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，是显着发病的一个来源。孩子们度过了 他们一天的大部分时间都在学校。该项目的近期目标是确定学校变革的作用—— 特定环境暴露和分子生物标志物以及哮喘发病率。候选人/PI 是 医师科学家，在以患者为导向的研究方面拥有专业知识，并经营着一家由 NIH 全额资助的哮喘/过敏研究机构 临床研究中心。自从 4 年前授予这架 K-24 以来，她在以下方面取得了巨大成功 通过支持 5 个资助的 K-23 奖项进行指导，并以 2 个新 U01 的 PI 身份扩展她的项目 1 R01 与其他多个 NIH 资助的临床合作。这次更新对于维持这一点至关重要 下一代以患者为中心的研究人员的生产力水平和指导。她的环境 包括无与伦比的社区关系、基础设施、资源和合作者。职业生涯 发展目标是确保为候选人提供足够的时间进行指导和耐心 面向临床研究活动。该奖项还将使她能够继续深造统计方法， 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 环境互动帮助她扩展以患者为导向的研究计划。这将使我们能够移动 实现我们进一步了解预测治疗的分子基础的总体目标 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 特定的过敏原/污染水平将与分子细胞外囊泡 (EV) 的变化和 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 唾液中的污染物与教室中过敏原和颗粒污染物的水平有关，并由 NIAID 进行了修改 SICAS-2 基于学校/教室的环境干预和哮喘健康结果并比较 他们使用 SICAS-1（我们的 NIAID 观察队列）存档的数据。我们也会比较这些 结果将年龄/性别匹配的没有哮喘的学生子集作为对照（NHLBI 资助的 EASY 队列）参加相同的教室，利用最先进的技术进一步解释我们的发现 技术。这项研究的影响可能会产生新的生物标志物，让我们了解 以学校为基础的针对对儿童哮喘很重要的环境暴露的干预措施的有效性 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.