Research Laboratory

My laboratory at the Research Institute of the McGill University Health Center (Montreal Children’s Hospital site), occupies 2,000 square feet of space and has all the necessary equipment for molecular genetics, including equipment bought with a 2005 CFI grant to the Montreal Diabetes Research Center: A state of the art Janus robotic system, a fluorescence polarization detector for genotyping and a FACSaria cell sorter were awarded specifically to me within this $14M grant. In addition, the Institute has all required shared facilities including tissue culture (three incubators and two hoods exclusive to my lab, including one of each dedicated to ES cell work).

Through the GriD and diabetes genetics projects, I am also in close contact with the McGill/Genome Quebec Innovation Center (MGQIC). Ghislain Rocheleau, one of my current post-docs, is physically located full-time at the MGQIC and three members of the technical personnel there are my former research assistants, trained by me. Co-authorships with TJ Hudson. A. Montpetit and R Sladek (cf. my publications list), three key people at MGQIC, indicate how closely I work with this facility, making state-of-the art cores directly accessible to my trainees.

Research Team
Five students have obtained Ph.D. from Dr. Polychronakos’ laboratory (1 in Dean’s list). Dr. Polychronakos has trained four post-docs three of whom are now on faculty in Canada and Europe, one in industry, plus a large number of MD fellows and summer students.

Publications

Scientific Highlights

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 2006 43:129-32, J Med Genet. 2005 42:266-70, Nature Genetics 37:111-2, 2005, Diabetes 2007 56:270-5, Diabetes 2007 56:1174-6) 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 2007 Aug 2; 448(7153):591-4) In Nature’s top ten list for August 2007.

• 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, Université de Montréal 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 Génome Québec. Four loci were discovered in Stage 1 (Nature 445(7130):881-5), 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, 2005, S18-24, Proc Natl Acad Sci, 2006, 103:11683-8 and Diabetes 2007 56:709-13) 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).
  

Recent publications

1. Qu H., Yang L., Montpetit A., Polychronakos C. Genetic control of alternative splicing in the TAP2 gene: Possible implication in the genetics of type 1 diabetes. Diabetes 2007 56:270-275,2007.
2. Qu HQ, Marchand L, Frechette R, Bacot F, Lu Y, Polychronakos C. No association of type 1 diabetes with a functional polymorphism of the LRAP gene. Molecular Immunology. 44:2145-8, 2007.
3. Qu HQ and Polychronakos C. Toward further mapping of the association between the IL2RA locus and type 1 diabetes. Diabetes 2007 Apr;56(4):1174-6.
4. Robert Sladek, Ghislain Rocheleau, Johan Rung, Christian Dina, Lishuang Shen, David Serre, Philippe Boutin, Daniel Vincent, Alexandre Belisle, Samy Hadjadj, Beverley Balkau, Barbara Heude, Guillaume Charpentier, Thomas J. Hudson, Alexandre Montpetit, Mark Prentki, Barry I. Posner, David J. Balding, DavidMeyre, Constantin Polychronakos, Philippe Froguel. A genome-wide association study identifies novel susceptibility loci for type 2 diabetes mellitus. Nature 2007 Feb 22;445(7130):881-5. I am the corresponding author in this paper.
5. A Genome-Wide Association Study Identifies KIAA0350 as a novel Type1 Diabetes Gene. Hakonarson H, Grant SF, Bradfield JP, Marchand L, Kim CE, Glessner JT, Grabs R, Casalunovo T, Taback SP, Frackelton EC, Lawson ML, Robinson LJ, Skraban R, Lu Y, Chiavacci RM, Stanley CA, Kirsch SE, Rappoport EF, Orange JS, Monos DS, Devoto M, Qu HQ, Polychronakos C. Nature 2007 Aug 2; 448(7153):591-4. (Co-corresponding author with H.H.).
6. Qu, H, Polychronakos C. The TCF7L2 locus and type 1 diabetes. BMC Med Genet 2007 Aug 3;8(1):51.
   

Short Biography

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 Université de Montréal (Hôpital 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 Paediatrics, associate in Experimental medicine and Human Genetics) since 1983, at the rank of full professor since 2000.

Dr. Polychronakos has authored more than 80 original research papers and a number of reviews and book chapters.