prof. Jan Gettemans (PhD)
The nanobody lab specializes in the development and characterization of nanobodies against proteins broadly considered potential drug targets. Camelidae nanobodies offer several advantages over conventional antibodies. They are 10 times times smaller but have similar specificity and binding affinities as conventional antibodies. Nanobodies are coded by a single exon, and thus can be amplified by PCR and expressed in large amounts in various hosts. They can also be used as excellent tools in the structural and functional characterization of their target antigens. Thus, the nanobody lab has developed extensive expertise in knocking out verifiable functions of proteins in cells using nanobodies. One can i.e. “knockout” specific protein domains or protein-protein interactions, while the antigen is still being expressed in the cell. In this way, nanobodies can serve two purposes; they can be used as new research tools to study protein function in vitro and in living cells, and they offer potential for the development of novel therapeutic applications.
Using nanobody technology, we have focused on the study of proteins that regulate cancer cell migration, invasion and metastasis, with an emphasis on the actin cytoskeleton. Our specific contributions to the field are that we have been able to demonstrate that nanobodies act as high-affinity antagonists of protein function in the cytoplasm of cells, without the need to alter protein expression, and we have succeeded in triggering protein loss-of-function by intracellular redistribution of endogenous proteins to different subcellular loci. Our lab uses a comprehensive approach, in which biochemistry, protein chemistry, cell biology and molecular biology are blended and integrated.
- Cortactin and fascin-1 regulate extracellular vesicle release by controlling endosomal trafficking or invadopodia formation and function. Scientific Reports, 2018 (PMID: 30353022)
- Inhibitory cortactin nanobodies delineate the role of NTA- and SH3-domain-specific functions during invadopodium formation and cancer cell invasion. FASEB Journal, 2017 (PMID: 28235780)
- A nanobody modulates the p53 transcriptional program without perturbing its functional architecture. Nucleic Acids Research, 2014 (PMID:25324313)
- Stratifying fascin and cortactin function in invadopodium formation using inhibitory nanobodies and targeted subcellular delocalization. FASEB Journal, 2014 (PMID:24414419)
- Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia. Journal of Biological Chemistry, 2016 (PMID:26945069)
- Nanobodies as Versatile Tools to Understand, Diagnose, Visualize and Treat Cancer. EbioMedicine, 2016 (PMID:27514728)
- A nanobody targeting the F-actin capping protein CapG restrains breast cancer metastasis. Breast Cancer Research, 2013 (PMID:24330716)