Glycobiology and glycopathology

Research project

The group studies the mechanisms of protein glycosylation and the alterations they undergo in pathological processes, particularly neoplasms. Tumors have often been observed to exhibit variations in the level of expression of glycosyltransferases, the enzymes that synthesize carbohydrate chains. These variations lead to the expression of altered sugar chains which, in addition to being important diagnostic and prognostic markers, fuel tumor progression by exacerbating the neoplastic phenotype. The research group genetically modifies tumor cell lines to alter the expression of glycosyltransferases relevant to tumor progression, in order to study the effect of the modification on the neoplastic phenotype and on the global gene expression profile. The aim of the research is to identify alterations in glycosylation of particular clinical importance and to understand the mechanisms that lead these alterations to modify the tumor phenotype. The studies focus in particular on glycosyltransferases involved in the biosynthesis of the terminal portions of the carbohydrate chains in colon cancer, including ST6GAL1, B4GALNT2, and FUT6.

A second line of research, conducted in close collaboration with researchers from the University of Insubria in Varese and the University of Milan, is focused on the characterization of congenital diseases of glycosylation (CDGs), autosomal recessive pediatric diseases caused by mutations in glycosyltransferase genes. The group contributes to the in vitro characterization of the enzymatic properties of mutant glycosyltransferases.

Ongoing research goals

Ongoing research goals: In recent years, thanks in part to European funding under the H2020 "Glycocan" project, the group has investigated the effects of the expression of glycosyltransferases ST6GAL1, B4GALNT2, and FUT6 on the gene expression profile and phenotype in colorectal cancer cells. The most important finding so far concerns B4GALNT2, which (in the models studied so far) plays a role in attenuating the neoplastic phenotype and stemness through a profound remodeing of gene expression. Among the next short-term objectives is seeking to understand the transcriptional regulatory mechanisms of B4GALNT2 in the normal and cancerous colon, and extending the study to new experimental models.

Studies on CDGs have contributed to the characterization of new pathological variants of the ST3GAL3 and ST3GAL5 glycosyltransferases.