A5046930101- Advanced Proteomics Techniques and Applications
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Protease and Inhibitor Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Stress Responses and Cortisol
- SARS-CoV-2 detection and testing
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Immune Response and Inflammation
- Genetic factors in colorectal cancer
- Peptidase Inhibition and Analysis
- Angiogenesis and VEGF in Cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Biosimilars and Bioanalytical Methods
- Peroxisome Proliferator-Activated Receptors
- Cancer Genomics and Diagnostics
- Mass Spectrometry Techniques and Applications
- Acute Myeloid Leukemia Research
- Effects of Radiation Exposure
- Kruppel-like factors research
- S100 Proteins and Annexins
- TGF-β signaling in diseases
- Clinical Laboratory Practices and Quality Control
University Medical Centre Mannheim
2013-2024
Heidelberg University
2014-2024
University Hospital Heidelberg
2014-2024
Central Institute of Mental Health
2015
Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism form tight structural associations, which were first observed ultrastructural studies decades ago. PO-ER associations have been suggested to impact on a diverse number of physiological processes, including metabolism, phospholipid exchange, metabolite transport, signaling, PO biogenesis. Despite their fundamental importance cell mechanisms by regions ER become tethered POs are unknown, particular...
Abstract Objectives Assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prevalence and immunity is cornerstones in the fight against COVID-19 pandemic. For pandemic control, reliable assays for detection anti-SARS-CoV-2 antibodies are required. This pilot external quality assessment (EQA) scheme aimed to independently assess participants’ clinical performance testing, identify shortcomings practice evaluate suitability format. Methods The EQA consisted eight...
Exosomes are small lipid bilayer vesicles that defined by their endocytic origin and size range of 30-140 nm. They constantly produced different cell types, both healthy abnormal cells, can be isolated from almost all body fluids.Little information exists in isolating exosomes plasma due to the complexity its content presence contaminating proteins. We carried-out liquid chromatography-mass spectrometry (LC-MS/MS) analyses plasma-derived 4 donors obtained 2 coupled methodologies:...
Ongoing technical and bioinformatics improvements in mass spectrometry (MS) allow for the identifying quantifying of enrichment increasingly less-abundant proteins individual fractions. Accordingly, this study reassessed proteome mouse liver peroxisomes by parallel isolation from a mitochondria- microsome-enriched prefraction, combining density-gradient centrifugation with semi-quantitative SWATH-MS proteomics approach to unveil novel peroxisomal or peroxisome-associated proteins. In total,...
Mass spectrometry (MS) offers a wide range of possibilities for analyzing biological samples containing complex mixtures proteins and peptides, by generating proteome profiles. The aim most profiling experiments is identification changes in protein patterns that are related to certain disease or clinical status might therefore be used improve diagnosis, staging, monitoring (1). Reproducibility spectra generated matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS crucial...
The Interleukin-1/Toll-like receptor signaling pathway is a crucial within the innate immune system and use of mass spectrometric techniques became valuable to investigate signal transduction pathways. To date only few reports exist that focus on identification novel intermediates TLR pathway. Here we used this approach systematically identify new interaction partners subsequently characterized them functionally. We identified 14-3-3 theta as member complex. With genetic complementation...
Distinct proteins have been demonstrated to be posttranslationally modified by covalent transamidation of serotonin (5-hydropxytryptamin) glutamine residues the target proteins. This process is mediated transglutaminase (TGase) and has termed "serotonylation." It also shown that other biogenic amines, including neurotransmitters dopamine norepinephrine, can substitute for serotonin, implying a more general mechanism "monoaminylation" this kind protein modification. Here we transamidated...
Abstract Early diagnosis of life‐threatening invasive aspergillosis in neutropenic patients remains challenging because current laboratory methods have limited diagnostic sensitivity and/or specificity. Aspergillus species are known to secrete various pathogenetically relevant proteases and the monitoring their protease activity serum specimens might serve as a new approach.For characterization identification secreted proteases, culture supernatant fumigatus was fractionated using free flow...
The progression of many solid tumors is characterized by the release tumor-associated proteases and detection tumor specific proteolytic activity in serum specimens a promising diagnostic tool oncology. Here we describe mass spectrometry-based functional proteomic profiling approach that tracks ex-vivo degradation synthetic endoprotease substrate colorectal patients.A reporter peptide (RP) with amino acid sequence WKPYDAAD was synthesized has known cleavage site for cysteine-endopeptidase...
