Experimental and Translational Research
Since the 1990s, the group investigates the nature and clinical relevance of fluid and ion transport across biological membranes, both at the level of renal tubular epithelia and across the peritoneal membrane.
Regulation of body fluid homeostasis is of vital importance for all terrestrial organisms. In most mammals, the maintenance of the hydration status and normal plasma electrolytes levels critically depends on the appropriate handling of water and ions by the kidneys. This essential function involves specific transport systems operating in the epithelial cells lining kidney tubules. The study of these processes in various segments of the kidney, their regulation and ontogeny, and the pathophysiology of inherited renal disorders including tubulopathies and polycystic kidney disease, has provided essential information about the mechanisms of water and solute handling by the nephron in health and disease. Insights obtained through these investigations are relevant for common conditions such as blood pressure regulation, kidney stones, progression of renal failure, and cardiovascular complications of renal diseases.
The knowledge of transport mechanisms also led us to work on the molecular basis of water and solute transport across the peritoneal membrane, with the aim of improving peritoneal dialysis, a therapeutic modality for patients with end-stage renal disease. For instance, the group characterized innovative mouse and rat models of PD, established the influence of uremia and nitric oxide on the peritoneal membrane, documented the role of genetic factors to explain individual variability in transport parameters, substantiated the link between vascular proliferation and loss of ultrafiltration, contributed to delineate the role of water channels in PD, and depicted molecular mechanisms of the immune response during acute PD-related peritonitis and their impact on membrane integrity and transport.
Our research programs are based on a multi-disciplinary approach including studies on patients, human and mouse genetics, and analysis of mouse and cellular models. Over the years, our studies benefited from fruitful international collaborations, leading us to initiate and participate in several European networks. These collaborations allow us to develop our projects using genome, transcriptome and proteome analyses; genome-wide association studies; conditional KO and randomly mutagenized mice; in translation with studies of human tubular disorders collected at the European level.
Recent publications
The NLRP3 Inflammasome Has a Critical Role in Peritoneal Dialysis-Related Peritonitis. Hautem N*, Morelle J*, Sow A, Corbet C, Feron O, Goffin E, Huaux F, Devuyst O J Am Soc Nephrol. 2017 Jul;28(7):2038-2052.
Tubular proteinuria in patients with HNF1α mutations: HNF1α drives endocytosis in the proximal tubule. Terryn S, Tanaka K, Lengelé JP, Olinger E, Dubois-Laforgue D, Garbay S, Kozyraki R, Van Der Smissen P, Christensen EI, Courtoy PJ, Bellanné-Chantelot C, Timsit J, Pontoglio M, Devuyst O Kidney Int. 2016 May;89(5):1075-89.
TRPV4 is associated with central rather than nephrogenic osmoregulation. Janas S, Seghers F, Schakman O, Alsady M, Deen P, Vriens J, Tissir F, Nilius B, Loffing J, Gailly P, Devuyst O Pflugers Arch. 2016 Sep;468(9):1595-607.
Ultrafiltration Failure and Impaired Sodium Sieving During Long-Term Peritoneal Dialysis: More Than Aquaporin Dysfunction? Morelle J, Sow A, Hautem N, Devuyst O, Goffin E. Perit Dial Int. 2016 Mar-Apr;36(2):227-31.
Water and solute transport across the peritoneal membrane. Morelle J, Devuyst O. Curr Opin Nephrol Hypertens. 2015 Sep;24(5):434-43.
Molecular Physiology of Water Balance. Morelle J, Goffin E, Devuyst O. N Engl J Med. 2015 Jul 9;373(2):196.
Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis. Morelle J, Sow A, Hautem N, Bouzin C, Crott R, Devuyst O, Goffin E. J Am Soc Nephrol. 2015 Oct;26(10):2521-33.
Quantification of osmotic water transport in vivo using fluorescent albumin. Morelle J, Sow A, Vertommen D, Jamar F, Rippe B, Devuyst O. Am J Physiol Renal Physiol. 2014 Oct 15;307(8):F981-9.
AqF026 is a pharmacologic agonist of the water channel aquaporin-1. Yool AJ, Morelle J, Cnops Y, Verbavatz JM, Campbell EM, Beckett EA, Booker GW, Flynn G, Devuyst O. J Am Soc Nephrol. 2013 Jun;24(7):1045-52.
Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression. Trudu M, Janas S, Lanzani C, Debaix H, Schaeffer C, Ikehata M, Citterio L, Demaretz S, Trevisani F, Ristagno G, Glaudemans B, Laghmani K, Dell'Antonio G; SKIPOGH team, Loffing J, Rastaldi MP, Manunta P, Devuyst O, Rampoldi L. Nat Med. 2013 Dec;19(12):1655-60.