Pilot Project Recipients Year 11

Analyzing Dried Blood Spots to Explore Nutritional and Environmental Exposures among Mother-Child Pairs

Dried Blood Spot Metabolomes of Mother-Infant Dyads Reveal Novel Suites of Nutritional and Environmental Exposures

PI: Dana Barr, School of Public Health, Environmental Health

Children are highly vulnerable to environmental exposures which, when combined with diet deficiencies, can lead to long-lasting health implications. Among children under 5 years old, an estimated 26% of deaths are attributed to environmental exposures, and approximately half of deaths are associated with undernutrition. Yet, knowledge gaps exist regarding how mothers’ environmental exposures impact their children, during both pregnancy and infancy. Small molecules in the blood, called metabolites, can reflect the body’s response to environmental exposures and diet. This project measures metabolites and environmental chemicals found in dried blood spot samples among mother-child pairs in low- and middle-income countries with high rates of undernutrition. To identify and measure these metabolites and environmental chemicals in the dried blood spot samples, we use high-resolution untargeted and targeted analysis. Untargeted analysis lets us detect small molecules associated with diet deficiencies and environmental exposures, and targeted analysis lets us quantify specific environmental exposures. We will use the presence, absence, and quantity of these measures to tell us how nutritional and environmental exposures interact and impact the body, as well as how these exposures impact multiple generations.

How this study advances exposome science: Each person has a unique set of life course exposures that influence their health, yet the interactions of nutritional and environmental exposures together are poorly understood. This study presents a less-invasive method to study these interactions in a personalized manner. Through active participation among our study participants in African and Latin American countries, our project explores the unique challenges these communities face and aims to improve health equity and inform policy and science-driven interventions

The Effects of Manganese-Induced Toxicity in the Brain

Study Title: Mechanism of manganese induced pro-inflammatory signal transduction in brain

PIs: Avanti Gokhale and Erica Werner, Department of Cell Biology Emory University.

Excess manganese is hazardous to human health due to its negative effects on brain cells, especially in susceptible populations such as workers in the mining industry and residents near manganese alloy manufacturing sites. Children are particularly vulnerable since their bodies have not yet developed the mechanisms for manganese removal, leading to increased accumulation in the body. Currently, the affected cellular pathways and overall biological responses to manganese exposure are not fully understood. We have identified a novel mechanism by which manganese affects mitochondrial function (the cellular process that converts energy from food to cellular energy), leading to the generation of abnormal RNA molecules (which are responsible for protein formation in the body).  We believe that these molecules initiate inflammation, leading to dysfunction and ultimately, death of cells in the brain. In this study, we test approaches to block the initiation of inflammation and identify which brain cells are the most susceptible to manganese by employing a test tube model of brain development. These advances will help detect early biological measures of manganese exposure, identify susceptible individuals, and develop intervention strategies to offset short- and long-term effects of metal toxicity.

How this study advances exposome science: This study explores the interaction between toxic environmental exposures, genetic predisposition to disease, and adaptive cellular responses to develop interventions that protect public health. Results from this study aim to protect workers and residents from inequitable exposure to manganese, for example, by informing policy regarding occupational health and hazardous manufacturing sites.

Environmental Toxicants, Ovarian Health, and Infertility

Study Title: Mapping the Follicular Fluid Exposome for Environmental Determinants of Infertility

PI: Anna Knight, School of Medicine, Gynecology and Obstetrics

Exposure to environmental toxicants is particularly concerning for women trying to get pregnant, as these exposures may negatively impact the function of the ovaries (the female organs that produce eggs) or increase infertility and miscarriage rates. One of the ways to study how environmental toxicants impact fertility is by looking at follicular fluid from the ovaries that is collected during in vitro fertilization (IVF) treatment. Follicular fluid bathes and carries nutrients to the developing eggs. Toxicants in this fluid can be identified based on their chemical signal, and can be compared to IVF treatment success, such as the number of eggs a woman has remaining and whether or not she becomes pregnant. These toxicants can also be compared to biological indicators of ovarian aging, such as hormone levels or number and quality of remaining eggs. This study will be one of the first to identify relationships between environmental toxicants in the ovarian environment and reproductive aging and success in IVF. Findings can help inform better counseling and treatment development for women experiencing infertility.

How this study advances exposome science: This study will provide insight into how environmental toxicants impact fertility and pregnancy, which can inform infertility treatment and counseling. This study’s population is racially diverse; many prior IVF studies focus on majority-white cohorts or do not consider race. As Black women are more likely to experience infertility, this study advances exposome research by including a much more diverse patient population than typical in studies of IVF.

