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.

病理和成像核的主要目的是提供准确的表型表征 肺血管重塑，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pH的相关模型中。为了实现这些目标，我们将 根据特定方法执行8个任务，旨在整合高质量的组织加工， 免疫组织化学和具有高通量成像方法和激光捕获的立体学 该ppg中所有4个项目的微分解。 目标1：提供肺血管重塑的定性和定量评估 在项目1-4中，人类，牛肉和新生小牛，大鼠和小鼠的摄入量。我们建议4个特定任务 支持此特定目标，其中包括：实验计划（任务1），收集，处理和 表型实验肺（任务2），肺血管重塑的形态和立体学（任务 4），以及形态数据与特定项目目标和目标的整合（任务8）。 目标2：确定研究中研究的表达模式和丰度 实验性肺。我们提出了5个具体任务来支持这一特定目标，其中包括计划 实验（任务1），组织处理（任务2），形态学和立体学（任务3），激光捕获 显微解剖（LCM；任务7），以及形态数据与项目目标和目标的集成（任务8）。 目标3：特定目标3：获得转录组和蛋白质组学的高质量mRNA和蛋白质 从项目中操纵的动物的特定肺血管结构和病变的研究 1-4。我们提出了5个特定任务来支持这一特定目标，其中包括实验计划（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整合 目标（任务8）。 目标4：将特定目标2中的关键表达发现转化为人类控制和PAH肺。我们 提出六项特定任务来支持特定目标，其中包括实验计划（任务1），组织 处理（任务2），人体组织研究（任务3），形态学和立体学（任务4），LCM（任务7）和 将形态数据与特定项目目标和目标的整合（任务8）。 实现这些目标的最重要的是核心领导中的科学专业知识。这 病理和成像核心由DRS领导。鲁宾·M·厄（Rubin M. Tuder），一种实验和实践肺 病理学家在肺动脉高压的病理学和病理学方面具有主要专业知识，并在支持的支持下 Raphe Nemenoff博士是癌症领域的经验丰富的研究员 成像针对免疫系统和补体的成像。病理和成像核心的新颖性在于 关于独特的资源，无与伦比的专业知识和整体实验广度，可以集成 与所有四个项目有关的人类翻译。