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 a phosphodiesterase gene - phosphodiesterase 11A (PDE11A), were identified in patients with bilateral adrenocortical hyperplasia. A mouse model of PDE11A deficiency is being studied, and mutations of this gene are being sought in other endocrine tumors.
| Hodes, Aaron; Lodish, Maya B; Tirosh, Amit et al. (2017) Hair cortisol in the evaluation of Cushing syndrome. Endocrine 56:164-174 |
| London, Edra; Nesterova, Maria; Stratakis, Constantine A (2017) Acute vs chronic exposure to high fat diet leads to distinct regulation of PKA. J Mol Endocrinol 59:1-12 |
| Tirosh, Amit; Hannah-Shmouni, Fady; Lyssikatos, Charalampos et al. (2017) Obesity and the diagnostic accuracy for primary aldosteronism. J Clin Hypertens (Greenwich) 19:790-797 |
| Keil, Margaret F; Briassoulis, George; Stratakis, Constantine A et al. (2016) Protein Kinase A and Anxiety-Related Behaviors: A Mini-Review. Front Endocrinol (Lausanne) 7:83 |
| Keil, Margaret F; Zametkin, Alan; Ryder, Celia et al. (2016) Cases of Psychiatric Morbidity in Pediatric Patients After Remission of Cushing Syndrome. Pediatrics 137: |
| Briassoulis, George; Keil, Margaret F; Naved, Bilal et al. (2016) Studies of mice with cyclic AMP-dependent protein kinase (PKA) defects reveal the critical role of PKA's catalytic subunits in anxiety. Behav Brain Res 307:1-10 |
| Correa, Ricardo; Zilbermint, Mihail; Berthon, Annabel et al. (2015) The ARMC5 gene shows extensive genetic variance in primary macronodular adrenocortical hyperplasia. Eur J Endocrinol 173:435-40 |
| de Alexandre, Rodrigo B; Horvath, Anelia D; Szarek, Eva et al. (2015) Phosphodiesterase sequence variants may predispose to prostate cancer. Endocr Relat Cancer 22:519-30 |
| Lai, Jin-Ping; Lee, Chyi-Chia; Crocker, Melissa et al. (2015) Isolated Large Cell Calcifying Sertoli Cell Tumor in a Young Boy, not Associated with Peutz-Jeghers Syndrome or Carney Complex. Ann Clin Lab Res 3:2 |
| Zilbermint, Mihail; Stratakis, Constantine A (2015) Protein kinase A defects and cortisol-producing adrenal tumors. Curr Opin Endocrinol Diabetes Obes 22:157-62 |
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