Our laboratory studies the biology of adipose tissue, with particular emphasis on the transcriptional pathways that regulate adipocyte differentiation and physiology. We utilize a variety of approaches in vitro and in vivo to identify and characterize novel transcription factors and to place them…
more in the context of their pathways and with the biology they regulate. We have been especially interested in using integrated chromatin state mapping, computational motif finding, and cellular biological approaches to identify such transcription factors. Our recent studies have identified IRF3, IRF4, COUP-TFII, and PLZF as anti-adipogenic factors that were previously unsuspected to play a role in adipocytes. Another area of interest concerns the mechanisms by which adipocytes regulate systemic physiology, particularly insulin sensitivity and nutrient homeostasis. We have been interested in the molecular basis of insulin resistance, and have shown using genomic approaches that reactive oxygen species play an important causal role in the etiopathogenesis of this condition. We are now focusing on epigenetic mechanisms of insulin resistance, using whole genome localization of methylated DNA and histone modifications in insulin resistant and insulin sensitive adipocytes to identify core changes that signify the resistant state. These will, we hope, lead us to a better understanding of the pathways involved in insulin resistance, and ultimately put us on the road to new therapeutic interventions.
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