dr. Thomas Naert (PhD)

CRIG member
Thomas Naert

Postdoctoral researcher  - Unit for developmental biology - VIB-UGent
Principal investigator: prof. Kris Vleminckx (PhD)

Research focus

Since long mice models have been the mainstray method for the identification of novel therapeutic targets for treatment of cancers. However, with the targeted nucleases revolution it has become possible to generate genuine genetic knockout models in the aquatic model organism Xenopus tropicalis. As such, we generated the first ever genuine genetic cancer model in Xenopus by targeting of the apc gene with the TALENs technology. This APC tumor model phenocopies familial adenomatous polyposis and develops desmoid tumors with high penetrance (95%) and short latency (1-1.5months). Additionally, we developed the first ever CRISPR/Cas9 tumor model in a non-mammal and showed that by multiplex targeting of Rb1 and Rbl1 we are able to induce retinoblastoma with high penetrance (>73%) and low latency (median time 70 days). These models are currently being exploited in order to identify novel therapeutic targets, this by multiplex disruption of the potential therapeuthic targets within the established cancer model. We firmly believe that lower vertebrate cancer models which profoundly recapitulate the clinical situation, will be key in order to have the biomedical community conform to the requests from the public and policymakers to reduce the amount of mammals used in pre-clinical studies. Whilst models with closer evolutionary distance to humans will always be necessary for validating studies performed in those models with further evolutionary distance, we feel that lower vertebrate models can provide significant advantages during earlier stages of drug discovery and for rapid therapeutic target identification.

Biography

  • IWT-grant (strategic basic research) (2014-2018)
  • Emmanuel van der Schueren - Kom op tegen Kanker (2019)

Key publications

  • TALEN-mediated apc mutation in Xenopus tropicalis phenocopies familial adenomatous polyposis. Oncoscience, 2015 (PMID: 26097888)
  • CRISPR/Cas9 mediated knockout of rb1 and rbl1 leads to rapid and penetrant retinoblastoma development in Xenopus tropicalis. Sci. Rep., 2016 (PMID: 27739525)
  • TALENs and CRISPR/Cas9 fuel genetically engineered clinically relevant Xenopus tropicalis tumor models. Genesis, 2017 (PMID: 28095622)
  • RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6. Nature. 2018 (PMID: 29769720)

Contact & links