PROJECT SUMMARY Research: There is a growing body of literature showing an association between childhood obesity and asthma morbidity. For reasons not fully understood, overweight/obese children with asthma are at an increased risk for worse asthma, particularly those with lower socioeconomic status and living in inner-city areas. This proposal details a five-year plan to provide the candidate, Perdita Permaul, MD, with the training and expertise to evaluate the role body mass index plays in the relationship between allergic inflammation and asthma morbidity in an established cohort of inner-city children with asthma enrolled in the School Inner-City Asthma Study (PI: Phipatanakul). This important and unique study involves the collection of extensive allergic phenotypic and outcomes data and potential biomarkers linking these two chronic diseases. Moreover, she has included an innovative and novel translational piece to examine leptin receptor expression on human basophils across BMI percentiles and the role that leptin plays in basophil activation, uniting basophil biology with phenotypic and functional data. Candidate: Dr. Permaul's long-term goal is to become an independent clinical/translational NIH funded investigator focused on patient-oriented research in pediatric asthma, and more specifically, in studying the association between childhood obesity and asthma morbidity. In order to achieve this goal, her short-term career objectives are to obtain further didactic training in environmental epidemiology, clinical and translational research, advanced biostatistics, as well as practical skills in cohort building, exposure assessment, laboratory techniques and biomarker analysis. This will be accomplished with formal classes, fieldwork and collaborative work to learn how to recruit, consent, and maintain a cohort, benchwork, attendance at institutional/national conferences, and guidance from established mentors and a multidisciplinary advisory board with the relevant expertise. This will result in a unique combination of practical skills and scientific knowledge that will successfully position her for her first R01 application and an independent career as a physician-scientist. Environment: Dr. Permaul will perform her research training and career development activities at world- renowned major academic institutions. She will work under the mentorship of Dr. Phipatanakul, an expert in environmental epidemiology and asthma, in addition to an extraordinary team of researchers, including Drs. Wayne Shreffler, Carlos Camargo, and Brent Coull, who have committed their time, resources, and expertise to facilitate Dr. Permaul's career development and the successful completion of the proposed project. During this award period, Dr. Permaul will complete the Program in Clinical and Translational Science through the Harvard Clinical and Translational Science Center and formal coursework at the Harvard School of Public Health. The academic environment created by the mentor, the institution, Harvard University and its affiliates provides a fertile ground for learning and collaborating specific to her research.

PROJECT NARRATIVE Despite a known association between childhood obesity and asthma, there is a paucity of data on how elevated body mass index in children leads to worse asthma symptoms. The goal of this research project is to evaluate the effect of body mass index on allergic inflammation and asthma morbidity in an urban pediatric cohort with asthma. This very important work will provide significant phenotypic insight into the connection between childhood obesity and inner- city asthma morbidity and will reveal potential biomarkers linking the two.