Curriculum Vitae. NAME Colin R. Dunstan EDUCATION/TRAINING

Transcription

1 NAME Colin R. Dunstan EDUCATION/TRAINING Curriculum Vitae POSITION TITLE Associate Professor Biomedical Engineering, University of Sydney Australia INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY University of Sydney BSc(Hons) 1977 Science University of New South Wales MSc 1980 Biomedical Engineering University Sydney PhD 1991 Medicine/Bone Biology A. Positions and Honours Positions and Employment 2008 to present, Associate Professor, Biomedical Engineering, Department of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney , Principal Science Officer, ANZAC Research Institute, Concord, NSW, Australia Conjoint Appointment as Principal Research Fellow, University of Sydney, Faculty of Medicine ; Senior Research Scientist/Associate Director, Amgen Inc. Thousand Oaks, ; Senior Scientist, OsteoSA Inc. San Antonio ; Adjunct Assistant Professor. The University of Texas Health Science Center at San Antonio Senior Science Officer. Concord Repatriation and General Hospital, Sydney, Australia. Honors and Distinctions NSW BioFirst Award, Commonwealth Postgraduate Research Award Other Experience 2008 Member of the Sydney University Tissue Engineering Network (SUTEN) 1980 to present Member of the American Society for bone and Mineral Research 2003 to present Member of the Australian and New Zealand Bone and Mineral Society Member of the Endocrine Society 2007 to present Member of the Sydney University Cancer Network Editorial Board Member: Journal of Bone Mineral Research ) , and 2010 to present Endocrinology ( ). Ad-hoc reviewer for Lancet, Nature, Br Med J, J Bone Mineral Res, Endocrinol, J Clin Endocrin Metab, Osteoporosis Int., Calcif Tissue Int, Bone and many others. Expert Panel Member and Reviewer for National Health&Medical Research Council, Australia, Reviewer for New Zealand Medical Research Council, and others. Page 1

2 B. Major research achievements: I have been actively involved in research into bone metabolism since 1977 as indicated by 138 original research publications (more than 20,000 citations, H index 50). The majority of my research experience has been in the study of metabolic bone disease in a clinical setting as assessed by bone histomorphometry, and the investigation of the biological actions on bone of cytokines and growth factors in animal models. At the beginning of 2008 I was appointed as Associate Professor in the Biomedical Engineering group at the University of Sydney. In this position I developed a research interest in biomaterials and their interactions with cells and tissues and use for drug release leading to two patents and 7 publications. My current and other recent research at the ANZAC Research Institute focused on interactions between cancer cells and bone cells, and on regulation of bone resorption and bone formation. This work has recently produced a cover article in Cancer Research, a leading journal of this field, detailing the importance of the bone remodeling environment in the growth of breast cancer bone metastases. My work in the regulation of bone formation is marked by a recent publication in J Biol Chem. From I was employed at Amgen Inc, California as a Senior Research Scientist to evaluate the roles of RANK, RANKL and osteoprotegerin (OPG) in the regulation of bone resorption. These studies have revolutionized understanding of the regulation of osteoclast activity, and enabled the development of Denosumab now approved for use in breast and prostate cancer metastasis. In addition I gave scientific oversight and leadership to a program to develop denosumab as a clinical candidate for the treatment of osteoporosis and metastatic bone disease (currently in phase 3 studies). This importance of this work is highlighted by three patents, two publications in CELL describing OPG (2518 citations) and RANKL (2657 citations) and one article in NATURE on effects of RANKL deficiency (1668 citations). I worked with Greg Mundy and Brendan Boyce in San Antonio from characterizing genetically modified animals, evaluating bone anabolic effects of fibroblast growth factors in vivo, and characterizing the lytic effects of human breast cancer cell lines in a mouse xenograft model. Of particular note was my contribution to an article in NATURE describing the phenotype of osteocalcin knockout mice (710 citations). C. Selected peer-reviewed publications 1. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G. Increased bone formation in osteocalcin-deficient mice. Nature 1996; 382: Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan H-L, Trail G, Sullivan J, Dary E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Amgen EST Program, Boyle WJ. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell 1997, 89: Yoneda T. Sasaki A. Dunstan C. Williams PJ. Bauss F. De-Clerck YA. Mundy GR. Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J Clin Invest 1997, 99: Bucay N, Sarosi I, Dunstan CR, Morony M, Tarpley J, Capparelli C, Scully S, Tan H-L, Xu W, Lacey DL, Boyle WJ, Simonet WS. Osteoprotegerin deficient mice develop early onset osteoporosis and arterial calcification. Genes and Development, : Lacey DL, Timms E, Tan H-L, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian Y-X, Kaufman S, Sarosi I, Shalhoub V, SenaldI G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin (OPG) ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998, 93: Page 2

