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.
Our Goals
Understanding the molecular mechanisms underlying circadian and metabolic physiology, and how these contribute to homeostasis yet may be overcome by harmful environmental factors, leading to metabolic diseases.
Our Focus
- Nuclear receptor REV-ERBα, a key repressive component of the circadian clock that coordinates biological rhythms of metabolism in liver, adipose, and other tissues.
- Nuclear receptor PPARγ, the master regulator of adipocyte biology, whose ligands have potent antidiabetic activity, a key transcriptional link between obesity and diabetes.
- Thyroid hormone receptors, mediating the powerful metabolic effects of thyroid hormones, controlling energy metabolism
- Nuclear receptor corepressors and histone deacetylase 3 (HDAC3), functioning as a multiprotein integrator of the function of nuclear receptors and other transcription factors, with tissue-specific functions that protect from challenges to the circadian, nutritional, and thermal environment.
- Transcriptional regulation of circadian rhythms and metabolism, focused on the specific factors above as well as unbiased discovery of critical additional factors and pathways.
Our Approach
The Lazar lab has pioneered a systems approach to physiology that combines state-of-the-art in vivo “omics” with genetic and environmental manipulations and detailed metabolic phenotyping. This approach has had a major impact on our current understanding of the pathophysiology of obesity and diabetes, leading to new concepts linking the epigenome to metabolism and stimulating novel translational approaches for the treatment and prevention of metabolic diseases.