Professor, Biological Chemistry
B.A., University of Vermont
Ph.D., Purdue University
Postdoctoral, University of Wisconsin
This laboratory is studying signals regulating the formation and functioning of osteoblasts, cells that produce and mineralize the extracellular matrix of bone, and is applying this knowledge to regenerate mineralized tissues for eventual clinical use. Research is focused on mechanisms controlling osteoblast-specific gene expression with particular emphasis on the roles of bone-associated transcription factors, hormones/growth factors, cell:extracellular matrix interactions, and mechanical force in this process. Endocrine/juxtacrine factors under study include several bone morphogenetic proteins (BMPs), fibroblast-derived growth factors and parathyroid hormone. Specific projects include:
- studies to elucidate the mechanism through which cell-extracellular matrix interactions, hormonal/growth factor signals and mechanical force activate the osteoblast-specific transcription factor, RUNX2, by MAP kinase and related phosphorylation events.
- Analysis of regulatory interactions between RUNX2 and other nuclear proteins including DLX5/6 and ATF4.
- development of gene therapy approaches to stimulate bone regeneration through the controlled expression of BMPs and other morphogenic compounds.
- Studies to elucidate the mechanism of hydroxyapatite crystal formation in bone using Raman spectroscopy (in collaboration with Dr. Mike Morris-Chemistry).
My research group is part of the University of Michigan Musculoskeletal Research Center and the Center for Craniofacial Regeneration, an interactive group of researchers in the Schools of Medicine, Dentistry and Engineering having the common goal of conducting basic and applied research directed toward treating diseases of mineralized tissues.
1998,2004 Mentor to Am. Society for Bone and Mineral Research Young Investigator Awardees, Dr. G. Xiao and C. Ge
2001 President, IADR Mineralized Tissues Group
2006 Chair of the Skeletal Biology, Structure and Regeneration Study Section at the Center for Scientific Review at NIH
2008 Distinguished Scientist Award for Basic Research in Biological Mineralization, International Association for Dental Research
Xiao G, Jiang D, Thomas P, Benson MD, Guan K, Karsenty G and Franceschi RT . MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J Biol Chem 275:4453-4459, 2000 PMID: 10660618
Benson MD, Xiao G, Bargeon J, Kim A, Franceschi RT Characterization of an Element in the Bone Sialoprotein Promoter which is Required for Its Osteoblastic-Selective Expression. J. Biol. Chem .275:13907-13917, 2000.
Xiao G, Jiang D and Franceschi RT , FGF-2 induction of the osteocalcin gene requires MAPK activity and phosphorylation of the osteoblast transcription factor, Cbfa1/Runx2. J Biol Chem 277:36181-36187, 2002.
Franceschi RT , Ge C, Xiao G, Roca H and Jiang D. Transcriptional Regulation of Osteoblasts. In:Skeletal Biology and Medicine, Part A, Aspects of Bone Remodeling. (Zaidi M, Ed., Blackwell, Boston) Ann. NY Acad Sci 1116:196-207, 2007. PMID: 18728356
Ge C, Xiao G, Jiang D and Franceschi RT . Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. J Cell Biology 176:709-718, 2007. PMID: 17325210
Franceschi RT . Biological approaches for bone regeneration using gene therapy. Crit. Rev. Oral Biol. Med. J Dental Res 84:1093-1103, 2005.
Koh J-T, Zhao Z, Wang Z, Lewis I, Krebsbach PH and Franceschi RT . Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration. J Dental Res 87:845-849, 2008. PMID: 18719211