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Laboratory of Metabolism
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Research
The Laboratory of Metabolism conducts research in the areas of chemical carcinogenesis, mammalian development and gene control, and cell cycle control.
There are six sections in the laboratory: (1) the Nucleic Acids Section is involved in the study of drug and carcinogen metabolism and the mechanism of action of genotoxic and nongenotoxic carcinogens. Chemical carcinogens are actively metabolized and the extent of this metabolism is believed to be the major determinant in the carcinogens? effects on organisms. They can be either neutralized to nonhazardous derivatives or activated to metabolites that can damage DNA, mutate genes, and sometimes transform cells. The pathways of metabolism and the enzymes involved in rodent model systems and humans are under investigation. Carcinogen metabolizing enzymes and receptors that mediate the biological activity of genotoxic and nongenotoxic carcinogens, respectively, are being studied; (2) the Endocrinology Section is engaged in the regulation of thyroid hormone synthesis and the mechanisms of organogenesis. The thyroid enhancer-binding protein (T/EBP) is involved in organogenesis of the lung, thyroid, pituitary, and hypothalamus, and in tissue-specific gene control. The pathways involved in programmed development are under study; (3) the Chemistry Section examines the mechanisms of cell cycle regulation with emphasis on the polo kinase, a novel enzyme involved in the control of mitosis. Yeast and higher eukaryotic cells are used as model systems; (4) the Protein Section studies the high-mobility group proteins (HMGs) associated with chromatin and their effects on transcription, replication, recombination, and repair. Structural biology, cell biology, and gene knock-out mice are used to examine the function of these abundant nuclear proteins; (5) the Gene Regulation Section investigates the biology of mammalian B?ZIP transcription factors. Probes are designed to inhibit the activity of these proteins and tested using transgenic mouse models and adenoviral delivery systems; (6) the Metabolic Control Section investigates the physical chemistry and activities of P450s. Monoclonal antibodies are being used as probes to investigate the role of P450s in human drug metabolism.
This page was last updated on 6/14/2006.
