Cliniques universitaires Saint-Luc

Service de néphrologie

Recherche

Research in the Division of Nephrology
Laboratory of Nephrology: http://www.uclouvain.be/en-nefr.html

In most mammals, including humans, the regulation of body fluid homeostasis depends on the appropriate handling of water and solutes by the kidney. Our understanding of the mechanisms involved in body fluid homeostasis has substantially improved with the molecular identification and structural characterization of key proteins (channels, transporters, or their regulators) that facilitate the movement of water and ions across biological membranes. The discovery of these molecules, initiated by classical biochemical approaches, has considerably benefited from the molecular genetics analysis of inherited diseases. Mutations in a series of genes, leading to their dysfunction, are associated with inherited renal diseases collectively called "tubulopathies". Investigation of such tubulopathies yielded crucial informations about the mechanisms involved in water and solute handling by the kidney, and the regulation of extracellular fluid volume. In turn, these insights improved the diagnosis, follow-up and treatment of renal diseases complicated by dehydration, electrolyte disorders, hypertension, growth retardation, nephrolithiasis, and progressive renal failure.
Our research projects focus on the physiology of transport mechanisms and the pathophysiology of inherited kidney disorders. Using a combination of in vivo phenotyping and cell and molecular approaches, we investigate the function, regulation, development, and pathophysiology of channels and transporters in the normal and diseased state. These translational studies are relevant for the detection, understanding, and treatment of human diseases due to defective renal function and dysregulation of body fluid homeostasis. These topics represent the core of the research activities supervised by Prof. O. Devuyst since 1997, in close integration with the clinical and teaching activities at the UCL Medical School in Brussels. These investigations provided new insights in essential processes such as the regulation of endocytosis and the transport of proteins, the biogenesis of lysosomes, the regulation of salt reabsorption, and the water handling by various nephron segments. We also investigate the mechanisms of renal disease progression in polycystic kidney disease, by analyzing the importance of modifier genes and testing various mouse models. Over the years, we also developed an interest in the mechanisms of water and solute transport across the peritoneal membrane, with the aim of improving the efficiency of water and solute removal during peritoneal dialysis, an important therapeutic modality for patients with end-stage renal disease.
During the years 1997-2007, our research activity has generated 10 doctoral theses et more than 150 original papers published in the top nephrology (JASN, Kidney Int, AJKD) and multi-disciplinary (NEJM, Lancet, Nat Genet, JBC, Am J Pathol, PNAS, Pflügers Arch, Am J Physiol) journals. Our projects are supported by a competitive funding obtained at the national and international level, including three grants from the EU. Through international collaborations (Euregene, Eunefron, Regenet networks), we are extending these investigations using genome, transcriptome and proteome analyses, new transgenic mouse models and model organismss and cutting-edge imaging techniques, in parallel with phenotype and genetic studies of patients harbouring kidney disorders.