Dr. Constantine A. Stratakis was named the Scientific Director of the Division of Intramural Research (DIR) of the NICHD in August 2011, after serving as the Acting Scientific Director since July 2009. Dr. Stratakis was formally trained as pediatrician and medical geneticist. During the last 20 years, he has made significant contributions to the fields of endocrinology and genetics: he is well known for many discoveries, but he is most famous for the identification and characterization of the gene for Carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD), as well as the more recent molecular elucidation of a whole class of disorders associated with bilateral adrenocortical hyperplasias (BAHs) and the genetic defects associated with the Carney-Stratakis syndrome (CSS), comprising heritable paragangliomas and gastrointestinal stromal tumor syndrome.
Dr. Stratakis trained first at the Endocrine Unit, University of Athens in the early 1980s, and there he participated in the first efforts to establish congenital hypothyroidism screening in Greece; this work was followed by establishing assays for SHBG, HCG, GH, IGF-I and IGF-II, all of which continued to be used by Greek academic and commercial labs until the mid-1990s. Subsequently, Dr. Stratakis was fortunate to train with some of the best in endocrinology, including: Professor J-P Luton at Hospital Cochin, Paris, France, where he was introduced into the world of Cushing syndrome; Professor X. Bertagna, with whom he now collaborates; and eventually, he joined Dr. George P. Chrousos’ laboratory at the Developmental Endocrinology Branch (DEB), NICHD, NIH. After completing an internship and residency in pediatrics, and two fellowships in medical genetics and pediatric endocrinology (the three clinical specialties that he currently holds board certifications for), Dr. Stratakis returned to NICHD to pursue his independent career, where he rose through the ranks to become the director of the Program on Developmental Endocrinology and Genetics, which includes the now-dissolved DEB. In 2002, he also became the director for the Fellowship Program in Pediatric Endocrinology.
Dr. Stratakis was the first to identify germline mutations in PRKAR1A, encoding the regulatory subunit of protein kinase A, as the cause of CNC and PPNAD. His mentor and friend, Dr. J. Aidan Carney (Mayo Clinic), was instrumental in this collaborative work: Stratakis expanded on Carney’s meticulous phenotyping to characterize a variety of adrenocortical tumors which led to a new classification of these hyperplasias (BAHs) based on genetic, biochemical, and histological features. Dr. Stratakis’ clinical and translational investigation carries significant clinical implications. Gene-based testing for CNC, PPNAD, and CSS patients can result in earlier diagnosis, more effective treatment, organ-specific surveillance and prophylaxis. As part of related investigations on a syndrome that is not related to PPNAD or CNC, but that predisposes one to adrenal and other tumors, he and Dr. Carney described a disorder that bears their names (Carney-Stratakis syndrome). Dr. Stratakis and his colleagues followed the PRKAR1A gene discovery with the elucidation of cAMP signaling pathway’s role in adrenal and other endocrine tumors by utilizing in vitro experiments and creating mouse models to understand tissue-specific effects of abnormalities of the cAMP-dependent protein kinase (PKA) enzyme. More recently, using a combination of new genome-wide technology and clever extrapolation of PKA signaling facts, Stratakis and team identified mutations in the phosphodiesterase (PDE) genes 11A and 8B (PDE11A, PDE8B) in a variety of tumors. This work was published in Nature Genetics and the New England Journal of Medicine. These observations, in turn, gave rise to analyzing the role of the PDEs in tumorigenesis, a previously unsuspected connection.
Dr. Stratakis was the first recipient of the Endocrine Society-Pharmacia International Award for Excellence in Published Clinical Research (JCEM 1998;83:1348) in 1999, and 2000, 2005, and 2007 NIH Merit Awards. Dr. Stratakis has been honored nationally and internationally by invitations from the academic centers around the world by visiting professorships from Harvard University to The Free University of Berlin to, more recently, the University of Adelaide, Australia. He serves on several editorial boards, and he was recently named Deputy Editor of the Journal of Clinical Endocrinology and Metabolism, the leading journal in endocrinology.