S. Jeffrey Dixon
Professor
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Ph. D. University of Toronto |
Our studies focus on the cellular and molecular mechanisms underlying the formation and destruction of bone and cartilage. We study the function and regulation of osteoblasts (bone forming cells), chondrocytes (cartilage forming cells) and osteoclasts (bone resorbing cells). Bone loss in inflammatory diseases, such as periodontitis and rheumatoid arthritis, and metabolic diseases, such as osteoporosis, arises from imbalance between the rates of bone formation and resorption. Therefore, we are particularly interested in understanding the physiological regulation of these processes, and in identifying therapeutic agents that inhibit loss of bone and cartilage. We investigate cell behavior using a variety of approaches, including fluorescence spectrophotometry, patch-clamp electrophysiology, microphysiometry, live-cell imaging and molecular biology. Our studies are supported by the Canadian Institutes of Health Research (CIHR), the Canadian Arthritis Network of Centres of Excellence, and pharmaceutical & biotech industries.
Komarova, S.V., Pereverzev, A., Shum, J.W., Sims, S.M. and Dixon, S.J. Convergent signaling by acidosis and receptor activator of NF-ÿB ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts. Proc. Natl. Acad. Sci. USA 102: 2643-2648, 2005. Korcok, J., Raimundo, L.N., Du, X., Sims, S.M. and Dixon, S.J. P2Y6 nucleotide receptors activate NF-ÿB and increase survival of osteoclasts. J. Biol. Chem. 280: 16909-16915, 2005. Jones, D.H., Nakashima, T., Sanchez, O.H., Kozieradzki, I., Komarova, S.V., Sarosi, I., Morony, S., Rubin, E., Sarao, R., Hojilla, C.V., Komnenovic, V., Kong, Y.Y., Schreiber, M., Dixon, S.J., Sims, S.M., Khokha, R., Wada, T. and Penninger, J.M. Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440: 692-696, 2006. Panupinthu, N., Zhao, L., Possmayer, F., Ke, H.Z., Sims, S.M. and Dixon, S.J. P2X7 nucleotide receptors mediate blebbing in osteoblasts through a pathway involving lysophosphatidic acid. J. Biol. Chem. 282: 3403-3412, 2007. Panupinthu, N., Rogers, J.T., Zhao, L., Solano-Flores, L.P., Possmayer, F., Sims, S.M. and Dixon, S.J. P2X7 receptors on osteoblasts couple to production of lysophosphatidic acid: a signaling axis promoting osteogenesis. J. Cell Biol. 181: 859-871, 2008.
