A5051077634- Glycosylation and Glycoproteins Research
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Pancreatic function and diabetes
- Advanced Proteomics Techniques and Applications
- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- Carbohydrate Chemistry and Synthesis
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Gene expression and cancer classification
- Protein Interaction Studies and Fluorescence Analysis
- Protein purification and stability
- thermodynamics and calorimetric analyses
- Analytical Chemistry and Chromatography
- Dysphagia Assessment and Management
- Field-Flow Fractionation Techniques
- Plant Toxicity and Pharmacological Properties
- Caveolin-1 and cellular processes
- Diabetes Management and Research
- Complement system in diseases
University of Zagreb
2016-2025
Innsbruck Medical University
2019
Universität Innsbruck
2019
Heinrich Heine University Düsseldorf
2017
Deutsches Diabetes-Zentrum e.V.
2017
German Center for Diabetes Research
2017
Fine structural details of glycans attached to the conserved N-glycosylation site significantly not only affect function individual immunoglobulin G (IgG) molecules but also mediate inflammation at systemic level. By analyzing IgG glycosylation in 5,117 individuals from four European populations, we have revealed very complex patterns changes with age. Several (including FA2B, FA2G2, and FA2BG2) changed considerably age combination these three can explain up 58% variance chronological age,...
Objective Glycans attached to the Fc portion of IgG are important modulators effector functions. Interindividual differences in glycome composition large and they associate strongly with different inflammatory autoimmune diseases. IKZF1 , HLA–DQ2A/B BACH2 genetic loci that affect show pleiotropy systemic lupus erythematosus (SLE), indicating a potentially causative role aberrant glycosylation SLE. We undertook this multicenter case–control study determine whether SLE is associated altered...
Recovery after cardiac surgery is a complex process that has to compensate for both individual variability and extensive tissue damage in the context of systemic inflammation. Protein glycosylation essential many steps inflammatory cascade, but due technological limitations role variation inflammation not been addressed until now. We analysed composition total plasma IgG N-glycomes 107 patients undergoing surgery. In nearly all individuals N-glycome underwent same pattern changes first 72 h,...
Effector functions of immunoglobulin G (IgG) are regulated by the composition a glycan moiety, thus affecting activity immune system. Aberrant glycosylation IgG has been observed in many diseases, but little is understood about underlying mechanisms. We performed genome-wide association study N-glycosylation (
Rising awareness of the universal importance protein N-glycosylation governs development further advances in N-glycan analysis. Nowadays it is well known that correct glycosylation essential for proper function, which emanates from its important role many physiological processes. Furthermore, involved inpathophysiology multiple common complex diseases. In vast majority cases, profiles are analyzed enzymatically released glycans, can be derivatized order to enhance sensitivity Techniques...
ObjectiveTo determine the extent to which genetic and epigenetic factors contribute variations in glycosylation of immunoglobulin G (IgG) humans. Methods76 N-glycan traits circulating IgG were analyzed by UPLC 220 monozygotic 310 dizygotic twin pairs from TwinsUK. A classical study design was used derive additive genetic, common unique environmental components defining variance these traits. Epigenome-wide association analysis performed using Illumina 27k chip. Results51 76 glycan studied...
Immunoglobulin G (IgG) is the most abundant serum antibody which structural characteristics and effector functions are modulated through attachment of various sugar moieties called glycans. Composition IgG N-glycome changes with age an individual in different diseases. Variability glycosylation within a population well studied known to be affected by both genetic environmental factors. However, global inter-population differences have never been properly addressed. Here we present...
Immunoglobulin G (IgG) is a major effector molecule of the human immune response, and aberrations in IgG glycosylation are linked to various diseases. However, molecular mechanisms underlying protein still poorly understood. We present data-driven approach infer reactions pathway using large-scale mass-spectrometry measurements. Gaussian graphical models used construct association networks from four cohorts. find that glycan pairs with high partial correlations represent enzymatic known...
Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment. However, considering its heterogeneity, subjects with similar parameters do not necessarily have the same functional status. To overcome this limitation novel biomarkers for COPD been investigated. Therefore, we aimed to explore potential value of N-glycans as and examine individual variation plasma protein immunoglobulin G (IgG) glycosylation profiles in healthy...
Abstract Establishing causal relationship between epigenetic marks and gene transcription requires molecular tools, which can precisely modify specific genomic regions. Here, we present a modular extensible CRISPR/dCas9-based toolbox for editing direct regulation. It features system expression of orthogonal dCas9 proteins fused to various effector domains includes multi-gRNA simultaneous targeting orthologs up six loci. The C- N-terminal fusions with DNMT3A TET1 catalytic were thoroughly...
