Nanobody Lab


Supervisor: Prof. dr. Jan Gettemans

Master StudentsDoctoral StudentsTechnical Staff
Brian De Dobbelaer
Evy Doolaege
Judith Misseeuw
Laurence Bertier
Els Beghein
Anneleen Steels
Tim Hebbrecht
Tijs Merckaert
Olivier Zwaenepoel

Positions available (PhD, post-doc): please contact

Research Focus

Many proteins nowadays are considered as a drug target. However, many proteins display multiple functions and interact with a plethora of other proteins. Therapeutic drugs other than antisense oligonucleotides should ultimately affect a specific protein function in cells, while leaving other functions intact. It is therefore paramount to develop new tools that meet these requirements. Moreover, a great number of proteins involved in the etiology or progression of various diseases are considered undruggable. The lack of specific antagonists stems from the fact that such proteins do not display any catalytic activity.

Nanobodies can be useful to fill this gap. A nanobody corresponds with the variable part of the heavy chain of heavy chain antibodies from Camelidae. It is the smallest antigen binding fragment that completely retains its binding affinity and specificity. Nanobodies provide a unique stepping stone to identify ‘weak spots’ in proteins, blocking of which triggers a measurable therapeutic effect. Our lab has acquired extensive expertise in knocking out verifiable functions of proteins in cells using nanobody technology leading to a protein domain knock-out.

We implement nanobody technology with a specific focus on ‘antigens’ (intracellular proteins) that play a role in cancer, inflammation and amyloid diseases. We investigate regulation of cancer cell migration, invasion and metastasis with emphasis on polypeptides that regulate organization of the actin cytoskeleton. Using single domain antibodies one can temper in vivo functions of selected proteins without affecting their expression level. This selectivity allows modulation of the function of one domain by a specific intrabody at any time without interfering with other activities of the target protein. A comprehensive approach is pursued in which biochemistry, protein chemistry, cell biology/molecular biology and proteome analysis are blended and integrated.

Keywords: single domain antibody - protein domain knock-out - intrabody - cancer - invasion.

Selected Publications


Van Deun et al. EV-TRACK: transparant reporting and centralizing knowledge in extracellular vesicle research. Nature meth. 14, 228-232.

Bertier, L., Boucherie, C., Zwaenepoel, O., Vanloo, B., Van Troys, M., Van Audenhove, I., Gettemans, J. Inhibitory cortactin nanobodies delineate the role of NTA- and SH3-domain specific functions during invadopodium formation and cancer cell invasion. FASEB J., in press.

Verhelle, A., Nisha, N., Everaert, I., Van Overbeke, W., Supply, L., Zwaenepoel, O., Peleman, C., Van Dorpe, J., Lahoutte, T., Devoogdt, N., Derave, W., Marinee, C.K., VandenDriessche, Y., Gettemans, J. AAV9 delivered bispecific nanobody attenuates amyloid burden in the gelsolin amyloidosis mouse model. Hum. Mol. Gen., in press.


Gross, C., Wiesmann, V., Millen, S., Kalmer, M., Wittenberg, T., Gettemans, J., Thoma-Kress, A.K. (2016) The Tax-Inducible Actin-Bundling Protein Fascin Is Crucial for Release and Cell-to-Cell Transmission of Human T-Cell Leukemia Virus Type 1 (HTLV-1). PLoS Pathog. 12, e1005916.

Beghein, E., Van Audenhove, I., Zwaenepoel, O., Verhelle, A.., De Ganck, A., and Gettemans, J. (2016) A new survivin tracer tracks, delocalizes and captures endogenous survivin at different subcellular locations and in distinct organelles. Sci Rep., 6:31177.

Verhelle, A., and Gettemans, J. (2016) A Nanobody Based Approach to Amyloid Diseases, the Gelsolin Case Study. Book chapter, in ‘Exploring new findings on Amyloidosis’. Chapter 13. p313-335.

Van Audenhove, I., and Gettemans, J. (2016) Nanobodies as Versatile Tools to Understand, Diagnose, Visualize and Treat Cancer. EBioMedicine 8, 40-48. Review

Verhelle, A., Van Overbeke, W., Peleman, C., De Smet, R., Zwaenepoel, O., Lahoutte, T., Van Dorpe, J., Devoogdt, N., and Gettemans, J. (2016) Non-Invasive Imaging of Amyloid Deposits in a Mouse Model of AGel Using 99mTc-Modified Nanobodies and SPECT/CT. Mol Imaging Biol 8:40-8. Review.

Van Audenhove, I., Denert, M., Boucherie, C., Pieters, L., Cornelissen, M., and Gettemans, J. (2016) Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia. J Biol Chem 291, 9148-9160

Van Audenhove, I., and Gettemans, J. (2016) Use of Nanobodies to Localize Endogenous Cytoskeletal Proteins and to Determine Their Contribution to Cancer Cell Invasion by Using an ECM Degradation Assay. Methods Mol Biol 1365, 225-241


Van Overbeke, W., Wongsantichon, J. Everaert, I., Verhelle, A., Zwaenepoel, O., De Ganck, A., Loonchanta, A., Burtnick, L.D., Hochepied, T. Haigh, J., Cuvelier, C., Derave, W., Robinson, R., and Gettemans, J. (2015). An ER-directed gelsolin nanobody targets the first step in amyloid formation in a gelsolin amyloidosis mouse model. Hum. Mol. Genet. 24, 2492-2507.

