Research Projects

Enzymatic glycosidase of cell surface proteoglycans and extracellular matrix (ECM) is critical for tissue remodeling and cell signaling. Heparanase is one of endoglycosidase predominantly modulate the heparan Sulfate (HS) structure-functions. Aberrant expression of heparanase has been correlated with the malignancy of various tumor types. Therefore, inhibiting heparanase activity is a promising tool in cancer treatment. Many attempts were made to design heparanase inhibitors using small carbohydrate scaffolds, monoclonal antibodies and organic inhibitors. However, designing effective inhibitors for heparanase appears to be extremely challenging. This is attributed to the high structural diversity of heparan sulfates, including sulfation patterns, uronic acid composition and heterogeneity. Herein, we proposed to develop innovative immunization strategy that exploits heparan sulfate (HS) molecular mimicry to produce inhibitor antibodies that block the heparanase activity and cancer cells metastasis and proliferation. More specifically, we proposed to synthesize HS and its mimetics, which involved in heparanase activity. These biomimetic heparin analogs will be tested first with DC/T-cells coculture assay to check their immunogenicity. Finally the best heparin biomimetics will be immunized and its antibodies response will be screen against native HS sequences, heparanase activity and cancer therapy.