Federal Grant Award Summary

The University of Pennsylvania received a $609,027 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded June 5, 2026, with completion targeted for February 28, 2030. The award funds research investigating ciliated cell bitter taste receptors (T2Rs) in cystic fibrosis (CF) and chronic rhinosinusitis (CRS). The research examines how T2R signaling pathways in airway ciliated cells detect gram-negative bacterial products and stimulate nitric oxide production to enhance ciliary beating, kill bacteria, and potentially inactivate respiratory viruses. The project focuses on understanding why T2R signaling is reduced in CF cells due to CF transmembrane conductance regulator (CFTR) dysfunction and how genetic polymorphisms in the TAS2R38 gene may contribute to infection susceptibility in CF and CRS patients.

The research deliverables include enhanced knowledge of T2R cell physiology in airway ciliated cells and characterization of distinct T2R signaling pathways unique to motile cilia as opposed to taste cells. By developing a more complete understanding of T2R function and regulation in respiratory epithelium, the project aims to identify potential therapeutic targets for enhancing respiratory innate immunity. This work may ultimately support the development of T2R-based therapies that could reduce susceptibility to gram-negative bacterial infections in CF patients and those with specific TAS2R gene polymorphisms, potentially reducing reliance on conventional antibiotics and associated antibiotic resistance pressures.