Hedda Johannesen

• Johannesen, Hedda; Bjerregaard-Andersen, Kaare; Abdel-Rahman, Noha Mansour Hassan; Heggelund, Julie Elisabeth; Mykland hoås, Helene; Abraha, Fana; Bousquet, Paula; Høydahl, Lene Støkken; Burschowsky, Daniel; Rojas, Gertrudis; Oscarson, Stefan; Løset, Geir Åge & Krengel, Ute (2018). Crystal structure of an L chain optimised 14F7 anti-ganglioside Fv suggests a unique tumour- specificity through an unusual H-chain CDR3 architecture. Scientific Reports.  ISSN 2045-2322.  8(1) . doi: 10.1038/s41598-018-28918-5 Vis sammendrag

  Targeted cancer immunotherapy offers increased efficacy concomitantly with reduced side effects. One antibody with promising clinical potential is 14F7, which specifically recognises the NeuGc GM3 ganglioside. This antigen is found in the plasma membrane of a range of tumours, but is essentially absent from healthy human cells. 14F7 can discriminate NeuGc GM3 from the very similar NeuAc GM3, a common component of cell membranes. The molecular basis for this unique specificity is poorly understood. Here we designed and expressed 14F7-derived single-chain Fvs (scFvs), which retained the specificity of the parent antibody. Detailed expression and purification protocols are described as well as the synthesis of the NeuGc GM3 trisaccharide. The most successful scFv construct, which comprises an alternative variable light chain (VLA), allowed structure determination to 2.2 Å resolution. The structure gives insights into the conformation of the important CDR H3 loop and the suspected antigen binding site. Furthermore, the presence of VLA instead of the original VL elucidates how this subdomain indirectly stabilises the CDR H3 loop. The current work may serve as a guideline for the efficient production of scFvs for structure determination.

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• Johannesen, Hedda; Hoås Mykland, Helene; Heggelund, Julie Elisabeth; Bjerregaard-Andersen, Kaare; Løset, Geir Åge & Krengel, Ute (2018). An anti-ganglioside scFv for cancer therapies.
• Johannesen, Hedda; Mykland hoås, Helene; Heggelund, Julie Elisabeth; Bjerregaard-Andersen, Kaare; Løset, Geir Åge & Krengel, Ute (2018). 14F7, An anti-ganglioside scFv for cancer therapies.
• Johannesen, Hedda; Mykland Hoås, Helene; Heggelund, Julie Elisabeth; Bjerregaard-Andersen, Kaare; Løset, Geir Åge & Krengel, Ute (2018). 14F7, an antibody that recognises a tumour-specific ganglioside with high specificity.
• Johannesen, Hedda; Hammerstad, Marta; Hersleth, Hans-Petter & Andersson, K. Kristoffer (2017). A structural and functional investigation of ribonucleotide reductase class III.
• Hammerstad, Marta; Hersleth, Hans-Petter; Lofstad, Marie; Johannesen, Hedda; Tomter, Ane Berg; Røhr, Åsmund Kjendseth & Andersson, K. Kristoffer (2016). Structural Insight into the Function of Ribonucleotide Reductase.
• Johannesen, Hedda & Foss, Øystein (2016). Grensesprengende kjemi – et heftig møte mellom magi, myter og vitenskap.
• Johannesen, Hedda; Hersleth, Hans-Petter; Hammerstad, Marta & Andersson, K. Kristoffer (2016). A Structural and Functional Investigation of Ribonucleotide Reductase Class III In Bacillus Cereus.
• Johannesen, Hedda; Hersleth, Hans-Petter; Hammerstad, Marta & Andersson, K. Kristoffer (2016). A structural and functional investigation of Ribonucleotide reductase Class III in Bacillus cereus. NBS-nytt.  ISSN 0801-3535.  s 65- 65
• Johannesen, Hedda; Bousquet, Paula; Løset, Geir Åge & Krengel, Ute (2014). L`ASSASSINA PROTEIN THAT SPECIFICALLY KILLS TUMOUR CELLS.
• Johannesen, Hedda; Krengel, Ute; Løset, Geir Åge & Bousquet, Paula (2014). The Assassin - Recombinant single-chain Fv production of the anti-tumour antibody 14F7.
• Johannesen, Hedda (2013). A PERFECTLY DESIGNED TRAP: A MOLECULE THAT SPECIFICALLY KILLS TUMOUR CELLS.
• Johannesen, Hedda (2013). Snikmorderen - Vinner av Kjemi Grand Prix. Vis sammendrag

  Proteinet 14F7 dreper kreftcelle. For 8 millioner år siden skjedde det en mutasjon som gjorde at vi mennesker ikke lenger klarte å lage et spesifikt karbohydrat, men når en vanlig celle blir til en kreftcelle dukker dette sukkeret opp igjen i cellen. 14F7 binder seg til dette karbohydratet og lager et hull i cellen slik at den dør. Jeg ønsker å finne ut av hvordan 14F7 binder til karbohydratet. Hvis jeg kan oppdage hvordan 14F7 og sukkermolekylet interagerer kan jeg jobbe med å forbedre bindingen slik at 14F7 blir enda mer effektiv.

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