Research Awards Recipients

Lay Abstract

The health of an organism largely depends on the accuracy of signals sent among constituent cells. Much of this information is transmitted inside cells through specific proteins, called protein kinases. Activity of protein kinases contributes to the maintenance of normal cell structure and function, while disorders in protein kinase activation or function can contribute to disease. Diseases of the renal glomerulus (the filtering unit of the kidney), especially those initiated by immunological processes ("glomerulonephritis"), account for approximately half of the causes of chronic kidney disease in Canada. Treatment of patients with kidney disease with dialysis and kidney transplantation has resulted in a dramatic improvement in the survival of patients, but at a large cost to the Canadian economy. Fundamental research into the disordered mechanisms that lead to glomerulonephritis is essential to the understanding of these diseases, an understanding that will ultimately lead to therapy and prevention. In this proposal, we will study abnormalities in cellular pathways in the glomerulus involving a protein kinase called SLK, and how disordered regulation of SLK leads to kidney disease. Previously, we generated mice with a genetic deletion of SLK in podocytes, cells that are critical for sustaining glomerular function. Mice with SLK deletion develop podocyte injury and abnormalities of the structure supporting cellular architecture (“cytoskeleton”). Furthermore, glomerular disease is more aggressive in mice with SLK deletion. The proposed studies will use a tissue-culture system and animal models of glomerulonephritis to characterize mechanisms by which SLK regulates the cytoskeletal structure in podocytes, and how dysregulation contributes to the cause of disease. Elucidation of such basic mechanisms of the causes of disease will lead to testing of therapies in preclinical (animal) models. This approach is likely to be the most productive in the development of treatment strategies for slowing progression of human glomerulonephritis.