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Duke University

Superfund Research Program

Duke University Superfund Research Center - Developmental Exposures: Mechanisms, Outcomes and Remediation

Center Director: Richard T. Di Giulio
Co-Investigator: Heather M. Stapleton
Grant Number: P42ES010356
Funding Period: 2000-2022
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Summary (2017-2022)

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 Program (SRP) Center 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 Duke SRP Center helps inform risk assessments on these hazardous chemicals and test the feasibility of novel remediation strategies.

Research conducted within the Duke SRP Center 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 their center is "Developmental Exposures: Mechanisms, Consequences and Remediation." The researchers remain committed to investigating the vulnerability of the developing organism to hazardous chemical exposures. Within the Duke SRP Center, the researchers emphasize research on both Agency for Toxic Substances and Disease Registry 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 affect development. Mechanisms of action that are central to the mission and research conducted within the Duke SRP Center 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 Duke SRP Center projects is effects on neurobehavioral and neurodevelopmental outcomes from these exposures. 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 Duke SRP Center is well poised to support these endeavors. The interdisciplinary team of biomedical/environmental scientists and engineers provide the Duke SRP Center 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 Duke SRP Center directly addresses the program mandates by investigating health effects, risks, and remediation of hazardous substances in an interdisciplinary fashion. In addition to responding to SRP mandates, Duke SRP Center research, research translation, and community engagement activities are also highly relevant to numerous stakeholders, including the Environmental Protection Agency.