Daniel Abankwa, Professor within the Department of Life Sciences and Medicine at the University of Luxembourg, has recently gained a total of €1.2 million competitive funding from the Luxembourg National Research Fund (FNR) for three cancer related bilateral research projects that will commence in fall. All projects are conducted in collaboration with outstanding international colleagues. The projects address very diverse questions of RAS biology, both fundamental (projects PolaRAS2 and RAS-NANOME), and applied in nature (RAS-NANOME, HRAS-PPI).
“We are incredibly grateful for this funding, not only from the FNR, but also from the partnering funding bodies, the Deutsche Forschungsgemeinschaft (DFG, Germany), NWO (Netherlands) and BBSRC (UK). We have worked extremely hard last year and it is great this is coming to fruition,” says Prof. Daniel Abankwa who heads the Cancer Cell Biology and Drug Discovery group.
“These are very exciting times in the 40-year history of RAS research, as we see finally the first direct RAS inhibitors showing effects in the clinic. These results support the notion that targeting RAS is exceptionally important in cancer,” explains Prof. Abankwa.
As one of the first identified oncogenes, RAS signalling has typically been associated with cell proliferation, but recent data suggest that its dysfunction in cancer goes well beyond that. This is addressed in the project PolaRAS2, where sophisticated microscopy methods will be applied in order to understand how RAS proteins drive stem cell defining cellular processes, which could be at the origin of every tumour. Prof. Abankwa says his research group is fortunate to team up with a world leader in STED-superresolution microscopy, Prof. Christian Eggeling (Leipnitz-IPTH and Faculty of Physics and Astronomy University of Jena, Germany). The organisation of RAS on the nanoscale, a dimension at the transition between atomic details and the size of cellular organelles, is one of the specialities of the Abankwa group at UL.
The second project, RAS-NANOME, focuses on regulators of the nanoscale membrane organisation of RAS, called nanoclustering. Importantly, some of these regulators may have the potential to become important cancer targets. “We will test all proteins of a cell for their activity to regulate RAS nanoclustering,” says Prof. Abankwa. Collaboration partner Prof. Ian Prior and his team from the University of Liverpool have a strong expertise in testing all cellular proteins.
The third project, HRAS-PPI, aims at developing a new prototype drug that can block RAS activity. “This is a very active area of RAS research at the moment, as finally RAS has gotten into therapeutic reach. We will develop a so called peptidomimetic, as an inhibitor of a protein-protein interface. Interfaces are notoriously difficult to target with standard, small-molecule drugs. Therefore, we joined forces with organic chemist Prof. Tom Grossmann (VU Amsterdam, The Netherlands), an expert in peptidomimetics,” describes Prof. Abankwa. At the end of this project the team expects to have a tool compound that will be significant for the research community and will help to convince funders, to further support research on this approach. “Drug development is a very expensive, more than 10-year long process with many failures. In all our RAS drug development approaches we therefore try to develop a strong, mechanism driven and biomarker supported rational. Several examples in the recent years have demonstrated that academic labs can be important innovation contributors,” summarises Prof. Abankwa. With this in mind, Prof. Abankwa is optimistic that the next years will show some breakthroughs in understanding and drug-targeting RAS in cancer. He believes that the dynamic and supportive environment at the University of Luxembourg could be significant in strengthening RAS research in the heart of Europe.