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.
Endocr Pathol. 2018 Oct 25;:
Kapur A, Singh N, Mete O, Hegele RA, Fantus IG
Endocr Connect. 2018 May;7(5):739-748
Mori Y, Ko E, Furrer R, Qu LC, Wiber SC, Fantus IG, Thevis M, Medline A, Giacca A
Am J Physiol Endocrinol Metab. 2018 Mar 01;314(3):E201-E205
Jin T, Song Z, Weng J, Fantus IG
Endocrinology. 2018 Jan 23;:
Lu H, Bogdanovic E, Yu Z, Cho C, Liu L, Ho K, Guo J, Yeung LSN, Lehmann R, Hundal HS, Giacca A, Fantus IG
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



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