research interests


Dioxin acts by altering the transcription of specific genes; the chemical serves as a prototype for environmental contaminants that elicit responses via receptor-dependent mechanisms. As a model response for studying dioxin action, we analyze the mechanism by which TCDD induces the transcription of the CYP1A1 gene. Cyp1A1 encodes cytochrome P450 1A1, a microsomal enzyme that oxygenates certain lipophilic aromatic hydrocarbons, such as the carcinogen benzo(a)pyrene, during their metabolic processing to water-soluble derivatives. We use mouse hepatoma cells as an experimental system, and our studies employ a variety of biochemical, genetic, and molecular biological techniques to analyze the mechanism of gene transcription and dioxin action. Our experiments have contributed to the elucidation of a novel transcriptional control system, which involves two regulatory bHLH/PAS proteins, a variety of protein-DNA interactions and protein-protein interactions, and alterations in chromatin structure. Our findings have generated new insights into the pathways by which cells respond to environmental stimuli by altering the expression of specific genes.

click on image for area of interest:


[transcriptional control]  [bHLH/PAS proteins]  [protein-DNA interactions]  [chromatin structure]  [protein-protein interactions]  [hypoxia-response genes]

Originally created by Felix W. Frueh
Updated and maintained by Caroline Johnston
Updated 7/99