Project Grant R01HL185359

The National Heart, Lung, and Blood Institute awarded The Regents of the University of California, San Francisco $3,205,321 on August 20, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate the genetic and molecular mechanisms of prostaglandin E2 (PGE2)-EP4-induced goblet cell metaplasia in asthma.

The project combines biophysical, cellular, molecular, and genetic analyses to determine how EP4 receptor activation promotes goblet cell hyperplasia in airway epithelium through the CREB signaling pathway using primary human airway epithelial cells cultured at air-liquid interface. The research establishes the relationship between airway PGE2 metabolites, epithelial activation, and clinical outcomes in severe asthma by leveraging the SARP3 cohort, which provides extensive clinical phenotyping including CT mucus scores and longitudinal outcomes. The work also investigates how EP4 expression is regulated in airway epithelium in health and disease. The approach includes chemical inhibitors targeting specific signaling pathways, mucus gel rheology assessment via magnetic microwire rheometry, and gene expression analysis in airway epithelial cells by genotype. The project aims to identify novel therapeutic targets for mucus dysfunction in both T2-high and T2-low asthma and define patient populations most likely to benefit from pathway-specific interventions based on clinical and genetic features.

Performance occurs in San Francisco, California. The award period runs through May 31, 2030.