K24: Midcareer Investigator Award: Urban School Allergen Exposure and Childhood Asthma

项目概要/摘要 儿童哮喘，特别是在城市环境中，是一个显着的发病率的来源。孩子们度过了 在学校的大部分时间。该项目的近期目标是确定学校变化的作用- 特定环境暴露和分子生物标志物与哮喘发病率之间的关系。候选人/PI是 医生科学家，在以患者为导向的研究方面具有专业知识，并经营着一家由NIH完全资助的哮喘/过敏症 临床研究中心。自从4年前获得K-24以来，她在以下方面取得了极大的成功： 通过支持5个资助的K-23奖项并在2个新的U 01上担任PI来扩展她的计划， 和1 R 01与多个其他NIH资助的临床合作。这种更新对于维持这一点至关重要 生产力水平和指导下一代以患者为导向的研究人员。她的环境 包括无与伦比的社区关系、基础设施、资源和协作者。职业生涯 发展目标是确保候选人将有足够的时间进行指导和耐心 面向临床的研究活动。该奖项还将使她能够进一步在统计方法， 研究设计、分子生物学、表型和内型驱动的生物标志物精准医学，以及 环境的相互作用，以帮助她扩大她的病人为导向的研究计划。这样我们就可以 我们的总体目标是进一步了解预测治疗的分子基础 反应和疾病病理生理学，这将使她能够开发和设计干预措施，以减少 儿童哮喘的严重程度和发病率。研究假设是，课堂/学校的变化 特异性过敏原/污染水平将与分子细胞外囊泡（EV）变化相关， 哮喘发病率我们将使用两阶段验证方法来比较数量、大小和miRNA货物 唾液中的过敏原与教室水平的过敏原和颗粒污染物有关，并被NIAID修改 SICAS-2学校/教室为基础的环境干预和哮喘健康结果和比较 他们与SICAS-1（我们的NIAID观察队列）存档的数据。我们还将比较这些 结果在一个年龄/性别匹配的学生没有哮喘作为对照（NHLBI资助的EASY 队列）参加相同的教室，以进一步解释我们的研究结果，利用最先进的 技术.这项研究的影响可能会导致新的生物标志物，可以告诉我们关于 以学校为基础的干预措施对儿童哮喘重要的环境暴露的有效性， 它的免疫调节，解决了一个关键的公共卫生问题。

Project Summary / Abstract Childhood asthma, particularly in urban environments, is a source of significant morbidity. Children spend the majority of their day in school. The immediate goal of this project is to determine the role of changes in school- specific environmental exposures and molecular biomarkers and asthma morbidity. The Candidate/PI is a physician scientist with expertise in patient oriented research and runs a fully NIH funded asthma/allergy clinical research center. Since this K-24 was awarded 4 years ago she has been extremely successful in mentoring by supporting 5 funded K-23 awards and expanding her program with her role as PI on 2 new U01s and 1 R01 with multiple other NIH funded clinical collaborations. This renewal is critical to maintaining this level of productivity and mentoring of the next generation of patient-oriented researchers. Her environment includes unparalleled community relationships, infrastructure, resources, and collaborators. Career Development Goals are to ensure that the candidate will be provided sufficient time for mentoring and patient oriented clinical research activities. The award will also allow her to further her education in statistical methods, study design, molecular biology, phenotype and endotype driven biomarker precision medicine, and environment interactions to help her expand her patient oriented research program. This will allow us to move towards our overall goal of further our understanding of molecular underpinnings in predicting treatment response and disease pathophysiology, which will allow her to develop and design interventions to reduce the severity and incidence of childhood asthma. The research hypothesis is that changes in classroom/school specific allergen/pollution levels will be associated with molecular extracellular vesicle (EV) changes and asthma morbidity. We will use a two stage validation approach to compare number, size, and miRNA cargo in saliva are associated with classroom levels of allergens and particulate pollutants and modified by the NIAID SICAS-2 school/classroom based environmental intervention and asthma health outcomes and compare them with data archived from SICAS-1 (our NIAID observational cohort). We will also compare these results in a subset of age/gender matched students without asthma as controls (the NHLBI funded EASY cohort) attending the same classrooms to further the interpretation of our findings utilizing state of the art techniques. The impact of this research may result in novel biomarkers that could inform us about the efficacy of school-based interventions against environmental exposures important to childhood asthma and its immune modulation, addressing a critical public health problem.