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Deborah Novack, MD, PhD

Professor, Medicine

Phone314-454-8472

Fax314-454-5047

Emailnovack@wustl.edu

Additional Titles

  • Professor, Pathology & Immunology

Education

  • MD, PhD: Washington University, St. Louis, MO (1995)
  • Residency, Fellowship: Washington University, St. Louis, MO (2002)

Board Certifications

  • Anatomic Pathology, Board Certified

Recognition

  • 2016: Washington University School of Medicine Alumni Achievement Award
  • 2009: The American Society for Clinical Investigation Elected Member
  • 2007: American Society for Bone and Mineral Research (ASBMR) Career Enhancement Award
  • 2004: Harold Frost Young Investigator Award
  • 2001: American Society for Bone and Mineral Research (ASBMR) Young Investigator Award
  • 1993: Spencer T. and Ann Olin Award for Excellence in Graduate Research, Washington University

 

Clinical Interests

  • Metabolic Bone Pathology
  • Breast Pathology

Research Interests

My lab studies mechanisms of pathological bone loss.  Most work 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 important 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. Additional ongoing work addresses the role of alternative NF-kB in osteoblasts and the role of mitochondria in bone 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 and collaborate on basic and translational breast cancer studies. 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

2015-Present Associate Editor  Journal of Bone and Mineral Research
2013-2015 Associate Editor Connective Tissue Research
2014 Co-Section Editor Current Osteoporosis Reports, Osteoimmumology Section Vol. 12, Issue 1
2011-2015 Member Editorial Board Journal of Bone and Mineral Research

