Bone Center: Faculty: Gregory R. Mundy, M.D.

Dr. Mundy was appointed Director of the VUMC Center for Bone Biology in July, 2006. Prior to this, he was Assistant Dean for Clinical Research, Professor of Cellular and Structural Biology, and Interim Director of the San Antonio Cancer Institute at the University of Texas Health Science Center at San Antonio. He was the Heyser Professor of Bone and Mineral Metabolism and the Head of the Division of Endocrinology and Metabolism in the Department of Medicine as well as the Program Director of the Frederic C. Bartter Clinical Research Unit at the Audie L. Murphy Veterans Administration Hospital from 1980 until 2001. He received his M.B., B.S. degree from the University of Melbourne (1966) and his MD degree from the University of Tasmania (1973). He did his medical residency at the Royal Hobart Hospital and then joined the University of Tasmania as Lecturer in Medicine (1970). He passed the ECFMG (1966) and FLEX (1973). He passed the Boards in Internal Medicine (1975) and Boards in Endocrinology and Metabolism (1977). He was a Research Associate in Clinical Pharmacology at the University of Rochester (1972-1974), and Assistant and Associate Professor of Medicine, University of Connecticut (1974-1980). He is a Member (1970) and Fellow (1973) of the Royal Australasian College of Physicians. Dr Mundy was a recipient of the Fuller Albright Award of the American Society for Bone & Mineral Research (ASBMR) in 1982, an NIH MERIT Award in 1986, and was the William F. Neuman Awardee of the ASBMR in 1999. In 1999, he was named a University of Texas Health Science Center Presidential Distinguished Scholar. Dr. Mundy has been elected to membership of both the American Society for Clinical Investigation (ASCI) and the Association of American Physicians (AAP). He has founded four biotechnology startup companies for drug discovery in osteoporosis. He is the Immediate Past-President of the International Bone and Mineral Society, a Past-President of ASBMR and a former Chairman of the Research Grants Committee of the National Osteoporosis Foundation (NOF). He currently serves on the Boards of Directors of the NOF and the International Myeloma Foundation. Dr Mundy, who has served on several NIH Study sections in the past, was a member of the Advisory Council of the National Institute of Arthritis and Musculo-Skeletal Disorders (1997-2001).

Gregory R. Mundy, M.D. University of Tasmania 1973		John A. Oates Chair in Translational Medicine Director, Vanderbilt Center for Bone Biology Professor of Medicine, Pharmacology, Orthopaedics, Cancer Biology
Phone: Fax: Email:	(615) 322-6110 (615) 343-2611 gregory.r.mundy@vanderbilt.edu


Dr. Mundy was appointed Director of the VUMC Center for Bone Biology in July, 2006. Prior to this, he was Assistant Dean for Clinical Research, Professor of Cellular and Structural Biology, and Interim Director of the San Antonio Cancer Institute at the University of Texas Health Science Center at San Antonio. He was the Heyser Professor of Bone and Mineral Metabolism and the Head of the Division of Endocrinology and Metabolism in the Department of Medicine as well as the Program Director of the Frederic C. Bartter Clinical Research Unit at the Audie L. Murphy Veterans Administration Hospital from 1980 until 2001. He received his M.B., B.S. degree from the University of Melbourne (1966) and his MD degree from the University of Tasmania (1973). He did his medical residency at the Royal Hobart Hospital and then joined the University of Tasmania as Lecturer in Medicine (1970). He passed the ECFMG (1966) and FLEX (1973). He passed the Boards in Internal Medicine (1975) and Boards in Endocrinology and Metabolism (1977). He was a Research Associate in Clinical Pharmacology at the University of Rochester (1972-1974), and Assistant and Associate Professor of Medicine, University of Connecticut (1974-1980). He is a Member (1970) and Fellow (1973) of the Royal Australasian College of Physicians. Dr Mundy was a recipient of the Fuller Albright Award of the American Society for Bone & Mineral Research (ASBMR) in 1982, an NIH MERIT Award in 1986, and was the William F. Neuman Awardee of the ASBMR in 1999. In 1999, he was named a University of Texas Health Science Center Presidential Distinguished Scholar. Dr. Mundy has been elected to membership of both the American Society for Clinical Investigation (ASCI) and the Association of American Physicians (AAP). He has founded four biotechnology startup companies for drug discovery in osteoporosis. He is the Immediate Past-President of the International Bone and Mineral Society, a Past-President of ASBMR and a former Chairman of the Research Grants Committee of the National Osteoporosis Foundation (NOF). He currently serves on the Boards of Directors of the NOF and the International Myeloma Foundation. Dr Mundy, who has served on several NIH Study sections in the past, was a member of the Advisory Council of the National Institute of Arthritis and Musculo-Skeletal Disorders (1997-2001).
Current research interests in Dr. Mundy’s group include drug discovery in osteoporosis, the effects of tumors on the skeleton, osteoclast and osteoblast biology and development of the skeleton. Dr. Mundy is currently the principal investigator on 3 R01 grants, one VA Merit Review grant, and a National Institute funded Program Project Grant on the effects of tumors on the skeleton. He is in the top 2% of all NIH awardees in terms of extra-mural funding over the past 25 years. Dr. Mundy's publications number more than 500 papers and book chapters, and he has published 2 monographs on calcium homeostasis and bone remodeling and its disorders.
	Figure 1: Volume rendered MicroCT images of mice bearing parental MDA231 or MDA231 tumor cells overexpressing Gli2. Gli2 is a signaling molecule in the Hedgehog signaling pathway. Dr. Mundy’s laboratory has demonstrated that expression of Gli2 up regulates parathyroid hormone related protein (PTHrP), a known mediator of osteolysis caused by breast cancer metastases to bone. Note the increased bone destruction evident in the MDA231/Gli2 bearing mouse.
	Figure 2: Histological section of the mid-tibial metaphyses of the same mice as in Figure 1. Note the decreased trabecular bone and the increased tumor (T) in the MDA231/Gli2 mouse.
Research Techniques: Small Animal Imaging Quantitative Bone Histomorphometry

