Translating glycans into biomarkers

Alterations in glycosylation have been associated with the development and progression of many types of cancers and other chronic and acute diseases. Structural glycan analysis on purified proteins often provides the best “biomarker” information but is time consuming and can take days or often weeks for the analysis of only a handful of samples. To address this limitation, our group has developed a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins. This method combines the method of antibody arrays and imaging mass spectrometry to create a new method of multiplexed N-glycan analysis. Importantly, this assay requires only a few microliters of serum and utilizes simplified processing workflows that require no protein purification or sugar modifications prior to analysis. This method is referred to as the GlycoTyper. In this method, N- linked glycans are PNGase F released on slide from antibody captured glycoproteins and are directly analyzed by MALDI-TOF mass spectrometry. We have used this methodology to identify biomarkers of pre-malignant and malignant liver disease. Our plan is to transition this method, which utilizes novel glyco-technology into the commercial setting. To help translate this finding we propose to establish an inter-disciplinary, multi-institutional research team, working in strategic alliance with both industry and clinical partners to validate our identified biomarker. This application represents a true synergistic effort between the group at the Medical University of South Carolina (MUSC), the clinical group at the University of Texas Southwestern Medical Center (UTSW), and an industrial partner GlycoPath Inc, who has licensed this technology. We believe that this multidisciplinary team will lead to the rapid and rigorous examination of the proposed biomarker panel.