Pathophysiological role of vitamin D signalling

1α,25-dihydroxy-vitamin-D3, the active form of vitamin D, has potent anti-inflammatory and anti-proliferative activities, and represents a therapeutic option for many pathologies. However, the doses required induce hypercalcemia, resulting in calcification of the kidneys, heart and blood vessels, leading to dysfunction of these organs. In addition, various rare diseases induced by abnormal vitamin D signaling are characterized by hypercalcemia secondary to high 1α,25-dihydroxy-vitamin-D3 levels. The expression of the vitamin D receptor (VDR) in the intestine and kidneys is essential for calcium homeostasis.

This project aims to dissect the mechanisms underlying VDR activities in intestinal and renal cells in mouse models of rare diseases induced by abnormal vitamin D signaling. In addition, we characterize novel vitamin D analogues with VDR antagonistic activity or with dissociated pro-calcemic and anti-inflammatory and/or antiproliferative activities for the treatment of rare diseases, as well as auto-immune disorders and cancers, respectively