3 6. Dunstan CR, Boyce R, Boyce BF, Garrett IR, Izbicka E, Burgess WH, Mundy GR. Systemic administration of acidic fibroblast growth factor (FGF-1) prevents bone loss and increases new bone formation in ovariectomized rats. J Bone Mineral Res 1999, 14: Kong Y-Y, Yoshida H, Sarosi I, Tan H-L, Timms E, Capparelli C, Morony S, Oloveira-Dos- Santos AJ, Van G, itie A, Dunstan CR, Lacey D, Mak TW, Boyle WJ, Penninger JM. OPGL is a key regulator or osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 1999, 397: Lomaga MA, Yeh, W.C, Sarosi I, Duncan GS, Furlonger C, Ho A, Morony S, Capparelli C, Van G, Kaufman S, van der Heiden A, Itie A, Wakeham A, Khoo W, Paige CJ, Cao Z, Goeddel DV, Lacey DL, Dunstan CR, Boyle WJ, Mak TW. TRAF6-Deficient Mice are Osteopetrotic and Defective in Interleukin-1, Interleukin-18, CD40 and LPS Signaling. Genes and Development 1999, 13: Burgess TL, Qian Y-X, Kaufman S, Ring BD, Van G, Capparelli C, Kelley M, Hsu H, Boyle WJ, Dunstan CR, Hu S, Lacey DL. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol : Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, Tan H-L, Elliott G, Kelley MJ, Sarosi I, Wang L, Xia X-Z, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass M, Boyle WJ. The TNFR related protein RANK is the osteoclast differentiation and activation receptor for osteoprotegerin ligand. Proc Natl Acad Sci 1999, 96: Capparelli C, Kostenuik PJ, Morony S, Starnes C, Weimann B, Van G, Scully S, Qi M, Lacey DL, Dunstan CR. Osteoprotegerin Prevents and Reverses Hypercalcemia in a Murine Model of Humoral Hypercalcemia of Malignancy. Cancer Research 2000, 60: l. 12. Li J, Sarosi I, Yan XQ, Morony S, Capparelli C, Tan HL, McCabe S, Elliott R, Scully S, Van G, Kaufman S, Juan SC, Sun Y, Tarpley J, Martin L, Christensen K, McCabe J, Kostenuik P, Hsu H, Fletcher F, Dunstan CR, Lacey DL, Boyle-WJ. RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci USA 2000, 97: Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Leese PT, Dunstan CR. The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone and Mineral Research 2001, 16: Morony S, Capparelli C, Sarosi I, Lacey DL, Dunstan CR, Kostenuik PJ. Osteoprotegerin (OPG) inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis. Cancer Res 2001, 61: Khosla S, Arrighi HM, Melton LJ, Atkinson EJ, O'Fallon WM, Dunstan C,.Riggs BL. Correlates of osteoprotegerin levels in women and men. Osteoporosis 2002; 13: Ashcroft AJ, Cruickshank SM, Croucher PJ, Perry MJ, Rollinson S, Lippitt JM, Child JA, Dunstan C, Felsburg PJ, Morgan GJ, Carding SR. Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin. Immunity : Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Leese PT, Holmes GB, Dunstan CR, DePaoli AM. A single dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to nuclear factor-b ligand (RANKL), in postmenopausal women. J Bone Mineral Research 2004; 19: Zheng Y, Zhou H, Brennan K, Blair JM,, Modzelewski JRK, Seibel MJ, Dunstan CR. Inhibition of Bone Resorption, Rather than Direct Cytotoxicity, Mediates the Anti-Tumour Actions of Ibandronate and Osteoprotegerin in a Murine Model of Breast Cancer Bone Metastasis. Bone : Seibel MJ, Dunstan C, Zhou H, Allan CM, Handelsman DJ. Sex steroids, not FSH, influence bone mass Cell (letter) : Zheng Y, Zhou H, Modzelewski JRK, Kalak R, Blair JM, Seibel MJ, Dunstan CR. Accelerated Bone Resorption, Due to Dietary Calcium Deficiency, Promotes Breast Cancer Tumor Growth in Bone. Cancer Res (19): Zhou H, Mak W, Zheng Y, Dunstan CR, Seibel MJ. Osteoblasts directly control lineage commitment of mesenchymal progenitor cells through WNT signaling. J Biol Chem. 283: , Pivonka P, Zimak J, Smith DW, Gardiner BS, Dunstan CR, Sims NA, Martin TJ, Mundy GR. Model structure and control of bone remodeling: A theoretical study. Bone : Page 3

