Peter Zaphiropoulos

Professor Peter Zaphiropoulos

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+46 8 608 91 51
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Dissecting Hedgehog Signaling - role of RNA-based mechanisms

Our research interests are currently focused at providing a better molecular understanding of the role of Hedgehog signaling in cancer development. This pathway, originally identified in Drosophila, is one of the major developmental cascades, and its deregulation may result cancerous transformation, with the first example being the most common form of skin cancer, basal cell carcinoma. We are now addressing regulatory mechanisms of Hedgehog signal transduction that implicate microRNA molecules as well as mRNA variants of signaling components. For clinical models of the Hedgehog signaling-mediated events, the childhood cancers of meddulloblastoma and rhabdomyosarcoma are mostly investigated, with the ultimate goal being the development of future therapeutic interventions.

Recent accomplishments

2008: Functional analysis of novel variants of the terminal effector of Hedgehog signaling, the transcription factor GLI1
2007: Functional analysis of novel variants of the receptor of the Hedgehog signal, the transmembrane protein PTCH1
2006: Identification of a novel negative interaction of PTCH1 on the activity of GLI1
2004: Identification and functional analysis of a novel PTCH1 variant, PTCH1-1C
2004: Identification and functional analysis of variants of the PTCH1 paralog, PTCH2
2002: Identification of mRNA molecules generated by trans-splicing

Core group members

Peter Zaphiropoulos and Takashi Shimokawa
Peter Zaphiropoulos and Takashi Shimokawa

Senior Researcher Takashi Shimokawa

E-mail:

PhD Student Ramesh Palaniswamy

PhD Student Ulrica Tostar

Co-workers

Funding

Selected publications

Zaphiropoulos, P.G. and Shimokawa, T.

Splicing variations in components of Patched/Hedgehog signaling.

Trends Cell Mol. Biol. (in press)

Shimokawa, T., Tostar, U., Lauth, M., Palaniswamy, R., Kasper, M., Toftgård, R., and Zaphiropoulos, P.G.

Novel human glioma-associated oncogene 1 (GLI1) splice variants reveal distinct mechanisms in the terminal transduction of the Hedgehog signal.

J. Biol. Chem. (2008) 283, 14345-14354.

Shimokawa, T., Svärd, J., Heby-Henricson, K., Teglund, S., Toftgård, R., and Zaphiropoulos, P.G.

Distinct roles of first exon variants of the tumor suppressor Patched1 in Hedgehog signaling.

Oncogene (2007) 26, 4889-4896

Lindström, E., Shimokawa, T., Toftgård, R., and Zaphiropoulos, P.G.

PTCH1 mutations  distribution and analyses.

Human Mutat. (2006) 27, 215-219

Tostar, U., Malm, C.J., Meis-Kindblom, J.M., Kindblom, L.G., Toftgård, R., Undén, A.B.

Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development.

J Pathol. (2006) 208, 17-25.

Rahnama, F., Shimokawa, T., Lauth, M., Finta, C., Kogerman, P., Teglund, S., Toftgård, R., and Zaphiropoulos, P.G.

Inhibition of GLI1 gene activation by Patched1.

Biochem. J. (2006) 394, 19-26

Shimokawa, T., Rahnama, F., and Zaphiropoulos, P.G.

A novel first exon of the Patched1 gene is up-regulated by Hedgehog signaling resulting in a protein with pathway inhibitory functions.

FEBS Lett. (2004) 578, 157-162.

Rahnama, F., Toftgård, R., and Zaphiropoulos, P.G.

Distinct roles of PTCH2 splice variants in Hedgehog signaling.

Biochem. J. (2004) 378, 325-334.

Finta, C. and Zaphiropoulos, P.G.

Intergenic mRNA molecules resulting from trans-splicing.

J. Biol. Chem. (2002) 277, 5882-5890.

Last modified by: Maria Sjögren 2009-11-12