Superfund Research Program
Molecular Mechanisms and Models for Exposure
Center Director: Robert H. Tukey
Grant Number: P42ES010337
Funding Period: 2000-2022
The Superfund Basic Research Program at the University of California-San Diego began in 2000. The central goal of the program is to implement modern scientific approaches to identify and characterize genomic stress responses elicited by waterborne pollutants found at Superfund sites. The program is comprised of nine research projects (seven biomedical, two non-biomedical), and three research support cores (DNA microarray technology, macromolecular analysis, and mouse genetics and phenotyping). Administrative, outreach and training cores are also included.
The central hypothesis of this program is that analysis of patterns of gene expression in vivo and in vitro will identify additional biomarkers of environmental injury and lead to more accurate mechanistic endpoints that can be used for risk assessment and remediation decisions. By developing innovative methodologies to identify biological responses that are caused by exposure to environmental contaminants and by defining the exposure pathway, this program will have the tools to assess mechanisms of toxicity mediated through cell signaling and gene expression. The basic research component is focusing on the role of Superfund chemicals on signal transduction, the identification of target genes regulated by these chemicals and the development of models for bioremediation and detection. Three projects investigate mechanisms of oxidative stress, signal transduction, and transcriptional regulation. Molecular approaches to study expression and regulation of Phase I and II drug metabolism are the focus of two projects, and one project studies the mechanistic and molecular actions attributed to cholinesterase inhibition by organophosphates. The final biomedical project is investigating endocrine disruptors in the environment and their influence on gene expression. The two non-biomedical projects are integrated along the same themes that were developed in the biomedical projects. The first project examines how plants are protected from metal toxicity, and the signal transduction pathways activating these responses, as well as creating transgenic plants and lower organisms that can be used for highly cost-effective bioremediation of metals. The second non-biomedical project examines the transformation of metals by bacteria to understand the mechanisms involved in the natural attenuation of metal pollution and develop new bioremediation strategies.