Down syndrome and the fetal exposome
Stephanie Sherman and Judy Fridovich-Keil, Emory University, School of Medicine
Down syndrome (DS) is typically considered to be primarily a genetic disease caused by trisomy 21 and characterized by a range of clinically significant outcomes. Although DS is genetically based, there is a high degree of variability in symptoms that are unexplainable by genetic factors alone. Drs. Stephanie Sherman and Judy Fridovich-Keil are working towards determining if the broad range of phenotypic outcomes seen in DS can be explained by variability in the in utero environment. Maternal exposures and changes in fetal metabolism due to altered genetics may both be playing a role in altering this environment. Utilizing both targeted and untargeted approaches through analytical chemistry and metabolomics techniques, the fetal exposome will be characterized by second trimester amniotic fluid samples as well as a subset with matched maternal serum samples. Through quantifying and identifying differences between trisomy 21 and non-trisomy 21 controls, this pilot aims to take the first step in understanding how altered fetal genetics may lead to varied responses to environmental exposures and potential consequences due to increased susceptibility to abnormal development. Future studies would further elucidate how prenatal exposures might contribute to clinically significant birth outcomes associated with DS and how those exposures might be modified to mediate negative effects.
Dr. Stephanie Sherman is a professor in the Department of Human Genetics at the School of Medicine at Emory. Her research focuses using genetic epidemiologic approaches to understand the underlying genetic mechanisms of Down syndrome and fragile X syndrome and the resulting phenotypic consequences on intellectual and developmental disabilities.
Dr. Judy Fridovich-Keil is a professor in the Department of Human Genetics at the School of Medicine at Emory. Her research focuses on the roles of galactose and galactose metabolism in normal development, homeostasis and disease.
PFOA and ulcerative colitis in adolescents
Kyle Steenland, Emory University, School of Public Health
A previous cohort study of perfluoroctanoic acid (PFOA) exposed individuals from West Virginia identified a strong association between cumulative PFOA exposure and ulcerative colitis. Ulcerative colitis is a chronic inflammatory disease of the large intestine. Given the specific association between ulcerative colitis and PFOA (none was seen for Crohn’s disease or other autoimmune diseases), there may be a unique role for PFOA in the molecular pathology of ulcerative colitis. This association will be tested in samples from individuals diagnosed with pediatric ulcerative colitis at Emory between 2009 and 2015. These results will be compared with PFOA measures in corresponding NHANES samples nationally representative of baseline exposure in order to assess if cases have higher PFOA levels. If this hypothesis is confirmed, further research could be completed to explore these relationships in other cohorts and explore what is occurring mechanistically.
Dr. Kyle Steenland is a professor in the Department of Environmental Health at the Rollins School of Public Health at Emory. His research focuses utilizing epidemiologic methods to investigate the role of pesticides in relation to neurodegenerative disease, adult lead exposure and cancer, and PFOA and various disease outcomes.
Environmental influences on the microbiome and preterm birth in African Americans: a metabolomic pathway analysis
Erin Ferranti, Emory University, School of Nursing
Exposures occurring during critical periods of development can result in adverse outcomes with lifelong effects. However, the exact role of endogenous and exogenous exposures on preterm birth is not well understood, including why there are persistently wide racial disparities for this outcome after controlling for known risks. Exposures such as toxicants and stress have been proposed as potential factors in these disparities. Considering this hypothesis, Dr. Ferranti will investigate the complex interactions of environmental exposures, the microbiome and the metabolome. Utilizing computational and bioinformatics methods, she will analyze the metabolic pathways of pregnant women during two prenatal time periods. The goal of this pilot study is to identify maternal prenatal environmental toxicant exposures and any systemic metabolic profiles associated with preterm birth and related risk conditions. As an extension of this goal, Dr. Ferranti will investigate the maternal microbiome-metabolite and environmental toxicant-metabolite correlations that are linked to preterm birth. Through this work, the project strives to discover the metabolic pathways underlying co-occurring risk factors for preterm birth to ultimately aid in preventing these outcomes in the future.
Dr. Erin Ferranti is an assistant research professor at the Nell Hodgson Woodruff School of Nursing at Emory. Her research focuses on the contribution of diet quality to the gut microbiome and cardiometabolic outcomes in pregnancy and the postpartum timeframe.
Aryl hydrocarbons in mesenchymal stem cell immunomodulation and carcinogenesis
Jacques Galipeau, Emory University, School of Medicine
Environmental exposures and the aryl hydrocarbon receptor (AHR) is a well-explored area of research given the known links to multiple human diseases but much less is known about the impact of endogenous AHR ligands and how those signaling pathways impact immunity. Dr. Galipeau’s previous research has revealed that tissue resident stem cells express the aryl hydrocarbon receptor and are responsive to endogenous and exogenous hydrocarbons. For this pilot project, he hypothesizes that endogenously and environmentally generated ligands may share signaling pathways and that these relationships can be modeled using patient-derived tissue-resident stromal cells to better understand how aryl hydrocarbon metabolism is linked to immune responses. This project aims to characterize transcriptional events initiated by aryl hydrocarbons, investigate the metabolic and functional effects of AHR ligands on the immunomodulatory properties of mesenchymal stromal cells and ultimately increase the understanding of the impact of aryl hydrocarbons on tissue stem cell biology.
Dr. Jacques Galipeau is a professor in the Department of Hematology and Medical Oncology, Pediatrics and Medicine in the School of Medicine at Emory, co-director of the Winship Cancer Institute Tumor Immunology-Immunotherapy Initiative, and director of the Emory Personalized Immunotherapy Center. His research focuses on development of cell and gene therapy for catastrophic illness including cancer, immune and cardiovascular disease.