Research interests: The research in this group is aimed at increasing our understanding of the molecular bone-renal mechanisms that maintain a healthy mineralized skeleton and dentition. Since this dynamic-process is disturbed dramatically in many tumor-acquired and inherited diseases we are also studying these diseases in the hope that our findings will help to improve clinical treatment. In collaboration with an international consortium (HYP-consortium) we successfully identified the primary gene defect in an inherited bone-renal disease, X-linked hypophosphatemic rickets (HYP). This disease is characterized by severe under-mineralization of the skeleton and marked changes in renal-phosphate handling and vitamin D metabolism. We named this novel gene PHEX (acronym: phosphate regulating gene with homologies to endopeptidases on the X-chromosome). This discovery has stimulated new research and provided new reagents aimed at unraveling the molecular pathways downstream of the primary PHEX gene-product defect. More recently, we were the first to characterize and clone a completely novel bone-matrix protein (MEPE) from patients with tumor-induced osteomalacia. Also, we have demonstrated biological activity of this new MEPE protein and confirmed a direct interaction with PHEX. Our research indicates that a small acidic, protease-resistant MEPE-peptide that we named ASARM-peptide, could potentially be the first ‘biological bisphosphonate’ described. This peptide occurs in MEPE and some related family proteins (SIBLINGs) and the acronym ASARM stands for acidic-serine-aspartate-rich-MEPE-associated motif. The biological and physicochemical properties of the ASARM-peptide are remarkably similar to etidronate, a bisphosphonate. The ASARM-peptide (like etidronate) inhibits mineralization in-vivo and in-vitro and impacts on renal phosphate handling. Our research confirms ASARM-peptides play a major role in regulating mineralization, bone resorption and renal calcification. Clinical interests: Tumor and familial bone-renal mineral metabolism disorders.