4 23. Zheng Y, Zhou H, Fong-Yee C, Modzelewski JRK, Seibel MJ, Dunstan CR. Bone Resorption increases tumour growth in a mouse model of osteosclerotic breast cancer metastasis. Clin Exp Metastasis 2008;25(5): Zhou H, Mak W, Kalak R, Street J, Fong-Yee C, Zheng Y, Dunstan CR, Seibel M. Glucocorticoid Dependent Wnt Signaling by Mature Osteoblasts Is a Key Regulator of Cranial Skeletal Development in Mice. Development 2009, 136, Ooi LL, Zhou H, Kalak, R, Zheng Y, Conigrave AD, Seibel MJ, Dunstan CR. Vitamin D deficiency promotes human breast cancer growth in a murine model of bone metastasis. Cancer Res : Zreiqat H, Ramaswamy Y, Wu C, Paschalidis A, Lu Z, James B, Birke O, McDonald M, Little D, Dunstan CR. The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering. Biomaterials : Ooi LL, Zheng Y, Zhou H, Trivedi T, Conigrave AD, Seibel MJ, Dunstan CR. Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis. Bone : Allan CM, Kalak R, Dunstan CR, McTavish KJ, Zhou H, Handelsman DJ, Seibel MJ. Follicle-stimulating hormone increases bone mass in female mice. Proc Natl Acad Sci (52): Zheng Y, Zhou H, Ooi LL, Snir D, Dunstan CR, Seibel MJ. Vitamin D Deficiency Promotes Prostate Cancer Growth in Bone. The Prostate : Wang Y, Pivonka P, Buenzli PR, Smith DW, Dunstan CR. Computational Modeling of Interactions between Multiple Myeloma and the Bone Microenvironment. PLOS ONE : (11) e27494 )(pages 1-20). 31. Lu ZF, Wang GC, Dunstan CR, Chen YJ, Lu WY, Davies B, Zreiqat H. Activation and Promotion of Adipose Tissue-derived Mesenchymal Stem Cells by Tumour Necrosis Factor-Alpha Preconditioning for Bone Tissue Engineering. J Cell Physiol 2013 (in press). 32. Roohani Esfahani SI, Dunstan CR, Li JJ, Lu ZF, Davies B, Pearce S, Field J, Williams R, Zreiqat H. Unique microstructural design of ceramic scaffolds for bone regeneration under load. Acta Biomaterialia (in press accepted 23/2/2013), D. Major Research Support (over the past 5 years) Current NHMRC Grants NHMRC Seibel, Zhou, Gundberg, Dunstan. The role of the osteoblast in mediating glucocorticoid-induced diabetes and obesity. $800K NHMRC Murray, Duke, Cui, Ching, Dunstan, Pharmacological development of synthetic analogues of cytochrome P450-mediated omega-3 fatty acid epoxides as novel anti-metastatic agents, $836K Past Grants NHMRC Dunstan, Seibel, Zhou, Blair "Bone Resorption and Breast Cancer Metastasis Period of support: 01/01/2005 to 31/12/2007. Total: $420K NHMRC Zreiqat, Dunstan Novel coatings for orthopaedic implants $429K NHMRC Seibel, Zhou, Dunstan, Krozowski. Glucocorticoid effects on bone: the role of the osteoblast Period of support: Total: $455K ARC DP Martin, Dunstan Pivonka Bone regulation cell interactions to bone disease, , $270K University of Sydney Cancer Research Fund. Seibel, Dunstan Bone and tumour necrosis following anti-resorptive treatment $86,000 Australian Orthopaedic Association, Novel coatings for orthopaedic application, Zreiqat H, David Sonnabend, Dunstan C, $58,799 ( ) NHMRC Zreiqat Dunstan. Harnessing the physiological effects of strontium and zinc to produce novel biomaterials for orthopaedic applications. $539,500. ( ) Page 4

5 Patents Dunstan, Colin, R.; Izbicka, Elzbieta; Mundy, Gregory; Burgess, Wilson; Jaye, Michael. Use of Fibroblast Growth Factors to Stimulate Bone. International Patents WO 95/24211, WO96/ Simonet, Scott; Dunstan, Colin; Sarosi, Ildiko; Mammals lacking the expression of osteoprotegerin. International Patent WO 99/ Dunstan, Colin R. Compositions and methods for the prevention or treatment of cancer and bone loss associated with cancer. International Patent WO 01/17543 A2. Dunstan, Colin R.; Wooden, Scott; Mann, Michael Benjamin. OPG fusion protein compositions and methods. International Patent WO 01/18203 A1. Zreiqat, Wu, Dunstan Preparation and application of Strontium modified hardystonite (Sr- Ca2ZnSi2O7 ) for use as Scaffolds and coatings for skeletal tissue regeneration. Australian patent application granted. Page 5