MUCINS: A BLACK BOX OF BIOLOGY
The overarching goal of the Malaker Lab is to develop methods that allow for mass spectrometry analysis of mucins, which are densely O-glycosylated proteins. Understanding mucin structure and site-specific glycosylation will allow us to unravel the complex relationship between mucins and human disease. Projects are broadly broken down into three main areas:
Investigating Glycosylation in Immunity, Cancer, and Disease
We apply glycoproteomic technologies to understand how glycosylation regulates protein function in biological and disease contexts. Current projects investigate mucin-domain glycoproteins involved in immune signaling, cancer progression, and mucosal biology, including TIM-family immune checkpoints, PILRA, CA125/MUC16, and MUC2. We are also interested in glycoproteins found in biological fluids such as tears and airway secretions, where altered glycosylation may contribute to inflammatory and autoimmune disease. By combining glycoproteomics with biochemical, structural, and functional studies, we are uncovering how glycans influence molecular recognition, immune regulation, and cell-cell communication.
Glycoproteomic Method Development
A major focus of the Malaker Laboratory is the development of mass spectrometry-based technologies for the analysis of densely O-glycosylated proteins and mucin domains. We develop new enrichment strategies, mucinase-enabled workflows, and ionization methods that improve the detection and characterization of challenging glycopeptides. Recent efforts include the development of GlycoFASP workflows, new mucinases with distinct cleavage preferences, and technologies aimed at improving the analysis of highly acidic and sulfated glycans. Together, these approaches expand the analytical toolbox available for studying glycoproteins with molecular precision.
Computational and Community Glycoproteomics
Reliable interpretation of glycoproteomic mass spectrometry data remains a major challenge due to the complexity and heterogeneity of glycans. Our laboratory participates in collaborative efforts to improve glycoproteomic informatics, benchmarking, and data reproducibility across the field. We are involved in large-scale community studies evaluating glycoproteomic software performance and identifying best practices for glycopeptide identification and site localization. Our goal is to help develop practical, accessible, and standardized approaches that make glycoproteomics more robust and broadly usable for the scientific community.
