Matrix Metalloproteinase Driven Lung Inflammation in RSV disease

描述（由申请人提供）：该提案描述了一个为期5年的指导培训计划，为候选人Michele Kong博士提供炎症的细胞和分子机制，基质破坏，蛋白酶抗蛋白酶失衡和rsv诱导呼吸衰竭发病机制等领域的强化培训，这将有助于她发展成为一名独立的研究者。孔博士长期以来在学术上表现优异，并致力于研究事业。在她的职业发展和研究活动中，Kong博士将受到免疫学，炎症和蛋白酶生物学领域公认的领导者J. Edwin Blalock博士和Amit Gaggar博士的指导。孔博士还组建了一个在炎症、传染病和转化研究领域具有专业知识的咨询委员会（Dr. Kong）。Rich Whitley, Namasivayam Ambalavanan， Eric Sorscher和JP Clancy)，他们都承诺Kong博士将成功完成提议的研究目标，并协助她过渡到成为一名独立的医生科学家。阿拉巴马大学伯明翰分校（UAB）结合了最先进的研究设施、优秀的职业发展资源和广泛的临床基础，为培养医生和科学家提供了理想的环境。本研究的基本假设是：1)RSV能有效刺激人气道上皮细胞释放MMP-9， MMP-9通过融合蛋白水解促进RSV在气道上皮细胞内的增殖；2) MMP-9促进RSV感染，是早期病毒诱导的肺部炎症和损伤的调节剂；3) rsv诱导的小儿呼吸衰竭患者MMP-9活性异常，与下游趋化PGP片段的产生及病情严重程度的临床指标直接相关。在此职业发展奖励期间，候选人的短期目标是完成该研究计划的目标，获得UAB临床和转化科学生物医学硕士学位，每年参加科学会议并提交五篇或更多同行评审的出版物。在奖励期的后半段，她将提交独立R01资助申请。她的长期目标是建立一个独立的研究项目，最终目标是基于对基质破坏，气道和肺部炎症的更好理解，识别新的生物标志物并创造新的RSV疾病治疗方法，重点是宿主防御和宿主-病原体相互作用。

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.