Bioactivation and metabolism of vitamin D including vitamin D-mediated effects on cellular function

This research is focused on enzymes and genes of importance for vitamin D bioactivation, metabolism and function. Effects on these processes by endogenous and pharmacological compounds are studied. Many drugs result in adverse side-effects, including increased risk of bone disease. We study the mechanisms by which anti-inflammatory, anti-viral and anti-epileptic drugs affects cells, with particular focus on the bone and the central nervous system. Vitamin D is needed for regulation of calcium levels in the body and vitamin D deficiency leads to skeletal diseases such as rickets in children and osteomalacia/osteoporosis in adults. The biologically active form, 1alpha,25-dihydroxyvitamin D3, is formed through metabolic activation. The activated form of vitamin D blocks cell division and increases cell differentiation. Vitamin D analogues (synthetic compounds with vitamin D-like effects) are used in the treatment of psoriasis and are of interest in development of new cancer therapy. In addition, epidemiological data during recent years have indicated that vitamin D may have many more targets than previously known. Altered vitamin D levels in plasma have been linked to a number of different conditions including neuropsychiatric and neurodegenerative disease. For these reasons, it is important to obtain more knowledge about the enzymes and genes in activation and metabolism of vitamin D and the roles of the formed metabolites. Part of this project is focused on cellular effects of vitamin D and vitamin D analogues in order to explore previously unknown functions of these compounds. 

External collaborators: Östen Ljunggren, Dept. of Medical Sciences, UU, Jan Gustafsson, Dept. of Women’s and Children’s Health, UU Jonas Bergquist and Kumari Ubhayasekera, Dept. of  Chemistry-BMC, UU