Daniel Madriz Sørensen
Guest researcher, Visiting researcher
2200 København N.
During my PhD I screened a large set of small molecule compounds in search of inhibitors of important enzymes in the initiation and elongation of GalNAc type O-glycosylation.
GalNAc type O-glycosylation is one of the most abundant forms of protein glycosylation in animals. Truncated O-glycoproteins, displaying only the initial GalNAc known as the Tn- antigen, and its related salylated form STn, are displayed on membrane glycoproteins of most cancers and have been shown to contribute to cancer development. The Tn and STn antigens have thus been explored as cancer specific targets for antibodies and other immunotherapeutic approaches.
By developing a cell based screening platform and screening a large set of small molecule compounds, we found two candidate molecules, which can inhibit GalNAc type O-glycosylation, as well as Glycoseaminoglycans (GAGs) and the elongation of N-glycans.
Interestingly, these compounds highly upregulated the expression of Tn antigen on the surface of treated cells. Furthermore, we have now characterized their dynamics and kinetics and are currently exploring how these compounds promote cancer-like truncated O-glycans, what their molecular target is and whether this phenomenon can be used to improve targeting by glycosylation specific antibodies