Mucin domains are densely O-glycosylated modular protein domains found in a wide variety of cell surface and secreted proteins. Mucin-domain glycoproteins are key players in a host of human diseases, especially cancer, but the mucinome remains poorly understood. The two most pressing questions regarding mucin structure and function are: (1) what do mucin-domain glycoproteins look like at the molecular (i.e. glycoproteomic) level? And (2) how does mucin domain structure and glycan content contribute to the overall protein function? To answer these questions, we are developing mass spectrometric methods to sequence mucin-domain glycoproteins, including unique mucin-selective enrichment techniques, new clean-up methods, and augmented glycoproteomic software. Additionally, we are combining glycoproteomic methods with structure/function assays in order to better understand the roles that mucin domains play within the cellular milieu. Ultimately, we envision our technologies will contribute greatly to understanding mucin dysregulation in diseases such as cancer, inflammatory bowel disease, and cystic fibrosis.

Mucinomics as the next frontier of mass spectrometry

ACS Spring 2022

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