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.

Renny T. Franceschi
PhD

ABOUT

OVERVIEW

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.


FOCUS AREAS

Control of gene expression in bone

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.

Extracellular matrix control of bone and cartilage development

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.

Gene therapy approaches for bone 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.

DIRECTOR

RENNY T. FRANCESCHI, BA, PhD

Marcus L. Ward Collegiate Professor
Professor, Department of Periodontics and Oral Medicine, School of Dentistry
Professor, Department of Biological Chemistry, School of Medicine
Professor, Department of Biomedical Engineering

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.

PUBLICATIONS

Key publications:

Biomechanical stimulation of osteoblast gene expression requires phosphorylation of the RUNX2 transcription factor

2012; J Bone Miner Res; Li Y | Ge C | Long JP | Begun DL | Rodriguez JA | Goldstein SA | Franceschi RT

Genetic inhibition of PPARɣ S112 phosphorylation reduces bone formation and stimulates marrow adipogenesis

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)

Discoidin domain receptor 2 controls bone formation and marrow adipogenesis

2016; J Bone Miner Res; Ge C | Wang Z | Zhao G | Li B | Liao J | Franceschi RT

Selective role of discoidin domain receptor 2 in murine temporomandibular joint development and ageing

2017; J Dent Res; Ge C | Mohamed F | Binrayes A | Kapila S | Franceschi RT

Advanced BMP Gene Therapies for Temporal & Spatial Control of Bone Regeneration

2013; J Dental Res-Crit Rev Oral Biol Med; Wilson CG | Martín-Saavedra FM | Vilaboa-Díaz N | Franceschi RT

View the complete list of publications

PERSONNEL

Chunxi Ge, MD, PhD
Associate Research Scientist

chunxige@umich.edu

Yan Li, PhD
Research Lab Specialist

yanlili@umich.edu

Fatma Mohamed, BDS, MS
Graduate student, PhD Candidate

fmohamed@umich.edu

ALUMNI

Kun Young Park, PhD
(1986 - 1987, Postdoctoral fellow)

Professor, Pusan National University, Korea

Anna R. Giuliano, PhD
(1987 - 1989, Co-chair of Thesis Committee)

H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

M. Douglas Benson, PhD
(1993 - 2000, Chair of Thesis Committee)

Associate Professor, Baylor College of Dentistry

Ghouzi Xiao, MD, PhD
(1995 - 1999, Postdoctoral fellow)
1999 - 2005, Research Investigator)

Professor, Dept of Biochemistry, Rush University School of Medicine

Professor and Chair, Dept of Biology, Southern University of Science and Technology, Shenzhen, PRC

Rajaram Gopalakrishnan, DDS, PhD
(1999 - 2002, Postdoctoral fellow)

Professor, University of Minnesota School of Dentistry

Shuying Yang, PhD
(2000 - 2001, Postdoctoral fellow)

Associate Professor, University of Pennsylvania School of Dentistry

Mataborn Phimphilai, PhD
(2001 - 2005, Chair of Thesis Committee)

Associate Professor, Chaing Mai University (Thailand)

Zhuoran Zhao, DDS, PhD
(2002 - 2006, OHS PhD Chair of Thesis Committee)

DDS Private Practice

Chunxi Ge, MD, PhD
(2003 - 2007, Postdoctoral fellow)

Associate Research Scientist, University of Michigan School of Dentistry

Hernan Roca, PhD
(2003 - 2006, Research Investigator)

Associate Research Scientist, University of Michigan School of Dentistry

Jeong-Tae Koh, DDS, PhD
(2004 - 2006, Visiting Scientist)

Professor, Chonnam University

Nan E. Hatch, DDS, PhD
(2006 - 2008, Postdoctoral Fellow, TEAM Training Grant)

Associate Professor, Chair, Orthodontics and Pediatric Dentistry University of Michigan School of Dentistry

Tae-Geon Kwon, DDS, PhD
(2007 - 2009, Visiting Scientist)

Professor & Chair, Dept of Oral and Maxillofacial Surgery, Kyungpook Natl University

Xiang Zhao, PhD
(2007 - 2012, Postdoctoral Fellow)

National Cell Bank for Tissue Engineering, Beijing, PRC

Yan Li, PhD
(2007 - 2009, Postdoctoral Fellow)

Sr. Research Associate, UM School of Dentistry

Qian Yang, PhD
(2007 - 2009, Research Associate)

Oral & Maxillofacial Surgery Resident, MGH/Harvard

Christopher Wilson, PhD
(2007 - 2013, Postdoctoral Fellow, TEAM Training Grant)

Staff Scientist, Bioventus, Boston, MA

Guisheng Zhao, PhD
(2010 - 2014, Research Associate)

Scientist , Mt Sinai Hospital, NY, NY

Francisco Martin Saavedra, PhD
(2011 - 2012, Postdoctoral Fellow)

Scientist, Hospital Universitario La Paz-IdiPAZ & CIBER-BBN Madrid

Binbin Li, DDS, PhD
(2012 - 2013, Visiting Scientist)

Professor, Peking University

Hui Li, PhD
(2012 - 2014, Visiting Scientist)

Assistant Professor, Central South University

PRESS

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.

Read the Paper

CONTACT

FRANCESCHI LAB
1011 N. University, Rm 3328
Ann Arbor, MI 48109-1078
rennyf@umich.edu
734-763-7381 | Fax: 734-763-5503