Vitamin D is a potent regulator of cellular functions in a variety of tissues. Research within our group is aimed at defining the clinical importance of this by exploring novel responses and mechanisms associated with vitamin D. These include classical actions of vitamin D in the bone and so-called non-classical effects of vitamin D, notably as a regulator of immune responses.
Vitamin D, mTOR and the regulation of osteoblast function.
Vitamin D plays a key role in maintaining the skeleton by regulating calcium and phosphate homeostasis – vitamin D-deficiency leads to the bone disease rickets in children and osteomalcia in adults. However, vitamin D can also influence other components of the skeleton, notably the cells that control bone turnover. In a series of studies we have shown that the proliferation and differentiation effects of active vitamin D (1,25-dihydroxyvitamin D, 1,25(OH)2D) on bone-forming osteoblasts involve suppression of mTOR signaling.
Novel mechanisms involved in regulating the transcriptional effects of vitamin D.
As a steroid hormone, the active form of vitamin D, 1,25(OH)2D, can modulate gene transcription following binding to its cognate nuclear receptor, the vitamin D receptor (VDR), and interaction with target gene promoter DNA.
Antibacterial effects of vitamin D.
We now know that in addition to its classical effects on the skeleton vitamin D is a potent regulator of other important physiological responses. Prominent amongst these effects is the interaction between vitamin D and the immune system. In collaboration with Dr Robert Modlin and Dr Philip Liu at UCLA, we have established a series of studies to explore the antibacterial properties of vitamin D.
Vitamin D, immune regulation and chronic kidney disease.
The kidney is the main tissue for conversion of precursor 25OHD to active 1,25(OH)2D, and this activity is greatly compromised in patients with chronic kidney disease (CKD).