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Research GroupsIron homeostasis in health and disease

Research Focus 1: Hereditary hemochromatosis

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Major research in the lab aims to understand molecular mechanisms involved in hereditary hemochromatosis (HH), the most prevalent genetic disorder in the western world. The disease is mainly caused by mutations in the HFE gene, which codes for a MHC class I like molecule. Work from our lab and others demonstrated that HFE is required for appropriate hepatic expression of the iron hormone and anti-microbial peptide hepcidin: expression of this negative regulator of duodenal iron absorption is decreased and cannot be appropriately adjusted in response to elevated hepatic iron levels in Hfe-deficient mice and HH patients.

These findings further our understanding of the molecular mechanism of Hfe function and suggest that the primary locus of Hfe function is the liver and not the duodenum, as was previously hypothesized. Indeed, using tissue-specific Hfe knock-out mice we recently unambiguously demonstrated that local Hfe expression in hepatocytes serves to maintain physiological iron homeostasis, answering this longstanding question in medicine. Using the conditional Hfe knock-out mouse lines established we now will investigate additional, especially extra-hepatic functions of the broadly expressed Hfe protein.

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