SITE SEARCH

Associate Professor, Internal Medicine Associate Professor, Pathology and Immunology 602 Yalem Office: (314) 454-8472 Lab: (314) 454-5975 E-mail: NOVACK@WUSTL.EDU Web-site: http://pathology.wustl.edu/faculty/index.php?user=815&pageload=indi&passed=&sort= Pub Med Search

Research

My lab has focused on the study of osteoclasts, the cells that resorb/remove bone to allow normal bone turnover. These cells are hematopoietic-derived cells of the monocyte lineage that differentiate in the bone microenvironment under the influence of the cytokine RANKL. OCs attach to the bone surface via integrins and form an extracellular compartment, the resorption lacuna, into which they secrete acid and proteases to degrade the organic and mineral components of bone. Activity of these cells is critical for bone homeostasis, but their abnormal activation is responsible for pathological bone loss in many settings, including osteolytic breast cancer metastases. Our work has centered on the role of NF-kB signaling in osteoclasts, particularly in the context of cancer metastasis to bone and inflammatory arthritis. NF-kB activation is known to be involved in the inflammatory response in autoimmune diseases, and it also plays imporant but complex roles in the pathogenesis of many types of cancer, include breast cancer. Because NF-kB is active in so many cell types, with different physiological effects, it is important to understand the role of NF-kB in bone cells, as well as in specific tumor and immune cells. We employ a variety of knockout and transgenic mice, as well as pharmacological treatments either inhibit or activate specific NF-kB pathways, using a combination of bioluminescent imaging, microCT, and histomorphometric analyses. Our ultimate goal is to guide the development of therapies that preserve bone structure and function while effectively targeting tumor and immune cells. My clinical research interests include analyzing bone biopsies for studies of metabolic bone diseases such as osteoporosis and hypophosphatasia, using both qualitative and quantitative histomorphometric approaches. In addition, I work with clinicians to describe new or rare bone diseases. In the future I hope to combine my laboratory studies of breast cancer bone metastasis with analysis of clinical samples to better translate our findings to patients.

Editorial Responsibilities
	2010 - Present	Editorial Board	Journal of Bone and Mineral Research

DBBS Graduate Program Affiliation
	Molecular and Cellular Biology

Diagnostic Expertise
	metabolic bone biopsy
	breast pathology

Clinical Interest
	Anatomic and Molecular Pathology - Metabolic Bone Pathology
	Anatomic and Molecular Pathology - Breast Pathology

