The Kidney Foundation of Canada

Dr. Tomoko Takano

Dr. Tomoko Takano

McGill University Health Centre Research Institute, QC

Role of the Rac1 activator, beta-PIX, in the pathogenesis of proteinuria


2018-2020:  $100,000 |  Biomedical Research Grants  |  Category: Glomerulonephritis

Lay Summary

Leakage of proteins into urine (proteinuria) is a hallmark of many kidney diseases. When you have a lot of proteinuria, you are more likely to progress to kidney failure. This is why it is important to find effective treatments to stop proteinuria. Current treatments are non-specific; they are not always effective while they can cause a lot of undesired side effects. What is blocking the discovery of specific and effective treatments is the fact that we do not know how proteinuria develops. Normal kidneys have a barrier function that allows the passage of water and waste products into the urine while retaining proteins that are essential for body function. In the kidney, cells called podocytes are maintaining this barrier function. When podocytes are injured, this causes proteinuria. The proposed research will define what is happening in podocytes when they are injured.
 
Our recent research identified that in proteinuric kidney diseases, the molecule called Rac1 is activated in podocytes and this leads to podocyte malfunction. When the Rac1 activation is persistent, podocytes are eventually lost in the urine and that leads to kidney failure. Thus, blocking Rac1 is a promising treatment strategy for proteinuria. However, Rac1 is expressed in all the cells in the body and blocking Rac1 itself will likely harm the body. Instead, we have identified a protein, called beta-PIX, which regulates Rac1 activity in podocytes. We will study how beta-PIX works in podocytes and establish if it could be a good therapeutic target. The results of the research will help us understand how proteinuria occurs and allow the development of a better therapeutic approach.
 

Biography

Tomoko Takano is a Professor of Medicine at McGill University, staff adult nephrologist at the McGill University Health Centre (MUHC) and senior scientist at the MUHC Research Institute. Dr. Takano received her M.D. from University of Tokyo and completed residency in Internal Medicine and Nephrology at University of Tokyo. Following clinical training in Nephrology, she obtained a Ph.D. in Biochemistry at University of Tokyo and completed post-doctoral training at the Brigham and Women’s Hospital in Boston and Royal Victoria Hospital in Montreal. Dr. Takano’s research focuses on glomerular podocyte biology and pathogenesis of proteinuria. Clinically, she contributes to the Chronic Kidney Disease Centre and the Glomerulonephritis Clinic. She is a founder and co-Director of the MUHC Kidney Disease Biorepository and the Chair of the Scientific Committee of the Canadian Society of Nephrology. She has been a member of various scientific committees including the Canadian Institute of Health Research and the Kidney Foundation of Canada.