A5039166302- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Alzheimer's disease research and treatments
- Metabolomics and Mass Spectrometry Studies
- Machine Learning in Bioinformatics
- Muscle Physiology and Disorders
- Bioinformatics and Genomic Networks
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Biotin and Related Studies
- Cardiomyopathy and Myosin Studies
- S100 Proteins and Annexins
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
- Heat shock proteins research
- Neurological diseases and metabolism
- Cellular transport and secretion
- RNA Research and Splicing
- RNA regulation and disease
- Analytical Chemistry and Chromatography
- Skin and Cellular Biology Research
- Gene expression and cancer classification
Ruhr University Bochum
2016-2025
University of Luxembourg
2024
Luxembourg Institute of Health
2024
The Ohio State University Wexner Medical Center
2023
St. Marien Hospital
2021
University of Ljubljana
2021
University of Bonn
2021
Max Perutz Labs
2021
University of Vienna
2021
Charité - Universitätsmedizin Berlin
2006-2019
The autophagy-lysosome pathway (ALP) regulates intracellular homeostasis of the cytosolic protein SNCA/alpha-synuclein and is impaired in synucleinopathies, including Parkinson disease dementia with Lewy bodies (DLB). Emerging evidence suggests that ALP influences SNCA release, but underlying cellular mechanisms are not well understood. Several studies identified exosome/extracellular vesicle (EV) fractions. EVs generated multivesicular body compartment either released upon its fusion plasma...
Parkinson's disease (PD) is a systemic clinically defined by the degeneration of dopaminergic neurons in brain. While alterations gut microbiome composition have been reported PD, their functional consequences remain unclear. Herein, we addressed this question an analysis stool samples from Luxembourg Study (n = 147 typical PD cases, n 162 controls).All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed self-reporting...
Currently data-dependent acquisition (DDA) is the method of choice for mass spectrometry-based proteomics discovery experiments, but data-independent (DIA) steadily becoming more important. One most important requirements to perform a DIA analysis availability suitable spectral libraries peptide identification and quantification. Several studies were performed addressing evaluation library performance protein in measurements. But so far only few experiments estimate effect these on...
Titin-based myofilament stiffness is defined by the expression levels of cardiac titin-isoforms, N2B and N2BA, phosphorylation elastic titin domains N2-B unique sequence (N2-Bus) PEVK. Phosphorylation N2-Bus cGMP-dependent protein kinase (PKG) or cAMP-dependent (PKA) decreases stiffness, whereas PEVK-domain PKC increases it. We aimed to identify specific sites within phosphorylated PKA PKG determine whether differential changes in domain could affect passive human failing hearts. Using mass...
The purpose of this study was to profile cerebrospinal fluid (CSF) from early-stage PD patients for disease-related metabolic changes and determine a robust biomarker signature diagnosis.By applying non-targeted mass spectrometry-driven approach, we investigated the CSF metabolome 44 sporadic yet without treatment (DeNoPa cohort). We compared all detected metabolite levels with those measured in 43 age- gender-matched healthy controls. After analysis, validated results an independent cohort...
Lewy bodies, a pathological hallmark of Parkinson's disease (PD), contain aggregated alpha-synuclein (αSyn), which is found in several modified forms and can be discovered phosphorylated, ubiquitinated truncated. Aggregation-prone truncated species αSyn caused by aberrant cleavage this fibrillogenic protein are hypothesized to participate its sequestration into inclusions subsequently leading synaptic dysfunction neuronal death. Here, we investigated the role calpain vivo generating two...
Abstract Parkinson’s disease (PD) is a highly heterogeneous disorder influenced by several environmental and genetic factors. Effective disease-modifying therapies robust early-stage biomarkers are still lacking, an improved understanding of the molecular changes in PD could help to reveal new diagnostic markers pharmaceutical targets. Here, we report results from cohort-wide blood plasma metabolic profiling patients controls Luxembourg Study detect disease-associated alterations at level...
Different search programs were compared to judge their particular efficiency in protein identification. We established a human blood platelet map and identified tyrosine-phosphorylated proteins. The cytosolic fraction of platelets was separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) phosphorylated proteins detected Western blotting using anti-phosphotyrosine antibodies. Visualized spots excisted, digested with trypsin analyzed matrix assisted laser...
Abstract In order to identify new molecular markers for pancreatic intra‐epithelial neoplasias (PanINs), the precursor lesions of ductal adenocarcinoma, we established a proteomics approach analysing microdissected PanIN cells. Due limited amount proteins available from microdissection, developed procedure including fluorescence dye saturation labelling in combination with high resolution two‐dimensional gel electrophoresis. With this were able analyse extracted 1000 cells up 2500 protein...
Background Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, associated with underlying neoplasms. PNP characterized by the production of autoantibodies targeting proteins plakin cadherin families involved in maintenance cell architecture tissue cohesion. Nevertheless, identity an antigen Mr 170,000 (p170), thought to be critical pathogenesis, has remained unknown. Methodology/Principal Findings Using...
The influence of protein phosphorylation on the kinetics cytochrome c oxidase was investigated by applying Western blotting, mass spectrometry, and kinetic measurements with an oxygen electrode. isolated enzyme from bovine heart exhibited serine, threonine, and/or tyrosine in various subunits, except subunit I, using phosphoamino acid-specific antibodies. revealed slight inhibition uptake presence ATP, as compared ADP. Mass spectrometry identified Ser-34 at IV Ser-4 Thr-35 Va. Incubation...
Filaminopathy is a subtype of myofibrillar myopathy caused by mutations in FLNC, the gene encoding filamin C, and histologically characterized pathologic accumulation several proteins within skeletal muscle fibers. With aim to get new insights aggregate composition, we collected aggregates control tissue from biopsies six patients harboring three different FLNC laser microdissection analyzed samples label-free mass spectrometry approach. A total 390 were identified, 31 those showed...
Sporadic inclusion body myositis (sIBM) pathogenesis is unknown; however, rimmed vacuoles (RVs) are a constant feature. We propose to identify proteins that accumulate within RVs.RVs and intact myofibers were laser microdissected from skeletal muscle of 18 sIBM patients analyzed by sensitive mass spectrometry approach using label-free spectral count-based relative protein quantification. Whole exome sequencing was performed on 62 patients. Immunofluorescence patient mouse muscle.A total 213...
Protein inference connects the peptide spectrum matches (PSMs) obtained from database search engines back to proteins, which are typically at heart of most proteomics studies. Different yield different PSMs and thus protein lists. Analysis results one or multiple is often hampered by data exchange formats lack convenient intuitive user interfaces. We present PIA, a flexible software suite for combining engine runs turning these into consistent results. PIA can be integrated analysis...
Abstract Parkinson's disease can be caused by mutations in the α‐synuclein gene and is characterized aggregates of protein. Aggregates are degraded autophago‐lysosomal pathway. Since Rab7 has been shown to regulate trafficking late endosomes autophagosomes, we hypothesized that over‐expressing might beneficial disease. To test this hypothesis, expressed pathogenic A53T mutant HEK 293 cells Drosophila melanogaster . In cells, EGFP ‐Rab7‐decorated vesicles contain α‐synuclein. over‐expression...
Secondary mitochondrial dysfunction is a feature in wide variety of human protein aggregate diseases caused by mutations different proteins, both the central nervous system and striated muscle. The functional relationship between expression mutated largely unknown. In particular, mechanism how this drives disease process still elusive. To address issue for myopathies, we performed comprehensive, multi-level analysis pathology skeletal muscles patients with intermediate filament desmin...