Grantee Research Project Results
2016 Progress Report: Toxicogenomics-based Mechanistic Multimedia Exposure Assessment and Child Development
EPA Grant Number: R836155C002Subproject: this is subproject number 002 , established and managed by the Center Director under grant R836155
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Center Director: Alshawabkeh, Akram
Title: Toxicogenomics-based Mechanistic Multimedia Exposure Assessment and Child Development
Investigators: Gu, April Z , MacIntosh, Helen Suh , Manjourides, Justin
Current Investigators: Gu, April Z , Vulpe, Christopher D. , MacIntosh, Helen Suh , Weisman, David , Manjourides, Justin , Fasullo, Michael
Institution: Northeastern University
Current Institution: Northeastern University , The State University of New York Polytechnic Institute , University of California - Berkeley , University of Massachusetts - Boston
EPA Project Officer: Hahn, Intaek
Project Period: September 1, 2015 through August 31, 2019 (Extended to August 31, 2021)
Project Period Covered by this Report: November 1, 2015 through June 1,2016
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text | Recipients Lists
Research Category: Human Health , Children's Health
Objective:
Project 2 will employ novel in vitro, high throughput screening (HTS) assays to yield new toxicity information needed to reveal the impacts of exposure to complex pollutant mixtures on pathways relevant to neonatal and early childhood development. Significant challenges remain in understanding the complex risks that pollutant mixtures and their metabolites pose for human health. These challenges motivate a new paradigm for toxicity evaluation that is based on an in vitro mechanistic and genetic pathway-based approach that allows combinations of exposures and outcomes to be tested comprehensively yet feasibly. To address this need, we have developed an approach that uses in vitro HTS to measure translational changes in targeted genetic pathways occurring in response to pollutants and pollutant mixtures. Importantly, these pollutants and mixtures are drawn directly from environmental sources, such as water and air, and also from biological matrices like urine. They are then passed through in vitro preparations of human and non-human cells, where we measure biomarkers of oxidative stress, DNA damage and inflammation. These pathways and biomarkers were selected based on their established association with CRECE-relevant neonatal and early childhood health outcomes and because the biomarkers are found at measurable concentrations in the urine and sera of exposed individuals. Through this approach, we are able to provide pathway- and sample-specific fingerprints of pollutant exposures and their effects that can inform environmental epidemiological studies and even be used themselves as biomarkers of exposure in these studies.
Through close collaboration with CRECE’s other two projects, this project will inform epidemiological studies of our cohort of 600 Puerto Rican children. These studies leverage data and infrastructure established under PROTECT, a highly productive National Institute of Environmental Health Sciences (NIEHS)-funded pregnancy study of a cohort of 1,800 pregnant women from Puerto Rico’s northern coast. This project will provide its HTS findings and exposure biomarker measures to Projects 1 and 3, thus allowing those projects to perform health effect analyses for pollutant mixtures identified as toxic by the HTS, and to examine the association of exposure biomarkers with neonatal and early childhood health outcomes.
Progress Summary:
For year 2015-2016, we have focused on establishing the infrastructure and techniques required for implementing the CRECE project, including identifying sampling locations for well and ground waters, setting up a new clinic and recruiting participants, optimizing water and urine sample extraction pre-treatment methods, training related personnel for experimental and data analysis skills and obtaining IRB approval for all necessary sample subjects. The accomplished activities and results are summarized as following:
Aim 1. Toxicity of Pollutant Mixtures in Puerto Rican Drinking Water. We have evaluated and compared two different water sample extraction pre-treatment techniques for their recovery rate and reproducibility. The two techniques include a conventional solid phase extraction (SPE) method that has been widely used for environmental samples, and a tea-bag equilibrium extraction method newly developed by Dr. Roger Giese’s lab at Northeastern University. The preliminary results showed much improved recovery rate and reproducibility with the tea-bag method, which will be adopted by this study. We have conducted initial testing with tap water samples to refine assays and protocols, and quantify the robustness, reproducibility and sensitivity for tap water samples analysis.
Aim 2. Toxicity of Puerto Rican Air Pollutant Mixtures. The PR team is working with Project 1 to select and establish air-monitoring stations. We are conducting preliminary evaluation of air sample extraction methods for organic pollutants mixtures as well as for metals. The sample-specific impacts of PM2.5 components will be assessed using HTS assays for oxidative stress, DNA damage, and inflammation, with results reported as quantitative pathway- and chemical-specific biomarker measures and toxicity fingerprints.
Aim 3. Toxicity of Chemicals and Metabolites Found in Urine. We have evaluated two urine sample extraction pre-treatment techniques comparing their recovery rate and reproducibility. The two techniques include a conventional solid phase extraction (SPE) method, and another newly developed tea-bag equilibrium extraction method by Dr. Roger Giese’s lab at Northeastern University. The preliminary results showed much improved recovery rate and reproducibility with the tea-bag method, which will be adopted by this study.
Future Activities:
The overall goal of next reporting period is to obtain and finish the experimental and data analysis of up to 20 each of the water, urine and air samples from PR sites as described in the goals. We also will collaborate with Co-PIs and consultants with bioinformatics expertise to establish the initial framework and platform for data collection, storage, and exploration of up to two different data correlation and clustering analyses. Prior to the field sample mixture toxicity analysis, experimental protocols for sampling, sample pre-treatment, and pollutants extraction will be further refined and optimized to ensure the reproducibility, robustness and reliability of the techniques and resulted data.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
Other subproject views: | All 11 publications | 1 publications in selected types | All 1 journal articles |
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Other center views: | All 68 publications | 47 publications in selected types | All 47 journal articles |
Type | Citation | ||
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Lan J, Gou N, Rahman SM, Gao C, He M, Gu AZ. A quantitative toxicogenomics assay for high-throughput and mechanistic genotoxicity assessment and screening of environmental pollutants. Environmental Science & Technology 2016;50(6):3202-3214. |
R836155 (2020) R836155C002 (2016) |
Exit Exit Exit |
Supplemental Keywords:
toxicogenomics, environmental exposure, biomarkers, pathway-specific effectsRelevant Websites:
Environmental Biotechnology Laboratory Exit
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R836155 Center for Research on Early Childhood Exposure and Development in Puerto Rico Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836155C001 Air Pollution Impacts on Neonatal and Early Childhood Development
R836155C002 Toxicogenomics-based Mechanistic Multimedia Exposure Assessment and Child Development
R836155C003 Biomarker Epidemiology of In Utero Environmental Exposures and Child Development
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
1 journal articles for this subproject
Main Center: R836155
68 publications for this center
47 journal articles for this center