Selected Publications
	Novack DV. Role of NF-êB in the skeleton.. Cell Res. 21(1):169-82., 2011 Abstract
	Whyte MP, Wenkert D, McAlister WH, Novack D, Nenninger AR, Zhang X, Huskey M, Mumm S.. Dysosteosclerosis presents as an "osteoclast-poor" form of osteopetrosis: Comprehensive investigation of a 3-year-old girl and literature review.. J Bone Miner Res. [Epub ahead of print], 2010 Abstract
	Napoli N, Novack D, Armamento-Villareal R.. Bisphosphonate-associated femoral fracture: implications for management in patients with malignancies.. Osteoporos Int. 21(4):705-8., 2010 Abstract
	Yang C, McCoy K, Davis JL, Schmidt-Supprian M, Sasaki Y, Faccio R, Novack DV. NIK Stabilization in Osteoclasts Results in Osteoporosis and Enhanced Inflammatory Osteolysis.. PLoS ONE 5(11): e15383. doi:10.1371/journal.pone.0015383., 2010 Abstract
	Armamento-Villareal R, Napoli N, Diemer K, Watkins M, Civitelli R, Teitelbaum S, Novack D. Bone turnover in bone biopsies of patients with low-energy cortical fractures receiving bisphosphonates: a case series.. Calcif Tissue Int. 85:37-44, 2009 Abstract
	Vaira, S., Johnson, T., Hirbe, A.C., Alhawagri, M., Anwisye, I., Sammut, B., O’Neal, J., Zou, W., Weilbaecher, K.N., Faccio, R., and Novack, D.V.. RelB is the NF-kB subunit downstream of NIK responsible for osteoclast differentiation.. Proc. Natl. Acad. Sci. 105:3897-3902., 2008 Abstract
	Ramanadham, S., Yarasheski, K.E., Silva, M.J., Wohltmann, M., Novack, D.V., Christiansen, B., Tu, X., Zhang, S.,Lei, X., and John Turk. Age-Related Changes in Bone Morphology are Accelerated in Group VIA Phospholipase A2 (iPLA2B)1-Null Mice. Am. J. Pathol 172:868-81., 2008 Abstract
	Whyte M.P., McAlister W.H., Novack D.V., Clements K.L., Schoenecker P.L., Wenkert D.. Bisphosphonate-Induced Osteopetrosis: Novel Bone Modeling Defects, Metaphyseal Osteopenia, and Osteosclerosis Fractures After Drug Exposure Ceases.. J. Bone Miner Res 23:1698-1707, 2008 Abstract
	Vaira, S., Alhawagri, M., Anwisye, I., Kitaura, H., Faccio, R., and Novack, D.V.. RANKL activates an apoptotic JNK pathway opposed by RelA/p65.. J. Clin. Invest. 118:2088-2097., 2008 Abstract
	Cremasco, V., Graham, D.B., Novack, D.V., Swat, W. and Faccio, R. Vav/PLCg2 pathway controls neutrophil-dependent inflammatory response during rheumatoid arthritis. Arthritis and Rheumatism 58:2712-2722., 2008 Abstract
	Li, X., Qin, L., Bergenstock, M., Bevelock, L.M., Novack, D.V., and Partridge, N.C.. Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts.. J Biol Chem 282(45):33098-106, 2007 Abstract
	Matsuzaki, H., Wohl, G.R., Novack, D.V., Lynch, J.A., and Silva, M.J.. Damaging Fatigue Loading Stimulates Increases in Periosteal Vascularity at Sites of Bone Formation in the Rat Ulna.. Calcif Tissue Int 80:391-9., 2007 Abstract
	Mao, D., Epple, H., Uthgenannt, B., Novack, D.V., and Faccio, R. PLCg2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2.. J Clin Invest 116: 2869-2879, 2006
	Armamento-Villareal, R., Napoli, N., Panwar, V., and Novack, D.. Suppressed bone turnover during alendronate therapy for high-turnover osteoporosis. N Engl J Med 355: 2048-2050., 2006
	Kitaura H, Sands MS, Aya K, Zhou P, Hirayama T, Uthgenannt B, Wei S, Takeshita S, Novack DV, Silva M. NIK controls lymphocyte and osteoclast activities in inflammatory arthritis. J. Clin. Invest. 115: 3418-3427, 2005
	Zhao, H, Kitaura, H, Sands, MS, Ross,FP, Teitelbaum,SL, Novack,DV. Critical role of B3 integrin in experimental post-menopausal osteoporosis. J.Bone and Mineral Research, 20: 2116-2123, 2005
	Choi ET, Khan MF, Leidenfrost BA, Collins ET, Boc KP, Villa BR, Novack DV, Parks WC, and Abendschein. â3 integrin mediates smooth muscle cell accumulation in neointima arfter carotid ligation in mice. Circulation; 109: 1564-9, 2004
	Weng S, Zemany L, Standley KN, Novack DV, La Regina M, Bernal-Mizrachi C, Coleman T, Semenkovich CF. â3 integrin deficiency promotes atherosclerosis and pulmonary inflammation in high-fat-fed, hyperlipidemic mice. Proc Natl Acad Sci U S A 100:6730-5, 2003
	Faccio R, Novack DV, Zallone A, Ross FP, Teitelbaum SL. Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by â3 integrin. J Cell Biol. 162: 499-509, 2003
	Novack DV, Yin L, Hagen-Stapleton A, Schreiber RD, Goeddel DV, Ross FP, Teitelbaum SL. The IêB function of NF-êB2 p100 controls stimulated osteoclastogenesis. J Exp. Med. 198; 771-781, 2003
	Novack DV, Feng X, Faccio R, Ory DS, Aya K, Boyer MI, McHugh KP, Ross FP, and Teitelbaum SL. A Glanzmanns mutation in â3 integrin specifically impairs osteoclast function. J Clin Invest 107: 1137-1144, 2001
	Cenci S, Weitemann MN, Roggia C, Namba N, Novack D, Woodring J, and Pacifici R. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-á. J Clin Invest 106: 1203-1204, 2000
	Whyte MP, Totty WG, Novack DV, Zhang X, Wenkert D, Mumm S.. Camurati-engelmann disease: Unique variant featuring a novel mutation in TGFâ1 encoding transforming growth factor beta 1 and a missense change in TNFSF11 encoding RANK ligand.. J Bone Miner Res. 2010 Nov 4. [Epub ahead of print], Abstract