Air Pollution Effects on Children with Sickle Cell Disease

Study Title: Effects of Ambient Air Pollution on the Exposome in Kids with Sickle Cell Disease

PI: Ben Kopp, School of Medicine, Pediatrics

Sickle cell disease is a severe, lifelong disease, and children with sickle cell disease (cwSCD) can suffer from severe pain episodes and lung and other organ damage. Because cwSCD often come from underserved backgrounds, their health can be influenced by social determinants of health (SDOH) such as unhealthy neighborhood environments. SDOH are part of the public health exposome (PHE), which includes stressors from every aspect of our surrounding environment over a lifetime. However, SCD treatments do not currently include the PHE. We think that PHE components including air pollution will be associated with inflammation in cwSCD, which predispose them to worsened lung disease and more frequent pain episodes. Our study will follow cwSCD over time and determine how environmental pollutants predict inflammation and clinical disease. We will use blood and airway samples to monitor immune responses along with satellite pollution recordings. This study will develop personalized, predictive profiles that include previously overlooked environmental exposures combined with immune system measures, which will allow for preventative rather than reactive treatment. Preventive treatment will help avoid devastating SCD complications that are caused by environmental health inequities.

How this study advances exposome science: By using a new framework of long-term pollution burden, public health risk factors, and immune responses combined to predict clinical responses, this study lays the groundwork to improve the health of all people with SCD who are disproportionately impacted by environmental health inequities.

Investigating the Effects of Air Pollution Exposures on Human Metabolic Responses and Cardiovascular Health

Metabolome-wide Association Study on Air Pollution Exposures and Cardiovascular Diseases in the Emory Cardiovascular Biobank (MAC Study)

PI: Donghai Liang, School of Public Health, Environmental Health

The relationship between residential exposures to outdoor air pollution and poor health outcomes has been well documented. Additionally, there is now mounting evidence that exposure to air pollution contributes to cardiovascular disease and deaths. However, little is known about how air pollution affects bodily processes, specifically, how the body’s metabolic processes change in response to air pollution and contribute to cardiovascular disease. The purpose of this study is to identify specific biological measures of air pollution in relation to cardiovascular health. We will use metabolomics data (measurements of the small molecules as a result of metabolism) analyzed from 800 participants previously enrolled in the Emory Cardiovascular Biobank and combine it with individual-level estimates of past exposure to air pollution using a previously developed model. Together, these data will allow for identifying indicators and mechanisms through which air pollution may cause adverse effects on cardiovascular health outcomes.

How this study advances exposome science: This study will lay the foundation for future studies to understand the biological mechanisms through which air pollution may have negative effects on cardiovascular health. Specifically, by identifying the biological mechanisms underlying the toxicity of air pollutants on cardiovascular health, we can better identify high risk individuals and develop intervention strategies to address the health impacts of air pollution exposures. Because many communities of color are inequitably exposed to high levels of air pollution, this project has the potential to advance health equity and environmental justice.  

Evaluating the Associations of Heavy Metal Levels with Interstitial Lung Disease

PI: Lucian Marts, School of Medicine, Department of Medicine

Interstitial lung disease (ILD) refers to a variety of inflammatory and scarring disorders of the lungs. ILD symptoms range from mild to severe and can limit one’s quality of life and lifespan. Previous research shows that cobalt and tungsten exposure may lead to a specific type of ILD referred to as hard metal lung disease, but the connection between ILD and exposure to other heavy metals has not been evaluated in detail. Communities across Georgia face multiple potential sources of heavy metal exposure, such as industrial slag in the soil of an Atlanta neighborhood and inactive mines in rural northwest Georgia. This project aims to measure the levels of 25 different heavy metals – including mercury, arsenic, and aluminum – in blood from individuals with ILD and without ILD to determine whether the levels of some heavy metals are higher in individuals with ILD. If individuals with ILD appear to have increased heavy metal blood levels, we will look for geographic clusters among these individuals in order to identify where current exposures are occurring and to prevent future exposures. 

How this study advances exposome science: This pilot study will use exposome methods to determine if exposure to heavy metals within the region may contribute to the development of ILD. We aim to identify local and regional areas with elevated heavy metals, with the ultimate goal of removing the sources of these exposures. This project has the potential to improve health equity by preventing heavy metal exposure among communities experiencing the inequitable burden of heavy metal contamination. 

Community-Based Particulate Matter Monitoring of Traffic and Transportation Pollution in Northwest Atlanta (NPU-G)

PI: Jeremy Sarnat, School of Public Health, Environmental Health

Exposure to particles in the air is linked with a range of adverse health effects such as increased heart and lung disease and death. Of particular concern are the risks of particle pollution from traffic and transportation sources. This pilot focuses on training a team of residents living in Atlanta Neighborhood Planning Unit G (NPU-G) to act as community field technicians to establish and maintain a particulate matter monitoring network among  their neighborhoods. NPU-G, located in northwest Atlanta and home of the former Bowen Homes public housing project, is undergoing rapid change and facing environmental stresses from numerous sources, including proposed commercial and industrial development along Hollowell Parkway and the expansion of I-285. This project aims to empower local nonprofits and NPU-G residents to be able to: a) identify current pollution hotspots within the neighborhood; and b) generate a baseline record of current pollution conditions to guide a future study aimed at reducing community exposures and improving health through the introduction of pollution reduction strategies, including planting tree barriers.  

How this study advances exposome science: In creating an extensive database of pollution monitoring data, this pilot will establish a critical basis to better understand NPU-G residents’ current and projected future environmental exposures, while also providing support for science-based interventions to improve public health. This project also aims to advance health equity by providing a community that has experienced historic disinvestment with the tools and resources needed to understand and address their air pollution exposures themselves.