Mark J. Birnbaum, Ph.D.
Professor of Biology
Biotechnology Council Liaison
B.S. and M.S. University of Maryland
Ph.D. University of North Carolina
Office: Mendel 352
Tel: 978-837-5000 ext 5276
Principles of Biology I and II, Cell Biology, Methods in Cell and Molecular Biology, Virology, Special Topics in Biology, Senior Thesis Research
Using Biotechnology to Identify New Potential Targets for Bone Loss Drug Therapy
My students and I work with research scientists at the University of Massachusetts Medical School and the University of Southern California Medical School to study bone biology.
Bone mass is dependent on osteoclasts that resorb bone, and osteoblasts that build new bone. Recent work has focused on the discovery of new potential molecular targets for bone loss drug therapy. Using a modern biotechnology approach, we combine bioinformatics of the human genome project with micro-chip/gene array technology, RNAi, and other technologies to identify targets and test them for physiological relevance during osteoclast differentiation. Using these methods, we have identified several new genes that function during osteoclastogenesis. Two membrane proteins, OGR-1 and OCS were highly expressed during osteoclast differentiation in vivo during rat and mouse bone development and in vitro. Inhibition by either RNAi or antibodies demonstrated that these gene products were required for optimal osteoclast differentiation. Studies are underway to determine if these two genes might be targets for therapies (antibodies, RNAi, or small molecules) designed to down-regulate osteoclast function and combat bone loss in vivo. Identification and study of other new potential osteoclast target molecules are ongoing.
Yang, M., Birnbaum, M.J., MacKay, C.A., Mason-Savas, A. and Odgren, P.R. 2007. Osteoclast stimulatory transmembrane protein (OC-SAMP), a novel protein induced by RANKL that promotes osteoclast differentiation. Journal of Cellular Physiology 215(2): 497-505.
Odgren, P.R., Birnbaum, M.J., Yang, M., Mailhot, G., Aubin, J., MacKay, C.A., Mason-Savas, A. 2006. Osteopetrotic mutations in rats and mice as tools to study tooth eruption: the role of chemokines in osteoclast differentiation in vivo. pp. 1-10. In Biological Mechanisms of Tooth Eruption, Resorption and Movement, Edited by Davidovitch, Z., Mah J., and S. Suthanara.
Odgren, P.R., MacKay, C.A., Mason-Savas, A., Yang, M., Mailhot, G.,, and Birnbaum, M.J. 2006. False-positive beta-galactosidase staining in osteoclasts by endogenous enzyme: studies in neonatal and month-old wild-type mice. Connective Tissue Research 47: 229-234.
Yang, M., Mailhot, G., Birnbaum, M.J., MacKay, C.A., Mason-Savas, A., and Odgren, P.R. 2006. Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1) during osteoclastogenis. Journal of Biological Chemistry 281: 23598-23605.
Zalavras C, Shah S, Birnbaum MJ, Frenkel B. 2003. Role of apoptosis in glucocorticoid-induced osteoporosis and osteonecrosis. Critical Review in Eukaryotic Gene Expression 13(2-4): 221-35.
Bab, I., Smith, E., Gavish, H., Attar-Namdar, M., Chorev, M., Chen, Y., Muhlrad, A.,Birnbaum, M., Stein, G., and Frenkel, B. 1999. Biosynthesis of osteogenic growth peptide via alternative translational initiation at AUG85 of histone h4 mRNA. Journal of Biological Chemistry 274: 14474-14481.
Rethinaswamy, A., Birnbaum, M.J., and Glover, C.V.C. 1998. Temperature-sensitive mutations of the CKA1 gene reveal a role for casein kinase II in maintenance of cell polarity in S. cerevisiae. Journal of Biological Chemistry 273: 5869-5877.
van Wijnen, A.J., van Gurp, M.F., de Ridder, M., Tufarelli, C., Last, T.J., Birnbaum, M.J., Vaughan, P.S., Giordano, A., Krek, W., Neufeld, E.J., Stein, J.L., and Stein, G.S. 1996. CDP/cut is the DNA binding subunit of transcription factor HiNF-D (cyclin A, CDC2, RB-related complex): a non-E2F mechanism for histone gene regulation at the G1/S phase cell cycle transition point. Proceedings of the National Academy of Sciences USA 93: 11516-11521.
Birnbaum, M.J., van Wijnen, A.J., Odgren, P.R., Last, T.J., Suske, G., Stein, G.S., and Stein, J.L. 1995. Sp1 trans-activation of cell cycle regulated promoters is selectively repressed by Sp3. Biochemistry 34: 16503-16508.
Birnbaum, M.J., Wright, K.L., van Wijnen, A.J., Ramsey-Ewing, A.L., Bourke, M.T., Last, T.J., Aziz, F., Frenkel, B., Rao, B.R., Aronin, N., Stein, G.S., and Stein, J.L. 1995. Functional role for Sp1 in the transcriptional amplification of a cell cycle regulated histone H4 gene. Biochemistry 34: 7648-7658.
Birnbaum, M.J., Clem, R.J., and Miller, L.K. 1994. An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with cys/his sequence motifs. Journal of Virology 68: 2521-2528.