Contact info

Dr Constantin Polychronakos
The Montreal Children's Hospital
2300, Tupper Street - C-244
Montreal, QC H3H 1P3

Tel: 1-514-412-4315
Fax: 1-514-412-4264
E-mail: [email protected]

Link to Polychronakos Lab webpage

Research keywords

Dr Polychronakos obtained his MD degree from the Aristotelian University (Greece) in 1972. He then immigrated to Canada and trained in Paediatrics at the University of Manitoba and Dalhousie, followed by a fellowship in Paediatric Endocrinology at the Universit� de Montr�al (H�pital Sainte-Justine). He trained in research at the McGill Polypeptide Hormone Laboratory under Dr Harvey Guyda for an additional three years, supported by a Medical Research Council fellowship. He has been on faculty at McGill (Department of Pediatrics, associate in Experimental medicine and Human Genetics) since 1983, at the rank of full professor since 2000.

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In the past 5 years my efforts have centered on elucidating the molecular genetics of diabetes. I have contributed to both the discovery of new loci and the elucidation of the mechanism of known ones.

A large-scale search for type 1 diabetes (T1D) susceptibility loci. Several years of attempts using the candidate-gene approach with relatively modest results (Diabetologia 49:958-961, 2006; J Med Genet 43:129-32, 2006; J Med Genet 42:266-70, 2005; Nature Genetics 37:111-2, 2005; Diabetes 56:270-5, 2007; Diabetes 56:1174-6, 2007) came to an end with the availability of high-density genotyping arrays that permitted a genome-wide association (GWA) study on my collection of 1,300 families with type 1 diabetes, funded by the Juvenile Diabetes Foundation and the Children's Hospital of Philadelphia. We identified two novel loci in Stage 1 (Nature 448(7153):591-4, 2007). In Nature's top ten list for August 2007 downloads.

A genome-wide association study for type 2 diabetes. I have contributed my expertise in genome-wide studies to the Diabetes Gene Discovery Group, a collaboration between McGill, Universit� de Montr�al and Centre National de Recherche Scientifique in Lille, France aimed at elucidating the genetics of type 2 diabetes by a GWA study in a French cohort of 3,500 cases and 3,500 controls, funded by Genome Canada and G�nome Qu�bec. Four loci were discovered in Stage 1 (Nature 445(7130):881-5, 2007), one of the first major proofs-of-principle for the GWA approach. I am corresponding author in this paper which had an accompanying "News and Views" write-up and was widely covered in the world media (e.g. New York Times, Boston Globe, Daily Telegraph, Newsweek website, CBC and CTV national evening news, front page in most major newspapers in Canada).

The insulin gene in type 1 diabetes (T1D). Following up on a previous observation that a polymorphism upstream of the insulin gene confers diabetes risk by modulating expression levels in the thymus which, we hypothesized, modulates insulin-specific T-cell tolerance (Nature Genetics 15:289-292, 1997; front page of the Montreal Gazette). I proceeded to test predictions of this model with functional studies in humans (Diabetes S18-24, 2005; Proc Natl Acad Sci 103:11683-8, 2006 and Diabetes 56:709-13, 2007) and a mouse KO with thymus-specific deficiency (Diabetes 51:1383-1390, 2002). We also pinpointed the rare cells in the thymus that make insulin (Diabetes 53:354-9, 2004) and show that insulin transcription in these cells depends on immune rather than metabolic stimuli (Diabetes 55:2595-601, 2006).

T1D association with CTLA4. My laboratory contributed to the dissection of the molecular and biochemical basis on which a haplotype at the CTLA-4 locus predisposes to T1D and other autoimmune endocrinopathies (J Biol Chem 277:46478-86, 2002; J Clin Endocrinol Metab 89:6257-65, 2004; Genes and Immunity 6:305-11, 2005; J Autoimmun 27:105-9, 2006).

Genomic imprinting. My laboratory published the first report of imprinting in a human gene (Nature Genetics, 1993 with accompanying editorial in Nature 363:94). Although I am no longer active in the field, I was invited to write the Imprinting in Human Disease article in the Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics (Wiley, 2006).

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