DBBS Graduate Program Affiliation

  • Molecular and Cellular Biology
  • Immunology

Publications

Pub Med Search

Phatarakyijnirund V, Mumm S, McAlister WH, Novack DV, Wenkert D, Clements KL, Whyte MP. Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9. Bone. 2015 Dec 31. pii: S8756-3282(15)00486-X. doi: 10.1016/j.bone.2015.11.022. [Epub ahead of print]
Luo X, Fu Y, Loza AJ, Murali B, Leahy KM, Ruhland, MK, Gang M, Su X, Zamani A, Shi Y, Lavine KJ, Ornitz DM, Weilbaecher KN, Long F, Novack DV, Faccio R, Longmore GD, Stewart SA. Stromal-initiated Changes in the Bone Promote Metastatic Niche Development. Cell Rep. 2016, 14:82-92.
Decker CE, Yang Z, Rimer R, Park-Min KH, Macaubas C, Mellins ED, Novack DV, Faccio R. Tmem178 acts in a novel negative feedback loop targeting NFATc1 to regulate bone mass. Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15654-9. doi: 10.1073/pnas.1511285112.
Frederiksen AL, Larsen MJ, Brusgaard K, Novack DV, Knudsen PJ, Schrøder HD, Qiu W, Eckhardt C, McAlister WH, Kassem M, Mumm S, Frost M, Whyte MP. Neonatal High Bone Mass With First Mutation of the NF-κB Complex: Heterozygous De Novo Missense (p.Asp512Ser) RELA (Rela/p65). J Bone Miner Res. 2015 Jul 14. doi: 10.1002/jbmr.2590.
Zeng R, Faccio R, Novack DV. Alternative NF-B regulates RANKL-induced osteoclast differentiation and mitochondrial biogenesis via independent mechanisms. J Bone Miner Res. 2015 Dec;30(12):2287-99. doi: 10.1002/jbmr.2584.
Krauss JL, Zeng R, Hickman-Brecks CL, Wilson JE, Ting JP-Y, Novack DV. NLPR12 provides a critical checkpoint for osteoclast differentiation. Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10455-60. doi: 10.1073/pnas.1500196112.
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 Oct;30(10):1852-63. doi: 10.1002/jbmr.2533.
Pritchard ZJ, Cary RL, Yang C, Novack DV, Voor MJ, Sankar U., Inhibition of CaMKK2 reverses age-associated decline in bone mass. Bone 2015 75:120-7.
Buchwald ZS, Yang C, Nellore S, Shashkova EV, Davis JL, Cline A, Ko J, Novack DV, DiPaolo R, Aurora R. A Bone Anabolic Effect of RANKL in a Murine Model of Osteoporosis Mediated through FoxP3+CD8 T-Cells. J Bone Miner Res. 2015 30:1508-22.
 Qu C, Bonar SL, Hickman-Brecks CL, Abu-Amer S, McGeough MD, Peña CA, Broderick L, Yang C, Grimston SK, Kading J, Abu-Amer Y, Novack DV, Hoffman HM, Civitelli R, Mbalaviele G. NLRP3 mediates osteolysis through inflammation-dependent and -independent mechanisms. FASEB J 2014 pii: fj.14-264804. [Epub ahead of print]
 Amend SR, Uluckan O, Hurchla M, Leib D, Novack DV, Silva M, Frazier W, Weilbaecher KN. Thrombospondin-1 Regulates Bone Homeostasis Through Effects on Bone Matrix Integrity and Nitric Oxide Signaling In Osteoclasts. J Bone Miner Res. 2015, 30(1):106-15.
 Noort AR, van Zoest KP, Weijers EM, Koolwijk P, Maracle CX, Novack DV, Siemerink MJ, Schlingemann RO, Tak PP, Tas SW. NF-κB-inducing kinase is a key regulator of inflammation-induced and tumour-associated angiogenesis. J Pathol. 2014, 234:375-85. PMCID: PMC4194146
 Whyte MP, Tau C, McAlister WH, Zhang X, Novack DV, Preliasco V, Santini-Araujo E, Mumm S. Juvenile Paget’s disease with heterozygous duplication in TNFRSF11A encoding RANK. Bone 2014, 68:153-61. PMCID: PMC4189967
 Whyte MP, Madson KL, Mumm S, McAlister WH, Novack DV, Blair JC, Helliwell TR, Stolina M, Abernethy LJ, Shaw NJ. Rapid skeletal turnover in a radiographic mimic of osteopetrosis. J Bone Miner Res. 2014. 29:2601-9.
 Alspach E, Flanagan KC, Luo X, Ruhland MK, Huang H, Pazolli E, Donlin MJ, Marsh T, Piwnica-Worms D, Monahan J, Novack DV, McAllister SS, Stewart SA. p38MAPK plays a crucial role in stomal-mediated tumorigenesis. Cancer Discov. 2014 Jun;4(6):716-29. PMCID: PMC4049323
 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; 210:2257-71. PMCID: PMC3804931
