The goal of this work is to understand the genetic and molecular mechanisms leading to disorders that affect the adrenal cortex, with emphasis on those that are developmental, hereditary and 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 other defects, other 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. CNC is a MEN syndrome affecting the pituitary, adrenal cortex, thyroid, and the gonads, and is associated with a variety of other tumors, including myxomas and schwannomas, and skin pigmentation defects (lentigines, cafe-au-lait spots, and nevi). We have identified the regulatory subunit type 1-A of protein kinase A (PKA), which is coded by the PRKAR1A gene as the gene responsible for most CNC patients. Thus, a significant part of our work is now focused on PKA-stimulated signaling pathways, PKA effects on tumor suppression and/or development, the cell cycle and chromosomal stability. Prkar1a-specific animal models have also been created to address the tumor-promoting effects of this gene and serve as models for possible therapies. In addition, genes that are mutated in patients with CNC-like and other froms of inherited adrenal tumors are being investigated. Most recently, mutations in PRKACA, PRKACB and ARMC5, as well as in phosphodiesterase genes - phosphodiesterase 11A (PDE11A) and PDE8B - were identified in patients with various forms of bilateral adrenocortical hyperplasias. We also identified GPR101 defects and described X-linked acrogigantism (X-LAG) in patients with growth hormone-producing lesions of the pituitary gland. Mouse models with the respective genetic defects are also being studied, and mutations of these genes are being sought in other endocrine tumors. We have also elucidated the causative genetic defects in Carney-Stratakis syndrome (CSS) and we continue our search for genes that are related to tumors that develop in association with CSS and a similar condition (Carney Triad).
| Espiard, Stéphanie; Knape, Matthias J; Bathon, Kerstin et al. (2018) Activating PRKACB somatic mutation in cortisol-producing adenomas. JCI Insight 3: |
| Hodes, Aaron; Meyer, Jerrold; Lodish, Maya B et al. (2018) Mini-review of hair cortisol concentration for evaluation of Cushing syndrome. Expert Rev Endocrinol Metab 13:225-231 |
| Tirosh, Amit; Auerbach, Adi; Bonella, Belen et al. (2018) Failure to Thrive in the Context of Carney Complex. Horm Res Paediatr 89:38-46 |
| Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Stratakis, Constantine A (2018) Interaction of AIP with protein kinase A (cAMP-dependent protein kinase). Hum Mol Genet : |
| Rushworth, R Louise; Torpy, David J; Stratakis, Constantine A et al. (2018) Adrenal Crises in Children: Perspectives and Research Directions. Horm Res Paediatr 89:341-351 |
| Ugolini, Maddalena; Keil, Margaret F; Paradiso, Enrica et al. (2018) Anxiety-like behavior and other consequences of early life stress in mice with increased protein kinase A activity. Behav Brain Res 348:22-30 |
| Saldarriaga, Carolina; Lyssikatos, Charlampos; Belyavskaya, Elena et al. (2018) Postoperative Diabetes Insipidus and Hyponatremia in Children after Transsphenoidal Surgery for Adrenocorticotropin Hormone and Growth Hormone Secreting Adenomas. J Pediatr 195:169-174.e1 |
| Tirosh, Amit; Valdés, Nuria; Stratakis, Constantine A (2018) Genetics of micronodular adrenal hyperplasia and Carney complex. Presse Med 47:e127-e137 |
| Makri, Angeliki; Bonella, Maria Belen; Keil, Margaret F et al. (2018) Children with MEN1 gene mutations may present first (and at a young age) with Cushing disease. Clin Endocrinol (Oxf) 89:437-443 |
| Rossi, Á D; Faucz, F R; Melo, A et al. (2018) Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil. J Intern Med : |
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