The entry of malignant hepatocytes into blood vessels is a key step in the dissemination and metastasis hepatocellular carcinoma (HCC). identification molecular mechanisms involved transmigration through endothelial barrier high relevance for therapeutic intervention prevention. In this study, we employed model that mimics vascular invasion using hepatic sinusoidal cells evincing mesenchymal-like, invasive phenotype by transforming growth factor (TGF)-β. Labelling respective cell populations...
The analysis of circulating tumor DNA (ctDNA) is at the threshold implementation into standard care for colorectal cancer (CRC) patients. However, data about clinical utility liquid profiling (LP), its acceptance by clinicians, and integration workflows in real‐world settings remain limited. Here, LP tests requested as part routine since 2016 were retrospectively evaluated. Results show restrained request behavior that improved moderately over time, well reliable diagnostic performance...
Deregulation of synaptic function and neurotransmission has been linked with the development major depression disorder (MDD). Tianeptine (Tian) used as antidepressant anxiolytic properties recently a nootropic to improve cognitive performance, but its mechanism action is unknown. We conducted proteomic study on hippocampal synaptosomal fractions adult male Wistar rats exposed chronic social isolation (CSIS, 6 weeks), an animal model after Tian treatment in controls (nootropic effect)...
Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement this treatment indication. Here, by combining 5-azacytidine (5-AZA) the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration erythroid differentiation hematopoietic stem progenitor cells (HSPCs) MN patients 20/31 cases (65%) versus 9/31 (29%) treated 5-AZA alone. This effect requires direct contact HSPCs bone marrow...
To determine the preanalytical quality of serum and plasma by monitoring time-dependent ex vivo decay a synthetic reporter peptide (RP) with liquid chromatography/mass spectrometry (LC/MS). Serum specimens were spiked RP proteolytic fragments monitored LC/MS at different time points ranging from 2 to 24 hours after blood withdrawal. The concentration changed in manner, respective profiles used classify according their span. Classification accuracy was high, values always above 0.89 for areas...
External quality assessment (EQA) is a key instrument for achieving harmonization, and thus high quality, of diagnostic procedures. As reliable test results are crucial accurate SARS-CoV-2 infection prevalence, vaccine response, immunity, successful management the ongoing COVID-19 pandemic, Reference Institute Bioanalytics (RfB) was first EQA provider to offer an open scheme anti-SARS-CoV-2 antibody detection.
The monitoring of tumor-associated protease activity in blood specimens has recently been proposed as new diagnostic tool cancer research. In this paper, we describe the screening a peptide library for identification reporter peptides (RPs) that are selectively cleaved serum from colorectal patients and investigate benefits RP multiplexing. A 144 RPs was constructed contained amino acid sequences abundant plasma proteins. Proteolytic cleavage monitored with MS. Five were tumor selected...
Chronic social isolation (CSIS)-induced alternation in synaptic and mitochondrial function of specific brain regions is associated with major depressive disorder (MDD). Despite the wide number available medications, treating MDD remains an important challenge. Although fluoxetine (Flx) most frequently prescribed antidepressant, its mode action still unknown. To delineate affected molecular pathways depressive-like behavior identify potential targets upon Flx treatment, we performed a...
Abstract: Anaemia of chronic disease (ACD) is a common finding involving iron deficiency and signs inflammation. Here, we report on two patients with ACD where persistent infection Chlamydophila (Chlamydia) pneumoniae (CP) was detected in bone marrow (BM) biopsies. Infection suspected by routine cytology confirmed immunofluorescence, electron microscopy, polymerase chain reaction (PCR) including different primer sets laboratories sequencing the PCR product. This first chlamydial presence BM...
Invasive aspergillosis (IA) remains difficult to diagnose in immunocompromised patients, because diagnostic criteria according EORTC/MSG guidelines are often not met and have low sensitivity. Hence there is an urgent need improve procedures by developing novel approaches. In the present study, we a proof of concept experiment for monitoring Aspergillus associated protease activity serum specimens purpose. Synthetic peptides that selectively cleaved proteases secreted from species were...