Sharon L Wardlaw, MD

The Neuroendocrine Program encompasses basic and clinical research and provides specialized care to patients with hypothalamic and pituitary disorders. Dr. Wardlaw has done clinical neuroendocrine research for over 25 years ranging from studies of normal pituitary physiology to the diagnosis and treatment of pituitary diseases, including prolactinomas, acromegaly, Cushing's disease and lymphocytic hypophysitis. A major clinical and basic research interest has been in the stress response and the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and of the ACTH precursor, proopiomelanocortin (POMC). An important research focus has been the regulation of POMC gene expression and peptide processing in the hypothalamus and on the physiology of the brain POMC-derived peptides, β-endorphin and α-MSH. Dr. Wardlaw was the first to show that POMC is regulated in hypothalamus by sex steroids in rodents and primates and that this is important in regulating the pituitary-gonadal axis. She has also demonstrated that POMC is regulated in the hypothalamus by glucocorticoids, opioids, dopamine and leptin. More recently Dr. Wardlaw has focused her basic research on the neuroendocrinology of obesity. Studies have centered on understanding how the brain senses levels of peripheral energy stores and integrates these signals to maintain energy balance. An exciting focus has been on the hypothalamic melanocortin system, which plays a critical role in maintaining energy balance in humans and animals. Dr. Wardlaw has shown in rodents, using pharmacological and transgenic models, that activation of the melanocortin system reduces body weight and adiposity and improves glucose metabolism, particularly in the setting of diet-induced obesity. These results suggest that long-term melanocortinergic activation could serve as a potential strategy for the treatment of obesity and its deleterious metabolic consequences. She has also shown that the melanocortin system plays an important role in modulating cytokine and neuroendocrine responses to inflammation in both rodent and primate models. Ongoing studies are characterizing the mechanisms by which the melanocortin system modulates energy expenditure, fuel oxidation and glucose metabolism in rodent models and are examining potential ways to safely activate this system for therapeutic benefit in the human. Dr. Wardlaw has helped to develop a clinical obesity research program to facilitate the translation of these animal studies to human obesity. Ongoing clinical studies are developing biomarkers to assess brain melanocortin activity in humans. Related clinical research focuses on understanding and reversing the neuroendocrine responses induced by weight loss in order to help maintain weight loss after dieting.