Research focus

​Many diseases are linked to aberrant function of structural proteins. Unlike enzymes, however, structural polypeptides lack a small catalytic center that is susceptible to inhibition by pharmacological compounds. As a result, structural polypeptides are quite often regarded as ‘undruggable’.

Single-domain antibodies were first discovered at the Free University of Brussels. Our work has shown that they act as high-affinity antagonists of structural proteins, even when they are expressed in the cytoplasm of eukaryotic cells. Using single-domain antibodies, one can temper in vivo functions of selected proteins without affecting their expression level. The approach is termed ‘immunomodulation’ and allows specific targeting of protein-protein interactions. This selectivity allows modulation of the function of one domain by the specific intrabody at any time, without interfering with other activities of the target protein. We apply single-domain antibody technology to proteins with a key role in various aspects of cancer and amyloid diseases in order to ascertain their therapeutic merit, as well as to understand their contribution to normal and pathophysiological cell behavior.

A comprehensive approach is pursued in which biochemistry, protein chemistry, cell biology/molecular biology and proteome analysis are blended and integrated.