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.