I George Fantus

I George Fantus, BSc, MD, FRCPC

The major research focus of the lab is the study of diabetic complications. We are examining the link betwee high glucose levels and 1) altered cell signaling; 2) oxidative stress; 3) excess O-glycosylation; and 4) abnormal gene expression. Our target organ model is the kidney. We have identified two novel pathological mediators and potential therapeutic targets: Src, a non-receptor tyrosine kinase, and thioredoxin-interacting protein (TxNIP). Src is activated by high glucose levels, and its inhibition blocks diabetic nephropathy in mice. TxNIP is upregulated by high glucose levels and promotes oxidative stress and apoptosis. Diabetic TxNIP-/- mice are protected from developing diabetic nephropaty. Studies to elucidate the specific mechanisms of action, signaling pathways and protein-protein interactions of these two proteins in diabetes are ongoing.

A second focus of our lab is to define the mechanisms of insulin resistance at the cellular and molecular level. Our goal is to develop new approaches for the treatment and prevention of insulin resistance. We are performing studies in insulin target tissues, adipocytes and muscle cells, all of which are rendered insulin resistant by metabolites (e.g., glucose and free fatty acids; cytokines and hormones). Recently, we have identified signaling pathways (e.g., by bradykinin) that can sensitize cells to insulin.
Am J Physiol Endocrinol Metab. 2017 Sep 01;313(3):E321-E334
Frigolet ME, Thomas G, Beard K, Lu H, Liu L, Fantus IG
BMC Pregnancy Childbirth. 2016;16(1):173
Feig DS, Murphy K, Asztalos E, Tomlinson G, Sanchez J, Zinman B, Ohlsson A, Ryan EA, Fantus IG, Armson AB, Lipscombe LL, Barrett JF, MiTy Collaborative Group
J Diabetes Metab. 2015 Jun 1;6(6):1-7
Midaoui AE, Talbot S, Lahjouji K, Dias JP, Fantus IG, Couture R
J Nutr. 2015 Sep 2;
Tian L, Zeng K, Shao W, Yang BB, Fantus IG, Weng J, Jin T
Atherosclerosis. 2015 Apr 25;241(1):111-120
Guo J, Breen DM, Pereira TJ, Dalvi PS, Zhang H, Mori Y, Ghanim H, Tumiati L, Fantus IG, Bendeck MP, Dandona P, Rao V, Dolinsky VW, Heximer SP, Giacca A
J Am Soc Nephrol. 2015 Apr 8;
Shah A, Xia L, Masson EA, Gui C, Momen A, Shikatani EA, Husain M, Quaggin S, John R, Fantus IG
J Endocrinol. 2015 Jan 21;
Pereira S, Shah A, Fantus IG, Joseph JW, Giacca A
Cell Signal. 2014 Dec 27;
Chen Z, Shao W, Xu F, Liu L, Lin B, Wei X, Song Z, Lu H, Fantus IG, Weng J, Jin T
Metabolism. 2014 Oct 25;
Pereira S, Breen DM, Naassan AE, Wang PY, Uchino H, Fantus IG, Carpentier AC, Gutierrez-Juarez R, Brindley DN, Lam TK, Giacca A
Diabetes Metab Res Rev. 2014 Jul 31;
Fantus IG

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Associate Scientist, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Professor, Departments of Medicine and Physiology, Division of Endocrinology, University of Toronto
Department of Medicine, Mount Sinai Hospital/University Health Network