People Joost Hoenderop Understanding tubulopathies

Tubular transport by the kidney tubule

Tubular transport of calcium, magnesium and sodium by the kidney tubule and the changes therein under pathological conditions are the focus. For acquired renal disorders, uncovering the underlying mechanism, prevention and rational treatments for drug-induced toxicities is a main focus.

Research group leader

Joost Hoenderop PhD
full professor

+31 (0)24 361 05 80
contact

Aims

Our research group has several aims.

  • One of our main goals is to elucidate the molecular mechanisms of tubulopathies.


Discoveries of our research group

We built up a substantial knowledge base and infrastructure in the field of molecular and cellular physiology of epithelial electrolyte transport. My team has studied epithelial transporters in great detail while working on various projects financed with grants at (inter)national organisations.

  • We were the first to identify the epithelial Ca2+ channel, baptized TRPV5, by functional expression cloning.

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    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. My 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.

  • Physiology and pathophysiology of Mg2+ homeostasis

    More recently, my group 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.

Team

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