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Mesenchymal stromal cells and bronchopulmonary dysplasia

间充质基质细胞与支气管肺发育不良

基本信息

批准号：
8879188
负责人：
Antonia Petrova Popova
金额：
$ 13.77万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-12 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8879188
关键词：
Actins Alveolar Alveolus Area Aspirate substance Bioinformatics Biological Markers Biology Bronchopulmonary Dysplasia Cell Proliferation Cells Childhood Childhood Asthma Chronic lung disease Clinical Clinical Investigator Clinical Research Collagen Confidence Intervals Coupled Data Deposition Development Disease Doctor of Medicine Dysplasia Enrollment Enzyme-Linked Immunosorbent Assay Experimental Designs Extracellular Matrix Proteins Fellowship Fiber Fibroblast Growth Factor Fibrosis Gene Expression Genes Goals Growth Factor Overexpression Growth Factor Receptors Health Immunoblotting Incidence Infant Informed Consent Lasers Lung Measures Medicine Mentors Mentorship Mesenchymal Messenger RNA Methods Michigan Microscopy Modeling Mus Myofibroblast NADPH Oxidase Neonatal Odds Ratio Outcome Paper Pathogenesis Patients Phenotype Pilot Projects Plasminogen Activator Play Premature Infant Proteins Public Health Schools Publishing Pulmonology Regression Analysis Research Research Personnel Role Sampling Signal Transduction Smooth Muscle Actin Staining Method Stromal Cells Supervision Testing Training Training Programs Transforming Growth Factors Translating Universities Vascular Endothelial Cell Work base biobank career connective tissue growth factor differential expression experience human tissue improved inhibitor/antagonist insight lung injury mRNA Expression overexpression patient oriented research periostin programs protein expression receptor binding response skills statistics

项目摘要

DESCRIPTION (provided by applicant): Antonia P. Popova, M.D., a pediatric pulmonologist, is focusing her career on bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurely-born infants. During her fellowship, Dr. Popova published 4 papers on BPD and lung mesenchymal stromal cells. During the proposed training, Dr. Popova will continue work with her Mentor, Marc Hershenson, and receive additional scientific direction from Co-Mentor Stephen Weiss, an expert in matrix biology. However, her main goal will to be to acquire skills needed to become an independent investigator in the conduct of patient-oriented research, and to translate basic discoveries to the clinical problem of BPD. To achieve this, Dr. Popova will enroll in the School of Public Health Clinical Research Masters Program and receive additional mentorship from Dr. Fernando Martinez, an established pulmonary clinical investigator. She will also take coursework in computational medicine and bioinformatics under the supervision of a third Co-Mentor, Dr. Santiago Schnell. Dr. Popova's general hypothesis is that mesenchymal stromal cell myofibroblastic differentiation and matricellular protein expression play critical roles in BPD pathogenesis. To test this, she proposes the three Specific Aims, each of which is paired with Specific Training Objectives: 1. Measure the gene expression of lung mesenchymal stromal cells, focusing on matricellular proteins. Specific hypothesis: Mesenchymal stromal cells maintain a stable phenotype of myofibroblastic differentiation that is coupled with matricellular protein expression. Tracheal aspirates of premature infants will be examined for matricellular protein expression and mesenchymal stromal cells. Stromal cell mRNA and protein expression will be measured by microarray and ELISA/immunoblotting. Training Objective: Develop experience and understanding in experimental design, informed consent, and management of a research team. 2. Correlate neonatal lung mesenchymal stromal cell matricellular protein expression with clinical outcomes. Specific hypothesis: Expression of the matricellular proteins predicts BPD development. Relative odds of BPD as a function of tracheal aspirate protein expression and mesenchymal stromal cell gene expression will be calculated using multivariate regression analysis. Training Objectives: Acquire experience and understanding in the areas of experimental design, statistics, computational medicine and bioinformatics. 3. Examine expression and localization of matricellular proteins in the lungs of premature infants. Specific hypothesis: Matricellular protein expression is increased in the lungs of infants with BPD. Using University of Rochester neonatal lung biorepository samples, matricellular protein expression will be assessed by laser capture microscopy, qPCR and stereology-based quantitative immunohistochemisty. Training Objective: Acquire experience/expertise in methods used to quantify gene expression in small samples of human tissue. Completion of this work will provide insight into the origins of BPD and provide training for Dr. Popova, facilitating her transition to independent investigator in patient-oriented research.

描述（由申请人提供）： Antonia P. Popova 医学博士是一名儿科肺科医生，她的职业重点是支气管肺发育不良 (BPD)，这是一种早产儿的慢性肺部疾病。 Popova 博士在研究期间发表了 4 篇关于 BPD 和肺间充质基质细胞的论文。在拟议的培训期间，波波娃博士将继续与她的导师 Marc Hershenson 合作，并接受联合导师、基质生物学专家 Stephen Weiss 的额外科学指导。然而，她的主要目标是获得成为一名独立研究者进行以患者为导向的研究所需的技能，并将基本发现转化为 BPD 的临床问题。为了实现这一目标，波波娃博士将报名参加公共卫生学院临床研究硕士项目，并接受资深肺部临床研究者费尔南多·马丁内斯博士的额外指导。她还将在第三位联合导师圣地亚哥·施内尔博士的监督下学习计算医学和生物信息学课程。 Popova 博士的一般假设是间充质基质细胞肌成纤维细胞分化和基质细胞蛋白表达在 BPD 发病机制中发挥着关键作用。为了测试这一点，她提出了三个具体目标，每个目标都与具体培训目标配对： 1. 测量肺间充质基质细胞的基因表达，重点关注基质细胞蛋白。具体假设：间充质基质细胞维持肌成纤维细胞分化的稳定表型，与基质细胞蛋白表达相结合。将检查早产儿的气管抽吸物的基质细胞蛋白表达和间充质基质细胞。将通过微阵列和 ELISA/免疫印迹测量基质细胞 mRNA 和蛋白质表达。培训目标：培养实验设计、知情同意和研究团队管理方面的经验和理解。 2. 将新生儿肺间充质基质细胞基质细胞蛋白表达与临床结果相关联。具体假设：基质细胞蛋白的表达可预测 BPD 的发展。将使用多元回归分析来计算作为气管抽吸物蛋白表达和间充质基质细胞基因表达的函数的 BPD 的相对几率。培训目标：获得实验设计、统计学、计算医学和生物信息学领域的经验和理解。 3. 检查早产儿肺部基质细胞蛋白的表达和定位。具体假设：BPD 婴儿肺部的基质细胞蛋白表达增加。使用罗切斯特大学新生儿肺生物样本库样本，通过激光捕获显微镜、qPCR 和基于体视学的定量免疫组织化学来评估基质细胞蛋白表达。培训目标：获得用于量化人体组织小样本中基因表达的方法的经验/专业知识。这项工作的完成将深入了解 BPD 的起源，并为 Popova 博士提供培训，促进她过渡为以患者为导向的研究的独立研究者。