Pilot Project Recipients Year 8

Environmental risk factors related to age at menopause among women with a gene premutation

Study Title: Fragile X-associated Primary Ovarian Insufficiency (FXPOI): elucidating environmental risk factors

PI: Emily G. Allen, Emory University, Department of Human Genetics; Co-I: Audrey Gaskins, Emory University Rollins School of Public Health, Department of Epidemiology

Our project will focus on identifying environmental risk factors associated with early menopause (menstruation ends before the age of 40) related to a gene premutation (an expansion in the number of repeated nucleic acids in a specific gene which is associated with fragile X disorders). Approximately 20-30% of women who carry these expanded repeats experience early menopause. Early menopause is also associated with reduced fertility and allows for a shorter reproductive window making it harder for these women to reach their family planning goals. We don’t know why only some women with these repeats suffer early menopause and others do not. To better understand this, we will enroll women who have these repeats – some who experienced early menopause and some who have not – into the study. We will ask them about their residential and occupational history and study how their cells have responded to environmental exposures using metabolomic analysis of blood samples. From this, we will be able to identify environmental factors associated with age at menopause in women with these repeats. By improving our ability to identify which women with these repeats are at greatest risk for early menopause, we may be able to help these women better meet their family planning goals. Identifying environmental risk factors associated with early menopause may also lead to new strategies for early detection, prevention and treatment in the general population.

How this study contributes to the exposome: Women are exposed to things throughout their lifetime, and this study aims to identify which exposures are related to early menopause specifically among women with a certain repeated gene sequence. These women are at particularly high-risk for early menopause, but our findings could potentially help us understand age at menopause in the general population as well.

Dr. Emily Allen is an Assistant Professor in the Department of Human Genetics. Her research focuses on fragile X syndrome and Down syndrome.

Assessing the effects of metal exposure on the development of fetal lungs in mice

Study Title: A novel model to assess effects of metal exposure on fetal lung development

PI: Xin Hu, Emory University School of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine; Co-I: Cherry Wongtrakool, Emory University School of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine and Atlanta VA Medical Center and Carmen J. Marsit, Emory University Rollins School of Public Health, Department of Environmental Health, Department of Epidemiology, and HERCULES Exposome Research Center

Exposure to heavy metals, such as cadmium (Cd) and arsenic (As), is a major public health concern and is relatively high in pregnant women and children. Furthermore, exposure to heavy metals has been associated with asthma and other respiratory diseases in children. There is an urgent need to understand whether a pregnant mother’s exposure to metals interferes with the lung development of the fetus and ultimately causes lung dysfunction in the child later in life. Our study will use mice to study how heavy metal exposure during pregnancy affects an early stage of airway development in fetal mice. The results will show us whether and how metal exposure harms the airway structure, which will allow us to further understand how environmental exposures contribute to the origins of lung diseases and identify prevention strategies.

How this study contributes to the exposome:  The findings will advance understanding of how environmental exposures that occur before birth contribute to the development of respiratory disease in children.

Dr. Xin Hu is an Assistant Research Scientist in transition to faculty in Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine in the Department of Medicine.  Her research interest is to study environmental contributions to lung disease and currently focuses on mitochondrial metabolic dysfunction in environmental induced lung injury and disease.

Does the air we breathe affect our risk for dementia?  

Study Title: Long-Term Effects of Air Pollutant Mixtures on Cognition in the Emory Healthy Aging Study

PI: Anke Huels, Emory University Rollins School of Public Health, Departments of Epidemiology & Environmental Health; Co-Is: Stefanie Ebelt, Emory University Rollins School of Public Health, Department of Environmental Health & Lance Waller, Emory University Rollins School of Public Health, Department of Biostatistics and Bioinformatics

Outdoor air pollution from traffic, power plants, and other industry is the largest environmental cause of disease and premature death in the world. Recent studies have shown that some particular air pollutants can also affect our brain and increase the risk for dementia, a cognitive decline that affects behavior and thought processes. However, in real life, we inhale more than one air pollutant at a time and the interaction between many pollutants might be particularly dangerous. Our study will use data from the Emory Healthy Aging Study (EHAS), which is the largest research study on aging in Atlanta. We will link EHAS questionnaire data with data on traffic-related air pollution for each participant based on their residential location. Using the linked database, we will estimate relationships between air pollutant mixtures and different stages of cognitive decline. The results of this study will promote awareness about the harmful effects of air pollution mixtures on the human brain.

