Ultra sensitive Tools for Human Health Research: Highlights from a K.C. Donnelly Externship

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By Erin Madeen, Ph.D. candidate and Project 1 Trainee

Erin Madeen working at the Lawrence Livermore National Laboratory.
Erin Madeen working at the Lawrence Livermore National Laboratory.

Using new technology at Lawrence Livermore National Laboratory (LLNL), Oregon State University researchers are able to perform a controlled study of the human metabolism of environmental contaminate PAHs for the first time.

The Williams Laboratory has studied PAHs (polycyclic aromatic hydrocarbons) for over a decade, traditionally relying on animal and in vitro models of metabolism and toxicity. PAHs are produced by the burning of carbon-containing materials, for example forest fires, charcoal grilling, and engine combustion. After production, PAHs cling to foods such as vegetables, cereal grains, or smoked meats. Some of these compounds cause cancer at high doses in animal models.

As a graduate student in the Williams Lab, one of my projects is to relate PAH data to human health.  With our partners at LLNL, a sensitive tool known as an AMS (accelerator mass spectrometer) is used to detect very small doses of PAHs in urine or blood plasma.  We gave a model PAH called DBC [Dibenzo (def,p) chrysene] to human volunteers in doses less than what can be found in a charbroiled burger. This research has not been possible until now because of potential toxicity risks.  Traditional non-AMS methods need a larger dose of DBC which could pose too high of a risk to study participants.

With the support of LLNL staff and the OSU Superfund Research Program, I received a K.C. Donnelly Externship Supplement through the NIEHS Superfund Research Program.  This award supported my travel to LLNL for this project. My experience at LLNL greatly solidified my understanding of and appreciation for AMS. Maintaining and continuously developing unique instrumentation, such as AMS, requires a highly specialized, dedicated, and flexible team.  The environment of a national laboratory is different from that of university research.  Most notably this difference is in the concentration of specialists in a particular field and the team approach to problem solving. It was humbling to observe the amount of time, resources, and effort that the LLNL AMS staff dedicated to training and to progress on our DBC project. This externship allowed me to experience being part of the AMS team and to process my own samples, providing valuable insight that will help guide further work on our projects.

Accelerator Mass Spectrometry (AMS) is an instrument traditionally used for carbon dating. It has been modified to detect stable isotopes in biological samples. The AMS at LLNL is unique because it is able to use liquid samples.  The liquid biological samples are separated according to the changes the body makes to DBC, known as DBC metabolites.  The carbon isotope added to the DBC chemical structure was used to identify several different metabolites in human urine and plasma.  This project is ongoing as we continue to develop a profile of the human metabolism of DBC over time.

Related journal publications:

From OSU Superfund Research Program

From LLNL

 

OSU Partners with PNNL for Biostatistics and Modeling Expertise

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Our Center is multi-investigator, multi-disciplinary and multi-institutional. In partnership with Pacific Northwest National Laboratories (PNNL), and other stakeholders and collaborators, we are developing new technologies to identify and quantitate known and novel polycyclic aromatic hydrocarbons (PAHs) found at many of the nation’s Superfund sites and assess the risk they pose for human health.

Women@Energy: Dr. Katrina Waters Photo credit: energy.gov
Women@Energy: Dr. Katrina Waters
Photo credit: energy.gov

The research projects in our Center collect large amounts of molecular and chemical data. This data includes measuring PAH mixtures in environmental samples, determining toxicity of PAH mixtures, and the mechanism(s) of action for these toxic endpoints.

Our Biostatistics and Modeling Core, lead by Dr. Katrina Waters, greatly enhances our Center by providing expert statistical and bioinformatics data analysis support and software solutions for data management and interpretation.

Katrina Waters recently became the Deputy Director for the Biological Sciences Division at the Pacific Northwest National Lab (PNNL). Her expertise is in computational biology, and she works collaboratively with all of the research projects and co-authors with them.

This multidisciplinary training of toxicology students and fellows at OSU and PNNL is a unique strength of our program. Our SRP Trainees have benefited greatly from the PNNL partnership.  Students have gone to the lab in Richland, WA to be trained in Bioinformatics, Statistics and Study Design. More training workshops are being scheduled for this summer and fall.

Waters presented at SOT’s FutureTox II: In Vitro Data and In Silico Models for Predictive Toxicology on January 16, 2014. Her talk was entitled Computational Tools for Integration of High Throughout Screening (HTS) Data. She utilized examples from the collaboration with Robert Tanguay and his zebrafish assay for toxicity testing (Project 3).

Susan Tilton
Susan Tilton works with Dr. Katrina Waters and the OSU SRP Biostatistics and Modeling Core Group

 

Dr. Susan Tilton, also from PNNL,  presented at FutureTox as well. The title of her presentation was ‘Pathway-based prediction of tumor outcome for environmental PAH mixtures’.  In this study, they developed a mechanism-based approach for prediction of tumor outcome after dermal exposure to PAHs and environmental PAH mixtures.  Their model was successfully utilized to distinguish early regulatory events during initiation linked to tumor outcome and shows the utility of short-term initiation studies in predicting the carcinogenic potential of PAHs and PAH mixtures.

“Dr. Waters and her group have proven to be of great value in not just the interpretation of extremely large and complicated data sets, but also in the “front-end” study design, which results in enrichment of the subsequent data obtained.”
– Dr. David Williams, OSU SRP Center Director

New Monthly Seminar Series to Highlight OSU SRP Trainees

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A new monthly seminar series will be held on the third Thursday of each month to highlight the research of the trainees.  The presentations begin at 12 noon and will be in the Hallie Ford Center room 115 on the OSU Campus.  Our partners at the Pacific Northwest National Laboratory (PNNL) will participate via video conferencing.   All are welcome to the presentations.

