Interests: Glutathione metabolism. Analytical cytology. In vitro toxicology. Transgenic models. Toxicology of reactive oxygen/nitrogen species. Toxicogenomics. Nanotoxicology. Systems and developmental toxicology. Air pollution. Bioactivation/carcinogenesis. Biomarkers. Cardiovascular disease. Genetic susceptibility to toxicants. Immunotoxicology. Liver, renal and respiratory toxicology. Risk assessment. Toxicology and aging. Xenobiotic metabolism.
Projects
Using transgenic mouse models of altered glutathione (GSH) synthesis to investigate the effects of altered GSH synthesis on susceptibility to various exposures, including air pollutants, engineered nanomaterials and various drugs and environmental chemicals. GSH is an important endogenous antioxidant that has roles in free radical scavenging, protecting against reactive oxygen/nitrogen species and in the metabolism/excretion of xenobiotics. We are conducting studies to determine the effects of genetically altered GSH synthesis on cellular susceptibility to toxicant-induced DNA, protein and lipid damage, cell signaling and apoptosis. We are also interested in the factors that regulate the expression of GSH-related genes in humans, rodents and other species.
Defining which physical and chemical characteristics of engineered nanomaterials (ENMs) predispose to toxicity and adverse health outcomes. We are participants in the NIEHS Centers for Nanotechnology Health Implications Research Consortium, together with Drs. Elaine Faustman and Michael Yost (DEOHS); William Altemeier (Pulmonary Medicine and UW Center for Lung Biology); Edward Kelly (Pharmaceutics), Xiaohu Gao (Bioengineering); and François Baneyx (Chemical Engineering and UW Center for Nanotechnology). This program is using in vitro toxicology, organotypic microphysiological systems, in vivo toxicology (including systems toxicology/mouse genetics) and risk assessment approaches to investigate the adverse effects of ENMs with the goals of elucidating the mechanisms by which they cause toxicity and inflammation, and using this mechanistic information to facilitate the design of safer ENMs.