Research interests

My laboratory is interested in the role of fibroblast growth factors (FGFs) and their receptors in the regulation of bone growth and homeostasis as well as mesoderm induction and development of the vasculature. FGFs play a significant role in the development of several tissues and organ systems. Recently, we have focused on the functional consequences of mutations in human FGF receptor genes that have been associated with several disorders of bone growth and development. Our laboratory has demonstrated that many of these mutations, which occur in either the extracellular, transmembrane or kinase domains of these receptors, and most often occur as single point mutations, result in constitutive activation of the receptor’s tyrosine kinase activity. We are currently investigating the changes in the signal transduction potential of these mutant receptors in an effort to determine the molecular etiology of these syndromes as well as potential strategies for therapeutic intervention. More recently, the laboratory has become interested in the feedback inhibition of the FGFR pathway by members of a gene family called sprouty, and a transmembrane domain protein called Sef.

Publications

• Yang, X., Harkins, L.K., Zubanova, O., Harrington, A., Kovalenko, D., Nadeau, R.J., Chen, P.Y., Toher, J.L., Lindner, V., Liaw, L., and Friesel, R. Overexpression of Spry1 in Chondrocytes Causes Attenuated FGFR Ubiquitination and Sustained ERK Activation Resulting in Chondrodysplasia. (Developmental Biology, in press, PMID 18582454).
• Connerney, J., Andreeva, V., Leshem, Y., Mercado, M.A., Yang, X., Friesel, R., and Spicer, D.B. Twist homodimers promote increased FGF-responsiveness and craniosynostosis. Developmental Biology, 318:323-334, 2008.
• Nadeau, R.J., Toher, J., Yang, X., Kovalenko, D., and Friesel, R. Regulation of Sprouty Stability by Mammalian Seven-in-Absentia Homolog 2. J. Cell. Biochem., 100:151-160, 2007.
• O’Neill, C.F., Urs, S., Cinelli, C., Lincoln, A., Nadeau R.J., Leon, R., Toher, J., Mouta-Bellum, C., Friesel, R., and Liaw, L. Notch2 Signaling Induces Apoptosis and Inhibits Human MDA-MB-231 Xenograft Growth. Am. J. Pathol., 171:1023-1036, 2007.
• Nikopoulis, G., Duarte, M., Bellum, S., Kubu, C., Friesel, R., Maciag, T., Prudovsky, I., and Verdi, J. Soluble Jagged1 Attenuates Lateral Inhibition Allowing for Clonal Expansion of Neural Crest Stem Cells. Stem Cells, 25:3133-3142, 2007.
• Yang, X., Webster, J.B., Kovalenko, D., Nadeau, R.J., Zubanova, O., Chen, P.-Y. and Friesel, R. Sprouty Genes are expressed in Osteoblasts and Inhibit FGF-mediated Responses. Calcif. Tissue Intl., 78:233-240, 2006.
• Kovalenko, D, Yang, X., Chen, P.-Y., Nadeau, R.J., Zubanova, O., Pidgeon, K. and Friesel, R. A Role for Extracellular and Transmembrane Domains of mSef in mSef-mediated Inhibition of FGF Signaling. Cellular Signaling, 18(11):1958-1966, 2006.
• Duarte M, Kolev V, Soldi R, Kirov A, Graziani I, Marta-Oliveira S, Kacer D, Friesel R, Maciag T, Prudovsky I: Thrombin induces rapid PAR1-mediated non-classical FGF1 release. Biochem. Biophys. Res. Comm., 350(3):604-609, 2006.
• Lindner, V., Wang, Q., Conley, B.A., Friesel, R.E. and Vary, C.P. Vascular Injury Induces Expression of Periostin: Implications for Vascular Cell Differentiation and Migration. Arterioscler. Thromb. Vasc. Biol., 25:77-83, 2005.
• Pyagay, P., Heroult, M., Wang, Q., Lehnert, W., Belden, J., Liaw, L., Friesel, R. and Lindner, V. Collagen Triple Helix Containing1 (Cthrc1), a Novel Secreted Protein in Injured and Diseased Arteries Inhibits Collagen Expression and Cell Migration. Circ. Res., 96:261-268, 2005.
• Yang, X., Kovalenko, D., Nadeau, R.J., Harkins, L.K., Mitchell, J., Zubanova, O., Chen, P-Y and Friesel, R. Sef Interacts with TAK1 and Mediates JNK Activation and Apoptosis. J. Biol. Chem., 279: 38099-38102, 2004.
• Kovalenko, D., Yang, X., Nadeau, R.J., Harkins, L.K. and Friesel, R., Sef Inhibits Fibroblast Growth Factor Signaling by Inhibiting FGFR1 Tyrosine Phosphorylation and Subsequent ERK Activation. J. Biol. Chem., 278: 14087-14091, 2003.
• Tsang, M., Friesel, R., Kudoh, T., .and Dawid, I.B. Identification of Sef, a Novel Modulator of FGF Signaling. Nat. Cell Biol., 4(2):165-169, 2002.
• Chong, L.D., Latimer, E., Kyun-Park, E., Friesel, R. and Daar I.O. FGF Receptor-Mediated Rescue of xEphrinB1-induced Cell Dissociation in Xenopus Embryos. Mol. Cell. Biol., 20(2):724-734, 2000.