Keynote: Redefining ‘environmental exposure’ to discover causes of chronic diseases
KEY NOTE SPEAKER:
Dr. Stephen Rappaport, PhD
Professor, Environmental Health Sciences
Director, Berkeley Center for Exposure Biology
Dr. Rappaport is a pioneer in the emerging field of ‘Exposure Biology’ and a prominent advocate of the concept of the ‘Exposome’ as a new paradigm for environmental health. His laboratory is conducting Exposome Wide Association Studies (EWAS) to discover causes of cancer and other chronic diseases. By profiling thousands of small molecules and protein adducts in archived blood from incident cases and controls, they are finding discriminating chemicals that point to potentially causal exposures. During his career, Prof. Rappaport has used environmental measurements and biomarkers to elucidate the human metabolism of several toxic chemicals, notably benzene, and to quantify interindividual variability in biomarker levels due to genetic, environmental and lifestyle factors.
Abstract
The publication of the human genome in 2003 led to speculation that genomic technologies would identify the causes of major chronic diseases, particularly cancer and cardiovascular disease, and would lead to personalized strategies for disease prevention. However, most genome-wide-association studies (GWAS) have not detected large effects of common genetic variants on disease incidence. The small effect sizes identified from single nucleotide polymorphisms (SNPs) in GWAS are consistent with studies of monozygotic twins that point to modest contributions of entire genotypes toward cancer and cardiovascular disease. Thus, in weighing the relative influences of heritable genetics and environmental exposures on chronic diseases, it appears that exposures and/or gene–environment interactions (G×E) are major causal factors. The clear implication is that scientists seeking unknown causes of chronic diseases should employ a balanced strategy that characterizes both heritable genetics and exposures at high resolution. However, in contrast to GWAS that detect millions of SNPs with high throughput, etiological studies of human exposures typically rely on low-throughput methods that target only a few hundred chemicals or mixtures.
In this lecture I will outline how environmental exposure can be defined by the blood exposome—the totality of chemicals circulating in blood. The blood exposome consists of chemicals derived from both endogenous and exogenous sources. Endogenous chemicals are represented by the human proteome and metabolome, which establish homeostatic networks of functional molecules. Exogenous chemicals arise from diet, vitamins, drugs, pathogens, microbiota, pollution and lifestyle factors, and can be measured in blood as subsets of the proteome, metabolome, metals, macromolecular adducts, and foreign DNA and RNA. To conduct ‘exposome-wide association studies’, blood samples should be obtained prospectively from subjects —preferably at critical stages of life—and then analyzed in incident disease cases and matched controls to find discriminating exposures. Results from recent metabolomic investigations of archived blood illustrate our ability to discover potentially causal exposures with current technologies.
Dr. Kim Anderson, PhD
Professor, Department of Environmental and Molecular Toxicology
Our research is focused in the field of environmental forensic chemistry which involves the application of chemical concepts to the interpretation, distribution, speciation, and bioavailability of chemicals in the environment (often litigious). We focus on persistent, bioaccumulative, toxic chemicals. We are working at several field sites, mostly throughout the state of Oregon, including the Portland Harbor Superfund Site, and several sites on the Willamette River. We work in several eco-system compartments: dominantly fish, surface waters and sediments. In addition, to classical techniques, we work on development and evaluation of in-situ techniques which mimic organisms, in order to better understand bioavailability. We also look at the effect of episodic events/inputs into an eco-system. She received her PhD in Chemistry from Washington State University.
Dr. Maude David, PhD
Assistant Professor, Department of Microbiology
Dr. Maude David's laboratory studies the gut-brain axis, to understand how microbes can impact our behavior, specifically in Autism Spectrum Disorder and Anxiety. She uses a crowd-sourced approach to collect lifestyle type information, diet habits, and samples. Her team is also working on identifying bottlenecks in microbial ecology and bioinformatics, bringing novel solutions to unravel microbial molecular mechanisms by optimizing new molecular methods and improving massive sequencing data annotation.
Dr. Jennifer Field, PhD
Professor, Department of Environmental and Molecular Toxicology
Current general research focuses on the development and application of quantitative analytical methods for organic micropollutants and their transformation products in natural and engineered systems. Early in her career, she focused on field-based research to investigate the fate and transport of surfactants in groundwater and wastewater treatment systems. She participated in interdisciplinary research with hydrologists and engineers in order to develop ‘push-pull’ tracer test methods for determining in-situ rates of reductive dechlorination and anaerobic biodegradation of aromatic hydrocarbons. She was a pioneer in the area of fluorochemical occurrence and behavior with a focus on groundwater contaminated by fire-fighting foams, municipal wastewater treatment systems, and in municipal landfill leachates. Her current research in the area of environmental analytical chemistry concentrates on the use of large-volume injections with liquid chromatography/mass spectrometry as a quantitative yet cost- and time-saving approach for the analysis of aqueous environmental samples.
Dr. Emily Ho, PhD
Professor, College of Public Health and Human Sciences
Endowed director of moore family center for whole grain foods, nutrition and preventive health
My research interests are in the area of antioxidants and gene expression and dietary chemoprevention strategies.
