Supported Research

Chronic kidney disease is a significant problem that poses a large burden on individuals and society. We currently do not have a treatment and therefore we need more research to understand how the disease develops and to design new therapies. This project is aimed to provide fundamental new knowledge about the molecular events that cause chronic kidney disease. The kidney tubules are made of specialized cells called epithelial cells, which create and maintain a barrier and allow only highly regulated exchange of materials through the layer.

These cells are vital for kidney function. In recent years it also became clear that the injury of these cells leads to pathological changes that contribute to chronic kidney disease. Specifically, injury induces the production of mediators in these cells, and these mediators augment scar formation in the tissue. Scar formation, a disease called fibrosis, is the outcome of chronic kidney disease, and it is incurable and cannot be halted. It destroys normal kidney tissue and causes the kidneys to fail. The details of how this happens, however, are not clear. The tubular cells are connected to each other through a protein complex that creates a specialized transport pathway between the cells. This complex is called the tight junction. We found that one of the proteins residing in the tight junctions, claudin-2, is lost in a chronic kidney disease mouse model. Further, when we mimicked experimentally this loss, we found that tubular cells had augmented production of fibrosis-generating mediators, suggesting that claudin-2 is a regulator of this important process.

Therefore, in this project, we have three main objectives. First, using cultured tubular cells, we wish to define the cellular and molecular pathways through which claudin-2 controls epithelial activity and production of harmful mediators. Second, we wish to demonstrate in animal models that claudin-2 indeed has the ability to control the generation of fibrosis. Third, we have designed interventions that can interfere with the loss of claudin-2 and will test whether these can improve the generation of fibrosis.
Our studies will uncover new mechanisms underlying molecular events during kidney disease and will start assessing approaches that could benefit by slowing the disease process.

Biography
Katalin Szaszi MD, PhD is a scientist at the Keenan Research Center (KRC) for Biomedical Science of the St Michael’s Hospital and an associate professor at the University of Toronto (Dept Surgery). She obtained MD and PhD degrees at the Semmelweis University in Budapest, Hungary and completed post-doctoral trainings at the Hospital for Sick Children and Toronto General Hospitals in Toronto. She was appointed as a scientist at the KRC in 2005.

Dr. Szaszi is a cell biologist studying tubular epithelial biology and pathophysiology in inflammation and fibrosis in the context of kidney disease. Their work is funded by CIHR, NSERC and The Kidney Foundation of Canada. She was a recipient of a KRESCENT New Investigator award from The Kidney Foundation and CIHR (2007-2010) and an Early Research Award from the Ontario Ministry of Innovation. She has more than 60 peer-reviewed well cited publications.