Over 30,000 Canadians suffer from kidney failure and will require dialysis or a transplant. Millions more have conditions such as diabetes and high blood pressure, which often lead to kidney disorders.
Dr. Sue Quaggin, a Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital and clinician at St. Michael’s Hospital, is one of Canada’s leading experts studying kidney disease. Treating patients, she sees first-hand some of the serious implications of the illness and also understands the importance of research.
“I’m very optimistic that in the next decade we’re going to see some great advances in treatments for our patients—and these advances hinge on insights gained in the lab into the molecular and signaling pathways that impact the development and severity of kidney diseases,” says Dr. Quaggin.
She discovered a gene critical for the development of the kidneys, heart and lungs, and is using it to study kidney development, in particular microscopic kidney filters called glomeruli that remove waste and excess fluids from the blood.
Dr. Quaggin’s research is focused on glomerulosclerosis—irreparable scarring of these filters that can lead to kidney failure.
“A better understanding of this process will be critical in the prevention and development of new treatments for kidney disease,” she says.
Dr. Quaggin’s discovery last year of a link between the cancer drug Avastin® and kidney damage received national and international media coverage. In a study published in the New England Journal of Medicine, she showed that one of the drug’s side effects, excess protein in the urine, was caused by inhibiting growth of blood vessels in the kidney. Awareness of this complication will assist physicians to better monitor patients taking the drug. Dr. Quaggin is also working to better understand the effects of other medications including rapamycin on the kidneys and pancreas, which will help clinicians prescribe these medications safely and more effectively.
She is collaborating with other Lunenfeld scientists including Dr. Helen McNeill, renowned for her studies of planar cell polarity—the process by which large-scale organization of cells is regulated.
Together, Drs. McNeill and Quaggin are investigating a gene called Ft (known as “fat”), which instructs cells how they should interact with each other to control tissue organization and growth. Work in fruit flies has shown that Ft regulates tissue organization, and has suggested that loss of Ft functioning might lead to kidney disease, specifically polycystic kidney disease.
“My tool of choice for investigating these complex processes and diseases is the fruit fly Drosophila, which offers powerful geneticadvantages,” says Dr. McNeill. “But with Dr. Quaggin’s incredible grasp of both the human disease, and mammalian models of the illness, we can rapidly test and apply models we have developed in the fly to study kidney diseases in humans.”
The team is also exploring the role and functioning of the Hippo pathway in kidney filtration and glomerulosclerosis, to help determine the molecular mechanisms leading to end-stage kidney failure.