Our work focuses on vitamin D in prevention and treatment of malignant diseases. Currently, we are interested in understanding molecular mechanisms affecting vitamin D anti-tumor activity. Specifically, we seek to understand the effect of onco-protein kinases on vitamin D signaling. We found that protein kinases CK2 and PIM1 regulate the expression of CYP24A1, a major enzyme responsible for inactivating vitamin D. We are developing strategies to inhibit the expression and/or activity of CYP24A1 thereby then enhancing the vitamin D anti-tumor action. We seek to understand the interaction between p53 and vitamin D in cancer since vitamin D demonstrates differential effect in p53 mutant vs p53 wild cancer cells. Using cell-based luciferase report assay, we are screening to discover small molecules for improving vitamin D anti-tumor action.