Biomedical Research Foundation Academy Of AthensAcademy Of Athens
Scientific Personnel

Argiris Argiris Efstratiadis, MD, PhD
Affiliated Investigator

Telephone : +30 210 6597 113
Fax : +30 210 6597 599
e-mail : arg@bioacademy.gr


Center :

Clinical, Experimental Surgery & Translational Research


Brief Bio

Dr. Argiris Efstratiadis earned his M.D. degree from the University of Athens in 1966. After completing a thesis on lipid metabolism, he received a Dr.Med.Sci. degree (equivalent to Ph.D.) from the same university in 1971. He then began graduate studies at Harvard, and earned a Ph.D. in Biology in 1976. He was a Fellow of the Harvard Society of Fellows and then a faculty member in the Department of Biological Chemistry, Harvard Medical School. He received a career development award from the Juvenile Diabetes Foundation (1980-83). He joined Columbia University (Medical School; College of Physicians and Surgeons) as a Professor of Genetics and Development in 1982 (he became Emeritus Professor in 2009). He was instrumental in the development of the Integrated Program in Cellular, Molecular and Biophysical Studies and served as its first director. He also served as Acting Chairman of the Department of Genetics and Development for four years and directed the Columbia Human Genome Program that contributed to the Human Genome Initiative a complete, annotated physical map of human chromosome 13. In 1998, he was elected corresponding member of the Academy of Athens. Today, he is Scientific Director of the Biomedical Research Foundation of the Academy of Athens (BRFAA).

Dr. Efstratiadis is internationally recognized both for pioneering advances in recombinant DNA technology and for contributions to the understanding of the structure, evolution and expression of eukaryotic genes. Efstratiadis and his colleagues were the first to develop the technology of cDNA cloning, which allowed them to sequence and characterize for the first time the structure of a eukaryotic mRNA (encoding rabbit b-globin). This pioneering work established an approach essential for the identification and mapping of eukaryotic genes and for the capability to synthesize in bacteria medically useful proteins (Dr. Efstratiadis was a member of the team that constructed for the first time a bacterium synthesizing insulin). Since then, he has made contributions to the study of the genes encoding globin, insulin and insulin-like growth factors (IGFs). In addition to work on molecular evolution, he discovered for the first time that functional genes can be generated by RNA retroposition. Also notable is the first in vivo description of lariat RNA splicing intermediates. Subsequently, gene targeting experiments in mice, allowed Efstratiadis and his colleagues to discover the first example of an endogenous gene (Igf2) that is subject to parental imprinting and to establish the IGF signaling system as the major determinant of growth during embryonic and postnatal development. More recently, his laboratory focused on mouse developmental genetics, with emphasis on the role of growth factors in normal development and malignancy, specifically mammary tumor progression, including research on the murine homologs of the breast cancer susceptibility genes Brca1 and Brca2, and the involvement of the Notch signaling pathway in breast tumors. Additional work on tumorigenesis includes the development of novel approaches for modeling cancer at anatomical sites of choice (“designer tumors”); preclinical studies to treat breast cancer in mice with drugs inhibiting IGF signaling (picropophyllin derivatives); studies on the involvement of stem cells in tumor initation; and development of mouse models for prostate and pancreatic cancer. In a broader context of generating animal models of human disease, the laboratory has performed research on the murine Huntington’s disease homolog and on pancreatic b-cell pathophysiology pertaining to diabetes, and has created genetically-modified mice simulating syndromes of fetal growth retardation, Laron dwarfism and overgrowth (Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes).

 

Selected Publications

 

Klinakis, A., Szabolcs, M, Chen, G., Xuan, S., Hibshoosh, H., and Efstratiadis, A. (2009). Igf1r as a therapeutic target in a mouse model of basal-like breast cancer. Proc. Natl. Acad. Sci. USA 106: 2359-2364.

Klinakis, A., Szabolcs, M., Politi, K., Kiaris, H., Artavanis-Tsakonas, S., and Efstratiadis, A. (2006). Myc is a Notch1 transcriptional target and a requisite for Notch1-induced mammary tumorigenesis in mice. Proc. Natl. Acad. Sci. USA 103: 9262-9267.

Politi, K., Kljuic, A., Szabolcs, M., Fisher, P., Lugwig, T., and Efstratiadis, A., (2004). “Designer tumors in mice. Oncogene 23: 1558-1565.

Ludwig, T., Fisher, P., Murty, V.V., and A. Efstratiadis. (2001). Development of mammary    adenocarcinomas by tissue-specific knockout of Brca2 in mice. Oncogene 20: 3937-3948.

Ludwig, T., Fisher, P., Ganesan, S., and A. Efstratiadis. (2001). Tumorigenesis in mice carrying a truncating Brca1 mutation. Genes Dev. 15: 1188-1193.

Lupu, F., Terwilliger, J.D., Lee, K., Segre, G.V., and Efstratiadis, A. (2001). Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev. Biol. 229: 141-162.

Baker, J., Liu, J.-P., Robertson, E.J., and Efstratiadis, A. (1993). Role of insulin-like growth factors in embryonic and  postnatal growth. Cell 75: 73-82

DeChiara, T.M., Robertson, E.J., and Efstratiadis, A. (1991). Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64: 849-859.

Soares, M.B., Schon, E., Henderson, A., Karathanasis, S., Cate, R., Zeitlin, S., Chirgwin, J.,  and Efstratiadis, A. (1985). RNA-mediated gene duplication: The rat preproinsulin  I gene is a functional retroposon. Mol. Cell. Biol. 5: 2090-2103.

Zeitlin, S., and Efstratiadis, A. (1984). In vivo splicing products of the rabbit b-globin pre-mRNA. Cell 39: 589-602.

Efstratiadis, A., Posakony, J.W., Maniatis, T., Lawn, R.M., O'Connell, C., Spritz, R., DeRiel, J.K., Forget, B.G., Weissman, S.M., Slightom, J.L., Blechl, A.E., Smithies, O., Baralle, F.E., Shoulders, C.C., and Proudfoot, N.J. (1980). The structure and evolution of the human b-globin gene family. Cell 21: 653-668.

Efstratiadis, A., Kafatos, F.C., and Maniatis, T. (1977). The primary structure of rabbit b-globin mRNA as determined from cloned DNA. Cell 10: 571-585.
 

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