 Whyte MP, Leelawattana R, Reinus WR, Yang C, Mumm S, Novack DV. Acute severe hypercalcemia after traumatic fractures and immobilization in hypophosphatasia complicated by chronic renal failure. J Clin Endocrinol Metab. 2013 Dec;98(12):4606-12.
 Mullins CD, Su MY, Hucthagowder V, Chu L, Lu L, Kulkarni S, Novack D, Vij R, Tomasson MH. Germinal center B-cells resist transformation by kras independently of tumor suppressor arf. PLoS One. 2013 Jun 25;8(6):e67941. PMCID: PMC3692489
 Buchwald ZS, Kiesel JR, Yang C, Dipaolo R, Novack DV, Aurora R. Osteoclast-induced Foxp3+ CD8 T-cells limit bone loss in mice. Bone 2013 56(1):163-73. PMCID: PMC3966133
 Cary RL, Waddell S, Racioppi L, Long F, Novack DV, Voor MJ, Sankar U. Inhibition of CaMKK2 stimulates osteoblast formation and inhibits osteoclast differentiation. J Bone Miner Res. 2013; 28(7): 1599-610. PMCID: PMC3688641
 Li Z, Pasteris JD, Novack D. Hypermineralized whale rostrum as the exemplar for bone mineral. Connect Tissue Res. 2013; 54(3): 167-75. PMCID: PMC3789591
 Yang C, Davis JL, Zeng R, Vora P, Su X, Collins L, Vangveravong S, Mach RH, Piwnica-Worms D, Weilbaecher KN, Faccio R, Novack DV. Antagonism of Inhibitor of Apoptosis Proteins Increases Bone Metastasis via Unexpected Osteoclast. Cancer Discovery 2013; 3(2):212-223. PMCID: PMC3570610
 Su X, Floyd DH, Hughes A, Xiang J, Schneider JG, Uluckan O, Heller E, Deng H, Zou W, Craft CS, Wu K, Hirbe AC, Grabowska D, Eagleton MC, Townsley S, Collins L, Piwnica-Worms D, Steinberg TH, Novack DV, Conley PB, Hurchla MA, Rogers M, Weilbaecher KN. The ADP receptor P2RY12 regulates osteoclast function and pathologic bone remodeling. J Clin Invest. 2012; 122(10):3579-3592. PMCID: PMC3461896.
 Vaira S, Yang C, McCoy A, Keys K, Xue S, Weinstein EJ, Novack DV, Cui X. Creation and Preliminary Characterization of a Leptin Knockout Rat. Endocrinology 2012; 153:5622-5628. PMCID: PMC3473197.
 Cremasco V, Decker CE, Stumpo D, Blackshear PJ, Nakayama KI, Nakayama K, Lupu TS, Graham DB, Novack DV, Faccio R. PKCδ deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts. J Bone Miner Res. 2012; 27:2452-2463 PMCID: PMC3498518.
 Flentie K, Kocher B, Gammon ST, Novack DV, McKinney JS, Piwnica-Worms D. A bioluminescent transposon reporter-trap identifies tumor-specific microenvironment-induced promoters in salmonella for conditional bacterial-based tumor therapy. Cancer Discov. 2012; 2(7):624-637. PMCID: PMC3395769.
 Bonar SL, Brydges SD, Mueller JL, McGeough MD, Pena C, Chen D, Grimston SK, Hickman-Brecks CL, Ravindran S, McAlinden A, Novack DV, Kastner DL, Civitelli R, Hoffman HM, Mbalaviele G. Constitutively activated NLRP3 inflammasome causes inflammation and abnormal skeletal development in mice. PLoS One. 2012; 7(4):e35979. PMCID: PMC3338787
 Mavers M, Cuda CM, Misharin AV, Gierut AK, Agrawal H, Weber E, Novack DV, Haines GK 3rd, Balomenos D, Perlman H. The cyclin dependent kinase inhibitor p21 is essential for resolution of murine inflammatory arthritis via its c-terminal domain. Arthritis Rheum. 2012; 64(1):141-152. PMCID: PMC3253189.
 Zhang K, Kim S, Cremasco V, Hirbe A, Novack DV, Weilbaecher K, Faccio R. CD8+ T cells Regulate Bone Tumor Burden Independent of Osteoclast Resorption. Cancer Res. 2011; Jul 15;71(14):4799-4808. PMCID: PMC3138866.
 Cyr AE, Novack D, Trinkaus K, Margenthaler JA, Gillanders WE, Eberlein TJ, Ritter J, Aft RL. Are we overtreating papillomas diagnosed on core needle biopsy? Ann Surg Oncol. 2011; Apr;18(4):946-951. PMCID: PMC3980447
 Whyte MP, Totty WG, Novack DV, Zhang X, Wenkert D, Mumm S. Camurati-Engelmann disease: Unique variant featuring a novel mutation in TGFβ1 encoding transforming growth factor β1 and a missense change in TNFSF11 encoding RANK ligand. J Bone Miner Res. 2011; 26(5):920-933. PMCID: PMC 3179308.


Assistant
Christina Grantham
314 454-8463
granthamc@wustl.edu

Lab Phone: 314 454-5975
Office Location: BJC-IH Building, Room 11611