José Alexandre Ribeiro de Castro Ferreira, PhD
Talk Title: Targeted Glycoproteomics for novel bladder cancer biomarkers: A step towards precision oncology
José Alexandre Ferreira holds a PhD degree in biochemistry/glycochemistry from the University of Aveiro (UA, Portugal) in collaboration with the University of Guelph (Canada). He was the main entrepreneur of GlyConStruct, aiming to design biotechnological solutions for producing glycopeptides of clinical interest (2008-2010). In 2010 he joined the Mass Spectrometry Center of UA as a postdoctoral research fellow to address key protein glycosylation in cancer issues combining glycomics and glycoproteomics. In 2012 he assumed the coordination of a research team in the Portuguese Institute of Oncology- Porto and has, since then, established a platform for graduate training in oncoglycobiology. Simultaneously, he has been involved in several funded actions focusing on the identification of glycan-based cancer biomarkers. As part of a Comprehensive Oncology Center of Excellence, his research presents a strong translational and market oriented character, which is expected to translate into novel glycan-based cancer drugs.
Bladder carcinogenesis and progression is accompanied by profound alterations in protein glycosylation at the cell surface, holding potential to improve disease management. Searching for prognosis biomarkers and novel therapeutic targets we have disclosed that advanced bladder tumours and corresponding metastasis express the sialyl-Tn (STn) antigen, which stems from a premature stop in O-glycosylation. STn overexpression was triggered by hypoxia and modulated protein functions in ways that favored motility and invasion, while promoting immune escape. A glycoproteomics approach based on Vicia villosa lectin-affinity chromatography enrichment and nanoLC-ESI-MS/MS supported by in silico data curation (NetOGlyc, Phanter, Oncomine, Cytoscape) identified several key cancer-associated glycoproteins (MUC16, CD44, integrins) carrying this posttranslational modification. In particular, MUC16 STn+-glycoforms were found for the first time in a subset of advanced-stage bladder tumours facing the worst prognosis. These observations support the existence of unique bladder cancer glycosignatures that should be comprehensively explored envisaging molecular-based precision oncology.