简介
During my graduate work I developed an interest in the genetics of endocrine diseases, especially those that present with a predisposition to endocrine tumors and other neoplasms. My career started in 1985 as a graduate student in the Endocrine Unit of the Medical School of The University of Athens under the mentorship of Prof. M. Batrinos, and as a biochemist (tech) in a Radioimmunoassay Lab at the Hospital Mitera, Athens, Greece. In Paris, France, I spent time with Jean Pierre Luton and Xavier Bertagna in 1988; I was exposed there to research on mainly adrenal and pituitary diseases. In 1989-1990, at the NIH lab of George Chrousos, I was part of the team that identified the first genetic defects in the human glucocorticoid receptor (J Clin Invest 1991;87:680). Following this post-doctoral fellowship in molecular endocrinology at the NIH, I continued with my clinical training at Georgetown University Medical Center, Washington, DC, where I finished a residency and two fellowships in Pediatrics, Pediatric Endocrinology and Medical Genetics & Dysmorphology. I was recruited back to NIH, trained in linkage analysis and cancer genetics, and started a laboratory (in 1995) studying the genetics of endocrine tumors in the context of a variety of genetic syndromes. In 2000, I identified the PRKAR1A gene causing Carney complex (CNC) (Nat Genet 2000;26:89); this gene is expressed in almost all human tissues and regulates protein kinase A (PKA) and, consequently, cAMP signaling. Prkar1a+/- animal models made in my laboratory addressed the participation of PRKAR1A in endocrine cell growth and neoplastic development of other tissues, such as the bone (PNAS 2010;107:8683). My laboratory identified phosphodiesterase (PDE) genes as potentially being involved in cAMP-related tumor growth (Nat Genet 2006;38:794; N Engl J Med 2008;358:750). We also identified defects affecting mitochondrial oxidation in endocrine tumors (N Engl J Med. 2007;357:1054) and in pediatric gastrointestinal tumors (GISTs) (PNAS 2011;108:314). In collaboration with the hospital I was trained in France, the ARMC5 gene was identified in macronodular adrenal hyperplasia (N Engl J Med. 2013;369:2105), a gene that we are now modeling in mice, fly and fish. Our laboratory identified the PRKACA and PRKACB genes in micronodular adrenal hyperplasia and Carney complex (N Engl J Med. 2014;370:1019 & 2014;370:1065, respectively). Most recently, our laboratory identified a new condition that we named X-LAG for “X-linked acrogigantism”; we then described the genetic defect that explains more than 80% of the cases of early gigantism and growth-hormone dependent overgrowth that appears to be due to abnormalities of an orphan G-protein coupled receptor (GPCR), GPR101 (N Engl J Med, 2014;371:2363). Ongoing genome-wide work aims at identifying genetic defects for Carney Triad, wild-type GISTs, endocrine hypertension (in association with adrenocortical tumors), pediatric gigantism, and other forms of adrenal and pituitary tumors. Molecular studies focus on PKA, PDEs, ARMC5, and GPR101. Over the years, my laboratory has trained more than 150 students, residents and fellows from all over the world but mostly Brazil, Greece, France, Italy and of course the United States. To date, most keep in touch and a great number are involved in health science research. At my lab we are very proud of this extended family that, thankfully, keeps growing. Finally, although my administrative duties have undoubtedly increased over the years, I am still seeing patients and families and teach medical trainees almost daily; I, thus, remain deeply committed to serving the “physician” part of being a physician scientist.
