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Argiris  Efstratiadis
Argiris Efstratiadis
Professor, Genetics and Development


Address: 1150 St. Nicholas Avenue Room 608 New York NY 10032
Phone: 212-851-5237
Fax: 212-851-5236
E-mail:

ae4@columbia.edu

Education and Training:
M.D. 1966, University of Athens
Ph.D. 1976, Harvard University
Affiliations:
bullet  Stem Cell Consortium
bullet  Department of Genetics and Development
bullet  Institute for Cancer Genetics
Training Activities:
bullet  Training Program in Genetics and Development
bullet  Integrated Program in Cellular, Molecular and Biophysical Studies
bullet  MD/PhD Program
Research Summary:
(800 words, max)
Role of growth factors in mammalian embryogenesis; mechanism of parental imprinting; physical mapping of human chromosome 13.

Current Research:
Growth, considered as an increase in size until a limit is attained, is a fundamental developmental process. In mammals, the body size limit, which is correlated with a variety of physiological parameters, is determined by the rate and duration of cell proliferation. During embryogenesis, growth, and also differentiation, are thought to occur by differential expression of hierarchies of genes functioning in a cascade fashion through complex developmental pathways. Genes encoding polypeptide growth factors and their receptors are among the key regulatory elements that provide combinations of products playing pivotal roles in the control of proliferative and determinative events in these developmental cascades.

The mammalian IGF family consists of two ligands (IGF-I and IGF-II), two receptors (type 1 and type 2; IGF1R and IGF2R) and at least six binding proteins (IGF-BPs). The main focus of the laboratory is the analysis of the developmental functions of the IGF system by a genetic approach using predominantly mutant mice generated by targeting of the Igf1, Igf2, Igf1r, Igf2r and Igf-bp3 genes. In addition, the gene encoding the growth hormone receptor was disrupted, to analyze the relationship between the roles of growth hormone and IGF-I in postnatal growth.

The results showed that IGF1R serves in vivo the signaling of both IGF-I and IGF-II, while the growth-promoting function of IGF-II is mediated in part through an additional interaction with the insulin receptor. IGF2R, on the other hand, serves for degradation of excess IGF-II. Interestingly, in the case of the IGF gene system, growth regulation is also influenced by the epigenetic process of parental imprinting (i.e. monoallelic gene expression depending on parental legacy).

In parallel, based on evidence about the involvement of IGF1R functions in tumor development, the laboratory has initiated an exploration of the role of the IGFs in cancer, with emphasis on mammary tumorigenesis. Thus, we are testing whether the severity of mammary tumors in transgenic mice that inevitably develop them could be reduced in genetic backgrounds lacking functions of the IGF system. In this context, to provide models of hereditary breast cancer, we are pursuing conditional mutagenesis of the Brca1 and Brca2 genes.
Publications:
(6 max)
1. Mason JL, Xuan S, Dragatsis I, Efstratiadis A, Goldman JE. : (2003) Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination.  J. Neuroscience  23(20): 7710-7718

2. Xuan S, Kitamura T, Nakae J, Politi K, Kido Y, Fisher PE, Morroni M, Cinti S, White MF, Herrera PL, Accili D, Efstratiadis A. : (2002) Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptor.  J. Clin. Invest  110(7): 1011-1019

3. Zhang M, Xuan S, Bouxsein ML, von Stechow D, Akeno N, Faugere MC, Malluche H, Zhao G, Rosen CJ, Efstratiadis A, Clemens TL. : (2002) Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization.  J. Biol. Chem.  277(46): 44005-44012

4. Kido Y, Nakae J, Hribal ML, Xuan S, Efstratiadis A, Accili D. : (2002) Effects of mutations in the insulin-like growth factor signaling system on embryonic pancreas development and beta-cell compensation to insulin resistance.  J. Biol. Chem  277(39): 36740-36747

5. Tycko B, Efstratiadis A.: (2002) Genomic imprinting: piece of cake.  Nature  417(6892): 913-914

6. Chiao E, Fisher P, Crisponi L, Deiana M, Dragatsis I, Schlessinger D, Pilia G, Efstratiadis A. : (2002) Overgrowth of a mouse model of the Simpson-Golabi-Behmel syndrome is independent of IGF signaling.  Dev. Biol  243(1): 185-206

URL for lab page:
 

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