How this study contributes to the exposome: In line with the concept of the “exposome”, our study accounts for the complexity of air quality, which consists of a mixture of many pollutants. Our pilot study will produce preliminary findings that will show the importance of studying the effects of air pollutant mixtures on the human brain, which will improve our understanding of the exposome for cognitive health.

Dr. Anke Huels is an Assistant Professor in the Department of Epidemiology, Rollins School of Public Health, with a joint appointment in the Gangarosa Department of Environmental Health. Dr. Huels’ research focuses on the association between outdoor and indoor air pollution with human health, methods and applications for the detection of gene-environment (GxE) interactions, and current challenges in the analysis of DNA methylation data.

Investigating the impact of air pollution exposures on human metabolic responses

Study Title: Metabolomics Wide Association Study on Ambient Air Pollution Exposure in the Cancer Prevention Study-II Nutrition Cohort (CPSII-MWAS-AIR)

PI: Donghai Liang, Emory University Rollins School of Public Health, Department of Environmental Health; Co-I: Jeremy Sarnat, Emory University Rollins School of Public Health, Department of Environmental Health and Ying Wang, American Cancer Society, Behavioral and Epidemiology Research

Air pollution is associated with a variety of adverse health outcomes. Evidence from the cohort in this study shows that certain types of air pollution increase the risk of death from cardiovascular (heart) disease and lung cancer. However, little is known about how the body’s cellular processes respond to air pollution and contribute to disease. The purpose of this study is to identify specific biological indicators of air pollution. We will use metabolomics data (measurements of the small molecules as a result of metabolism) analyzed from 1,438 women and the assessment of the women’s past air pollution exposure.  Together, these data will allow for identifying indicators of air pollution exposure and lay the foundation for future studies to understand the biological mechanisms through which air pollution may cause adverse effects on cancer and other health outcomes.

How this study contributes to the exposome: This study will serve as a proof-of-concept for future studies to apply metabolomics data to identify biological factors (metabolites) that mediate associations between various environmental exposures and adverse health outcomes.

Dr. Donghai Liang is an Assistant Research Professor in the Gangarosa Department of Environmental Health at Emory’s Rollins School of Public Health. Dr. Liang’s research focuses on health effects associated with exposures to air pollution and persistent organic pollutant using advanced exposure assessment and high-resolution metabolomics.

How do insecticides affect the gut and microbiome?

Study Title: Insecticide Exposure on Neurological Pathophysiologies in the Gut

PI: Timothy Sampson, Emory School of Medicine, Department of Physiology

Exposure to insecticides is a leading environmental risk for many neurological diseases such as anxiety, depression, autism, and Parkinson’s disease. These neurological conditions often occur simultaneously with symptoms outside of the brain, particularly symptoms of the gut, including constipation and inflammatory bowel disease. The intestinal tract and its community of resident microbes (the gut microbiome) is one of the first parts of the body to interact with oral exposures. For example, oral insecticide exposure often occurs from eating foods that carry insecticide residues. However, little is known about how the gut and its microbiome respond to insecticides. With growing evidence that the microbiome can contribute to neurological diseases, our study seeks to understand how insecticides affect the gut microbiome, the function of the gut, and ultimately impact the brain. We will treat mice with a low dose of oral insecticide and then measure changes to the gut microbiome and whether they are related to changes in intestinal function (such as constipation) over time. By identifying when and for how long these changes occur in the gut, we may be able to link how insecticides trigger these defects of the intestinal tract and lead to long-term consequences in the brain.

How this study contributes to the exposome: Our pilot study will provide an understanding towards how oral exposure to insecticides can directly change both the microbiome and the gut, which could contribute to neurological diseases.

Dr. Tim Sampson is an Assistant Professor in the Department of Physiology at the Emory School of Medicine. Dr. Sampson is broadly interested in the roles of the microbiome in modulating neurological diseases. Given the associations between altered gut microbiomes and various diseases, we seek to understand how environmental exposures shape the microbiome and how this dysbiosis impacts outcomes in neurological injury and diseases. Dr. Sampson’s lab works to dissect contributions of individual gut microbes and their metabolites in order to identify contributing or protective factors to neurological outcomes.

