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 hereditary and associated with multiple tumors and abnormalities in other endocrine glands (i.e. the pituitary gland). Our laboratory has studied families with Carney complex (CNC)and related syndromes and has identified two loci harboring genes for CNC on chromosomes 2 (2p16) and 17 (17q22-24). Through genetic linkage analysis and other molecular techniques, the participation of the two genomic loci on chromosomes 2 and 17 in the expression of the disease is being investigated. A comprehensive genetic and physical map of the 2p16 chromosomal region was constructed for the cloning of the CNC-causing gene. Studies in cultured primary tumor cell lines (established from our patients) identified a region of genomic instability in the center of this map. Tumor studies led to the identification of the PRKAR1A gene on 17q22-24 as the gene responsible for CNC in approximately 40% of the cases of the disease. PRKAR1A is a novel tumor suppressor gene; it is also the main regulatory subunit of protein kinase A, a central signaling pathway for many of the cellular fnctions and hormonal responses. In collaboration with other laboratories at the NIH, the functional consequences of PRKAR1A mutations are being investigated in cell lines; more recently, animal models with transgenic expression of mutant PRKAR1A are being created. In collaboration with Mayo Clinic, the genetic defects in patients with CNC-related syndromes (i.e., Peutz-Jeghers syndrome) are also being identified. A genome-wide screen for the identification of gene(s) responsible for inherited adrenocortical aldosteronomas (familial hyperaldosteronism type II - FH-II) was also completed in our laboratory, identifying a locus for FH-II on 7p22. A genome wide screen for the identification of a syndrome composed of familial paragangliomas, adrenal, gastric stromal and pulmonary tumors is ingoing. Additional work is being done collaboratively on the genetics of other endocrine tumors, including childhood adrenocortical cancer and pituitary tumors. Clinical projects include the functional characterization of benign adrenocortical tumors and the evaluation of the use of genetic markers in endocrine oncology.
| 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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