My work has focused on environmental factors in urban children and effective strategies to reduce and prevent asthma. We were the first to document the high prevalence of mouse allergen in urban apartments. We then went on to develop strategies to mitigate these exposures in homes. Taking note of the paucity of information in schools, where children spend so much of their lives, I then went on to develop strategies to study school exposures. I built an unprecedented network of community relationships, enabling me to perform studies that comprehensively discovered that school specific mouse allergen exposure triggers asthma morbidity and reduces lung function, adjusting for exposures in the home. We published in JAMA the first large scale school environment integrated pest management (IPM) and classroom HEPA filter clinical trial that showed that school IPM reduced asthma symptoms by 63% during the fall and winter, albeit not sustained. Classroom HEPA filters reduced airborne particiles and allergens but not enough to improve health, suggesting further work needs to be done to understand effect strategies for safe, healthy school environments which is of particular interest during and post pandemic. We have extended this work to understanding environmental exposures in sleep and children with other conditions besides asthma.
I am honored to leverage my carefully phenotyped cohorts to conduct high impact clinical and mechanistic studies with experts around me. With Joel Hirschhorn we identified that acute asthma exacerbation severity is attributable to rhinovirus infection and allergen sensitization, and that omalizumab (anti-IgE) reduces virally induced asthma severity. With Talal Chatila we identified novel mechanisms whereby TH17 cell-like reprogramming of Treg cells influences inflammatory phenotypes published in Nature Medicine and we have extended this work to identify other novel inflammatory pathways driven by NOTCH4 Tregs, IL6, and mutant alleles in the IL4 Q576 genotype, which is particularly problematic in minority populations and appears to drive inflammation in asthma and other allergic diseaes, including atopic dermatitis. I lead a NIAID funded genotype stratified trial evaluating the role of dupilumab, which acts on the IL4 receptor in vulnerable patients with asthma https://ideaasthma.org. I lead as overall PI of a NIAID-funded multi-center clinical trial using omalizumab (anti-IgE) as a strategy towards early asthma prevention in young preschool children https://parkstudy.org/.
I am Boston Pediatric PI for two NHLBI severe asthma consortia, the Severe Asthma Research Program and the PreCISE network and the NIAID Childhood Asthma in Urban Settings network. I was senior/corresponding author to the first randomized, blinded clinical trial, demonstrating that there was absolutely no difference in asthma outcomes between acetaminophen versus ibuprofen that was published in the New England Journal of Medicine. My biggest passion is mentoring and have successfully shepherded a team of junior NIH investigators many who have gone on to get their own funding including R01s.