Van Audenhove, I., Debeuf, N., Boucherie, C., and Gettemans, J. (2015). Fascin actin bundling controls podosome turnover and disassembly while cortactin is involved in podosome assembly by its SH3 domain in THP-1 macrophages and dendritic cells. BBA - Molecular Cell Research 1853, 940-952.

Bethuyne, J., De Gieter, S., Zwaenepoel, O., Garcia-Pino, A., Durinck, K., Verhelle, A., Hassanzadeh-Ghassabeh, G., Speleman, F., Loris, R., and Gettemans, J. (2014) A nanobody modulates the p53 transcriptional program without perturbing its functional architecture. Nucleic Acids Res 42, 12928-12938


Van Overbeke, W., Verhelle, A., Everaert, I., Zwaenepoel, O., Vandekerckhove, J., Cuvelier, C., Derave, W., and Gettemans, J. (2014). Chaperone nanobodies protect gelsolin against MT1-MMP degradation and alleviate amyloid burden in the gelsolin amyloidosis mouse model. Mol Ther 22, 1768-78.

Van Audenhove, I., Boucherie, C., Pieters, L., Zwaenepoel, O., Vanloo, B., Martens, E., Verbrugge, Ch., Hassanzadeh-Ghassabeh, Gh., Vandekerckhove, J., Cornelissen, M., De Ganck, A. and Gettemans, J. (2014). Stratifying fascin and cortactin function in invadopodium formation using inhibitory nanobodies and targeted subcellular delocalization. FASEB J 28, 1805-1818. doi: 10.1096/fj.13-242537.


Van Impe, K., Bethuyne, J., Cool, S., Impens, F., Ruano-Gallego, D., De Wever, O., Vanloo, B., Van Troys, M., Lambein, K., Boucherie, C., Martens, E., Zwaenepoel, O., Hassanzadeh-Ghassabeh, G., Vandekerckhove, J., Gevaert, K., Fernandez, L. A., Sanders, N. N., and Gettemans, J. (2013). A nanobody targeting the F-actin capping protein CapG restrains breast cancer metastasis, Breast Cancer Res 15, R116.

De Clercq, S., Boucherie, C., Vandekerckhove, J., Gettemans*, J., and Guillabert*, A. (2013). L-Plastin Nanobodies Perturb Matrix Degradation, Podosome Formation, Stability and Lifetime in THP-1 Macrophages. PLoS One.8,:e78108

Van Audenhove,  I., Van Impe, K., Ruano-Gallego, D., De Clercq, S., De Muynck, K., Vanloo, B., Verstraete, H., Fernández, L.A., and Gettemans,  J. (2013). Mapping cytoskeletal protein function in cells by means of nanobodies. Cytoskeleton (Hoboken). Oct;70, 604-622

De Clercq, S., Zwaenepoel, O., Martens, E., Vandekerckhove, J., Guillabert, A., and Gettemans, J. (2013). Nanobody-induced perturbation of LFA-1/L-plastin phosphorylation impairs MTOC docking, immune synapse formation and T cell activation. Cell Mol Life Sci, 70, 909-922.

PhD Defenses

Isabel Van Audenhove (2016): Nanobody-based high resolution mapping of actin regulators in cancer and immune cell invadosomes. Promotor: J. Gettemans

Wouter Van Overbeke (2015): Keeping mutant plasma gelsolin safe from harm: gelsolin nanobodies act as a chaperone against pathological proteolysis. Promotor: J. Gettemans

Jonas Bethuyne (2015): New Tools in Cancer Research - Nanobodies are more than just a one-trick pony. Promotor: J. Gettemans

Sarah De Clercq (2013): Modulating L-plastin function in immune cells by nanobodies: how small bodies can have large consequences. Promotor: J. Gettemans

Eline Remue (2011). Expanding the Zonula Occludens Interaction Web: catching PIP2 and TAZ. Promotor: J. Gettemans

Anske Vanden Abbeele (2010): Immunomodulation of gelsolin function in cancer cells using single domain antibodies (Nanobodies®). Promotor: J. Gettemans

Thomas Hubert (2010): Nucleoporin Nup62 in nucleo-cytoplasmic transport and cell migration. Promotor: J. Gettemans

Veerle Delanote (2009): Dissimilar nuclear trafficking of plastin isoforms and immunomodulation of cancer cell migration and invasion by use of L-plastin Camelid nanobodies. Promotor: J. Gettemans

Ariane De Ganck (2008): Nucleo-cytoplasmic shuttling of myopodin isoforms in relation to tumorigenesis. Promotor: J. Gettemans

Katrien Van Impe (2005): Nucleo-cytoplasmatisch transport of CapG, an actin-capping and pro-invasive protein. Promotor: J. Gettemans

Kris Meerschaert (2002): (Lyso)phospholipids as regulators of actin organization and PDZ-domain interactions. Promotor: J. Gettemans