Pilot Project Recipients Year 9

Investigating Biological Pathways through which Air Pollution and Folic Acid May Impact Female Fertility

Study Title: Traffic Related Air Pollution, Folic Acid, and DNA Methylation in the Follicular Fluid

PI: Audrey Gaskins, School of Public Health, Epidemiology

Traffic-related air pollution (e.g., emissions from motor vehicles) may lower fertility in women. Emerging evidence suggests that folic acid may help to lessen this impact, but it is currently unclear how. One possible pathway is epigenetics, the biological process that determines how much our genes are expressed (such as whether they are turned off or on). Genes are made up of DNA, and we are specifically interested in DNA methylation, a type of epigenetic mark on the DNA which can alter the expression of that specific gene. In general, if there are a lot of these epigenetic markers present on a gene that gene is less likely to be expressed. Traffic-related air pollution tends to decrease the amount of these epigenetic marks on the DNA, while dietary folate increases them. However, epigenetic modifications tend to differ across cell types (for example, in blood cells versus tissue-specific cells) and so it is unclear whether this same pattern will be present in cells commonly found in the ovarian follicular fluid (the fluid that surrounds the developing egg). This proposal aims to explore differences in DNA methylation of the follicular fluid among women undergoing infertility treatment with both high and low exposure to traffic-related air pollution and folic acid. The implications of these findings are large as alterations in DNA methylation of reproductive cells poses a risk for both the reproductive capacity of the exposed woman as well as risk to the next generation.

How this study advances exposome science: The results from this study will provide important insights into biological processes that underlie the associations between air pollution, folic acid, and female fertility.

Studying How Insecticides Damage Brain Cells

Study Title: Damage to A Cellular Clearance and Communication Process by Environmental Neurotoxins

Co-PIs: Zixu Mao, School of Medicine, Pharmacology; Michael Caudle, School of Public Health, Environmental Health

Pyrethroids are common ingredients of household insecticides and the unregulated use of these products in the home environment poses a significant risk for adverse health effects. The pyrethroids act as insecticides by damaging the nerves of the brain and body (i.e., neurotoxic effects) in insects. These neurotoxic effects have also been observed in humans with pyrethroid exposure. We want to understand how pyrethroids damage the brain, specifically, if they alter a process that is important for brain cells to clear unwanted materials and to communicate with each other. This is important because damage to this brain process can contribute to Parkinson’s disease, a neurodegenerative disorder. To test this, we will treat both cells and mouse models with pyrethroids and study how they affect this cellular process. Based on the results, a next step may be to develop a procedure to measure the level of stress caused to the brain cells, which helps determine the safe use of chemicals.

How this study advances exposome science: This study identifies how cellular systems are affected and respond to exposure to a commonly used household chemical.

Glial Brain Cells in Lead Toxicity: Protective or Inflammatory?

Study Title: Astrocyte Neuroprotection and Inflammation in Prenatal Pb Exposure

PI: Steven Sloan, School of Medicine, Human Genetics

People are exposed to lead through contaminated water, food and the environment. When pregnant women are exposed to lead it disrupts fetal brain development, often resulting in behavioral deficits and lower IQ in their children. To model these exposures and mirror normal fetal brain development, we will reprogram human skin cells to grow into organoids (a miniature and simplified 3D version of an organ) that create two types of brain cells—neurons and glia. Glia protect neurons in the brain from toxic exposures by generating antioxidants. In some cases, glia become inflammatory and stop generating antioxidants effectively. We will expose the organoids to different lead concentrations to determine the conditions when glia protect the brain from lead toxicity and when they become inflamed. This study tests how lead directly impacts glia and will help us understand how early-life lead exposures change brain function.

How this study advances exposome science: This study explains the role of glia in lead toxicity, helping us understand how exposure to lead early in life changes brain function.

