The University of Michigan School of Dentistry
Defective bone and cartilage formation leads to osteoporosis, osteoarthritis, periodontal degeneration and tooth loss; the goal of our laboratory is to understand signals controlling bone and cartilage formation and exploit this knowledge to regenerate skeletal tissues.
Our laboratory is studying signals regulating the formation and functioning of bone and cartilage and is applying this knowledge to regenerate skeletal tissues for eventual clinical applications. We use a variety of molecular approaches and make extensive use of cell/organ culture and transgenic mouse models.
Differentiation of mesenchymal stem cells to osteoblasts (bone forming cells) requires RUNX2, an essential transcription factor that functions by binding to regulatory regions of target genes. We showed that RUNX2 is activated by MAP kinase (ERK and p38)-mediated phosphorylation, which subsequently induces epigenetic changes to alter chromatin architecture and expression of genes involved in osteoblast function. This pathway is activated by a variety of signals including extracellular matrix-mediated mechanical loading and growth factors.
Lack of weight-bearing exercise is a major cause of osteoporosis and bone loss while increased loading stimulates bone formation. We recently showed that loading stimulates MAP kinase activity. In addition to activating RUNX2, MAP kinase suppresses PPARɣ, a transcription factor necessary for marrow fat formation. This finding may explain why osteoporosis is usually associated with elevated marrow fat and can be reversed by weight-bearing exercise. Ongoing studies are focused on determining how changes in RUNX2 and PPARɣ phosphorylation alter chromatin structure and transcriptional activity at the genomic level.
Interactions between cells and their extracellular matrix (ECM) are critical for growth, differentiation and tissue morphogenesis. Collagens are the major ECM components of bone; binding of osteoblast and chondrocyte progenitors to collagens is essential for cell proliferation and differentiation. Discoidin domain receptor 2 (DDR2) is a major collagen receptor in bone and cartilage. DDR2 mutations cause severe bone and cartilage defects in humans and mice including severe reductions in bone mass and degeneration of the temporomandibular joint and intervertebral discs. Ongoing studies are using transgenic models to understand how DDR2 functions in bone and cartilage and exploit this knowledge to design tissue engineering scaffolds for bone and cartilage regeneration.
In collaboration with Dr. M. Fabiilli, methods are being developed that use focused ultrasound to stimulate synthesis of growth factors at specific locations within regenerating tissues. Ongoing studies are using this approach to pattern the expression of angiogenic and osteogenic factors, thereby producing blood vessels and bone at specific locations in the body. These methods may have wide applications in regenerative medicine where patterned delivery of growth factors is critical to produce new tissues of defined shape and size.
Dr. Franceschi holds a BA degree (Zoology) from the University of Vermont and a PhD. in Biochemistry from Purdue University. After completing a two-year postdoctoral fellowship with Dr. Hector DeLuca at the University of Wisconsin-Madison, he joined the faculty at the Harvard University School of Public Health as an Assistant Professor of Biochemistry (1981-1988). He subsequently held Associate Professor positions at the University of Texas Dental Branch (1989-1992) and the University of Michigan Schools of Dentistry and Medicine (1993-2000). He is currently the Marcus L. Ward Collegiate Professor of Dentistry, Professor of Biological Chemistry and Professor of Biomedical Engineering. At the School of Dentistry, he served as Director of Research (1998-2000) and Associate Dean for Research (2002-2005). Other service positions include President of the IADR Mineralized Tissues Group (2000-2002), President of the Association for Osteobiology (2010-14) and service on a number of NIH Review Panels including Chair of the Skeletal Biology, Structure and Regeneration Study Section (2005-2007). Editorial Board positions include the Journal of Biological Chemistry, Journal of Bone and Mineral Research and Journal of Dental Research. Research in the Franceschi laboratory is focused on the study of signals regulating bone and joint formation with particular emphasis on roles of mechanical loading and extracellular matrix interactions. His group is also actively involved in the development of gene therapy approaches to stimulate bone and blood vessel regeneration through the controlled expression of regenerative factors. He has published more than 130 papers and been continuously funded by the NIH for the past 35 years. He was the 2008 winner of the Distinguished Scientist Award for Basic Research in Biological Mineralization presented by the International Association for Dental Research.
Dr. Franceschi enjoys teaching and mentoring students and postdoctoral fellows. Major teaching responsibilities in the School of Dentistry include Cell and Molecular Biology and Mineralized Tissues. Several former trainees from the Franceschi lab now hold prominent positions in universities throughout the world.
Dr. Franceschi is a Fellow of the American Academy for the Advancement of Science, the American Society for Bone and Mineral Research and the American Association for Dental Research.
Professor, Pusan National University, Korea
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Associate Professor, Baylor College of Dentistry
Professor, Dept of Biochemistry, Rush University School of Medicine
Professor and Chair, Dept of Biology, Southern University of Science and Technology, Shenzhen, PRC
Professor, University of Minnesota School of Dentistry
Associate Professor, University of Pennsylvania School of Dentistry
Associate Professor, Chaing Mai University (Thailand)
DDS Private Practice
Associate Research Scientist, University of Michigan School of Dentistry
Associate Research Scientist, University of Michigan School of Dentistry
Professor, Chonnam University
Associate Professor, Chair, Orthodontics and Pediatric Dentistry University of Michigan School of Dentistry
Professor & Chair, Dept of Oral and Maxillofacial Surgery, Kyungpook Natl University
National Cell Bank for Tissue Engineering, Beijing, PRC
Sr. Research Associate, UM School of Dentistry
Oral & Maxillofacial Surgery Resident, MGH/Harvard
Staff Scientist, Bioventus, Boston, MA
Scientist , Mt Sinai Hospital, NY, NY
Scientist, Hospital Universitario La Paz-IdiPAZ & CIBER-BBN Madrid
Professor, Peking University
Assistant Professor, Central South University
Assistant Professor, King Saud University College of Dentistry, Saudi Arabia
Postdoctoral Research Fellow, Ohio State University
2020; J Dent Res; Mohamed FF | Ge C | Binrayes A | Franceschi RT
2017; Curr Mol Bio Rep; Franceschi RT | Ge C
2009; J Biol Chem; Ge C | Jiang D | Xiao G | Roca H | Franceschi RT
2017; J Cell Physiol; Li Y | Ge C | Franceschi RT
2012; J Bone Miner Res; Li Y | Ge C | Long JP | Begun DL | Rodriguez JA | Goldstein SA | Franceschi RT
2017; Bone; Ge C | Zhoa G | Li B | Li Y | Sun H | Cawthorn W | MacDougald OA | Franceschi RT
(Selected for feature Research Highlights Article by Nature Reviews in Endocrinology, Nov 10, 2017)
2016; J Bone Miner Res; Ge C | Wang Z | Zhao G | Li B | Liao J | Franceschi RT
2017; J Dent Res; Ge C | Mohamed F | Binrayes A | Kapila S | Franceschi RT
Our recent publication (Ge C, Zhoa G, Li B, Li Y, Sun H, Cawthorn W, MacDougald OA and Franceschi RT. Genetic inhibition of PPARɣ S112 phosphorylation reduces bone formation and stimulates marrow adipogenesis. Bone 107:1-9, 2017) was selected for a feature Research Highlights Article by Nature Reviews in Endocrinology, Nov 10, 2017.
1011 N. University, Rm 3328
Ann Arbor, MI 48109-1078
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