AN IN VITRO, SYSTEMS GENETICS APPROACH TO UNDERSTANDING VARIATION IN RESPONSE TO OZONE IN HUMANS

Project Co-Leaders: Sabri Abdelwahab and Sarah Lester

We are leveraging a large lung tissue donor bank at UNC to study inter-individual differences in response to ozone. More specifically, we are culturing bronchial epithelial cells (BECs) at an air-liquid interface, exposing them to ozone, and characterizing the range of responses across donors. As depicted in the figure, we posit that genotype-dependent responses to ozone manifest as a result of differences in transcription factor (TF) binding and chromatin accessibility and thus gene expression in BECs (greater in the individual with the T/T genotype compared to the individual with the C/C genotype). These differences, in turn, lead to differential cytokine/chemokine secretion, epithelial permeability, and other adverse endpoints.

Image credit: Adelaide Tovar