The Kidney Foundation of Canada

dr john chan 

Dr. John S.D. Chan

Centre de recherche du CHUM, Quebec

Oxidative stress and molecular regulation of renal angiotensin-converting enzyme-2 (Ace2) and angiotensin 1-7 receptor (MasR) expression in diabetic nephropathy 

2017-2019:  $100,000  |  Biomedical Research Grants  |  Category: Diabetes


Dr. Chan is currently a Professor of Medicine at the Université de Montréal and the Chief of the Laboratory of Molecular Nephrology and Endocrinology at the Research Centre of Centre hospitalier de l'Université de Montréal (CRCHUM). Dr. Chan's research program seeks to understand the role(s) of intrarenal renin angiotensin system (RAS) and oxidative stress in the pathogenesis of diabetic nephropathy, with special emphasis on renal angiotensinogen gene expression and reactive oxygen species (ROS) generation on tubular apoptosis in diabetes. Dr. Chan has published over 100 papers in scientific journals and presented more than 250 abstracts in various scientific societies. Dr. Chan's research program is supported by several peer-reviewed granting agencies including the Canadian Institutes of Health Research, The Kidney Foundation of Canada, Canadian Diabetes Associate and Canadian Foundation of Innovation. 

Lay Summary

Diabetes and hypertension are major risk factors for the development of kidney failure in diabetes. Clinical and animal experimental studies demonstrate that chronic treatment with blockers of a hormonal system called the "renin-angiotensin system (RAS)" is effective in lowering blood pressure and in delaying the progression of kidney failure but not the cure. These findings establish that RAS activation is a major risk factor in the development of hypertension and kidney failure in diabetes. 

Angiotensin-converting enzyme-2 (Ace2) is the key enzyme (or protein) in the RAS that converts angiotensin-II (Ang II) to angiotensin 1-7 (Ang 1-7). Ang 1-7 interacts with its own receptor called MasR is downregulated in diabetic kidneys. The regulation of renal Ace2 and MasR expression, however, is not well understood. In this proposal, Dr. John Chan is examining a protein, called nuclear factor erythroid 2-related factor 2 (Nrf2) and how this protein is involved to down-regulate the expression of renal Ace2 and MasR in aggravating kidney damage in diabetes. Dr. Chan's studies will identify whether Nrf2 could be a therapeutic target in preventing nephropathy progression in diabetes.