Research interests

The interests of our laboratory focus on the regulation of cell type specification and differentiation, primarily studying how signal transduction pathways integrate to mediate the transcriptional control of these events. The two major projects that we are currently pursuing in the lab are: (1) Defining the molecular mechanisms governing the terminal differentiation of several different cell types, including muscle, bone, and endothelial cells. One of the goals of this project is to identify common elements of these pathways that when mutated or misregulated result in uncontrolled growth or cancer and may act as entry points for regulating cell growth and differentiation. (2) The second project is to characterize the transcriptional regulation of mesenchymal cell specification and differentiation from the cranial neural crest, which forms many of the bones of the face and skull. We are also contrasting and comparing this with the regulation of mesoderm specification during gastrulation. The neural crest is unique to the vertebrates and the goals of this project are to help shed light on the origin of vertebrates as well as on the mechanisms governing craniofacial development.

Publications

• Connerney J., and Spicer, D.B., (2010) Signal transduction pathways and their impairment in syndromic craniosynostosis, in Monographs in Human Genetics. Craniosynostoses: Molecular Genetics, Principles of Diagnosis and Treatment, H. Collmann, W. Kress, and M. Muenke, Editors. Karger. (in press).
• Spicer, D. (2009) FGF9 on the move. Nat. Genet. 41:272-273.

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• Brauner, I., Spicer, D.B., Krull, C.E., and Venuti, J.M., (2009) Identification of responsive cells in the developing somite supports a role for beta-catenin-dependent Wnt signaling in maintaining the DML myogenic progenitor pool. Dev. Dyn. (in press).

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• Min, C., Yu, Z., Kirsch, K.H., Zhao, Y., Vora, S., Trackman, P.C., Spicer, D.B., Rosenberg, L., Sonenshein, G.E., and Palmer, J.R., (2009) A loss of function polymorphism in the propeptide domain of the LOX gene and breast cancer. Cancer Res. 69:6685-93.

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• Connerney, J., V. Andreeva, Y. Leshem, M.A. Mercado, K. Dowell, X. Yang, V. Lindner, R.E. Friesel, and D.B. Spicer (2008) Twist1 homodimers enhance FGF responsiveness of the cranial sutures and promote suture closure. Dev. Biol. 318; 323-334.

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• Mancini ML, Verdi JM, Conley BA, Nicola T, Spicer DB, Oxburgh L, and Vary, CPH (2007) Endoglin is required for myogenic differentiation potential of neural crest stem cells. Dev. Biol. 308: 520-533.

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• Connerney, J., Y. Leshem, V. Andreeva, C. Muentener, M. Mercado, and D.B. Spicer. (2006) Twist dimer selection regulates cranial suture patterning and fusion. Dev. Dyn. 235: 1345-1357.

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• *Lesham Y., *D.B. Spicer, R. Gal-Levi, G. Shefer, and O. Halevy. (2000). Hepatocyte Growth Factor (HGF) inhibits skeletal muscle differentiation: a role for the bHLH protein Twist and the cdk inhibitor p27. J. Cell Physiol. 184: 101-109.

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• Isaac, A., M.J. Cohn, P. Ashby, P. Ataliotis, D.B. Spicer, J. Cooke, C. Tickle (2000). FGF and genes encoding transcription factors in early limb specification. Mech. Dev. 93: 41-48.

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• *Novitch, B.G., *D.B. Spicer, P.S. Kim, W.L. Cheung, and A.B. Lassar (1999). pRb is required for MEF2-dependent gene expression as well as cell-cycle arrest during skeletal muscle differentiation. Curr. Biol. 9: 449-459.

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• Spicer, D.B., J. Rhee, W.L. Cheung, and A.B. Lassar (1996). Inhibition of myogenic bHLH and MEF2 transcription factors by the bHLH protein Twist. Science 272: 1476-1480.

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• Halevy, O., B.G. Novitch, D.B. Spicer, S.X. Skapek, J. Rhee, G.J. Hannon, D. Beach, and A.B. Lassar (1995). Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD. Science 267: 1018-1021.

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• Skapek, S.X., J. Rhee, D.B. Spicer, and A.B. Lassar (1995). Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1-dependent kinase. Science 267: 1022-1024.

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