PHS 398 (Rev. 9/04), Biographical Sketch Format Page s8

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PHS 398 (Rev. 9/04), Biographical Sketch Format Page s8

BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME POSITION TITLE Roberta Faccio, Ph.D. Associate Professor

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) DEGREE INSTITUTION AND LOCATION YEAR(s) FIELD OF STUDY (if applicable) College of Chemistry and Pharmaceutical B.S. 1995 Chemistry, Pharmaceutical Technologies, University of Bari, Bari, Italy Technologies School of Medicine, University of Bari, Bari, Italy Ph.D. 1999 Cell Science and Biotechnologies

A. Personal statement As a faculty member in the Department of Orthopedics at Washington University for seven years, I have trained or am currently training several Ph.D. students. Also, I have trained postdoctoral fellows who hold independent faculty positions or became staff scientist. I participate in graduate student teaching and act on Ph.D admission and PhD thesis committees.

Positions and Honors Positions 2009 - present Associate Professor with tenure in the Department of Orthopedics, Washington University, St. Louis MO 2004 - 2009 Assistant Professor in the Department of Orthopedics, Washington University, St. Louis MO 2001 – 2004 Assistant Professor in Histology, School of Medicine, University of Bari, Italy 2000 – 2004 Research Associate, Department of Pathology and Immunology, Barnes-Jewish Hospital, St. Louis, MO 6-11/1996 1996 Research Fellow, The Scripps Research Institute, La Jolla, CA Awards 2001 Young Investigator Award, ASBMR 2005 John Haddad Young Investigator Award, AIMM-ASBMR 2005 ASBMR Career Enhancement Award 2006 Arthritis Investigator Award 2006 NIRA Award, ORS

Professional Societies and Organizations 2000 – present American Society for Bone and Mineral Research 2005 – present member of DBBS PhD program Washington University 2007 - present member of Subcommittee Endocrinology-B Scientific Merit Review Board 2010-present member NIH study section ZRG1 MOSS-C

B. Selected peer-reviewed publications (in chronological order) 1. R. Faccio, M. Grano, S. Colucci, A. Villa, G.Giannelli, V. Quaranta and A. Zallone. Localization and possible role of two different v3 integrin conformations in resting and resorbing osteoclasts. J Cell Science 2002, 115:2919-2929. PMID: 12082152 PHS 398/2590 (Rev. 09/04) Page Biographical Sketch Format Page 2. R Faccio, S Takeshita, A Zallone, FP Ross, SL Teitelbaum. c-Fms and the alpha(v)beta(3) integrin collaborate during osteoclast differentiation. J Clin Invest. 2003, 111(5):749-58. PMID: 12618529 3. R Faccio, DV Novack, A Zallone, FP Ross, SL Teitelbaum. Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by β3 integrin. J Cell Biol

2003, 162(3):499-509. PMID: 12900398 4. R Faccio, W Zou, G Colaianni, SL Teitelbaum, FP Ross. High dose M-CSF partially rescues the Dap12- / - osteoclast phenotype. J Cell Biochem, 2003 90 (5): 871-883. PMID: 14624447 5. K Fujikawa, AV Miletic, FW Alt, R Faccio, T Brown, J Hoog, J Fredericks, S Nishi, S Mildiner, SL Moores, J Brugge, FS Rosen, W Swat. Vav1/2/3-null mice define an essential role for Vav Family Proteins in Lymphocyte development and activation but a differential requirement in MAPK signaling in T and B cells. J Exp Med, 2003 198(10):1595-1608. PMID: 14623913 6. R Faccio, SL Teitelbaum, K Fujikawa, J Chappel, A Zallone, V L Tybulewicz, FP Ross and W Swat. Vav3 regulates osteoclast function and bone mass. Nature Medicine 2005 11(3):284-90. PMID: 15711558 7. S Tehrani, R Faccio, I Candrasekar, FP Ross, JA Cooper. Cortactin has an essential and specific role in osteoclast actin assembly. Mol Biol Cell. 2006 17(7):2882-95. PMID: 16611741 8. D. Mao, H. Epple, B. Uthgenannt, D.V. Novack, R. Faccio. PLCγ2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2. JCI 2006 116(11):2869-79. PMID: 17053833 9. R. Faccio, S. Takeshita, G. Colaianni, J. Chappel, A. Zallone, S.L. Teitelbaum, and F.P. Ross. M-CSF regulates the cytoskeleton via recruitment of a multimeric signaling complex to c-Fms Y559/697/721.J Biol Chem. 2007, 282(26):18991-9. PMID: 17420256 10. S. Takeshita, R. Faccio, J. Chappel, L. Zheng, X. Feng, J.D. Weber, S.L. Teitelbaum, and F.P. Ross. c- Fms Y559 is a major mediator of M-CSF induced proliferation of primary macrophages. J Biol Chem. 2007, 282(26):18980-90. PMID: 17420255 11. D.B. Graham, C.M Robertson, J. Bautista, F. Mascarenhas, M.J. Diacovo, V. Montgrain, S.K. Lam, V. Cremasco, W.M. Dunne, R. Faccio, C.M. Coopersmith, W. Swat. Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCgamma2 signaling axis in mice. J Clin Invest. 2007, 117(11):3445-52. PMID: 17932569 12. H. Epple, V. Cremasco, K. Zhang, D. Mao, G.D. Longmore, and R. Faccio. PLCgamma2 modulates integrin signaling in the osteoclast by affecting the localization and activation of Src kinase. Mol Cell Biol (2008). 28(11):3610-22. PMID: 18378693 14. V. Cremasco, D. Graham, D.V. Novack, W. Swat, R. Faccio. Vav/PLCgamma 2 pathway controls neutrophil-dependent inflammatory response during Rheumatoid Arthritis. Arthritis and Rheumatism (2008). 58(9):2712-2722. PMID: 18759305 14. H.J. Kim, K. Zhang, F.P. Ross, S.L. Teitelbaum, R. Faccio. Lyn, opposite from c-Src, negatively regulates osteoclastogenesis via its interaction with SHP-1 and Gab2. Proc Natl Acad Sci USA. (2009), 106(7):2325- 30. PMID: 19171907 15. Cremasco V., Benasciutti E., Cella M., Kisseleva M., Croke M., Faccio R. Phospholipase C gamma 2 Is Critical for Development of a Murine Model of Inflammatory Arthritis by Affecting Actin Dynamics in Dendritic Cells. PLOSone 2010 27;5(1):e8909. PMID: 20111715 16. CD8+ T cells Regulate Bone Tumor Burden Independent of Osteoclast Resorption.Zhang K, Kim S, Cremasco V, Hirbe A, Novack D, Weilbaecher K, Faccio R.Cancer Res. 2011 May 20. [Epub ahead of print] 17. The type II collagen N-propeptide, PIIBNP, inhibits cell survival and bone resorption of osteoclasts via integrin-mediated signaling.Hayashi S, Wang Z, Bryan J, Kobayashi C, Faccio R, Sandell LJ.Bone. 2011 Jun 24. [Epub ahead of print] 18. Biphenyl sulfonylamino methyl bisphosphonic acids as inhibitors of matrix metalloproteinases and bone resorption. Rubino MT, Agamennone M, Campestre C, Campiglia P, Cremasco V, Faccio R, Laghezza A, Loiodice F, Maggi D, Panza E, Rossello A, Tortorella P. ChemMedChem. 2011 Jul 4;6(7):1258-68. doi: 10.1002/cmdc.201000540. Epub 2011 Mar 15.

