The NIEHS Superfund Research Program (SRP) is hosting a seminar series focused on adverse outcome pathways (AOPs), which are structured ways to represent biological events leading to adverse health effects. In the first session, U.S. Environmental Protection Agency (EPA) staff will provide an introduction and overview of AOPs and discuss the AOP Knowledgebase, which is designed to house descriptions of the biological mechanisms underlying chemical toxicity in a structured manner.

The AOP framework was developed as a means for organizing biological and toxicological knowledge concerning the linkages between molecular-level perturbations of biological systems by stressors and the apical hazards (e.g., disease in humans, reduced survival, growth, reproduction in wildlife) that can result. As such, the AOP framework can help support greater use of mechanistic or pathway-based data in risk assessment and regulatory decision-making.

Daniel Villeneuve, Ph.D., will introduce the AOP framework, major principles that guide the development and description of AOPs within the AOP-knowledgebase, and will give examples of some prominent applications of AOPs.

Stephen Edwards, Ph.D., will discuss the design of the AOP Knowledgebase and how this supports both AOP development and use. It will include the assembly of AOP networks and their importance when using AOPs. It will also consider methods for developing AOP networks in an automated fashion to complement the expert-driven AOP development efforts within the AOP knowledgebase.

This webinar is also in support of an upcoming NIEHS/NHLBI Workshop, Understanding the Combined Effects of Environmental Chemical and Non-Chemical Stressors: Atherosclerosis as a Model, which will take place at NIEHS in Research Triangle Park, North Carolina, April 3 - 4, 2018. The goal of this workshop is to identify key biological mechanisms/pathways of the combined effects of chemical and non-chemical stressors associated with atherosclerosis. A critical research area that requires further exploration is the biological mechanisms and effects of exposure to both environmental chemicals (e.g., air pollution, polycyclic aromatic hydrocarbons, metals, pesticides) and non-chemical stressors (e.g., psychosocial, lifestyle, quality of life, poor nutrition, infectious agents, physical stressors) over time and the roles they may play in the development of disease (e.g., cancer, cardiac, metabolic, neurological). This workshop will bring together experts to discuss the state of the science pertaining to underlying biological pathways associated with, when combined, chemical and non-chemical stressors in relation to atherosclerosis. This workshop will use the AOP framework to assist in the discussion of the pathways considered by workshop participants.

Presenters:

Daniel L. Villeneuve, Ph.D., U.S. Environmental Protection Agency (Villeneuve.Dan@epa.gov or 218-529-5217)
Daniel L. Villeneuve, Ph.D., is a research toxicologist with the United States Environmental Protection Agency's Office of Research and Development (ORD). He received a BS in Water Resources and Zoology from the University of Wisconsin-Stevens Point and a Ph.D. in Zoology and Environmental Toxicology from Michigan State University. After doing a postdoctoral fellowship at Oregon State University, Dr. Villeneuve joined US EPA's Mid-Continent Ecology Division in 2004. Dr. Villeneuve currently serves as Project Lead for a cross-ORD research program focused on the development and application of adverse outcome pathways (AOPs). He has over 20 years of experience conducting freshwater ecotoxicology research and has been recognized with 17 US EPA Scientific and Technological Achievement Awards, three Bronze Medal awards, and is a US National Academy of Sciences and Kavli Foundation Fellow. Dr. Villeneuve has authored or co-authored over 160 peer-reviewed papers in the field of ecotoxicology and serves as an associate editor of Environmental Toxicology and Chemistry and an international expert advisor on Molecular Screening and Toxicogenomics to the Organization for Economic Cooperation and Development (OECD).

Stephen Edwards, Ph.D., U.S. Environmental Protection Agency (Edwards.Stephen@epa.gov or 919-541-0514)
Stephen Edwards, Ph.D., is a Systems Biologist within the U.S. Environmental Protection Agency's National Health and Environmental Effects Research Laboratory (EPA-NHEERL) in Research Triangle Park, N.C. Dr. Edwards is the EPA lead for an international effort to develop an Adverse Outcome Pathway (AOP) Knowledgebase, which is designed to house descriptions of the biological mechanisms underlying chemical toxicity in a structured manner. He is also leading an EPA effort to create computationally-predicted AOPs by integrating data from the published literature, omics databases, and HTS toxicity data. He serves as a senior advisor in the Office of Research and Development (ORD) on issues regarding the development of predictive toxicology models of disease using genomics, proteomics, and metabolomics. With a combination of experimental and computational experience, Dr. Edwards also serves as a liaison with the EPA’s National Center for Computational Toxicology (NCCT) and works on web-based tools to support systems biology research within the EPA. Dr. Edwards received his bachelor of science in chemistry from the University of North Carolina at Chapel Hill and his doctorate in pharmacology from Vanderbilt University Medical Center. Before joining the EPA, he served as a senior research scientist and research fellow at Rosetta Inpharmatics (Merck & Co.), in Seattle, Washington, a recognized leader in computational and systems approaches to drug development.

Moderator:

Michelle Olive, Ph.D., National Heart, Lung, and Blood Institute (olivem@mail.nih.gov or 301-435-0550)
Michelle Olive, Ph.D. is the Deputy Branch Chief of the Atherosclerosis and Coronary Artery Disease Branch at the Cardiovascular Sciences Division of the National Heart Lung and Blood Institute (NHLBI) extramural program at the National Institutes of Health (NIH). She manages a basic, translational and early clinical research portfolio in the areas of atherosclerosis, vascular biology, inflammation, non-coding genome, microbiome and rare vascular disease. She oversees a Trans-NIH program that fosters collaboration between Intramural and Extramural Investigators and the NIH Clinical Center.

Webinar Slides and References:

• Slide Presentation for Daniel L. Villeneuve, Ph.D., U.S. Environmental Protection Agency:
  • Adobe Acrobat format (60.5MB/PDF)
  • Microsoft PowerPoint format (18.8MB/PPTX)
• Slide Presentation for Stephen Edwards, Ph.D., U.S. Environmental Protection Agency:
  • Adobe Acrobat format (7.85MB/PDF)
  • Microsoft PowerPoint format (5.13MB/PPTX)

Webinar Slides and References:

• Slide Presentation for Daniel L. Villeneuve, Ph.D., U.S. Environmental Protection Agency:
  • Adobe Acrobat format (60.5MB/PDF)
  • Microsoft PowerPoint format (18.8MB/PPTX)
• Slide Presentation for Stephen Edwards, Ph.D., U.S. Environmental Protection Agency:
  • Adobe Acrobat format (7.85MB/PDF)
  • Microsoft PowerPoint format (5.13MB/PPTX)

Additional Resources:

• Adverse Outcome Pathway (AOP) Research Brief
• Adverse Outcome Pathways, Molecular Screening and Toxicogenomics
• AOP-Wiki Training Courses
• About "Pathways"
• Developing and Applying Adverse Outcome Pathways: What You Need to Know

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Date of Seminar:

 October 11, 2017: Adverse Outcome Pathways: Session I - Introduction to the Adverse Outcome Pathway Framework

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