dr. Louis Delhaye (PhD)

CRIG member
Louis Delhaye


Postdoctoral fellow –
. OncoRNALab, Center for Medical Gentics (UGent)

. Department of Biomolecular Medicine (UGent)
. VIB-UGent Center for Medical Biotechnology (VIB, UGent)

PI: prof. Sven Eyckerman (PhD) & prof. Pieter Mestdagh (PhD)

 

Research focus

An increasing number of studies support the involvement of long non-coding RNAs (lncRNAs) in cancer. Targeting lncRNAs is an appealing opportunity as lncRNA expression can be highly tissue-specific, potentially reducing toxic side-effects in normal cells. Nevertheless, therapeutic targeting of lncRNAs remains quite a challenging endeavor. As ASO technology is advancing in the clinic, several limitations have surfaced. Most notably, chemically modified phosphorothioate (PS) gapmer ASOs bind many intracellular proteins with high avidity, thereby mislocalizing them and altering their function and stability in an RNase H1-dependent manner, effectively inducing apoptosis and thus treatment toxicity. Steric blocking ASOs do not recruit RNase H1 as they do not contain a DNA gap, but rather are built entirely from RNA nucleotides. 2’ modifications of these nucleotides, such as 2’MOE, have been shown to completely mitigate the cytotoxic effects that are induced by the PS backbone. Currently 7 out of 10 clinically approved ASOs are fully modified ASOs (i.e. containing both PS and 2’ modifications on all nucleotides) that block interactions between the splicing machinery and splice junctions in specific mRNAs to alter splicing. However, fully modified ASOs can also be exploited to block the binding between RNA and other proteins. To efficiently develop such ASOs, one must be able to map RNA-protein interfaces. We aim to identify RNA-protein interaction interfaces of cancer-specific lncRNAs with the intent to develop ASOs that sterically block these interactions and evaluate the therapeutic potential of these ASOs in vivo.
 

Biography

  • 2013-2015 MSc in Biology: Cell and Systems Biology, UAntwerpen
  • 2016-2022 PhD student at Department of Biomolecular Medicine, UGent
  • 2022-present Postdoctoral fellow at Center for Medical Biotechnology, VIB-UGent
  • 2022-present Postdoctoral fellow at OncoRNALab, UGent
     

Key publications

  • RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition, Science Advances (2022) (PMID: 35857500)
  • Orthogonal proteomics to unravel the HOTAIR interactome, Sci Rep (2022) (PMID: 35087108)
  • The long non-coding RNA SAMMSON is essential for uveal melanoma cell survival, Oncogene (2022) (PMID 34508176)
     

Contact & links