Perelman School of Medicine at the University of Pennsylvania

Lazar Lab

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Welcome to the Lazar Lab

The Lazar lab studies the transcriptional regulation of metabolism. Metabolic diseases, including diabetes and obesity, have a strong genetic basis, yet their increasing prevalence has been fueled by an environmental replete with fattening diets, insufficient physical activity, and exposure to light around the clock. The goal of the Lazar lab is to understand the homeostatic mechanisms that control physiological metabolism and how these are overcome by harmful environmental factors. The focus is on nuclear receptors and HDAC3-containing corepressor complexes, whose functions are interrogated using a combination of genomic, proteomic, bioinformatic, and metabolic phenotyping methods. Of particular interest is the circadian nuclear receptor Rev-erbα, a key repressive component of the circadian clock that coordinates biological rhythms of metabolism in liver, adipose, and other tissues. Another focus is on nuclear receptor PPARγ, the master regulator of adipocyte differentiation. Ligands for PPARγ have potent antidiabetic activity, and thus PPARγ represents a key transcriptional link between obesity and diabetes. HDAC3 is also of great interest as an integrator of the activities of nuclear receptors and other transcription factors, with tissue-specific functions that protect from challenges to the circadian, nutritional, and thermal environment.