Doug Spicer

Contact Information

Phone:
(207) 396-8150

Email/web:
spiced@mmc.org
View Website

Address:
Maine Medical Center Research Institute
Center for Molecular Medicine
Scarborough, ME 04074

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.

Selected Publications

Connerney J, Spicer DB. Signal transduction pathways and their impairment in syndromic craniosynostosis, in Monographs in Human Genetics. Craniosynostoses: Molecular Genetics, Principles of Diagnosis and Treatment, M. Muenke, H. Collmann, W. Kress, and B.D. Solomon, Editors, Karger. 2011; 28-44.
Guzzo R, Andreeva V, Spicer DB*, and Drissi H*. Persistent expression of Twist1 in chondrocytes causes growth plate abnormalities and dwarfism in mice. J Int Dev Biol. 2011; 55:641-7. *equal contribution. Read Abstract
Tang Y, Urs S, Boucher J, Bernaiche Y, Venkatesh D, Spicer DB, Vary CP, and Liaw L. Notch and TGF? signaling pathways cooperatively regulate vascular smooth muscle cell differentiation. J Biol Chem. 2010; 285(23):17556-63. Read Abstract
Yang X, Kilgallen S, Andreeva V, Spicer DB, Pinz I, and Friesel R. Conditional expression of Spry1 in neural crest causes craniofacial and cardiac defects. BMC Dev Biol. 2010; 11;10:48. Read Abstract
Chakraborty S, Wirrig EE, Hinton RB, Merrill WH, Spicer DB, Yutzey KE. Twist1 promotes heart valve cell proliferation and extracellular matrix gene expression during development in vivo and is expressed in human diseased aortic valves. Dev Biol. 2010;34(1)7:167-79. Read Abstract
Karaczyn A, Bani-Yaghoub M, Tremblay R, Kubu C, Cowling R, Adams TL, Prudovsky I, Spicer D, Friesel R, Vary C, Verdi JM. Two novel human NUMB isoforms provide a potential link between development and cancer. Neural Dev. 2010; 5:31. Read Abstract
Spicer, D. (2009) FGF9 on the move. Nat. Genet. 41:272-273. Read Abstract
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. 2009; 239:222-36 Read Abstract
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. Read Abstract
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. Read Abstract or Download file (PDF)
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. Read Abstract or Download file (PDF)
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. Read Abstract or Download file (PDF)
*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. Read Abstract
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. Read Abstract or Download file (PDF)
*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. Read Abstract or Download file (PDF)
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. Read Abstract or Download file (PDF)
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. Read Abstract or Download file (PDF)
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. Read Abstract or Download file (PDF)