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.

病理学和成像核心的主要目标是提供准确的表型特征 肺血管重塑、记录补体的激活、评估炎症和分离mRNA 和蛋白质，在患病的IPAH人肺和相关的PH模型中。为了实现这些目标，我们将 根据具体方法执行8项任务，旨在整合高质量的组织处理， 免疫组织化学、高通量成像方法和激光捕获的体视学 这个PPG中所有4个项目的显微解剖。 目的1：为肺血管重构提供定性和定量的评价 项目1-4中的人类、公牛和新生小牛、大鼠和小鼠。我们提出了4项具体任务 支持这一具体目标，其中包括：计划实验(任务1)、收集、处理和 实验肺表型(任务2)、肺血管重构的形态和体视学(任务2) 4)，并将形态数据与具体的项目目标和目的相结合(任务8)。 目标2：确定研究的候选分子的表达模式和丰度 实验性肺。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)、形态和体视学(任务3)、激光捕获 显微解剖(LCM；任务7)；形态数据与项目目标和目的的整合(任务8)。 目标3：特定目标3：为转录和蛋白质组学获得高质量的mRNA和蛋白质 来自项目中操纵动物的特定肺血管结构和损伤的研究 1比4。为了支持这一具体目标，我们提出了5项具体任务，其中包括实验计划(任务1)、 组织处理(任务2)、LCM(任务7)以及将形态数据与特定项目目标和 目标(任务8)。 目的4：将特定目的2中的关键表达结果翻译到人类对照和PAH肺。我们 提出六项具体任务以支持具体目标，其中包括实验计划(任务1)、组织 加工(任务2)、人体组织研究(任务3)、形态和体视学(任务4)、激光共聚焦显微镜(任务7)和 将形态数据与具体的项目目标和目的相结合(任务8)。 在实现这些目标方面，最重要的是核心领导层的科学专长。这个 病理和影像核心由鲁宾·M·图德尔博士领导，他是一名实验性和实践性肺 在肺动脉高压的病理学和病理生物学方面具有主要专业知识的病理学家，在 拉菲·涅门诺夫博士，癌症领域经验丰富的研究员，拥有多探针免疫方面的专业知识 以免疫系统和补体为目标的成像。病理学和影像核心的新颖性在于 在独特的资源、无与伦比的专业知识和总体实验广度上，允许整合 以及与所有四个项目相关的人工翻译。