 |
|
|
Jan Gettemans
Targeting "undruggable" Proteins Using Single Domain Antibodies
VIB Department of Medical Protein Research, UGent
PhD: Univ. of Ghent, Ghent, Belgium, '93
VIB Group leader since 1998 |
e-mail
phone +32 9 264 93 40
ADDRESS |
Current team members
Group leader: Jan Gettemans
Postdoctoral scientists: Ariane De Ganck, Aude Guillabert, Katrien Van Impe, Thomas Hubert
Ph.D. Students: Eline Remue, Jonas Bethuyne, Marianthi Tatari, Sarah De Clercq, Wouter Van Overbeke
Support personnel: Ciska Boucherie, Evelien Martens, Olivier Zwaenepoel
Keywords
single domain antibody - protein domain knock-out - intrabody - cancer - invasion
Science
Many diseases are linked to aberrant function of structural proteins. As opposed to enzymes however, structural polypeptides lack a small catalytic centre that is susceptible to inhibition by pharmacological compounds. As a result, structural polypeptides are quite often considered 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 to ascertain their therapeutic merit, as well as to understand their contribution to normal and pathophysiological cell behavior.
A comprehensive approach is persued in which biochemistry, protein chemistry, cell biology/molecular biology and proteome analysis are blended and integrated.
Selected Publications
Delanote V, Vanloo B, Catillon M, Friederich E, Vandekerckhove J, Gettemans J
An alpaca single-domain antibody blocks filopodia formation by obstructing L-plastin-mediated F-actin bundling
FASEB J 24, 105-18, 2010
Van Den Abbeele A, De Clercq S, De Ganck A, De Corte V, Van Loo B, Soror S, Srinivasan V, Steyaert J, Vandekerckhove J, Gettemans J
A llama-derived gelsolin single-domain antibody blocks gelsolin-G-actin interaction
CELL MOL LIFE SCI 67, 1519-35, 2010
Hubert T, Vandekerckhove J, Gettemans J
Exo70-mediated recruitment of nucleoporin Nup62 at the leading edge of migrating cells is required for cell migration
TRAFFIC 10, 1257-71, 2009
De Corte V, Van Impe K, Bruyneel E, Boucherie C, Mareel M, Vandekerckhove J, Gettemans J
Increased importin-{beta}-dependent nuclear import of the actin modulating protein CapG promotes cell invasion
J CELL SCI 117, 5283-5292, 2004
Preisinger C, Short B, De Corte V, Bruyneel E, Haas A, Kopajtich R, Gettemans J, Barr a
YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3zeta
J CELL BIOL 164, 1009-1020, 2004
Search Publications
|
|