Mark Herman, MD

The Role of Hepatic Nutrient Sensing Mechanisms in Diabetes and Cardiometabolic Disease

My laboratory seeks to understand the molecular mechanisms underlying the metabolic syndrome, a constellation of pathologies including obesity; insulin resistance; impaired glucose metabolism; non-alcoholic fatty liver disease; and dyslipidemia, which predispose to the development of diabetes and cardiovascular disease. To approach this complex problem, we investigate the molecular mechanisms by which cells in key metabolic tissues, particularly the liver, sense and respond to nutrients and hormonal signals. By understanding how cells integrate these diverse signals into coherent metabolic programs, we hope to delineate the mechanisms by which fuel homeostasis is regulated and how these processes go awry in disease states. To this end, we have recently discovered a novel, potent isoform of a carbohydrate sensing transcription factor, carbohydrate-responsive element binding protein beta (ChREBP-beta), which is a critical regulator of glycolytic and de novo lipogenic gene programs and regulates glucose homeostasis. Using a combination of genetic mouse models and cellular models coupled with clinical translational studies in human subjects, we are determining ChREBP-beta’s role in diverse features of the metabolic syndrome. Ultimately, through improved understanding of the regulation of basic metabolic processes, we hope to lay the groundwork for new approaches to prevent and treat metabolic disease.

References.

1. Herman MA, Peroni OD, Villoria J, et al. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature 2012; 484(7394):333–8. PMCID: PMC3341994.

 

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