null Andrey Cybulsky, MD
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.
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.
Tousson-Abouelazm N, Papillon J, Guillemette J, Cybulsky AV. Urinary ERdj3 and mesencephalic astrocyte-derived neutrophic factor identify endoplasmic reticulum stress in glomerular disease. Lab Invest. 2020, 100, 945-958.
Woychyshyn B, Papillon J, Guillemette J, Navarro-Betancourt JR, Cybulsky AV. Genetic ablation of SLK exacerbates glomerular injury in adriamycin nephrosis in mice. Am J Physiol Renal Physiol. 2020, 318, F1377-F1390.
Navarro-Betancourt JR, Papillon J, Guillemette J, Iwawaki T, Chung CF, Cybulsky AV. Role of IRE1α in podocyte proteostasis and mitochondrial health. Cell Death Discovery, 2020, 6, 128.
Navarro-Betancourt JR, Papillon J, Guillemette J, Iwawaki T, Chung CF, Cybulsky AV. The unfolded protein response transducer IRE1α promotes reticulophagy in podocytes. Biochim Biophys Acta, 2022, 1868, 16639.