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Welcome to Dr. Mitch Lazar's lab website. Our laboratory studies the mechanisms by which nuclear receptors link gene transcription mechanisms to metabolism. The study of thyroid hormone receptors and Rev-erbalpha have led to a series of discoveries related to the mechanism of nuclear receptor-mediated repression. These include the regulation of Rev-erba by heme ligand and lithium destabilization, the composition of core nuclear receptor corepressor-histone deacetylase complexes, the corepressor "CoRNR" nuclear receptor interaction motif, and the activation of histone deacetylase function by corepressor binding. We are particularly interested in the mechanisms by which the the corepressor-deacetylase interaction epigenetically governs metabolism and circadian rhythm. The lab is also studying the linkage of the nuclear receptor PPARgamma to adipocyte differentiation, insulin resistance, and type 2 diabetes on a genome wide scale. In addition we study resistin, which we discovered as a novel adipocyte-specific hormone that impairs insulin action in rodents. We are currently determining the metabolic and inflammatory phenotypes of mouse models with humanized resistin expression and function.
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