We develop and apply LC-MS/MS–based glycomic strategies to define sialylated and sulfated glycotopes across diverse mouse and human cells and tissues, with particular interest in Gal-6-O- and GlcNAc-6-O-sulfated structures that modulate Siglecs recognition. A major analytical focus is the structural resolution of extended polyLacNAc and keratan sulfate carriers, including their chain length, branching and site-specific sulfation. These approaches are being used to understand how sulfated glycan architecture is generated, how it shapes Siglec-dependent immune regulation, and how such pathways are altered in cancer, the nervous system and other settings of immune homeostasis.

In parallel, we use advanced glycopeptide MS/MS to map heterogeneous N- and O-glycosylation at individual sites and integrate these data with cryo-EM/cryo-ET, high-speed AFM, molecular modeling and other biophysical approaches. Studies of coronavirus spike proteins, PTPRA and other glycoproteins have moved this work beyond glycosylation cataloguing toward treating experimentally defined glycans as structural variables that influence protein architecture, conformational dynamics and molecular recognition. This effort has also driven the development of more rigorous glycopeptide-analysis workflows that exploit the complementary strengths of current software tools.