Laurent Schild, Full Professor, Director of the DPT
Laurent Schild obtained a diploma in medicine in 1979 from the Medical School of the University of Lausanne and a Doctorate in Medicine in 1984. From 1984 to 1990, he was postdoctoral fellow at Yale University Medical School, first in the laboratory of Prof. Giebisch at the Department of Cellular and Molecular Physiology, then at the Department of Pharmacology in the laboratory of Prof. Moczydlowski.
He returned to Lausanne in 1990, at the Department of Pharmacology & Toxicology, and started an indepedendent group of research, working on the pharmacology of ion channels. He closely collaborated with Prof. B. C. Rossier for the understanding of the structure, the function and the regulation of the epithelial sodium channel (ENaC). Presently, he is full Professor of Pharmacology and Director of the Department of Pharmacology.
Epithelia form barriers that separate the body fluids from the outside world, and serve to maintain their water and solute composition. To achieve this essential function, epithelial cells are capable of vectorial transport of solutes and water thanks to ion pumps, transporters or channels located in plasma cell membranes. The epithelial sodium channel ENaC allows the entry of Na+ ions into the cell and mediates vectorial transcellular transport of sodium. In the kidney, ENaC is responsible for the fine tuning of urinary Na+ excretion that allows the maintenance of a strict balance between the daily salt intake and Na+ elimination. In the lung ENaC participates in Na+ secretion in the airway epithelia, in order to maintain constant the airway surface liquid. Human genetic studies have demonstrated the role of ENaC in the control of extracellular fluid volume and blood pressure. In mice, ENaC gain of function targeted in the lung leads to a cystic fibrosis-like lung disease.
Our research investigates the cellular and molecular mechanisms that control the activity of the epithelial Na channel ENaC. More specifically, we are interested in the relations between the ENaC structure and the activity of the channel; in this context, we also investigate ENaC-associated proteins that contribute to channel function. Finally, we develop new strategies to control ENaC activity, using specific pharmacological ligands designed to target defined functional domains of the channel.
In industrial countries, hypertension affects 15 to 20% of the adult population, and represents a major risk factor for cardiovascular events such as myocardial infarct or stroke. Plethora of evidence from animal, clinical and epidemiological studies have demonstrated the role of dietary sodium intake in the development of hypertension. In this context, ENaC represents the ideal target for pharmacological agents to control blood pressure.
Key words: Epithelial sodium channel, Renal transport, Sodium homeostasis, Ion channels, Aldosterone, Hypertension