Roberta Faccio, Ph.D.

Associate Professor
Orthopaedic Surgery
Cell Biology and Physiology

Molecular Cell Biology Program
Immunology Program

  • 314-747-4602

  • 314-362-8603

  • 314-362-0334

  • 8233

  • 11615 BJCIH

  • faccior@wustl.edu

  • arthritis, inflammation, cancer, bone metastases, osteoclasts

  • interactions between bone and immune cells in inflammation and cancer

Research Abstract:

Excessive bone loss in rheumatoid arthritis and some bone metastasis is mostly due to an abnormal activation of the immune system leading to stimulation of osteoclasts (OCs). We have recently identified a novel role for phospholipase C gamma 2 (PLCγ2) as central mediator of osteoclast differentiation and function, neutrophil activation and dendritic cell-mediated T cell activation.

We are now focusing on the mechanism by which PLCγ2 exert its functionality in the context of arthritis. In particular, diacylglycerol (DAG) is a downstream product of PLCγ2 catalytic activity and data from our group and others indicate that it mediates PLCγ2 function in OCs and immune cells. Thus, reduced DAG production in PLCγ2-/- mice could be, at least in part, responsible for high bone mass phenotype and for the protective effect against inflammatory arthritis. By using mice lacking DAG-dependent protein kinase Cs and diacylglycerol kinases, which convert DAG into phosphatidic acid, we aim at investigating the contribution of DAG signaling downstream of PLCγ2 in osteoclasts and immune cells during inflammatory arthritis.

My lab is also interested in investigating the contribution of anti-tumor immune responses in the context of tumor bone metastases. Although the osteoclasts have been considered a critical target for tumor bone metastases, our recent findings indicate that aberrant immune functionality can also modulate tumor growth in bone independent of the osteoclasts. The overall goal of this project is to expand the current model of tumor bone vicious cycle to include myeloid cells (DC, macrophages and myeloid suppressor cells) in development of bone tumor growth.

Selected Publications:

Capietto AH, Kim S, Sanford DE, Linehan DC, Hikida M, Kumosaki T, Novack DV, Faccio R. Down-regulation of PLCγ2-β-catenin pathway promotes activation and expansion of myeloid-derived suppressor cells in cancer. J Exp Med. 2013 Oct 21;210(11):2257-71

Mao D, Epple H, Uthgenannt B, Novack DV, Faccio R. PLCγ2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2. JCI 2006 116(11):2869-79.

Epple H, Cremasco V, Zhang K, Mao D, Longmore GD and Faccio R. PLCgamma2 modulates integrin signaling in the osteoclast by affecting the localization and activation of Src kinase. MCB 2008 28(11):3610-22.

Cremasco V, Graham D, Novack DV, Swat W, Faccio R. Vav/PLCgamma 2 pathway controls neutrophil-dependent inflammatory response during Rheumatoid Arthritis. Arthritis and Rheumatism. 2008 58(9):2712-2722.

Kim HJ, Zhang K, Zhang L, Ross FP, Teitelbaum SL, Faccio R. The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo. Proc Natl Acad Sci USA. 2009 106(7):2325-30.

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.

Zhang K, Kim S, Cremasco V, Hirbe AC, Collins L, Piwnica-Worms D, Novack DV, Weilbaecher K, Faccio R.CD8+ T cells regulate bone tumor burden independent of osteoclast resorption. Cancer Res. 2011 Jul 15;71(14):4799-808

Cremasco V, Decker CE, Stumpo D, Blackshear PJ, Nakayama KI, Nakayama K, Lupu TS, Graham DB, Novack DV, Faccio R. Protein kinase C-delta deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts. J Bone Miner Res. 2012 Dec;27(12):2452-63

Decker C, Hesker P, Zhang K, Faccio R. Targeted inhibition of phospholipase C γ2 adaptor function blocks osteoclastogenesis and protects from pathological osteolysis. J Biol Chem. 2013 Nov 22;288(47):33634-41

Zamani A, Decker C, Cremasco V, Hughes L, Novack DV, Faccio R. Diacylglycerol Kinase ζ (DGKζ) is a Critical Regulator of Bone Homeostasis via Modulation of c-Fos Levels in Osteoclasts. J Bone Miner Res. 2015 Apr 18.

Last Updated: 6/23/2015 10:19:17 AM

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