Amanda Poholek, PhD

Environmental triggers promote inflammatory T helper 2 (Th2) cell formation, which are central players in allergic asthma. We recently identified a previously unappreciated role for the transcriptional repressor Blimp-1 to promote Th2 cells in response to inhaled house dust mite allergen in a murine model of allergic asthma. Our more recent progress has now demonstrated that the Blimp-1 pathway driving Th2 cells is specific to the lung environment, suggesting tissue-specific factors are responsible for driving type 2 inflammation in response to inhaled allergens, providing new opportunities for discovery of therapeutic targets. To identify these lung-specific factors, we have used unbiased and innovative approaches combined with antigen specific methods of tracking Th2 cells responsive to allergens to determine how mucosal tissues such as the lung set a homeostatic niche unique to environmental exposure that predispose to allergic asthma. We hypothesize this is key to understanding the response to environmental allergens and development of subsequent allergic asthma. We expect at the conclusion of our studies to have identified key regulators of the lung tissue environment that may have clinical applications to all lung diseases.

Update: We have performed scRNAseq, scATACseq and Spatial Transcriptomics in a murine model of allergic asthma including the ability to track antigen specific responses via CITE-seq. These datasets will reveal the lung specific factors that promote Th2 responses to allergens that drive asthma.

Supported by the Mary Fuller Russell Fund