Dr. Samir Kelada (Associate Professor, Department of Genetics) has been awarded a new R21 grant from the National Institutes of Allergy and Infectious Diseases (NIAID) for his project titled “A New Mouse Model of Severe Asthma”.
The study is focused on characterization of the Collaborative Cross strain CC011, which represents a new, severe, “type-2-high” model of asthma. In the first aim, the team will identify which cell types (innate and adaptive) and pathways are integrally involved in CC011’s response to house dust mite allergen. They will determine if allergic inflammation is T cell-dependent and if CD4+ Th2 cell priming is augmented in CC011 mice compared to BALB/cJ mice. They will investigate if airway epithelial cell-derived alarmins (IL-25, IL-33, TSLP) are increased in CC011 mice and whether neutralization of these cytokines ameliorates allergic inflammation. Finally, they will determine if allergen-induced expansion and activation of ILC2s are enhanced in CC011 mice. In the second aim, the plan is to identify the genetic loci that harbor CC011’s susceptibility alleles using a quantitative trait locus mapping approach, and then leverage gene expression data from CC011 and other resources to identify candidate genes. These candidate genes will become the focus of future investigations. In total, the results will establish CC011+HDM as a new model of T2-high severe asthma, enabling its widespread use to identify and test new therapeutic approaches.