Constantin Polychronakos, MD
diabetes • genetics • genomics • autoimmunity • cell lineage
My research focuses on the genetic factors that determine risk for type 1 diabetes (T1D). This form of diabetes starts in childhood and is caused by a malfunction of the patient's own immune system, which fails to recognise the pancreatic b-cells that make insulin as "self", attacks and destroys them. Affected children require insulin injections four times a day or more and blood sugar testing by finger-prick at least as many times. Even with the best efforts, it is not always possible to maintain acceptable blood sugars, which can cause serious complications. We are using next generation sequencing to study how the DNA of diabetic children differs from that of healthy individuals and how the immune cells that do the damage (a tiny fraction) differ from the rest of the patient's normally functioning lymphocytes. We hope that this will lead to new ways of predicting and preventing T1D.
Genome-wide search for exonic variants affecting translational efficiency. Li Q, Makri A, Lu Y, Marchand L, Grabs R, Rousseau M, Ounissi-Benkalha H, Pelletier J, Robert F, Harmsen E, Hudson TJ, Pastinen T, Polychronakos C, Qu HQ. Nature Communications. 2013;4:2260. doi: 10.1038/ncomms3260. PMID: 23900168.
Public funding for genomics: where does Canada stand? Polychronakos C. J Med Genet. 2012; 49(8):481-2. doi: 10.1136/jmedgenet-2012-101141. PMID: 22889850.
Rfx6 directs islet formation and insulin production in mice and humans. Smith SB, Qu HQ, Taleb N, Kishimoto NY, Scheel DW, Lu Y, Patch AM, Grabs R, Wang J, Lynn FC, Miyatsuka T, Mitchell J, Seerke R, Désir J, Vanden Eijnden S, Abramowicz M, Kacet N, Weill J, Renard ME, Gentile M, Hansen I, Dewar K, Hattersley AT, Wang R, Wilson ME, Johnson JD, Polychronakos C, German MS. Nature. 2010 Feb 11;463(7282):775-80. doi: 10.1038/nature08748. PMID: 20148032.
A genome-wide association study identifies KIAA0350 as a type 1 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, Rappaport EF, Orange JS, Monos DS, Devoto M, Qu HQ, Polychronakos C. Nature. 2007 Aug 2; 448(7153):591-4. Epub 2007 Jul 15. PMID: 17632545.
Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Vafiadis P, Bennett ST, Todd JA, Nadeau J, Grabs R, Goodyer CG, Wickramasinghe S, Colle E, Polychronakos C. Nature Genetics. 1997 Mar;15(3):289-92. PMID: 9054944.