A precision medicine approach to understand how epithelial alarmins drive asthma disease progression and exacerbations

Asthma involves different clinical phenotypes where underlying endotypes may be distinguished by immune responses of diseased epithelium. Bronchial epithelium is also target for respiratory infections that cause exacerbations and severe asthma.

We originally demonstrated that bronchial epithelial immune responses in asthma are dysregulated potentially defining asthma endotypes. By this approach, we originally predicted anti-exacerbation efficacy by targeting the alarmin TSLP. Thus, our current aims for this project: 1.

Determine roles of bronchial epithelial alarmins in regulating infection tolerance and antiviral resistance, respectively, in asthma. 2: Delineate involvement of epithelial alarmins in driving non-T2 asthma endotypes. 3: Drive cutting edge research on novel treatments targeting epithelial alarmins to prevent disease progression and asthma exacerbations.

We utilise our translational research platform involving clinical RCT studies, in depth molecular mechanistic studies involving bronchial epithelial cells from patients with distinct endotypes of asthma, and in vivo mouse models, all combined with advanced immunological and systems biology approaches.

This project provides new knowledge on clinically relevant molecular mechanisms in epithelium-driven inflammation in asthma including exacerbations and disease progression.

Our project will identify novel drug targets as well as patients best suited for biological therapy targeting epithelial alarmins.