Section on Endocrinology and Genetics
Constantine Stratakis, Section Head
We focus on understanding the genetic and molecular mechanisms leading to disorders that affect the adrenal cortex, with emphasis on developmental and hereditary disorders and those associated with adrenal hypoplasia or hyperplasia, multiple tumors, and abnormalities in other endocrine glands (especially the pituitary gland and, to a lesser extent, the thyroid gland). We have studied congenital adrenal hypoplasia caused by triple A syndrome and multiple endocrine deficiencies; familial hyperaldosteronism, adrenocortical and thyroid cancer, pituitary tumors, and multiple endocrine neoplasia (MEN) syndromes affecting the pituitary, thyroid, and adrenal glands; and Carney complex (CNC), an autosomal dominant disease. The regulatory subunit type 1-α (Riα) of protein kinase A (PKA), which is encoded by the PRKAR1A gene, is mutated in most CNC patients; we found phosphodiesterase-11A (PDE11A) mutations in patients with isolated adrenal hyperplasia and Cushing syndrome. We devote a significant part of our work to cyclic AMP/PKA-stimulated signaling pathways, PKA effects on tumor suppression and/or development, the cell cycle, and chromosomal stability. These projects are facilitated by prkar1a and pde11a gene mouse models in which we have knocked out the respective genes. We continue to conduct genome-wide searches for other genes responsible for CNC and related diseases of the adrenal and pituitary glands.