Recent Publications: Zhao M, Qiao M, Harris SE, Chen D, Oyajobi BO, Mundy GR: The Zinc Finger Transcription Factor Gli2 Mediates BMP-2 Expression in Osteoblasts in Response to Hedgehog Signaling. Molecular Cell Biology. 2006 Aug;26(16):6197-208. Sterling JA, Oyajobi BO, Grubbs B, Padalecki SS, Gupta A, Story B, Munoz S, Zhao M, and Mundy GR: The Hedgehog Signaling Molecule Gli2 Induces PTHrP Expression and Osteolysis In Metastatic Human Breast Cancer Cells. Cancer Research 2006, 66.Aug 1;66(15):7548-53. Mundy GR, Elefteriou F: Boning Up on Ephrin Signaling. Cell. 2006 Aug 4:126(3): 441-3. Gutierrez GE, Lalka D, Garrett IR, Rossini G, Mundy GR: Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations. Osteoporos Int 2006. Garrett IR, Chen D, Gutierrez G, Zhao M, Escobedo A., Rossini G, Harris SE, Gallwitz W, Kim KB, Hu S, Crews CM, Mundy GR: Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. J Clinical Investigation 2003, 111(11):1771-1782. Oyajobi BO, Franchin G, Williams PJ, Pulkrabek D, Gupta A, Munoz S, Grubbs B, Zhao M, Chen D, Sherry B, Mundy GR: Dual effects of macrophage inflammatory protein-1alpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood 2003, 102(1):311-319. Zhao M, Harris SE, Horn D, Geng Z, Nishimura R, Mundy GR, Chen D: Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation. J Cell Biol 2002, 157(6):1049-1060. Mundy GR: Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2002, 2(8):584-593. Gallwitz WE, Guise TA, Mundy GR: Guanosine nucleotides inhibit different syndromes of PTHrP excess caused by human cancers in vivo. J Clin Invest 2002, 110(10):1559-1572. Mundy GR, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G: Stimulation of bone formation in vitro and in rodents by statins. Science 1999, 286(5446):1946-1949.

Grants: Active: Merit Review 2003-2008 Veterans Administration Mechanism of Action of Statins on Bone Formation The major goal of this project is to examine the molecular interactions between the statins, drugs that stimulate bone formation, and nitric oxide generation by bone cells. 5R01 AR048801-04 2003-2008 NIH/NIAMS Effects of the Mevalonate Pathway on Bone Formation The major goal of this project is to examine the molecular interactions between the statins, drugs that stimulate bone formation, and nitric oxide generation by bone cells. R01 CA114000-02 2005-2010 NIH/NCI Gli Control of PTH-rP and Osteolysis in Breast Cancer The major goal of this project is to examine the Gli family of transcriptional regulators which represents an important molecular pathway that regulates PTH-rP expression in breast cancer cells, and subsequent breast cancer-mediated osteolysis. 1R01 AR050605-01-A1 2005-2009 NIH/NIAMS Ubiquitin-Proteasome Pathway and BMP-2 Expression The major goal of this project is to determine the molecular mechanisms by which inhibition of the ubiquitin-proteasome pathway increases osteoblast differentiation and bone formation, to determine the role of increased BMP-2 expression in these effects in vivo, and to clarity the role of the Gli family of transcription factors in the increases in BMP-2 expression. 2C76HF03583-02-00 2004-2006 Health Care and Other Facilities This is a subcontract to the International Myeloma Foundation for equipment. HHS; Health Resources and Services Administration Pending: 2P01-CA40035- 18 2006-2011 NIH/NCI Effects of Tumors on the Skeleton The major goal of this project is to identify novel molecular mechanisms responsible for important manifestations of cancer on the skeleton, including mechanisms responsible for the stimulatory effect of TGFβ on PTH-rP expression and subsequent osteolysis, regulation of expression of the bone resorbing peptide PTH-rP by breast cancer cells, molecular interactions between TGFβ and its receptor on breast cancer cells, and the role of the ubiquitin-proteasome pathway in myeloma progression and the associated bone disease. 7R01 CA114000-02 2005-2010 NIH/NCI Gli Control of PTH-rP and Osteolysis in Breast Cancer The major goal of this project is to examine the Gli family of transcriptional regulators which represents an important molecular pathway that regulates PTH-rP expression in breast cancer cells, and subsequent breast cancer-mediated osteolysis.