Project Grant R01ES036998

Federal Grant Award Summary

The National Institute of Environmental Health Sciences (NIEHS) awarded the University of North Carolina at Chapel Hill a Project Grant totaling $3,082,011 under the Environmental Health program (CFDA 93.113) for the period September 19, 2025, through September 18, 2029. The project focuses on identifying gene-by-environment (GxE) interactions between genetic variation and ozone (O3) exposure that contribute to common chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). The research employs genetically diverse mouse populations—specifically the Diversity Outbred (DO) and Collaborative Cross (CC)—as discovery platforms to systematically identify gene-environment interaction quantitative trait loci (QTLs) for both acute and chronic O3 exposure responses.

The deliverables include the identification of causal genes at a previously identified locus on chromosome 15 in mice (specifically distinguishing between ANGPT1 and RSPO2), discovery of additional GxE QTLs for acute and chronic O3 responses, and translation of findings from mouse models to human populations through targeted genetic variant analysis. The research team will validate findings using existing genotype and air pollution exposure data from three human epidemiological studies, including an acute O3 challenge dataset and multi-ethnic air pollution cohorts, thereby bridging preclinical discovery with clinical validation in diverse human populations.