Heparan sulfate – biosynthesis, functions and pathophysiological implications

Heparan sulfate (HS) is a polysaccharide expressed ubiquitously on the cell surface and in the extracellular matrix, having essential functions in animal development and pathophysiology.

One major challenge in the field is to understand the complicated biosynthesis process orchestrated by the actions of 11 different enzymes, generating the complex molecular structure of HS that have multifaceted biological activities.

Our aims are: 1) Understand the interactions/modulations of selected enzymes and their effect on HS structure and biological activities; 2) Explore the potential for treatment of diseases by targeting HS-protein interaction and heparanase.

Heparin/HS-mimetics prepared by different approaches will be applied in cells and disease models, using unique transgenic mice.

Two researchers with profound knowledge and skill in HS-structure analysis, protein biochemistry and animal experiments will work full-time on the project. Collaborations are organized with international and national experts including the SciLifeLab platforms.

The results are expected to clarify fundamental aspects of HS biology, especially the roles of HS and heparanase in inflammation and fibrosis.

The new knowledge obtained will be of great value to the increasing interest in developing drugs that selectively interfere with HS-protein interactions.

The outcome will provide essential information for continued translational studies, aiming at developing novel drugs for the treatment of the diseases.