Current Projects

Birth defects are the leading cause of infant mortality with one out of every 33 live births in the United States resulting in birth defects. The lack of known, modifiable environmental factors associated with birth defects remains a significant barrier to progress. Therefore, this innovative project will use statistical methods to directly quantify the impact of potential interventions on toxic metal mixtures exposure as a strategy for reducing the risk of birth defects. The overarching hypothesis of this proposal is that we can use routinely collected surveillance data to identify the public health burden of birth defects in North Carolina due to toxic metals exposure, as well as identify interventions to maximize reductions in this burden under realistic constraints on cost and feasibility.

The project aims to build on the success of The Extremely Low Gestational Age Newborns (ELGAN) Study which evaluates the relationship between perinatal inflammation and neurodevelopment impairments among individuals born extremely preterm (before 28 weeks gestation). The proposed project aims to add information about environment exposures, neurodevelopmental outcomes of study participants at 15 and 18 years of age, and placental epigenetic variation, a mechanism that could link inflammation early in life to neurodevelopmental impairments. The hypothesis of this proposal is that prenatal exposures can initiate early life inflammation, thus increasing the risk of neurodevelopmental impairments. The research has the potential to help the development of therapies targeting epigenetic processes to prevent or ameliorate cognitive disability, thus improving the quality of life for individuals who survive extremely premature birth in the United States. The findings could also apply to children who are not born prematurely.

Although the link between iAs exposure and type-2 diabetes is strongly supported by data from epidemiologic and laboratory studies, the diabetogenic effects of iAs exposure during specific developmental windowsand the underlying mechanism remain poorly understood. In addition,the role of iAs metabolism as a key factor modifying the effects of iAs at these exposure windows is also unclear. Growing evidence suggests that both prenatal and postnatal exposure to iAs increase risk of diabetes. However, the disease phenotype may depend on the exposure window. This project usesmice to characterize diabetic phenotype associated with pre-and postnatal exposure to iAs and identify the underlying mechanism. The results of this project will help to improve treatment and prevention of diabetes associated with iAs exposure in both adults and children exposed to iAs in utero.

The interdisciplinary Superfund Research Program at the University of North Carolina at Chapel Hill (UNC-SRP) addresses the serious public health challenges faced by communities in North Carolina and across the nation related to inorganic arsenic (iAs). The UNC-SRP mission is to develop new solutions for iAs reduction and disease prevention through mechanistic and translational research to ultimately inform regulation and Superfund site cleanup efforts. This is addressed in three aims: (1) Discover biological mechanisms and susceptibility factors underlying iAs-associated metabolic dysfunction/diabetes; (2) Develop novel methods and technologies to predict iAs contamination and reduce iAs exposure; (3) Translate the science of the UNC-SRP to key stakeholders in NC and the larger SRP program, and engage vulnerable communities. You can read more here: https://sph.unc.edu/superfund-pages/srp/

It has been established that chronic exposure to iAs is associated with risk of type 2 diabetes (T2D) and that metabolism of inorganic arsenic (iAs) into its methylated forms is a critical component in determining T2D risk in humans. Results of population studies carried out by our team suggest that polymorphisms in arsenic methyltransferase (AS3MT) and in several other genes involved in iAs metabolism or in the regulation of glucose homeostasis may also contribute to T2D risk. The central hypothesis of this project is that multiple genes and haplotypes (in addition to As3mt) will be tied to diabetic phenotypes associated with iAs exposure. This research will use a translational approach in two mouse populations, the Diversity Outbred and the Collaborative Cross, and a human population with arsenic-associated type 2 diabetes. Data generated by this project could suggest new risk assessment and prevention strategies in populations where iAs exposures are common and where remediation efforts aiming to reduce human exposure to iAs failed.

This project addresses a critical gap in the understanding of sexual dimorphism in both infant and children’s health outcomes, where males are often at increased risk for disease. The project’s hypothesis is that sexual epigenetic dimorphism in the placenta influence responses to perinatal stressors andpredict fetal growth restriction and neurodevelopment later in life. To address this, we use an “-omics” and systems-wide approach to identify biomarkers of, and potential mechanisms for, adverse pregnancy outcomes (fetal growth restriction and neurodevelopmental impairment in the offspring). The aims of this project are strengthened through the ELGAN study, an existing US-based cohort of children born extremely prematurely (i.e., before 28 weeks of gestation). With the potential for public health impact,this research may inform the development of therapies targeting epigenetic processes to prevent or ameliorate cognitive dysfunction.

The Extremely Low Gestational Age Newborns (ELGAN) cohort comprises over one thousand children born at least 3 months early between 2002 and 2004 at 14 different hospitals in five states. The ELGAN study team has assessed these premature babies at birth, two, ten, and 15 years of age. We are in the midst of collecting and analyzing data collected when study participants are 17-21 years of age. The NIH selected ELGAN, along with similar studies in the United States, to join in a study of about 50,000 children to learn about Environmental influences on Child Health Outcomes (ECHO). The ECHO program seeks to understand the effects of environmental exposures—including physical, chemical, biological, social, behavioral, natural, and built environments-on childhood health and development. The studies included focus on four key pediatric outcomes that have a high public health impact: Upper and lower airway, Obesity, Pre-, peri-, and postnatal outcomes, and Neurodevelopment. The overall goals of ECHO are like those of the former National Children’s Study (NCS), but with modified approaches leveraging preexisting longitudinal research projects that include more than 50,000 children from 83 cohorts across the United States. Together, ELGAN-ECHO tracks children born prematurely to determine how gestational age and environmental exposures can affect health as preterm children develop. The overall objective is to learn how the environment can be modified to improve the health of children in the United States. Downstream analyses of samples include measuring perfluorinated compounds, heavy metals, microbiome, gene expression and regulation, as well as epigenetic changes.