C. Ongoing Research Support 1) Arthritis Investigator FACCIO (PI) 07/01/010-06/30/12 PHS 398/2590 (Rev. 09/04) Page Biographical Sketch Format Page Arthritis Foundation $92,593/year (2 years) 2.4 calendar Role of PLCγ2 in juvenile arthritis The major goals of this project are to determine the role of PLCγ2 in macrophage activation syndrome a lethal complication of juvenile arthritis. Role: PI

2) 2R01AR053628 FACCIO (PI) 01/01/11-12/31/15 NIH/NIAMS $269,999/year 6 calendar Regulatory pathways in osteoclasts and immune cells The major goals of the project is to determine the role of DAG-mediated signaling in osteoclasts, neutrophils and dendritic cells in the context of inflammatory arthritis. Role: PI

3) Shriners Hospital FACCIO (PI) 01/01/11-12/31/14 $230,000/year 3 calendar Role of PKCdelta in osteoclasts and immune cells The major goals of the project is to determine the role of PKCdelta-mediated signaling in osteoclasts, neutrophils and dendritic cells in the context of inflammatory bone loss. Role: PI

Completed Research Support ASBMR Career Enhancement Award FACCIO (PI) 05/01/05 – 04/30/07 $35,000 Inhibition of osteolytic lesions due to breast cancer by mutein RANKL R223A The major goal of this project is to identify the role of the mutated form of RANKL in an in vivo model of breast cancer. Arthritis Investigator Award FACCIO (PI) 07/01/08-06/30/10 Arthritis Foundation $75,000/year (2 years) Role of PLCγ2 in rheumatoid arthritis The major goals of this project are to determine the role of PLCγ2 in the development of inflammation and bone erosion during inflammatory arthritis. Arthritis Investigator Award - Renewal FACCIO (PI) 07/01/08-06/30/10 Arthritis Foundation $90,000/year 1.2 calendar Role of PLCγ2 in rheumatoid arthritis The major goals of this project are to analyze development of inflammation and bone erosion in PLCγ2-/- mice during arthritis. In particular the project focuses on the role of PLCγ2 in B cell-mediated inflammatory responses during arthritis. Furthermore, we also aim to determine the in vivo anti-inflammatory effect of a PLCγ2 blocking peptide encompassing the two SH2 domains of the protein during arthritis. R01 AR 52921 FACCIO (PI) 09/01/06-08/31/10 NIH/NIAMS $198,000/year 6.96 calendar Regulatory mechanisms of osteoclast differentiation and function The major goals of the project are to generate PLCγ2 mutants to clarify the role of the catalytic activity and the adapter function of PLCγ2 during regulation of OC differentiation using in vivo and in vitro models. Supplement 3R01AR053628-04S1 FACCIO (PI) 09/25/09-08/24/10 NIH/NIAMS $125,000/year 2.4 calendar Regulatory mechanisms of osteoclast differentiation and function The major goal of this project is to analyze the role of PLCγ2 in dendritic cell function. MD-II-2009-179 Children Discovery Institute FACCIO (PI) 02/01/09-1/31/11 PHS 398/2590 (Rev. 09/04) Page Biographical Sketch Format Page $100,000/year 0.84 calendar Novel Integrin/PLCgamma2/NF-kB Pathway in Neutrophils During Arthritis The major goals for this project are to characterized the role of PLCγ2 in N function; 2) identify the PLCγ2 signaling complex by Mass Spectrometry; 3) determine key NF-κB target genes induced by integrin-mediated adhesion in WT and PLCγ2-/- neutrophils.

PHS 398/2590 (Rev. 09/04) Page Biographical Sketch Format Page

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