THURSDAY, JAN. 16TH

12-12:30 P.M.

Hallie Ford Center room 115

Printable flyer

Andy Larkin
Andy Larkin

 

Mobile maps, apps, and augmented reality for personalized air quality informatics

Andy Larkin, Ph.D. candidate, SRP Trainee

Dept. of Environmental and Molecular Toxicology

 

 

 

 

Madeen_Erin
Erin Madeen

 

Human in vivo kinetics and dynamics of high molecular weight PAH, dibenzo(def,p) chrysene, utilizing liquid sample accelerator mass spectrometry

Erin Madeen, Ph.D. candidate, SRP Trainee

Dept. of Environmental and Molecular Toxicology

 

 

If you have questions or need special assistance, please contact Naomi Hirsch, 541-737-8105.

New Mercury Education Project in Partnership with EPA and Rural School

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This year the EPA Partners in Technical Assistance Program (PTAP) Pilot has launched the first project with a school located near the Black Butte Mine Superfund Site in rural Cottage Grove, Oregon.

“The overall objective of PTAP is to expand opportunities for cooperation between EPA and colleges, universities or nonprofits with the shared goal of assessing and addressing the unmet technical assistance needs of impacted communities. Through PTAP, colleges, universities, and nonprofit organizations cooperate with EPA and voluntarily commit to assist communities with their unaddressed technical assistance needs. At this time, PTAP is in the pilot phase, working with NIEHS Superfund Research Program grantees as PTAP pilot partners. Following this pilot phase, the intention is to expand this project so that any interested colleges, universities or nonprofits may also join the PTAP.”

OSU Superfund Research Program has begun a partnership with EPA through this Pilot to help them expand upon their community outreach capabilities surrounding the Black Butte site.

On December 18, 2013, we met with Laurie Briggs, the Principal of the London School, because she had a strong desire to give her students and their families’ science and environmental health knowledge. About 100 rural K – 8th grade students go to London school.

Our visit included getting to know one another, listening to the needs of the school, and a school tour. We were impressed with the beauty and organization. The school built and maintains a 1/4-acre organic garden, and has a trail to a river flowing behind the property.  72% of the students qualify for free/reduced lunch, and delicious healthy meals are cooked on site.

For this project, we plan to:

1) Maintain communication through monthly meetings, and share notes and project milestones on our web site. [Our next meeting is January 30th, 2014 at OSU.]

2) Address community and educational needs.

  • Create a hands-on, project-based integrated curriculum related to the science of the Superfund site and mercury contamination that can serve as a model for other rural, small schools.
  • Discuss ways to educate the students and community and expand and build a sustainable partnership.

3) Provide training opportunities for SRP Trainees wanting outreach experience.

4) Help students understand career opportunities in environmental and life sciences.

 

 

Project Team from left Diana Rohlman (OSU SRP CEC), Alanna Conley (EPA, Region 10), Dan Sudakin (OSU SRP RTC), Laura Briggs (London School Principle), Naomi Hirsch (SRP RTC OSU). Not pictured: Corey Fisher (OSU SRP CEC), Melissa Dreyfus (EPA Headquarters Superfund Community Involvement Program), Kira Lynch, (EPA Region 10, Science and Tech Liaison), and Richard Muza (Region 10 - Black Butte Mine, Project Manager)
The Project Team from left Diana Rohlman (OSU SRP CEC), Alanna Conley (EPA, Region 10), Dan Sudakin (OSU SRP RTC), Laura Briggs (London School Principal), Naomi Hirsch (OSU SRP RTC). Not pictured: Corey Fisher and Molly Kile (OSU SRP CEC), Melissa Dreyfus (EPA Headquarters Superfund Community Involvement Program), Kira Lynch, (EPA Region 10, Science and Tech Liaison), and Richard Muza (Region 10 – Black Butte Mine, Project Manager)

 

 

 

 

Zebrafish Publication Receives Editor’s Highlight

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Congratulations to the lab of Dr. Robert Tanguay, Project 3 Leader!
The manuscript, Multidimensional In Vivo Hazard Assessment Using Zebrafish, accepted October 2013 in Toxicological Sciences, has been published in the January 2014 journal (in the Safety Evaluation section) with an Editor’s Highlight.

January 2014 Toxicological Sciences journal
January 2014 Toxicological Sciences journal

The Tanguay group uses the embryonic zebrafish model to demonstrate the utility of high throughput screening for toxicology studies. The group evaluated the 1060 US EPA ToxCast Phase 1 and 2 compounds on 18 distinct outcomes. With four doses for each compound the group generated a dizzying number of data points highlighting the importance of bioinformatics analysis in these types of studies. The study shows how it is now possible to screen many of the tens of thousands of untested chemicals using a whole animal model in which one can literally see developmental malformations. —Gary W. Miller

Abstract

There are tens of thousands of man-made chemicals in the environment; the inherent safety of most of these chemicals is not known. Relevant biological platforms and new computational tools are needed to prioritize testing of chemicals with limited human health hazard information. We describe an experimental design for high-throughput characterization of multidimensional in vivo effects with the power to evaluate trends relating to commonly cited chemical predictors. We evaluated all 1060 unique U.S. EPA ToxCast phase 1 and 2 compounds using the embryonic zebrafish and found that 487 induced significant adverse biological responses. The utilization of 18 simultaneously measured endpoints means that the entire system serves as a robust biological sensor for chemical hazard. The experimental design enabled us to describe global patterns of variation across tested compounds, evaluate the concordance of the available in vitro and in vivo phase 1 data with this study, highlight specific mechanisms/value-added/novel biology related to notochord development, and demonstrate that the developmental zebrafish detects adverse responses that would be missed by less comprehensive testing strategies.

rb_210_img3Learn more about Tanguay’s zebrafish research