Our area of interest is the structure and function of heparan sulfate (HS). HSs play dynamic functional roles in a diverse number of biological events related to intracellular signaling, cell-cell interactions and tissue morphogenesis.
HS execute its function by the binding to a variety of molecules including growth factors, serine protease inhibitors and extracellular matrix proteins. The biological activities of HS largely depend on the amount and distribution of its sulfate groups that provide specific binding sites for proteins.
Our overall goal is to understand the mechanisms generating specific saccharide structures and to provide insight into the link between cell type specific expression of HS modifying enzymes and the biological function of the polysaccharide.
Our research focuses on:
1. UDP-glucose dehydrogenase, which converts UDP-glucose to UDP-glucuronic acid providing one of the building blocks for chain elongation
2. heparan sulfate polymerases (EXT1 and EXT2) giving rise to the polysaccharide backbone(mice with a gene trap mutation in Ext)
3. 2-O- and 6-O-sulfotransferases, incorporating sulfate groups in specific positions, generating biological active heparan sulfate.
4. Sulfs, cell associated HS 6-O endosulfatases, that remove sulfate groups in specific positions, thus modulating HS dependent growth factor signaling.