PhD conferral Timo W.M. de Groof - online
US28 nanobodies: A “VUN” example of targeting viral GPCRs
Timo W.M. de Groof
Prof.dr. Martine J. Smit, copromotor dr. Marco H. Siderius
Amsterdam Institute of Molecular and Life Sciences
The human cytomegalovirus (HCMV) is a virus that has infected 50-90% of the worldwide population. This infection is harmless for healthy individuals but can have serious consequences for persons with a weakened immune system. During organ transplantations, HCMV infection can result in the onset of different diseases, organ rejection or even mortality. In addition, HCMV infection results in enhanced growth of tumors including glioblastoma, an aggressive and incurable brain tumor. To date, the role of HCMV in these diseases is not fully known and there isn’t an effective treatment against HCMV infections.
One of the proteins encoded by HCMV is the G protein-coupled receptor US28. This viral receptor plays a crucial role in the HCMV life cycle and is essential for viral immune evasion but also stimulates tumor growth. Because of this important role of US28, Timo De Groof has identified nanobodies (antibody fragments derived from llamas) targeting this receptor and has investigated the potential of these nanobodies for different applications. On one hand, US28-targeting nanobodies have been tested as a potential cancer treatment by coupling them to toxic photosensitizer groups to enable selective killing of tumor cells. Moreover, the nanobodies have been used as antiviral treatment resulting in the recognition and clearance of HCMV-infected by the immune system. Finally, De Groof has used these nanobodies also for more fundamental research by using these nanobodies to get more insight how US28 modulates cellular signaling.Overall, the research of De Groof has led to the identification of multiple US28-targeting nanobodies that can be used as research tools and potential novel therapies to treat HCMV infections and different cancers including glioblastoma.