Interests: Developmental toxicology. Risk assessment methodologies. Molecular mechanisms of metals and pesticides. Biological monitoring. Birth defects. Children's health. Drug metabolism. Food additives and contaminants. In vitro toxicology. Nanotechnology. Pediatric environmental health. Pesticides and children. Reproductive toxicology. Risk communication and management. Toxicogenomics.
Neurodevelopmental toxicity of metals and pesticides. Identifying biochemical mechanisms of developmental toxicity and developing new methods for the evaluation of health risks posed by environmental agents. Major research efforts in the laboratory are currently directed toward metals, primarily methylmercury, arsenic, cadmium, pesticides, such as organophosphates, benomyl and N-Nitroso compounds, and other known carcinogens, mutagens and teratogens. In vitro experiments are performed using primary rat embryo cell cultures for CNS and limb tissues and embryonal carcinoma cells to investigate mechanisms of developmental toxicity of these agents. Embryonal fibroblasts are also isolated from transgenic animals and used to evaluate the role of specific gene pathways in toxicant induced developmental effects. Dr. Faustman's efforts in risk assessment include an effort to combine results derived from laboratory experiments to develop mechanistically based toxicokinetic and toxicodynamic models of developmental toxicity. Additionally, Dr. Faustman is involved in the development of new methods applicable to both cancer and non-cancer risk assessment. Currently, techniques are being developed to enhance our understanding of the cellular and molecular factors involved in normal and toxicant-perturbed neurodevelopment.
Gene expression analyses as early biomarkers of effect. The development of markers of toxicant effect that can be used to identify early adverse health risks from exposure to environmental agents is the focus of this effort. By detecting subtle, pre-clinical changes in health prior to the appearance of clinical symptoms, it may be possible to develop intervention strategies that can lead to a reduction in morbidity. One project involves the use of uroepithelial cells from individuals exposed to heat stress or heavy metals to look for molecular changes in stress response genes. Other projects examine sensitive developmental endpoints to understand early indicators of toxicant impacts following in utero exposure.
Mechanisms of methylmercury-induced developmental toxicity. Methylmercury is a known human developmental neurotoxicant. Current efforts to elucidate the mechanisms of toxicity of this agent include evaluation of the effects of methylmercury on the dynamics of cell cycling, alterations in mitochondrial function, stress activation, proteasomal perturbation and apoptosis in the primary rat embryonic CNS cells. Mechanistic experiments are underway to determine how gene changes observed in the methylmercury exposed cells are related to these cellular processes. Experimental procedures utilizing both microarray and 2D-PAGE/MS analyses will further our understanding of such processes.
Developmental neurotoxicity of metals: mechanisms of altered cell proliferation. Current efforts are focused on the possible role of altered mRNA and protein degradation in the observed alterations of cell cycle regulatory molecules by metals. Experimental procedures utilizing both microarray and 2D-PAGE/MS analyses will further our understanding of such processes. Such research will provide a basis for evaluating the effects of metals as developmental neurotoxicants and will provide a molecular basis for observed toxicity of metals on the developing nervous system.
Development of improved risk assessment methodologies. The goal of this project is to improve how we incorporate new scientific data and information into human health risk assessments. We have developed biologically based dose response (BBDR) models that show how to link basic mechanistic data from molecular and cellular toxicity studies with toxicological outcomes. Because of the tremendous resources that are committed to environmental control and remediation based on risk models, it is important to determine the level of uncertainty in these models. Several projects are currently underway to address these issues, including quantitative uncertainty analyses in exposure modeling, value-of-information analyses of improved biomarker information in risk assessments and decision analysis to optimize worker protection by selecting from alternative medical monitoring strategies.
Analysis of data from gene chip microarrays. Gene chip microarrays are a new technology that can be used to inexpensively assay the expression of thousands of genes simultaneously.This provides a new opportunity for constructing assays that may more precisely describe human response and health effects from exposures to environmental pollutants. This project explores how methods from environmental health, bioinformatics, statistics and computer science can be used to help investigators understand and sort through the information.
Pesticide exposure and toxicity in children. The Center for Child Environmental Health Risks Research is another major research effort. Researchers are working to understand the biochemical, molecular and exposure mechanisms that define children's susceptibility to pesticides. In addition, researchers are working to assess pesticide risks to normal development and learning.
Kinetics. What are the age- and pesticide-specific factors that must be considered in developing kinetic models for children of different ages exposed to different levels of chlorpyrifos, arsenic and azinphos methyl? How can we examine our current pesticide models to identify which parameters are most important in predicting pesticide blood levels following exposure? This project entails studying the mathematical sensitivity analysis and Monte Carlo techniques, and then the incorporation of these techniques into an existing pesticide exposure model.
Dynamics. Organophosphate pesticides such as chlorpyrifos are widely used in both agriculture and the home. The aim of the current project is to expand our knowledge of how this compound and its metabolites affect cellular differentiation events, focusing on cell cycle progression and apoptosis.
Modeling. This project is an analysis of cell cycle models and an examination of acetylcholinesterase inhibition data in order to generate dynamic models that simulate toxicity following pesticide exposure.
Improving risk management and regulation. The focus of this research is to examine and improve existing environmental, health and safety regulations at the federal, state and local levels by providing frameworks for incorporation of new technologies and application of new science.
Toxin exposure and seafood. Consumption of contaminated fish is a major route of exposure to biotoxins, including domoic acid, which is associated with neurobehavioral deficits. Our research has focused on analytical needs for testing of fish to assess potential health risks for all consumers. We are also looking at the human dietary and behavioral factors that influence susceptibility to domoic exposure and health risk.
The Fast Environmental Regulatory Evaluation Tool (FERET) is designed as a computerized benefit-cost template that has been developed from US EPA air pollution models to assess the potential health and economic benefits from reducing air pollution. Benefit-cost analysis is being used at the federal and state level to evaluate new regulations and regulatory alternatives. Future work will expand the current module dealing with air pollution issues to ground and surface water regulatory issues and to focus on children's health issues.
Comparative risk. A quantitative method for risk-benefit analysis that allows for consideration of diverse health endpoints is being developed to evaluate the health benefits associated with modifying environmental exposures.
Translational research converts environmental health science findings into tools that can be applied by health care providers, regulators and community residents to improve public health outcomes. This project will develop an integrated framework that identifies what we know about pesticide risks and children's health and how this information can be used to inform public health and policy to improve children's health.
Data integration and informatics. Coordinated efforts between oceanographic, public and environmental health research communities are needed to assess the risks to human health generated by the oceans. An Informatics Facility Core has been established to overcome the barriers involved in sharing, interpreting, translating, documenting and archiving data and information in an interdisciplinary and true collaborative research setting.
Health, oceans and urban land use. This project is developing an integrated spatial framework to quantify and assess the relationships between urban development, environmental stressors (pollution, pathogens), human exposure and associated effects on marine ecosystems and human health.