Keynote speakers

Cell surface glycans play crucial roles in establishing cell communication, adhesion, and migration. Specifically at the cancer cell surface, glycosylation is altered compared to healthy cells, displaying cancer-specific glycoforms. These cancer glycans affect tumor behavior, and can be targeted for treatment. Yet, resolving the precise structures, spatial organization, and regulatory mechanisms of glycoconjugates remains a major analytical challenge.To address this, we developed a suite of versatile mass spectrometry (MS)-based platforms enabling cell type-, cell surface-, and protein‑specific characterization of human glycosylation. Our in-depth LC-MS-based strategies allow deep structural elucidation of the different glycan classes and combining these methods with an array of glycoengineered human cell lines provides insights into glycan structures and their regulation in a cellular context. Complementing this, MS imaging provides spatial maps of N‑glycans within tissues and enables multi‑omic integration with metabolomics and lipidomics to reveal the metabolic context of glycan regulation. Finally, to specifically analyze the N-glycoprotein forms expressed at the cell surface, we combined LC-MS-based glycoproteomics with highly specific cell surface protein labeling and enrichment to study how specific proteins change their glycoforms under defined biological conditions.In summary, we present analytical tools required to study cellular glycosylation in health and disease as well as to track genetic or metabolic manipulation of the glycosylation machinery. Understanding these processes and identifying disease-specific glycoconjugates have important implications for their future use as therapeutic targets.  

Bacterial glycans are often comprised of rare D and L deoxy amino sugars, which are not present on the human cell surface. This peculiar structural difference allows discrimination between the pathogen and the host cell and offers avenues for target-specific drug discovery and carbohydrate-based vaccine development.  However, such complex glycans cannot be isolated with sufficient purity in acceptable amounts, and therefore chemical synthesis is a crucial step toward the development of these products.  We recently established short and convenient methodologies for the synthesis of orthogonally protected bacterial D and L-deoxy amino hexopyranoside and glycosamine building blocks starting from easily available D-mannose and L-rhamnose. The one-pot protocols rely on highly regioselective nucleophilic displacements of triflates. These procedures have been applied to the synthesis of highly immunogenic conjugation-ready bacterial glycans as well as zwitterionic oligosaccharides. The azide containing sugars also enabled metabolic oligosaccharide engineering studies that led to discovery of selective inhibitors of glycan biosynthesis. In this talk I will present our recent results on the total synthesis of highly complex and densely functionalized bacterial glycans and the application of rare sugars in selective detection and disarming of pathogens. The synthetic oligosaccharides provide valuable epitopes for immunological studies aimed at vaccine development

Cancer immunotherapy has markedly improved patient outcomes, with immune checkpoint inhibitors inducing durable remissions even in some patients with advanced malignancies. However, the majority of patients derive limited or no benefit from current immunotherapeutic strategies. Targeting cancer-associated glycans represents a promising approach to overcome resistance. This presentation will discuss the development of glycan-targeting antibodies for chimeric antigen receptor (CAR) T cells and bispecific antibodies, as well as strategies to glyco-engineer the tumor microenvironment to enhance antitumor immunity. Preclinical studies demonstrate that enzymatic or small-molecule modulation of tumor-associated glycans can significantly potentiate immunotherapy. Early-phase clinical trials evaluating these glycan-targeted approaches are now underway.