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My research is focused on the hormonal regulation of calcium metabolism, and includes projects involving the classic target tissues of bone and intestine as well as non classic tissues including the skin. One project attempts to understand the molecular mechanisms by which 1,25(OH)2 D regulates intestinal calcium transport, in particular calcium transport across the brush border. We are using animal models in which critical components of 1,25(OH)2 D signaling and the calcium transport process have been deleted in the intestine for this purpose. The second project is evaluating the effects of parathyroid hormone and insulin like growth factor-1 on bone formation, with particular interest in the effects of mechanical loading on the anabolic actions of these hormones, examining at the molecular level the signaling pathways mediating these hormones as affected by loading. As for the intestine, we are using animal models in which IGF-I and its receptor have been conditionally deleted in bone for these studies. The third project is examining the mechanisms by which calcium and 1,25(OH)2 D regulate keratinocyte differentiation. We are focusing on the calcium receptor and the vitamin D receptor, and the signaling pathways and transcriptional events mediated by their activation, again using animal models lacking the calcium receptor and vitamin D receptor in the epidermis. Xie Z, Singleton PA, Bourguignon LYW, Bikle DD. 2005. Calcium-induced human keratinocyte differentiation requires src- and fyn-mediated phosphatidylinositol 3-kinase dependent activation of phospholipase C-?1. Molec Biol Cell 16: 3236-3246 Xie Z, Chang S, Oda Y, Bikle DD. 2006. Hairless suppresses vitamin D receptor transactivation in human keratinocytes. Endocrinology 147:314-323 Bikle DD, Elalieh H, Chang S, Xie Z, Sundberg J 2006 Development and progression of alopecia in the vitamin D receptor null mouse. J Cell Physiol 207:340-353 Wang Y, Nishida S, Elalieh HZ, Long RK, Halloran BP, Bikle DD. 2006 The Role of IGF-I Signaling in Regulating Osteoclastogenesis. J Bone Min Res 21:1350-1358 Wang Y, Nishida S, Sakata T, Elalieh HZ, Chang W, Halloran BP, Doty SB, Bikle DD. 2006. Insulin-Like Growth Factor-I Is Essential For Embryonic Bone Development. Endocrinology 147:4753-4761 Hawker N, Pennypacker S, Chang S, Bikle D. Regulation of human epidermal keratinocyte differentiation by the vitamin D receptor and its coactivators DRIP205, SRC2, and SRC3. J Invest Dermatol (in press) T C-L, Chang W, Bikle DD. The role of the calcium sensing receptor in regulating intracellular calcium handling in human epidermal keratinocytes. J Invest Dermatol (in press). Xie Z and Bikle DD 2007. The recruitment of phosphatidylinositol 3-kinase to the E-cadherin/catenin complex at the plasma membrane is required for calcium-induced phospholipase C-? 1 activation and human keratinocyte differentiation. J Biol Chem (in press). |
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