Research

Current research is focused on mammalian developmental toxicology and attempts to elucidate biochemical mechanisms of teratogenesis. Particular emphasis is placed on investigations of how alterations in intracellular glutathione redox status produced by exposure to teratogenic chemicals misreguate transcription factor function and growth factor activity to produce dysmorphogenesis. Rodent and rabbit whole embryo culture systems and cell cultures are used for evaluation of the mechanisms of important embryotoxins/teratogens such as thalidomide, ethanol and PCBs.

Projects

Involvement of Glutathione and Thioredoxin in Mechanisms of Retinoic and Thalidomide Induced Toxicity in Cultured Rat Cranial Neural Crest Cells.

Redox Misregulation of NF-kB Activity in the Developing Rat Limb: A Mechanism for Thalidomide-Induced Limb Reduction Defects.

Redox Signaling in Organogensis-Stage Rodent Conceptuses

This project first seeks to characterize the different redox environments that are established and maintained within the intact rat and mouse conceptus (embryo proper and associated extraembryonic membranes). Concentrations, redox potentials, and flux for redox couples that make up the major redox circuits such as glutathione (GSH)/glutathione disulfide (GSSG), cysteine (cys)/cystine (cySS), and thioredoxin-reduced (TrxRED)/thioredoxin-oxidized (TrxOX) are being determined for each of the major tissues and fluid compartments of the conceptus. Exposure to redox-sensitive chemicals will allow us to determine the spatial and temporal extent to which different redox circuits are modified, thus leading to the identification of sensitive tissues and organs in the developing embryo.

The second phase of this project seeks to identify and characterize the specific proteins and pathways sensitive to redox regulation during development. These studies will utilize proteomic methods to isolate and identify critical molecules affected by exposure and environmental insult.

Thalidomide Induced Peripheral Neuropathy: Mechanistic Insights from Cultured Dorsal Root Ganglia.