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Research interests

My laboratory studies the differentiation of osteoclasts, particularly in the context of pathological bone loss, such as in osteoporosis, inflammatory arthritis, and cancer metastasis to bone. Osteoclasts are derived from hematopoietic progenitors in the myeloid lineage, under the influence of the TNF family cytokine RANKL. The binding of RANKL to its receptor RANK activates a number of signaling pathways, including NF-?B, MAPKs, and PI3K/Akt. Our current focus is on the NF-?B pathway, and the role of the various NF-?B family members, inhibitors, and regulatory kinases. It has recently been established that there are 2 main NF-?B pathways, the classical pathway activated rapidly by the IKK complex, leading to translocation of p65/p50 heterodimers, and an alternative pathway controlled by NIK, leading to slower accumulation of RelB/p52 complexes. Blockade of both NF-?B pathways abolishes osteoclast differentiation at a very early stage. We are now dissecting the role of these two pathways using multiple knockout mouse models, with in vitro models of osteoclast differentiation and in vivo models of pathological bone loss. Current projects include: 1) the role of NIK in inflammatory arthritis, 2) the mechanism by which the NF-?B subunit RelB enhances osteoclastogenesis, 3) the role of p65 in osteoclast progenitors, and 4) the importance of NF-?B pathways in bone metastasis.

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Research Output

Bruck syndrome 2 variant lacking congenital contractures and involving a novel compound heterozygous PLOD2 mutation

Mumm, S., Gottesman, G. S., Wenkert, D., Campeau, P. M., Nenninger, A., Huskey, M., Bijanki, V. N., Veis, D. J., Barnes, A. M., Marini, J. C., Stolina, M., Zhang, F., McAlister, W. H. & Whyte, M. P., Jan 2020, In : Bone. 130, 115047.

Research output: Contribution to journalArticle

  • 1 Scopus citations

    Distinct roles of interferon alpha and beta in controlling chikungunya virus replication and modulating neutrophil-mediated inflammation

    Cook, L. E., Locke, M. C., Young, A. R., Monte, K., Hedberg, M. L., Shimak, R. M., Sheehan, K. C. F., Veis, D. J., Diamond, M. S. & Lenschow, D. J., Jan 1 2020, In : Journal of virology. 94, 1, e00841-19.

    Research output: Contribution to journalArticle

  • 9 Scopus citations
  • 2 Scopus citations

    Juvenile Paget's Disease From Heterozygous Mutation of SP7 Encoding Osterix (Specificity Protein 7, Transcription Factor SP7)

    Whyte, M. P., Campeau, P. M., McAlister, W. H., Roodman, G. D., Kurihara, N., Nenninger, A., Duan, S., Gottesman, G. S., Bijanki, V. N., Sedighi, H., Veis, D. J. & Mumm, S., Aug 2020, In : Bone. 137, 115364.

    Research output: Contribution to journalArticle

  • Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

    Cline-Smith, A., Axelbaum, A., Shashkova, E., Chakraborty, M., Sanford, J., Panesar, P., Peterson, M., Cox, L., Baldan, A., Veis, D. & Aurora, R., Jun 1 2020, In : Journal of Bone and Mineral Research. 35, 6, p. 1174-1187 14 p.

    Research output: Contribution to journalArticle

  • 2 Scopus citations