Fibroblast growth factor signaling

In cooperation with partners from Veterinary Universities (Vienna and Raleigh NC) we performed FGF receptor (FGFR) expression studies on soft tissue sarcoma (STS) in a comparative setting on human and canine species. We identified most abundant expressed members of the FGFR family in STS.We are able to block FGFR signaling with molecular tools such as recombinant adenovirus for expression of dominant-negative receptor molecules and small molecule inhibitors. Our aim is to develop experimental cancer therapies.

Students: Nicole Reichmann, Heinrich Steinhoff

Alternative splicing of the IgIII loop of FGFRs 1-3 produces b- and c-variants.

These variants are involved in epithelial mesenchymal transition (EMT) that produces invasive, metastatic features during tumor progression. We study splicing regulatory proteins that influence this splice chose.Furthermore, we developcell models for colorectal cancer (CRC), ovarian cancer (OC) and STS with FGFR splice reporter systems using fluorescent proteins. Such systems permit real-time observation of splice choice in single cells in vivo and in vitro.

Figure. FGFR IIIb/IIIcsplice reporter systems. Schematic of bichromatic (green, red) fluorescence reporter constructs. Alternative splicing of IIIb and IIIc exons results transcripts with different reading frames. Transcripts express green or red chimeric fluorescence proteins and allow visualization of splice chose detection (Holzmann et al. 2012). 

Students: Victor Manuel Minoz Perez, n.n.
Collaborations:
Brigitte Marian, Michael Grusch, Bettina Grasl-Kraupp, Walter Berger, Klaus Holzmann (FGF Research Group, Institute of Cancer Research)
Marlene Hauck (NC State College of Veterinary Medicine, USA)
Miriam Kleiter, (University of Veterinary Medicine, Vienna)
Thomas Grunt (Medical University of Vienna)