I am currently interested in understanding the role of the antioxidant nutrients such as zinc in maintaining DNA integrity and cancer development. Specifically, I am concerned with the effects of zinc status on DNA damage, DNA repair and stress-response signal pathways. We are also becoming interested in the effects of zinc on the immune system, especially as we age. A large proportion of thepopulation does not eat enough zinc, especially the elderly, and hence may be at increased risk for cancer and other disorders.
Dr. Perry Hystad, PhD
Assistant Professor, College of Public Health and humans sciences
Dr. Perry Hystad is an Assistant Professor in the College of Public Health and Human Sciences at Oregon State University, USA. He is the program director for the environmental health program and PI of the Spatial Health Lab. His research focuses on connecting people to places to determine chronic disease risk factors and prevention opportunities. There are three major themes to his research: health impacts of air pollution; health impacts of the built environment; and the development of novel approaches for environmental exposure assessment. He has been PI and co-Investigator on several grants that assess air pollution and built environment exposures, determine associations with health outcomes, and translate this information into effective policy and prevention activities. Currently, he is PI of a 5-year NIH funded grant to examine the cardiopulmonary health effects from air pollution in the global prospective urban and rural epidemiology (PURE) study.
Dr. Javier Nieto, MD, PhD, MPH, MHS
Dean, College of Public Health and humans sciences
Dr. Nieto’s main areas of research interest are the epidemiology of chronic diseases, survey research, and epidemiologic methods. During the last few years, he has collaborated with researchers from the Pan American Health Organization (Washington DC), El Salvador, and Cuba on population studies assessing the magnitude and etiologic factors of an ongoing epidemic of chronic kidney disease in Central America. This epidemic is particularly pronounced in agricultural communities in Nicaragua and El Salvador, especially among sugar cane cutters. Heat stress/dehydration has been proposed as a potential etiologic factor, but the role of exposure to agrochemicals has not been ruled out. Nieto received his MD degree from the University of Valencia, Spain, MPH from University of Havana, Cuba, and MHS and PhD in Epidemiology from the Johns Hopkins Bloomberg School of Public Health.
Dr. Tom Sharpton, PhD
Assistant Professor, Department of Microbiology
Dr. Thomas Sharpton’s research is broadly directed towards ascertaining how commensal microbiota and their genomic characteristics (i.e., the microbiome) relate to health. His laboratory specializes in the development and application of high-throughput computational and statistical tools that characterize microbiome biology, and investigates how microbiomes are distributed across space, time, and host physiology. The Sharpton lab aims to develop testable hypotheses about how hosts and their microbiome interact, and strives to understand the evolutionary and ecological processes that influence community assembly, maintenance, and function within a host. Ultimately, this knowledge will be used to discover disease mechanisms, identify predicative and diagnostic biomarkers of disease, and develop tools to treat disease through manipulation of the microbiome. All of the data resources and software that his lab develops are freely available. He received his PhD from the University of California, Berkeley.
Dr. David Williams, PhD
Principal Investigator and Helen P. Rumbel Professor for Cancer Prevention, Linus Pauling Institute
Professor, Department of Environmental and Molecular Toxicology
My research interests are in the characterization and regulation of microsomal monooxygenase enzymes (Cytochromes P450 and Flavin-Containing Monooxygenases) active in drug metabolism and their involvement in the detoxication and/or bioactivation of drugs, xenobiotics, and endogenous compounds. In addition, a major focus of current research efforts is on diet and cancer. These studies employ both trout, mouse, and human cell culture models to address mechanistic questions. Currently, we are working on a model that addresses the issue of maternal diet on cancer risk for the fetus in later life. He received his PhD in biochemistry from Oregon State University.
Sharia M. Ahmed, MPH
PhD Candidate, College of Public Health and human sciences
PhD Advisor: Molly Kile
Sharia is a fourth year epidemiology student. She is broadly interested in applying advanced epidemiological methods to questions about environmental exposures, especially waterborne exposures. Her dissertation explores the relationship between gestational and early childhood arsenic exposure and infectious disease symptoms in childhood, using causal inference and longitudinal methods. She received her MPH in Global Epidemiology from Emory University and has previously worked at Oregon State University's College of Pharmacy, the International Centre for Diarrhoeal Disease Research, Bangladesh, and the Centers for Disease Control and Prevention.
Prarthana Shankar
PhD Candidate, Department of Environmental and Molecular Toxicology
PhD Advisor: Robyn Tanguay
Prarthana received her Bachelor of Science in Biology from California State University Fullerton in 2016, and is currently a third year graduate student. She is interested in exploring how the downstream targets of aryl hydrocarbon receptor activation, including long non-coding RNAs, are involved in PAH toxicity in the zebrafish model.
Yvonne Chang
PhD Candidate, Department of Environmental and Molecular Toxicology
PhD Advisor: Susan Tilton
Yvonne is a fourth year Toxicology PhD candidate. Her dissertation research evaluates the carcinogenic potential of polycyclic aromatic hydrocarbons and complex PAH mixtures using systems biology data generated from a human lung 3D cell culture model. She is also interested in mixtures toxicology and the applications of combined in vitro and in silico approaches in toxicity testing. Yvonne received her Bachelor of Science in Cell Biology from the University of California, Davis in 2015.