cell injury • glomerulonephritis • phospholipases • protein kinases • stress proteins
Diseases of the renal glomerulus, which acts as the filtering unit of the kidney – especially those diseases initiated by immunological processes (glomerulonephritis) – account for approximately half of the causes of chronic kidney disease in Canada. 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 perhaps prevention. Our research is directed at understanding the mechanisms of glomerular cell injury. We employ experimental animal models and molecular, biochemical and cell imaging approaches to elucidate the pathophysiology of human glomerular disease involving the podocyte. The ultimate goal of our research is to comprehensively understand the pathophysiology of podocyte injury in order to develop diagnostic bioassays and mechanism-based therapies for human glomerulonephritis. We study three research themes: characterization of mediators and development of therapies for glomerulopathies involving podocyte injury; extracellular matrix and cytoskeleton as determinants of signaling responses in podocytes and potential therapeutic targets; and protein kinase, SLK, a novel mediator of podocyte integrity and glomerular permselectivity.
Jaberi A, Hooker E, Guillemette J, Papillon J, Kristof AS, Cybulsky AV. Identification of Tpr and α-actinin-4 as two novel SLK-interacting proteins. Biochim Biophys Acta Mol Cell Res. 2015, 1853, 2539-2552.
Elimam H, Papillon J, Kaufman DR, Guillemette J, Aoudjit L, Gross RW, Takano T, Cybulsky AV. Genetic ablation of calcium-independent phospholipase A2γ induces glomerular injury in mice. J Biol Chem. 2016, 291, 14468-14482.
Kaufman DR, Papillon J, Larose L, Iwawaki T, Cybulsky AV. Deletion of inositol-requiring enzyme-1α in podocytes disrupts glomerular capillary integrity and autophagy. Mol Biol Cell. 2017, 28, 1636-1651.
Cybulsky AV, Papillon J, Guillemette J, Belkina N, Patino-Lopez G, Torban E. Ste20-like kinase, SLK, a novel mediator of podocyte integrity. Am J Physiol. 2018, 315, F186-F198.
Yee A, Papillon J, Guillemette J, Kaufman DR, Kennedy CRJ, Cybulsky AV. Proteostasis as a therapeutic target in glomerular injury associated with mutant alpha-actinin-4. Am J Physiol. 2018, 315, F954-F966.