate mRNA and proteins, in diseased IPAH human lungs and relevant models of PH. To accomplish these goals, we will perform 8 tasks based on specific methodologies, aimed at integrating high quality tissue processing, immunohistochemistry, and stereology with high throughput imaging approaches and laser capture microdissection for all 4 projects in this PPG. Aim 1: To provide qualitative and quantitative assessment of pulmonary vascular remodeling in lungs of humans, steers and newborn calves, rats, and mice in Projects 1-4. We propose 4 specific tasks to support this specific aim, which include: planning of experiments (task 1), collection, processing, and phenotyping experimental lungs (task 2), morphology and stereology of pulmonary vascular remodeling (task 4), and integration of morphological data with specific project goals and aims (task 8). Aim 2: To determine expression patterns and abundance of candidate molecules investigated in experimental lungs. We propose 5 specific tasks to support this specific aim, which include planning of experiments (task 1), tissue processing (task 2), morphology and stereology (task 3), laser capture microdissection (LCM; task 7), and integration of morphological data with project goals and aims (task 8). Aim 3: Specific Aim 3: To obtain high quality mRNA and protein for transcriptomic and proteomic studies from specific pulmonary vascular structures and lesions from animals manipulated in Projects 1-4. We propose 5 specific tasks to support this specific aim, which include planning of experiments (task 1), tissue processing (task 2), LCM (task 7), and integration of morphological data with specific project goals and aims (task 8). Aim 4: To translate the key expression findings in Specific Aim 2 to human control and PAH lungs. We propose six specific tasks to support the specific aim, which include planning of experiments (task1), tissue processing (task 2), human tissue studies (task 3), morphology and stereology (task 4), LCM (task 7), and integration of morphological data with specific project goals and aims (task 8). Foremost in accomplishing these goals is the scientific expertise within the leadership of the core. The Pathology and Imaging Core is led by of Drs. Rubin M. Tuder, an experimental and practicing pulmonary pathologist with major expertise in pathology and pathobiology of pulmonary hypertension, with the support of Dr. Raphe Nemenoff, an experienced investigator in the cancer field with expertise in multiprobe immune imaging targeting the immune system and complement. The novelty of the Pathology and Imaging Core lies on the unique resources, unmatched expertise, and overall experimental breadth, allowing for the integration and human translation pertaining to all four projects.

病理学和影像核心的主要目标是提供准确的表型特征 肺血管重塑、记录补体激活、评估炎症并分离 mRNA 和蛋白质，在患病的 IPAH 人肺和相关 PH 模型中。为了实现这些目标，我们将 根据特定方法执行 8 项任务，旨在整合高质量的组织处理， 使用高通量成像方法和激光捕获进行免疫组织化学和体视学 该 PPG 中所有 4 个项目的显微解剖。 目标 1：提供肺部肺血管重塑的定性和定量评估 项目 1-4 中的人类、阉牛和新生牛犊、大鼠和小鼠。我们提出4项具体任务 支持这一具体目标，其中包括：实验规划（任务 1）、收集、处理和 实验肺表型分析（任务 2）、肺血管重塑的形态学和体视学（任务 4) 以及将形态数据与具体项目目标相整合（任务 8）。 目标 2：确定所研究的候选分子的表达模式和丰度 实验肺。我们提出了 5 项具体任务来支持这一具体目标，其中包括规划 实验（任务 1）、组织处理（任务 2）、形态学和体视学（任务 3）、激光捕获 显微解剖（LCM；任务 7），以及形态学数据与项目目标的整合（任务 8）。 目标 3：具体目标 3：获得用于转录组和蛋白质组的高质量 mRNA 和蛋白质 对项目中操作的动物的特定肺血管结构和病变进行的研究 1-4.我们提出了 5 个具体任务来支持这一具体目标，其中包括实验规划（任务 1）、 组织处理（任务 2）、LCM（任务 7）以及形态数据与特定项目目标的集成 目标（任务 8）。 目标 4：将特定目标 2 中的关键表达结果转化为人类对照和 PAH 肺部。我们 提出六项具体任务来支持具体目标，其中包括实验规划（任务1）、组织 处理（任务 2）、人体组织研究（任务 3）、形态学和体视学（任务 4）、LCM（任务 7）和 将形态学数据与具体项目目标相结合（任务 8）。 实现这些目标的首要因素是核心领导层的科学专业知识。这 病理学和影像学核心由 Drs 领导。 Rubin M. Tuder，一位实验和实践肺 在肺动脉高压的病理学和病理生物学方面拥有主要专业知识的病理学家，并得到以下机构的支持 Raphe Nemenoff 博士是一位癌症领域经验丰富的研究人员，拥有多探针免疫方面的专业知识 针对免疫系统和补体的成像。病理和影像核心的新颖之处在于 独特的资源、无与伦比的专业知识和整体实验广度，允许整合 以及与所有四个项目相关的人工翻译。