Collaborating to Fight Common Cause of Kidney Disease
Diabetes is the most common cause of end-stage kidney disease in Canada. Now, with the help of a million-dollar Transformational Diabetes Team Research Grant from the Banting and Best Diabetes Centre, a team of U of T scientists is working to eliminate kidney scarring caused by the disease.
“Excess scar tissue in the kidney can lead to organ failure, requiring dialysis or transplantation to live,” says research team member Darren Yuen, a Professor in the Departments of Medicine and Laboratory Medicine and Pathobiology as well as a nephrologist and scientist at the Keenan Research Centre for Biomedical Science at St. Michael’s Hospital.
The grant opens the door to a new partnership called the Centre for Advanced Therapeutics in Diabetic Kidney Disease (CAT-DKD). It capitalizes on Toronto’s research capacity by combining basic and clinical research and bringing together endocrinology and nephrology together with molecular biology and chemistry.
One of the goals of the CAT-DKD is to become a world centre in discovery science, using cutting edge sequencing and pathway analysis of human samples to explore the altered pathways in human diabetic kidney disease; the development of chemical probes or small molecule tool compounds to do proof-of-concept validation studies for key pathways; to partner with other academic groups doing similar research as well as pharmaceutical and biotechnology companies interested in drug discovery for diabetic kidney disease; and teaching and training the next generation of academic researchers in drug discovery and development.
The Department of Medicine’s Professor Richard Gilbert leads the research, which focuses on identifying the mechanisms that cause kidney scaring in diabetes.
The human body perceives hyperglycemia, or high blood sugar, as an injury. In response, it creates scar tissue. Since people with diabetes may often have high blood sugar levels, their bodies constantly create new scars in the kidney.
The interdisciplinary team also includes Jeff Wrana and Aled Edwards, both of the Department of Molecular Genetics.
The team will measure which genes the body activates when scarring in the kidney begins. They will do this by testing samples of scarred kidney tissue collected from biopsies of people with dieabetes using a method called transcriptional sequencing.
Wrana is also a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital. He specializes in a test method that allows tissue samples collected several years ago to be analyzed and will look at which genes are activated in preserved pathology specimens.
Edwards, who is also appointed to the Department of Medical Biophysics, will look at the pathways uncovered and determine which compounds may block them to prevent scarring.
“Once we know what pathways are involved in activating the body’s scarring response, we’re well on our way to understanding how to block it,” says Gilbert, who holds the Canada Research Chair in Diabetes Complications and is also a scientist at the Keenan Research Centre for Biomedical Science and head of the Division of Endocrinology and Metabolism at St. Michael’s Hospital.
The four will also work toward developing and creating new treatments to prevent, slow, stop and perhaps even reverse this form of kidney disease.
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