Dr. Herman is an Associate Professor in the Endocrinology, Metabolism, and Nutrition Division at Duke University and a Faculty in the Duke Molecular Physiology Institute. He maintains an active general clinical endocrinology practice and teaches principles of endocrinology and metabolism to medical students, residents, and endocrine fellows. The Herman laboratory uses a multidisciplinary, systems approach to understand 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. This approach includes investigating how cells in key metabolic tissues like liver and intestine sense nutrients and how these diverse signals are integrated with hormonal cues into coherent genomic and metabolic responses. By delineating control mechanisms regulating key metabolic gene expression programs, we seek to gain insight into both normal and pathophysiological states contributing to cardiometabolic disease. Much of our current work focuses on a key carbohydrate sensing transcription factor, carbohydrate-responsive element binding protein (ChREBP) which coordinates genomic responses to glucose and fructose consumption and regulates systemic glucose and lipid homeostasis. This work includes discovery of distinct ChREBP isoforms which appear to mediate distinct aspects of these biological responses. Ongoing studies are focused on defining which of ChREBP’s transcriptional targets are critical for ChREBP’s pleiotropic metabolic effects. We have successfully translated molecular insights gleaned from our studies in model organisms to human clinical research by showing that activation of ChREBP transactivates the metabolic hormone FGF21 and increases circulating levels of this hormone in humans. Ongoing studies include identification of novel nutrient-induced hepatokines. We anticipate these studies will enhance our understanding of the pathways involved in metabolic disease and ultimately lead to new diagnostic and therapeutic strategies.
Mark A. Herman, MD