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Scar Wars: A new hope

Toronto, January 14, 2016

By Geoff Koehler

Drs. Richard Gilbert and Darren Yuen
Drs. Richard Gilbert and Darren Yuen

A pair of St. Michael’s clinician-scientists is part of a fantastic foursome of interdisciplinary researchers awarded a $1-million Transformational Diabetes Team Research Grant from the University of Toronto’s Banting and Best Diabetes Centre.

Led by Dr. Richard Gilbert, an endocrinologist and head of the Division of Endocrinology and Metabolism for St. Michael's Hospital, the team will be working to eliminate kidney scarring caused by diabetes.

One of the fundamental ways that the body responds to injury is by producing scar tissue. Forty-five per cent of all chronic disease in hospitals is related to fibrosis. As well as diabetes, scarring is at the root of most instances of heart or kidney failure. The same can be said for many cases of chronic lung disease that are not due to smoking.

“Scarring, or fibrosis, can help in the short-term—such as promoting healing after a cut or in walling off an infection so that it does not spread—but when an injury is chronic or repeated, the amount of scar tissue formed can be excessive and cause organ malfunction,” said Dr. Gilbert, who also holds the Canada Research Chair in Diabetes Complications.

Each time the body detects high blood sugar levels—also known as hyperglycemia—it perceives an injury and creates scar tissue. Because sugar levels are often high for someone with diabetes, the body will constantly create scarring in the kidney.

“Excess scar tissue in the kidney it can lead to organ failure, requiring dialysis or transplantation to live,” said Dr. Darren Yuen, a nephrologist with St. Michael’s and a member of the grant team. “Diabetes is now the most common cause of end-stage kidney disease in Canada.”

Using a method called transcriptional sequencing, researchers will test samples of scarred kidney tissue collected from biopsies of people with diabetes. They will measure which genes the body activates when scarring begins.

“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,” said Dr. Gilbert.

Drs. Gilbert, Yuen are both scientists with the Keenan Research Centre for Biomedical Science of St. Michael’s. They will take full advantage of diverse expertise in biomedical and clinical research to form a new consortium, the Centre for Advanced Therapeutics in Diabetic Kidney Disease. This transformational grant team capitalizes on the outstanding research capacity of Toronto, bringing endocrinology and nephrology together with molecular biology and chemistry.

Dr. Jeff Wrana, professor U of T’s Department of Molecular Genetics and senior investigator at Mount Sinai Hospital’s Lunenfeld-Tanenbaum Research Institute, will look at what genes are activated in preserved pathology specimens.

“Most groups using human scar tissue samples need fresh tissue but Dr. Wrana specializes in a method where he can test samples that were collected several years ago,” said Dr. Gilbert.

Dr. Aled Edwards, professor with the University of Toronto’s Department of Medical Biophysics, will look at the pathways uncovered and determine which compounds may effectively block them so as to prevent the scarring from taking place.

Together the team of Drs. Gilbert, Yuen, Wrana and Edwards will focus not only on identifying the mechanisms that cause excessive kidney scaring in diabetes but also on testing and developing new potential treatments that may stop fibrosis, seeking to prevent, slow and ultimately, even reverse the course of diabetic kidney disease.

The $1-million Transformational Diabetes Team Research Grant was made possible through the generous support of an anonymous donor to the Toronto General & Western Hospital Foundation.

This paper is an example of how St. Michael's Hospital is making Ontario Healthier, Wealthier, Smarter.

About St. Michael's Hospital

St. Michael’s Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in 27 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the hospital’s recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto.