Research conducted within the Duke University?s Superfund Research Center (DUSRC) focuses on a central research question: How does early life exposure to hazardous substances elicit developmental toxicity, and what are the later-life consequences? As such the theme of our center is ?Developmental Exposures: Mechanisms, Consequences and Remediation?, and we remain committed to investigating the vulnerability of the developing organism to hazardous chemical exposures. Within the DUSRC we emphasize research on both ATSDR priority chemicals (e.g. PAHs, metals, organophosphate chemicals) and emerging chemicals of concern (e.g. halogenated flame retardants) that are known to, or have potential to, adversely effect development. Mechanisms of action that are central to the mission and research conducted within the DUSRC include mechanisms underlying molecular and physiological effects from developmental exposures, mechanisms underlying ameliorations of and adaptations to these effects, and mechanisms and approaches to engineering solutions for the ultimate removal of these chemicals from the environment. A unifying theme across the DUSRC projects is effects on neurobehavioral and neurodevelopmental outcomes from these exposures. DUSRC researchers are conducting research using in vitro (e.g. cell culture) and in vivo (e.g. zebrafish, rats) models to determine effects of these hazardous chemicals on neurodevelopmental across projects, but several individual projects are also exploring effects on skeletal and fat development, cardiovascular development and bioenergetics. Of key interest is the ability of some contaminants to converge on similar phenotypes through multiple mechanisms of action. With the heightened interest in developing Adverse Outcome Pathways (AOPs) within regulatory agencies, the DUSRC is well poised to support these endeavors. Our interdisciplinary team of biomedical/environmental scientists and engineers provide the DUSRC with a unique opportunity to address and examine ?holistic? consequences of developmental exposures. This integration is central to evaluating the true risk from exposure to hazardous substances. The DUSRC directly addresses the program mandates by investigating health effects and risks and remediation of hazardous substances in an interdisciplinary fashion. In addition to responding to SRP mandates, the DUSRC?s research, research translation, and community engagement activities are also highly relevant to numerous stakeholders, including the Environmental Protection Agency.

Public Health Relevance

Early life exposure to hazardous chemicals can predispose individuals to adverse health outcomes that may manifest later in life (e.g. effects on brain development that lead to altered behavior later in life). The Duke University Superfund Research Center (DUSRC) conducts research to characterize the extent of these later life outcomes following exposure to polycyclic aromatic hydrocarbons (PAHs), organophosphate pesticides and flame retardants, halogenated phenolic compounds, and some metals. Cell-based and whole organism approaches are used in a complimentary fashion to conduct both high throughput and realistic exposure scenarios and provide insight into adverse outcome pathways that link initiating mechanisms with health outcomes. Research generated by the DUSRC will help inform risk assessments on these hazardous chemicals and test the feasibility of novel remediation strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010356-17
Application #
9671877
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Henry, Heather F
Project Start
2000-06-01
Project End
2022-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
17
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Earth Sciences/Resources
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Oliveri, Anthony N; Ortiz, Erica; Levin, Edward D (2018) Developmental exposure to an organophosphate flame retardant alters later behavioral responses to dopamine antagonism in zebrafish larvae. Neurotoxicol Teratol 67:25-30
Slotkin, Theodore A; Skavicus, Samantha; Seidler, Frederic J (2018) Developmental neurotoxicity resulting from pharmacotherapy of preterm labor, modeled in vitro: Terbutaline and dexamethasone, separately and together. Toxicology 400-401:57-64
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Rock, Kylie D; Horman, Brian; Phillips, Allison L et al. (2018) EDC IMPACT: Molecular effects of developmental FM 550 exposure in Wistar rat placenta and fetal forebrain. Endocr Connect 7:305-324

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