Research

Dr. Charmandari’s research work has focused on the hypothalamic-pituitary-adrenal axis and adrenal disorders. She investigated the pharmacokinetic parameters of cortisol in patients with Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency and demonstrated that alterations in cortisol pharmacokinetics at puberty account for the suboptimal control often observed in pubertal patients. She also showed that patients with the classic form of the disease have epinephrine deficiency, hyperinsulinism, insulin resistance, and hypertension compared with control subjects. These abnormalities predispose patients with CAH to the development of metabolic syndrome-related endothelial dysfunction and atherosclerotic cardiovascular disease in adulthood. Dr. Charmandari’s molecular research studies investigated the mechanisms of glucocorticoid action and in particular the molecular mechanisms underlying the syndrome of Primary Generalized Glucocorticoid Resistance (PGGR). She identified five novel mutations of the human glucocorticoid receptor (hGR) gene in patients with PGGR and determined the molecular mechanisms through which various natural hGR mutants impair glucocorticoid signal transduction. She also investigated the molecular mechanisms underlying the dominant negative effect of the hGRβ upon the hGRa, and showed that hGRβ suppresses the transcriptional activity of hGRa by competing with hGRa for binding to coactivators.