Novel biological functions of heparan sulfate and their pharmacological potentials

The polysaccharide heparan sulfate (HS) is ubiquitously expressed on cell surfaces and in the extracellular matrix, with essential functions in animal development and pathophysiology.

HS on the cell surface acts as co-receptor for a broad spectrum of cytokines and growth factors, in control of various signaling and cellular activities. The HS-degrading enzyme, heparanase, also widely expressed throughout the body, modulates these effects.

Based on our recent progress and findings, the aims are: 1) Uncover novel biological functions for HS, relating to immune responses and GPCR signaling; 2) Explore the potential for treatment of diseases by targeting HS-protein interactions and heparanase.

Unique transgenic mice and cells are applied to eludication of the molecular mechanisms; heparin/HS-mimetics prepared by different approaches will be tested in mouse models of rhreumatoid arthritis and lung inflammation/fibrosis.

One senior researcher with expertise and skill in biochemistry and cell biology and two postdocs experienced in animal experiments will work on the project. Collaborations with international and national experts are established.

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

The knowledge obtained will promote interest in developing drugs that selectively interfere with HS-protein interactions, as well as continued translational studies.