The SCEHSC Seminar Series presents
“High-Resolution Metabolomics: A Platform for Exposome Research”
Practical Considerations for Chemical Measurement by High-Resolution Metabolomics
Douglas Walker, PhD Candidate
Emory University, School of Medicine
Clinical Biomarkers Laboratory
Division of Pulmonary, Allergy, and Critical Care Medicine
Environmental Sustainability Laboratory
Department of Civil and Environmental Engineering
Friday, August 12, 2016
Soto Street II Building, Room 2902
2011 North Soto Street
Los Angeles, CA 90032
If you would like to attend the FREE seminar, please email email@example.com.
Douglas Walker received his BS in 2009 from the University of Massachusetts-Dartmouth in Civil and Environmental Engineering. He will be defending his doctoral dissertation in Environmental Engineering from Tufts University in September 2016, which was primarily completed in the laboratory of Dr. Dean Jones at Emory University. He is currently a member of the Clinical Biomarkers Laboratory and HERCULES Exposome Research Center, both at Emory University. The primary focus of his research is to integrate measures of environmental exposure, health outcomes and high-resolution metabolomics in both animal models and human populations. Application of this framework using advanced biostatistic/bioinformatic techniques provides a component for sequencing the human exposome and understanding the contribution of environmental exposures in disease pathophysiology.
Sequencing the human genome considerably advanced the understanding of human disease but did not fully achieve expectations in the identification of genetic polymorphisms underlying risk. Current estimates suggest that only 10-20% of diseases have a strong genetic component, with the remaining 80-90% attributable to the environmental exposures or gene-environment interactions. A more complete understanding of how environmental factors contribute to disease susceptibility and progression is required for mitigating risk, developing effective treatment strategies and identifying at risk populations; however, no unified method exists to characterize the sum involvement of lifestyle and environment in disease. High-resolution metabolomics (HRM) using liquid chromatography interfaced to ultra-high accuracy mass spectrometers is a promising analytical platform for untargeted environmental chemical surveillance and bioeffect monitoring. Improvements in HRM have made it possible to measure and characterize upwards of 15,000 unique features in biological samples, which include metabolites from core nutrient metabolism, lipids, the microbiome, diet-derived chemicals, pharmaceuticals and environmental contaminants. In the Clinical Biomarkers Laboratory at Emory University, efforts are underway to develop HRM as a unifying platform linking environmental exposures to internal dose, biological response and underlying mechanisms of chemical toxicity that contribute to exposure-related diseases. To date, we have analyzed over 3000 human samples with a wide range of well-characterized exposures, including occupational exposure to volatile organic compounds, ultrafine particles, burn pit exposures, diesel exhaust, combustion products and persistent organic pollutants. Association of the metabolic phenotype with external exposure and body burden estimates determined using traditional epidemiological approaches shows HRM can detect dose-related changes in exogenous chemicals and metabolic pathway perturbations linked to disease outcomes. Combined with complementary measures, such as inflammatory markers, gene expression, protein levels and/or physiological changes, it is possible to develop a systems-biology based approach to understanding chemical toxicology in humans. Thus, HRM is poised to provide a robust foundation for exposome research and facilitate development of a knowledge base of environmental chemicals, their distribution and associated effects among human populations.
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