Callan O'Connor

Natural genetic variation impacts the human response to chemical and environmental exposure, however genetic analyses to identify the specific variants and gene networks that underlie toxic response are difficult to accomplish in human populations, partially due to sampling methods, requisite sample sizes, and uncontrolled environments. Genetic reference populations like the Diversity Outbred (DO) mice mirror the genetic diversity of human populations, while offering high mapping power and exquisite experimental control. Taking advantage of this robust discovery platform, I am working with the Korstanje and Churchill laboratories to model gene by environment interactions using parallel in vivo and in vitro studies of arsenic (As) exposure in DO mice. Specifically, I am using high content cellular screening to determine the cytotoxic, genotoxic, and oxidative stress response of DO cells to in vitro As exposure. I aim to make previously unknown gene discoveries related to As exposure and validate my findings using CRISPR-Cas9 gene editing to show proof of concept.