Project description:To discover potential biomarkers of melanoma development and progression, we embarked on studies comparing the glycomic gene profiles of normal human epidermal melanocytes with human metastatic melanoma (MM) cells represented by A375 and G361 cell lines. Glycomic features embody all of those enzymatic, membranous and regulatory proteins that influence glycan ‘sugar’ formation/degradation on a cell. Comparative expression profiling of glycomic genes indicated that several genes were differentially expressed between normal melanocytes and MM cells. We speculate that glycome genes differentially expressed in MM cells help drive malignant and metastatic behavior of MM cells and could potentially serve as a biomarker(s) of melanoma progression.
Project description:Modification of proteins by glycans plays a crucial role in mediating biological functions in both healthy and diseased states. Mass spectrometry (MS) has emerged as the most powerful tool for glycomic and glycoproteomic analyses advancing knowledge of many diseases. Such diseases include those of the pancreas which affect millions of people each year. In this review, recent advances in pancreatic disease research facilitated by MS-based glycomic and glycoproteomic studies will be examined with a focus on diabetes and pancreatic cancer. The last decade, and especially the last five years, has witnessed developments in both discovering new glycan or glycoprotein biomarkers and analyzing the links between glycans and disease pathology through MS-based studies. The strength of MS lies in the specificity and sensitivity of liquid chromatography-electrospray ionization MS for measuring a wide range of biomolecules from limited sample amounts from many sample types, greatly enhancing and accelerating the biomarker discovery process. Furthermore, imaging MS of glycans enabled by matrix-assisted laser desorption/ionization has proven useful in complementing histology and immunohistochemistry to monitor pancreatic disease progression. Advances in biological understanding and analytical techniques, as well as challenges and future directions for the field, will be discussed.
Project description:Cell membrane protein glycosylation is dependent on the metabolic state of the cell as well as exogenous nutrients available. Although the metabolism and interconversion of monosaccharides have been well-studied, their incorporation into cell surface glycans and their corresponding glycoproteins remains relatively unknown. In this study, we developed a method to investigate quantitatively the incorporation pathways of dietary saccharides into specific glycans and glycoproteins on the cell membrane by treating intestinal Caco-2 and hepatic KKU-M213 cells with 13C-labeled monosaccharides and characterizing the resulting cell surface glycans and glycopeptides by LC-MS/MS. Time-course studies using uniformly labeled glucose revealed that the rate of incorporation was both glycan-specific and protein-dependent. Comparative studies using different dietary saccharides and multiple cell lines revealed the variance of monosaccharide utilization and interconversion in different tissues and organisms. The robust isotope-labeling and glycan profiling methods can provide a useful tool for differentiating glycosylation pathways and enhance the understanding of how dietary sugar intake affects health.
Project description:This data set contains all raw data files in the mzXML format that belongs to the manuscript: Profiling the Proteoforms of Urinary Prostate Specific Antigen by Capillary Electrophoresis Mass Spectrometry, by Alan B. Moran, Elena Dominguez Vega, Jan Nouta, Tamas Pongracz, Theo M. de Reijke, Manfred Wuhrer and Guinevere S.M. Lageveen-Kammeijer.
Project description:This data set contains all raw data files in the mzXML format that belongs to the manuscript: Profiling the Proteoforms of Urinary Prostate Specific Antigen by Capillary Electrophoresis Mass Spectrometry, by Alan B. Moran, Elena Dominguez Vega, Jan Nouta, Tamas Pongracz, Theo M. de Reijke, Manfred Wuhrer and Guinevere S.M. Lageveen-Kammeijer.
Project description:This data set contains all raw data files in the mzXML (for CE-ESI-MS data) or xy (for MALDI-TOF-MS data) format that belongs to the manuscript "Highly sensitive CE-ESI-MS analysis of N-glycans from complex biological samples" by Guinevere S.M. Lageveen-Kammeijer, Noortje de Haan, Pablo Mohaupt, Sander Wagt, Mike Filius, Jan Nouta, David Falck and Manfred Wuhrer.
Project description:the project aims to provide a glycomic and glycoproteomic approach to reveal S-layer glycosylation on lactobacillus kefiri aggregating and non-aggregating strains
Project description:People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.
Project description:We performed a large-scale, site-specific N-glycoproteome profiling study of human Alzheimer’s disease (AD) and control brains using mass spectrometry–based quantitative N-glycoproteomics. The study provided a system-level view of human brain N-glycoproteins and in vivo N-glycosylation sites and identified disease signatures of altered N-glycopeptides, N-glycoproteins, and N-glycosylation site occupancy in AD. Glycoproteomic data-driven network analysis showed 13 modules of co-regulated N-glycopeptides/glycoproteins, 6 of which are associated with AD phenotypes.