Grant: Project Grant

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 with a lot of undesired side effects and not always effective. 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 makes podocytes to malfunction. When the Rac1 activation is persistent, eventually podocytes are 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 two proteins, called beta-PIX and CdGAP that regulate Rac1 in podocytes. We will study how these proteins work in podocytes and establish if they could be good therapeutic targets. The results of the research will make us understand how proteinuria occurs and allow the development of a better therapeutic approach.