Bone and Connective Tissues/Tissue Engineering

DING XU, PhD  personal profile

Heparan Sulfate in Bone Remodeling and Inflammation

The main interest of the lab is to understand how proteins interact with heparan sulfate (HS), a highly negatively charged linear polysaccharide, and the physiological significance of the interactions in bone remodeling and inflammation. Universally expressed by all mammalian cells, HS is a major and often dominant component of the landscape at the cell surface and thus plays essential roles in cell signaling, cell-cell interactions and host-pathogen interactions. At the cell surface, HS interacts with hundreds of HS-binding proteins, many of which are important drug targets (such as TNF-alpha, interleukin-8 and FGF receptors). The dependence of these proteins on HS for normal function suggests that disrupting HS-protein interaction could be an effective means to block the activity of these HS-binding proteins. 

The goal of the lab is to dissect the structural determinants of HS-protein interactions by characterizing structures of HS/protein complexes (using X-ray crystallography and small-angle scattering), and to use this information to develop and test the pre-clinical efficacy of novel therapeutic agents (including monoclonal antibodies, oligosaccharides and small molecules) that target HS-protein interactions in cellular and animal models. The HS-binding proteins we are currently working on include receptor for advanced glycation end products (RAGE) and osteoprotegerin.