Translational research is conducted on syndromic dental anomalies in connection with the Reference Center for dental and oral rare diseases ORares set up by our team at the Assistance Publique – Hôpitaux de Paris. The team explores malformative syndromes associating Amelogenesis Imperfecta with renal and ocular manifestations including ectopic mineralization, myopia and/or proteinuria. We focus on two functional pathways: (1) The megalin-cubilin pathway is critical for renal protein reabsorption, physiological eye growth and most likely normal amelogenesis. Conditional ablation of these endocytic multiligand receptors in the above tissues mimics the human pathologies underlying their roles in the disease process. (2) The FAM20A-FAM20C involving pathway appears to be necessary for the post translational modifications of secretory proteins, normal and pathological biomineralization. Ongoing studies will establish the FAM20A interactome and identify possible therapeutic targets. Our disease/gene to cellular network approach includes phenotypic characterization of dental (A) and gingival tissues (B-D, as well as cell (E, F) and omics studies.