Using Big Data to Study the Relationship between Air Pollution and Alzheimer’s Disease

Study Title: A Big Data Approach to PM2.5 and Its Components and Alzheimer’s Disease

PI: Liuhua Shi, Emory University Rollins School of Public Health, Department of Environmental Health; Co-PIs: Kyle Steenland, Emory University Rollins School of Public Health, Department of Environmental Health; Yang Liu, Emory University Rollins School of Public Health, Department of Environmental Health; and Howard Chang, Emory University Rollins School of Public Health, Department of Biostatistics and Bioinformatics.

Alzheimer’s disease is the sixth leading cause of death in the United States, but the cause of Alzheimer’s disease is largely unknown. Emerging evidence suggests that air pollution likely plays an important role – especially fine particulate matter, which are very small particles of dust, metals, pollen, smoke, and liquid droplets that are less than 2.5 μm in diameter (PM2.5). It is likely that different components of PM2.5 (such as elemental carbon, metals, or sulfates) harm the nervous system. However, few studies have looked at which components of PM2.5 may contribute to Alzheimer’s. Identifying these specific components is necessary to minimize and prevent exposure (for example, by knowing the specific components one could potentially trace them back where they came from). This pilot study will use large datasets to predict and estimate the daily concentrations of major PM2.5 components in the US. We will compare these estimates to Medicare data for Alzheimer’s cases in the state to assess the relationship between long-term exposure to PM2.5 components and Alzheimer’s disease risks among the Medicare population (aged 65 and older).

How this study contributes to the exposome: This study will create high-resolution air pollution exposure datasets that can be used to study health conditions that may be related to exposure. The findings of this study can inform policy to regulate specific sources of air pollution that can help prevent or reduce the risk of Alzheimer’s disease.

Dr. Liuhua Shi is a Research Assistant Professor in the Gangarosa Department of Environmental Health at Emory’s Rollins School of Public Health. Dr. Shi’s research focuses on employing massive datasets, including satellite-retrieved high-resolution exposures and health data of all Medicare beneficiaries, to investigate how climate change and air pollution influence mortality and neurological diseases. 

Lead levels and retained bullet fragments from firearm injury

Study Title: Lead Toxicity and Retained Bullet Fragments: A Longitudinal Pilot Study of Lead Levels after Firearm Injury

PI: Randi N. Smith, Emory University School of Medicine and Rollins School of Public Health; Co-Is: Ziad Kazzi, Emory University School of Medicine, Department of Emergency Medicine and Georgia Poison Center & Christine Castater, Trauma/Clinical Care Fellow; Community collaborators: Aric Johnson, Grady Memorial Hospital & Jeffery Gates, community member

Overexposure to lead remains a major health problem for children and adults around the world.  Lead affects various organ systems, leading to adverse neurologic (brain and nervous system), cardiovascular (heart and blood vessels), hematologic (blood) and developmental effects.  In the US, elevated blood lead levels have been found in individuals with occupational (e.g. battery manufacturing, mining and painting industries) and environmental exposures (e.g. lead-based paint and contaminated drinking water).  Retained bullet fragments (RBFs) after firearm injury are another potential source of lead exposure with limited research. Given there is no standard medical guideline regarding removal of RBFs, individuals with RBFs may be exposed to lead for long periods of time.  Hence, this study plans to evaluate the blood levels of lead and other heavy metals in individuals with and without RBFs after firearm injury.  Data generated from this study about lead exposure from RBFs has the potential to impact clinical management guidelines and procedures for handling RBFs.

How this study contributes to the exposome: The results from this study will provide important insights about a long-term source of lead exposure that many individuals experience during their lifetime. 

Dr. Randi Smith is an Assistant Professor of Surgery in the Emory School of Medicine Department of Surgery with a joint appointment in the School of Public Health in the Department of Behavioral, Social, and Health Education Sciences.  She serves as a trauma surgeon, emergency/elective general surgeon and surgical critical care intensivist at Grady Memorial Hospital.  Her research interests includes violence/injury prevention, clinical outcomes and evaluation of the social and environmental determinants that impact health.