Endocrine Disrupting Chemicals and Metabolic Health in Guatemalan Adults

Study Title: Endocrine Disrupting Chemicals and Metabolic Flexibility in Guatemalan Adults

PI: Aryeh Stein, School of Public Health, Global Health

Chemicals that disrupt hormone function are known as endocrine disrupting chemicals (EDCs). There are hundreds of EDCs in common household and industrial products and the environment. For example, some food packaging, personal care products (such as toothpaste), and agricultural pesticides contain EDCs. Many EDCs can accumulate in human body tissues, remain in the environment for long periods of time, and be transported long distances by wind and water (persistent EDCs). Exposure to EDCs is linked with obesity and Type 2 diabetes, which are health consequences associated with altered metabolism (i.e., the breakdown of food and its transformation into energy). It is still a major challenge to evaluate and reduce these negative metabolic health consequences from EDC exposures. First, it remains unknown how much EDC exposure there is, especially among people living in low- and middle-income countries. Second, we do not fully understand the major risk factors related to greater EDC exposure. Third, downstream impacts of greater EDC exposures on metabolism and energy homeostasis (i.e., the body’s balance of food intake, energy production and expenditure) are unclear. One of our study objectives is to measure blood concentrations of persistent EDCs among adults in Guatemala. Our second objective is to evaluate the relationship between persistent EDCs and metabolism after consuming a meal. We will evaluate several indicators related to metabolism (such as metabolomic profiles, glucose, insulin). We expect that our study findings will improve our understanding of the impacts of EDC exposure on metabolic health. The broader study goal is to contribute to reducing metabolic diseases globally.

How this study advances exposome science: Many people are regularly exposed to low levels of EDCs, but the health consequences are unclear. Our study seeks to determine how low levels and mixtures of persistent EDCs impact metabolic health.

The Impact of Pollutants in the Environment on Gut Bacteria and Associations with Glucose Tolerance and Body Fat

Study Title: Persistent Organic Pollutants and Heavy Metals: Alterations in the Gut Metagenome and Links with Insulin Resistance and Body Composition Following Bariatric Surgery

Co-PIs: Tom Ziegler and Jessica Alvarez, School of Medicine, Division of Endocrinology,
Metabolism and Lipids

Our project builds on research showing that certain pollutants may impact the composition of the bacteria in the intestine (the “microbiome”). These microbiome changes caused by pollutants may predispose people to obesity and/or diabetes. Changes in the microbiome may also affect the outcomes bariatric surgery (weight-loss surgeries) such as the positive change in blood glucose and body fat. The goal of this study is to measure the type of bacteria in the intestine and of specific pollutants in blood and fat tissue of obese patients, both before and after bariatric surgery. We will compare changes in the microbiome and pollutant levels with bariatric surgery outcomes (glucose and body fat). We collected stool samples from before and 6-9 months after bariatric surgery in 27 adults in the Emory University Hospital Clinical Center to measure the intestinal microbiome. We also collected blood during these visits and small portions of body fat were obtained during the surgery itself, from which we will measure multiple pollutants. The study participants also have detailed studies of glucose tolerance and body fat before and after surgery.

How this study advances exposome science:  The project will provide new knowledge in our understanding of how specific pollutant exposures impact the gut microbiota and their link to chronic diseases such as diabetes and obesity in humans.

Collect, Connect, and Communicate:  Data Visualization for Neighborhood Exposure Assessments

PI: Lance Waller, School of Public Health, Biostatistics and Bioinformatics; Community Lead: Clarence Williams, Chapel Hill Neighborhood Organization, Dekalb County, GA

We live in a connected world with massive amounts of data at our fingertips. We can track our location, find directions, and compare prices with a glance at a mobile device. We can also explore multiple sources of information regarding local environmental exposures through data compiled and made available by national and state governments, research organizations, companies, and community groups. With so many types of data, it can be difficult to figure out what data we want, what tools we have to connect data from different sources, and what methods we have to communicate the data to ourselves and to our communities. In this project we use computer maps to link environmental data from different sources that relate to the same community. The project supports a partnership between the Chapel Hill Organization in Dekalb County and researchers at Emory University to create a set of computer tools to find, link, and map environmental data relating to pollutant exposures and citizen concerns in the Chapel Hill neighborhood. The tools will allow community members to see the exposures in maps of their neighborhood in order to gain an understanding of their potential exposures.

How this study advances exposome science: The exposome represents a summary of all the environmental exposures an individual may face where they live, work, worship, and go to school. This project provides maps of exposures so that individuals can see their potential exposures in these locations. By examining the locations where an individual spends time, the maps provide a visual assessment of that individual’s exposome and a tool that could be used by other communities in the future.