Daniel Bikle, MD, PhD
Daniel Bikle, MD, PhD
Hormonal regulation of calcium metabolism
In pursuing our studies we make extensive use of genetically modified mice. For the skeletal projects we conditionally delete IGF-I or its receptor, IGF-IR, from chondrocytes, osteoblasts and osteoclasts then ask how that affects skeletal development, response to PTH, response to skeletal unloading or reloading, and fracture healing. In the studies of skin we use mice lacking the vitamin D receptor (VDR), VDR coactivators such as MED1 and SRC3, the enzyme producing the active vitamin D metabolite, 1,25(OH)2D (CYP27B1), the calcium receptor, or key components in the hedgehog and wnt/beta-catenin pathways to examine the impact of such gene deletions on epidermal development, hair follicle cycling, and UVB induced tumor formation.
1. Oda Y, Chalkley RJ, Burlingame AL, Bikle DD 2010 The transcriptional coactivator DRIP/Mediator complex is involved in VDR function and regulates keratinocyte proliferation and differentiation. J Invest Dermatol 130:2377-2388.
2. Teichert A, Elalieh H, Elias P, Welsh J, Bikle DD. 2011. Over-expression of hedgehog signaling is associated with epidermal tumor formation in vitamin D receptor null mice. J Invest Dermatol 131:2289-2297
3. Long RK, Nishida S, Kubota T, Wang Y, Sakata T, Elalieh HZ, Halloran BP, and Bikle DD 2011 Skeletal unloading induced insulin-like growth factor-I (IGF-I) resistance is not shared by platelet-derived growth factor: the selective role of integrins in IGF-I signaling J Bone Min Res 26:2948-2958
4. Wang Y, Cheng Z, ElAlieh HZ, Nakamura E, Nguyen M-T, Mackem S, Clemens TL, Bikle DD, Chang W 2011 IGF-1R Signaling in Chondrocytes Modulates Growth Plate Development by Interacting with the PTHrP/Ihh Pathway. J Bone Min Res 26:1437-1446
5. Oda Y, Hu L, Bul V, Elalieh H, Reddy JK, Bikle DD 2012 Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alterations. J Invest Dermatol 132:1075-1083
6. Tu C-L, Crumrine D, Man M-Q, Chang W, Elalieh H, You M, Elias PM, and Bikle DD.2012. Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. J Invest Dermatol 132:2350-2359