About this research groupThis research group focuses on understanding tubulopathies. The focus is on the tubular transport of calcium, magnesium and sodium by the kidney tubule and the changes therein. For acquired renal disorders, uncovering the underlying mechanism, prevention and rational treatments for drug-induced toxicities is a main focus.
Our group has several aims.
- Understanding mineral homeostasis biology
- Elucidate molecular mechanisms
Several discoveries were made by our research group.
We were the first to identify the epithelial Ca2+ channel, baptized TRPV5, by functional expression cloning.
Molecular mechanisms of renal Ca2+ handling
We were the first to identify the epithelial Ca2+ channel, baptized TRPV5, by functional expression cloning. Defective TRPV5 function could ultimately impair the Ca2+ conserving capacity of the body and contribute to hypercalciuria and serious age-related bone disorders. Our group found that ablation of the TRPV5 gene in mice seriously disturbs renal Ca2+ handling, resulting in compensatory intestinal hyperabsorption and bone abnormalities. Using state-of-the-art approaches, new entry mechanisms have been identified that facilitate the transport of minerals in kidney and intestine. Multidisciplinary approaches were applied to study several regulatory aspects of these new ion channels, and we have uncovered several mechanisms including associated proteins, new hormones that modify the activity of the transport systems by phosphorylation, hydrolysis of extracellular N-linked sugar moieties or transcriptional regulation via their promoters.
We extended our research activities towards understanding Mg2+ homeostasis, an essential mineral whose regulation is not well understood.
Physiology and pathophysiology of Mg2+ homeostasis
We extended our research activities towards understanding Mg2+ homeostasis, an essential mineral whose regulation is not well understood. The rate-limiting Mg2+ influx channel, TRPM6, has been characterized by my group, and the functional implications of mutations, identified in patients, have been described. The first intracellular regulators and additional Mg2+-related transporters were identified and characterized. I provided evidence that mutations in TRPM6 in patients with type 2 diabetes are responsible for the hypomagnesemia, which is frequently observed in diabetes patients. Functional characterization of the mutated magnesiotropic genes in patients with Mg2+-related balance disorders elucidated the first molecular mechanisms of disease, opening the path for new treatment strategies.