Matrix Metalloproteinase Driven Lung Inflammation in RSV disease

RSV 疾病中基质金属蛋白酶驱动的肺部炎症

基本信息

批准号：
8842701
负责人：
Michele Kong
金额：
$ 11.83万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8842701
关键词：
Advisory Committees Alabama Antiviral Agents Area Award Biological Markers Biology Bronchiolitis Cells Chemotactic Factors Child Childhood Chimeric Proteins Clinical Clinical Sciences Clinical Trials Collagen Communicable Diseases Coupled Data Development Disease Management Doctor of Medicine Doctor of Philosophy Environment Epithelial Epithelial Cells Event Failure Funding Gelatinase B Generations Genetic Transcription Glycine Goals Health Host Defense Human Immunology In Vitro Infant Infection Inflammation Inflammatory K-Series Research Career Programs Knockout Mice Laboratories Leukocyte Elastase Lung Lung Inflammation Lung diseases Macrolides Master&apos s Degree Matrix Metalloproteinase Inhibitor Matrix Metalloproteinases Measures Mediator of activation protein Mentors Modeling Molecular Morbidity - disease rate Mus Outcome Outcome Measure Pathogenesis Pathology Pathway interactions Peer Review Peptide Hydrolases Peroxidases Physicians Pneumonia Production Proline Protease Inhibitor Proteins Proteolysis Publications Pulmonary Inflammation Research Research Activity Research Personnel Resources Respiratory Failure Respiratory Syncytial Virus Infections Respiratory physiology Respiratory syncytial virus Risk Sampling Science Scientist Severity of illness Signal Transduction Small Interfering RNA Specificity Stimulus Techniques Testing Tissue Inhibitor of Metalloproteinase-1 Training Training Programs Translational Research Translations Universities Ventilator Viral Viral Load result Viral load measurement Virus Diseases Virus Replication advanced disease airway epithelium airway inflammation base body system career career development clinically relevant cytokine disorder control endotracheal improved in vivo infancy inhibitor/antagonist injured airway long term hospitalization lung injury meetings mortality neutrophil new therapeutic target novel pathogen pediatric patients programs research and development research facility small molecule

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a 5-year mentored training program to provide the candidate, Dr. Michele Kong, with intensive training in the areas of cellular and molecular mechanisms of inflammation, matrix destruction, protease antiprotease imbalance and pathogenesis of RSV-induced respiratory failure, which will facilitate her development as an independent investigator. Dr. Kong has a long track record of academic excellence and commitment to a research career. In her career development and research activities, Dr. Kong will be mentored by J. Edwin Blalock, Ph.D. and Amit Gaggar, M.D., who are recognized leaders in immunology, inflammation and protease biology. Dr. Kong has also assembled an advisory committee with expertise in the fields of inflammation, infectious disease and translational research (Drs. Rich Whitley, Namasivayam Ambalavanan, Eric Sorscher and JP Clancy), all of whom have given Dr. Kong their commitment to the successful completion of the proposed research aims, and in assisting her transition to being an independent physician-scientist. The University of Alabama at Birmingham (UAB) provides the ideal environment for training physician-scientists by combining state of the art research facilities, excellent career development resources and a broad clinical base. The fundamental hypotheses of this proposal are: 1) RSV is a potent stimulus of MMP-9 release from primary human airway epithelial cells, and that MMP-9 facilitates RSV propagation in airway epithelia through fusion protein proteolysis; 2) MMP-9 facilitates RSV infection and is a modulator of early viral-induced lung inflammation and injury; 3) MMP-9 activity is dysregulated in pediatric patients with RSV-induced respiratory failure, directly correlating with the generation of downstream chemotactic PGP fragments and clinical indicators of disease severity. The candidate's short-term goals during the period of this career development award is to complete the aims of this research plan, obtain a Master's degree in Biomedical Science in Clinical and Translational Science at UAB, present annually at scientific meetings and submit five or more peer- reviewed publications. In the latter half of the award period, she will submit an application for independen R01 funding. Her long-term goals are to develop an independent research program with the ultimate goal of identifying new biomarkers and creating novel therapies for RSV disease, based on an improved understanding of matrix destruction, airway and lung inflammation, with an emphasis host defense and host- pathogen interaction.

描述（由申请人提供）：该提案描述了一项为期5年的指导培训计划，以向候选人Michele Kong博士提供深入的培训，并在炎症，基质破坏，蛋白酶抗原蛋白酶抗原蛋白酶的失效和RSV诱导的抗毒失败的病原体的炎症和分子机制方面进行了深入的培训。 Kong博士对研究职业的学术卓越和承诺有着悠久的记录。在她的职业发展和研究活动中，Kong博士将由J. Edwin Blalock博士指导。以及医学博士Amit Gaggar，他们是免疫学，炎症和蛋白酶生物学领域公认的领导者。 Kong博士还召集了一个咨询委员会，该委员会在炎症，传染病和翻译研究领域具有专业知识（Rich Whitley博士，Namasivayam Ambalavanan，Eric Sorscher和JP Clancy），所有这些都给了Kong博士，以成功地完成了求职研究的旨在，并协助了她的过渡性，并以独立的身份为您提供了一种独立的态度。伯明翰（UAB）阿拉巴马大学通过结合最先进的研究设施，出色的职业发展资源和广泛的临床基础，为培训医师科学家提供了理想的环境。该提案的基本假设是：1）RSV是从原发性人类气道上皮细胞中释放MMP-9的有效刺激，并且MMP-9促进通过融合蛋白蛋白蛋白蛋白蛋白质解析气道上皮的RSV传播； 2）MMP-9促进RSV感染，是早期病毒引起的肺部炎症和损伤的调节剂； 3）在RSV诱导的呼吸衰竭的小儿患者中，MMP-9活性失调，与下游趋化性PGP片段和疾病严重程度的临床指标直接相关。候选人在本职业发展奖期间的短期目标是完成本研究计划的目的，在UAB获得临床和转化科学生物医学科学硕士学位，每年在科学会议上举行，并提交五个或更多同行评审的出版物。在奖励期的后半部分，她将提交独立R01资金的申请。她的长期目标是制定一个独立的研究计划，其最终目标是确定新的生物标志物，并基于对基质破坏，气道和肺部炎症的深入了解，并为RSV疾病创建新颖的疗法，并强调宿主防御和宿主病原体相互作用。