Alpha-1-acid glycoprotein (AGP) is an acute phase in blood, which primarily synthetized the liver and whose biological role not completely understood. It consists of 45% carbohydrates that are present form five N-linked complex glycans. AGP N-glycosylation was shown to be changed many different diseases, some changes appear disease-specific; thus, it has a great diagnostic prognostic potential. However, glycosylation mainly analyzed small cohorts without detailed site-specific glycan...
Abstract Fibrinogen is a major plasma glycoprotein involved in blood coagulation and inflammatory responses. Alterations its glycosylation have been implicated various pathological conditions, yet site-specific N-glycosylation profile remains largely unexplored clinical context. Here, we present high-throughput LC-MS workflow for analysis of fibrinogen using cost-effective ethanol precipitation enrichment method. The method demonstrated good intra- inter-plate repeatability (CV: 5% 12%,...
Fibrinogen is a major plasma glycoprotein involved in blood coagulation and inflammatory responses. Alterations its glycosylation have been implicated various pathological conditions; yet, site-specific N-glycosylation profile remains largely unexplored clinical context. Here, we present high-throughput LC-MS workflow for analysis of fibrinogen using cost-effective ethanol precipitation enrichment method. The method demonstrated good intra- interplate repeatability (CV: 5% 12%, respectively)...
Exercise is known to improve many aspects of human health, including modulation the immune system and inflammatory status. Despite general understanding that exercise reduces inflammation, relation two not yet fully understood. N-glycosylation immunoglobulin G (IgG) total plasma proteins was previously shown reflect changes in pathways, which could provide valuable information further clarify effects. In order better understand relationship between physical activity we examined effect...
Abstract Aims/hypothesis We previously demonstrated that N-glycosylation of plasma proteins and IgGs is different in children with recent-onset type 1 diabetes compared their healthy siblings. To search for genetic variants contributing to these changes, we undertook a association study the protein IgG N-glycome diabetes. Methods A total 1105 patients from Danish Registry Childhood Adolescent Diabetes were genotyped at 183,546 markers, testing variable levels 24 39 N-glycan traits. In...
Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function immunoglobulin G (IgG) alters between pro- anti-inflammatory, based its glycosylation. IgG glycan synthesis highly complex dynamic.With use two different analytical methods for assessing glycosylation, we aim to elucidate link DNA methylation glycosylation by means epigenome-wide association studies. In total, 3000 individuals from 4 cohorts...
The N-glycosylation profile of total human plasma proteins could be a useful biomarker for various pathological states. Reliable high-throughput methods such profiling have been developed. However, studies relative importance genetic and environmental factors in regulating N-glycome are scarce. aim our study was to determine the role phenotypic variation N-glycan through estimates its heritability. Thirty-nine traits were analyzed 2816 individuals from TwinsUK data set. For majority traits,...
Abstract Low back pain (LBP) is a common debilitating condition which aetiology and pathogenesis are poorly understood. We carried out first so far analysis of associations between LBP plasma IgG N-glycome in sample 4511 twins from TwinsUK database assessed for LBP, lumbar disc degeneration (LDD) as its possible cause, IgG-glycan levels. Using weighted correlation network analysis, we established glycan modules featured by glycans that either promote or block antibody-dependent cell-mediated...
Recently, it was shown that children at the onset of type 1 diabetes (T1D) have a higher proportion oligomannose glycans in their total plasma protein N-glycome compared to healthy siblings. The most abundant complement component, glycoprotein C3, contains two N-glycosylation sites occupied exclusively by this glycans. Furthermore, system, as well previously associated with T1D. It is also known changes glycosylation can modulate inflammatory responses, so our aim characterize profile C3 For...
Protein glycosylation is the most common epiproteomic modification involved in numerous physiological and pathological processes. Previous studies reported strong associations between human plasma N-glycans age, prompting us to evaluate potential application of this biological phenomenon field forensics. Blood from 526 blood donors different parts Croatia was collected on bloodstain cards during period 2004-2007 stored at 4°C for 6-9 years. Glycosylation profiles bloodstains were analysed...
Prediction of type 2 diabetes mellitus (T2DM) and its preceding factors, such as insulin resistance (IR), is great importance it may allow delay or prevention onset the disease. Plasma protein N-glycome has emerged a promising predictive biomarker. In prospective longitudinal study, we included patients with first diagnosis impaired glucose metabolism (IR T2DM) to investigate N-glycosylation's value years before development.Plasma was profiled by hydrophilic interaction ultra-performance...
Abstract Aim Alpha-1-acid glycoprotein (AGP) is a highly glycosylated protein in human plasma and one of the most abundant acute phase proteins humans. Glycosylation plays crucial role its biological functions, alterations AGP N-glycome have been associated with various diseases inflammatory conditions. However, large-scale studies N-glycosylation general population are lacking. Methods Using recently developed high-throughput glycoproteomic workflow for site-specific analysis, 803...