FACULTY
David L. Eaton, PhD
Associate Vice Provost, Office of Research
Professor, Env. and Occ. Health Sciences
Dr. Eaton received his Ph.D. in pharmacology from the University of Kansas Medical Center (KUMC) in 1978. Following a post-doctoral fellowship in Toxicology at KUMC, he joined the faculty of the University of Washington in 1979. He served as Toxicology Program Director in the Department of Environmental Health from 1983-90, then as Associate Chairman of the Department from 1990-92, and as Associate Dean for Research in the School of Public Health from 1999-2005. He is currently Professor and Director of the Center for Ecogenetics and Environmental Health, an NIEHS Center of Excellence, at the University of Washington, and Associate Vice Provost for Research for the University of Washington. Dr. Eaton maintains his own active research and teaching program focused in the area of the molecular basis for environmental causes of cancer, and how human genetic differences in biotransformation enzymes may increase or decrease individual susceptibility to chemicals found in the environment. Nationally, he has served on the Board of Directors and as Treasurer of the American Board of Toxicology (1990-94), and as President of the Society of Toxicology (2001-02). He has also served on the Board of Environmental Studies and Toxicology, National Academy of Sciences /National Resource Council (1996-99), as a member of the Board of Directors and Vice-President of the Toxicology Education Foundation, and on the Board of Trustees of the Academy of Toxicological Sciences. He is an Elected Fellow of the American Association for the Advancement of Science and the Academy of Toxicological Sciences. He has published over 150 scientific articles and book chapters in the field of toxicology and risk assessment.
Contact Information
University of Washington
Office: A206, Roosevelt;
Suite 98, Gerberding Hall
Box 354695
Department of Environmental and Occupational Health Sciences
4225 Roosevelt Way NE #100
Seattle, WA 98105-6099
Tel: 206-685-3785
Tel: 206-543-8458
Fax: 206-685-4696
deaton@u.washington.edu
Links
Center for Ecogenetics and Environmental Health
Health and Environmental Resources for Educators
Why Me, Doc? What Scientists Know - and Don't Know - About Cancer
Affiliations
Center for Ecogenetics and Environmental Health
Research Interests
Biochemical toxicology, aflatoxin carcinogenesis, glutathione-mediated biotransformations of toxic chemicals, genetic susceptibility to environmental carcinogens, 'gene-environment' interactions
Education
PhD, Pharmacology and Toxicology, University of Kansas Medical Center 1978
Projects
Program/Grant Name: Center for Ecogenetics and Environmental Health
Funding Agency: NIH/NIEHS (P30 ES07033)
Many diseases of public health importance, such as most cancers, Alzheimer's Disease, Parkinson's disease, asthma, and even birth defects, arise through a complex interaction of genetics and environment. Investigators in the Center for Ecogenetics and Environmental Health are conducting research to understand how specific genetic traits increase or decrease an individual's likelihood of contracting a chronic disease or illness. For example, researchers are studying how genetic differences in the way people break down (metabolize) drugs and other chemicals might increase their chances of getting cancer when exposed to potentially cancer-causing chemicals in their workplace, diet or lifestyle activities (e.g., smoking). Other researchers in the Center are studying genetic traits that, when combined with exposure to substances in the diet or general environment, make individuals more likely to develop chronic neurological diseases such as Parkinson's disease. Other researchers are investigating the link between genetics and asthma, and environmental factors that might cause birth defects in genetically susceptible individuals. In addition to basic research, the Center includes a core devoted to the study of ethical, legal and social issues related to the use, and potential misuse, of genetic susceptibility information. The Community Outreach and Education Core within the CEEH develops workshops and educational materials, and promotes community education, in the environmental health sciences. Although based in the School of Public Health and Community Medicine, CEEH Investigators come from a variety of schools and departments across the University. Research findings from CEEH investigators will help unravel how genetics and environment interact to produce disease, and are an important extension of the exciting new information coming from the Human Genome Project.
Program/Grant Name: Isothiocyanates as Specific Antagonists to the Pregnane X-Receptor
Funding Agency: NIH/NIGMS (R01GM079280)
Natural, non-nutritive components in the diet – so called 'phytochemicals'- have potentially important biological effects on humans. Sulforaphane (SFN) is one such chemical, present in relatively high concentrations in broccoli and especially broccoli sprouts. Numerous studies have demonstrated that diets high in cruciferous vegetables (e.g., broccoli, cauliflower, Brussels sprouts, cabbage) are associated with decreased risk for some types of cancer, and SFN is among the putative 'chemopreventive' compounds thought to contribute to this anticancer effect. In the process of investigation how SFN induces the expression of 'antioxidant' genes, our laboratory discovered that SFN also decreases the expression of certain genes, including Cytochrome P450 3A4 (CYP3A4). This enzyme is responsible for metabolism of many drugs and chemicals, so diet-related decreases in the expression of CYP3A4 could have important pharmacological and toxicological consequences. Our laboratory demonstrated that the mechanism by which SFN decreased CYP3A4 expression was through inhibition of ligand binding to the Pregnane X-Receptor (PXR). PXR is a nuclear transcription factor that, when activated by endogenous and/or exogenous ligands, enhances the expression of CYP3A4 and a variety of other biotransformation genes. As activation of PXR via certain drugs is a common cause of adverse drug-drug interactions, inhibition of ligand activation of PXR could have important clinical relevance. This grant is funding a phase I clinical trial to determine if co-administration of SFN with the potent PXR ligand, rifampicin, can prevent the rifampicin-induced up-regulation of CYP3A4. Rifampicin is an antibiotic that is widely used throughout the world as a first line treatment for tuberculosis. However, because of its potent induction of CYP3A4, it is contraindicated in HIV/AIDS patients on antiretroviral therapy, since the increase in CYP3A4 makes the antiretroviral drugs ineffective. If SFN were able to prevent the rifampicin-mediated increase in CYP3A4, it might be possible to for it to be used for treating TB in HIV/AIDS patients.
