Guido David
Glycobiology and Developmental Genetics
VIB Department of Molecular and Developmental Genetics, K.U.Leuven

Guido David MD: Univ. of Leuven, Leuven, Belgium, '72 Postdoc: Stanford Univ. Medical School, California, USA, '76-'80 VIB Group leader since start VIB (1995) Scientific Director, Dept. of Human Genetics  1998-2006

e-mail phone +32 16 34 71 67 ADDRESS

Current team members
Group leader: Guido David
Postdoctoral scientists: Aurélie Melchior, Bart Roucourt, Patrick Vandormael
Ph.D. Students: Jeroen Vandecasteele, Maria Francesca Baietti
Support personnel: Christien Coomans, Gisèle Degeest, Helga Ceulemans, Ivana Katicic

Keywords
heparan sulfate proteoglycans - syndecan - glypican - heparanase - vesicular trafficking – morphogen-signaling

Science
We investigate the biology of the syndecans and glypicans, two distinctive families of cell surface heparan sulfate proteoglycan. Syndecans are trans-membrane proteins, while glypicans are linked to the cell surface via a GPI-anchor. Genetic evidence, in vertebrates and invertebrates, implicates both these type of proteoglycan in the control of morphogen signaling and cell fate determination, and the coordination of cell locomotion and behavior.

The general objective is to clarify how glypicans and syndecans, and the specialized membrane domains, cellular compartments and molecular scaffolds they associate with, ‘tune’ developmental programs. More in particular, we want to identify novel elements of the endocytic mechanisms cells use to build or read graded positional cues. It is expected that such understanding will teach us how to influence (stem) cell differentiation, neurogenesis, angiogenesis, axonal guidance and synaptogenesis, and how to exploit this knowledge for diagnostic and therapeutic purposes.

Specifically, we are using zebrafish as an in vivo model to relate specific glypicans to specific morphogen signaling pathways. We also use this animal model to validate genetic, biochemical and cell biological investigations, identifying molecular determinants that are essential for the ‘co-receptor’ functions of the glypicans, dictating their association with ligand and influencing the trafficking and signaling of ligand/receptor complexes. We are also exploring the hypothesis that important aspects of morphogen signaling may be initiated from endosomal compartments, as a result of heparanase activity on internalized ligand-receptor complexes, rather than form cell surfaces, where proteoglycan-bound morphogens might be mostly ‘inert’. We also aim to clarify whether secreted pro-heparanase has paracrine effects on cells, and whether blocking the uptake and endosomal activation of pro-heparanase (Vreys et al., 2005) might interfere with tumor angiogenesis, potentially identifying a novel target for cancer therapy. Finally, we are also investigating how this co-receptor system is or may be at fault in genetic and acquired disease, and perused by specific pathogens.

Luyten A, Mortier E, Van Campenhout C, Taelman V, Degeest G, Wuytens G, Lambaerts K, David G, Bellefroid E, Zimmermann P
The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical wnt signaling
MOL BIOL CELL 19, 1594-604, 2008



De Witte L, Bobardt M, Chatterji U, Degeest G, David G, Geijtenbeek T, Gallay P
Syndecan-3 is a dendritic cell-specific attachment receptor for HIV-1
P NATL ACAD SCI USA 104, 19464-9, 2007



Mortier E, Wuytens G, Leenaerts I, Hannes F, Heung y, Degeest G, David G, Zimmermann P
Nuclear speckles and nucleoli targeting by PIP2-PDZ domain interactions
EMBO J 24, 2556-2565, 2005



Zimmermann P, Zhang Z, Degeest G, Mortier E, Leenaerts I, Coomans C, Schulz J, N'kuli F, Courtoy j, David G
Syndecan Recycling Is Controlled by Syntenin-PIP2 Interaction and Arf6
DEV CELL 9, 377-388, 2005



De Cat B, Muyldermans S, Coomans C, Degeest G, vanderschueren B, Creemers J, Biemar F, Peers B, David G
Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements
J CELL BIOL 163, 625-635, 2003

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