Thesis Defense: Sarah Lowery

Please join Yale Chemistry for a thesis seminar with Sarah Lowery, Malaker Lab.

Title: MS-Enabled Analysis of Aberrant Mucin Glycosylation in Disease

Summary: Extracellular O-glycosylation is an abundant post-translational modification that is particularly enriched on the mucin family of proteins. Their dense glycosylation imparts a unique bottlebrush-like structure and unusual physicochemical characteristics important for functions including the formation of protective barriers and cell-cell signaling, among others. Aberrant mucin glycosylation, including changes in site occupancy and O-glycan structures, is strongly implicated in cancer and numerous other diseases. However, technical challenges posed by mucins have historically precluded most research to unravel the relationship between pathophysiological mechanisms and site-specific mucin O-glycosylation. The work herein describes the design, development, and implementation of MS-based techniques to define altered mucin glycosylation patterns in disease and explore the intracellular mechanisms driving such changes. 

The first part of this presentation will describe our efforts to characterize the O-glycosylation of apolipoprotein(a), the defining protein component of the highly atherogenic particle lipoprotein(a). In the second part, the design and application of a spatial mucinomics technique integrating both LC-MS glycoproteomics and MALDI imaging mass spectrometry to localize StcE-generated O-glycopeptides in patient-derived tumor tissue will be discussed.