Elucidating mechanisms of cadmium-induced toxicity and disease

Project 3 Leader: Rebecca Fry, UNC-Chapel Hill

Project Description

The toxic heavy metal cadmium is a high priority contaminant identified at more than one third of all Superfund Sites. While cadmium is a known and well studied carcinogen, Project 2 is designed to address cadmium’s effects as a developmental toxicant. Newborns exposed to cadmium during the prenatal period have increased risk for poor birth outcomes, including low birthweight. In addition to the immediate postnatal concerns, low birthweight is also associated with increased risk for chronic diseases later in life, such as diabetes, hypertension, and cardiovascular disease.

Project 3
We study gene-environment interactions of cadmium-induced effects on newborn birthweight in a pregnancy cohort from North Carolina. Results from this work will help identify genetic bases for cadmium-induced changes and determine reasons for susceptibility.
Rebecca Fry, PhD
Associate Professor, Project 3 Leader
While poor birth outcomes have been associated with environmental exposure to cadmium and other metals, the underlying biological mechanisms remain under studied. Integrating our preliminary findings and our interest in understanding how metal exposure influences pregnancy outcome in the United States, we are examining gene-environment interactions that influence cadmium-induced signaling of inflammatory response genes and will determine the association of pathway modulation with birthweight.

Our hypothesis is that gene-environment interactions influence cadmium’s effects on signaling of inflammatory response genes and that this signaling is associated with newborn birth outcomes. This study uses complementary in vitro and in vivo approaches to test our hypothesis. To identify genes that influence cadmium-induced toxicity, we are using a panel of cell lines derived from a genetically diverse human population. The integrated in vivo aims will assess the impact of fetal genotypes of inflammatory response genes on newborn birthweight and the interaction effects between fetal genotypes and cadmium exposure. The modulation of the expression levels of members of inflammatory response genes in newborns and association with maternal cadmium exposure will be determined. The role of DNA methylation in controlling the gene expression alterations will be established. The results obtained from this research will help to elucidate molecular pathways associated with cadmium-induced toxicity and disease.