RESEARCH STATEMENT

Our lab seeks to answer the question of “what makes people susceptible to developing common lung diseases like asthma and COPD after being exposed to air pollutants and/or indoor allergens?” We posit that gene-environment interactions (GxE)—that is, differences in susceptibility due to genetic variation—can help explain the range of susceptibility in the population. Our goal is to identify these GxE using unbiased, genome-wide approaches.

To identify these interactions, we employ two primary models systems, one in vitro and one in vivo (mouse), both of which contain abundant genetic diversity. The in vitro model involves  well differentiated airway epithelial cells, grown at an air-liquid interface, from hundreds of lung tissue donors (obtained from the Marsico Lung Institute Tissue Procurement Core). The in vivo models we use include two multi-parental mouse populations, namely the Collaborative Cross (CC) and Diversity Outbred (DO). These two populations, one inbred and one outbred, represent the next generation of tools for systems genetics and quantitative trait locus (QTL) mapping in the mouse.

For both model systems, we apply tightly controlled exposures, measure a suite of ozone exposure response phenotypes, and then use statistical approaches (quantitative trait locus mapping) to link genetic variants to exposure response phenotypes, integrating as many layers of biological information as possible (e.g., chromatin accessibility, gene expression, and protein expression).

We seek to connect our work to human health by testing hypotheses we derive based on our model systems in human populations. To accomplish this, we collaborate with several investigators who conduct genetic and epidemiologic investigations of asthma and other lung diseases.

Our lab is supported by the UNC Marsico Lung Institute/Cystic Fibrosis Center, the UNC Department of Genetics, and grants from the National Institute of Environmental Health Sciences and National Heart Lung and Blood Institute, both part of NIH.

Students: We are affiliated with three graduate school curricula at UNC, Genetics & Molecular Biology, Toxicology, and Bioinformatics & Computational Biology.