Helmut Meyer

Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V. | ISAS · Biomedical Department

Abnormal changes of neuronal tau-protein, such as phosphorylation and aggregation, are considered hallmarks of cognitive deficits in Alzheimer disease. Abnormal phosphorylation is thought to precede aggregation and therefore to promote aggregation, but the nature and extent of phosphorylation remained ill-defined. Tau contains ~85 potential phospho...

Abnormal changes in the neuronal microtubule-associated protein Tau, such as hyperphosphorylation and aggregation, are considered hallmarks of cognitive deficits in Alzheimer disease. Hyperphosphorylation is thought to take place before aggregation, and therefore it is often assumed that phosphorylation predisposes Tau towards aggregation. However,...

Results of Spearman correlation analysis

Characteristics of the patient cohort and laboratory data

Lipopolysaccharides (LPS) in the outer membrane of Gram-negative bacteria provide the first line of defense against antibiotics and other harmful compounds. LPS biosynthesis critically depends on LpxC catalyzing the first committed enzyme in this process. In Escherichia coli, the cellular concentration of LpxC is adjusted in a growth rate-dependent...

Background/aims: An estimated 80 million people worldwide are infected with viremic hepatitis C virus (HCV). Even after eradication of HCV with direct acting antivirals (DAAs), hepatic fibrosis remains a risk factor for hepatocarcinogenesis. Recently, we confirmed the applicability of microfibrillar-associated protein 4 (MFAP4) as a serum biomarke...

Peroxisomal biogenesis depends on the correct import of matrix proteins into the lumen of the organelle. Most peroxisomal matrix proteins harbor the peroxisomal targeting-type 1 (PTS1), which is recognized by the soluble PTS1-receptor Pex5p in the cytosol. Pex5p ferries the PTS1-proteins to the peroxisomal membrane and releases them into the lumen....

Extracellular vesicles (EVs) provide a complex means of intercellular signalling between cells at local and distant sites, both within and between different organs. According to their cell-type specific signatures, EVs can function as a novel class of biomarkers for a variety of diseases, and can be used as drug-delivery vehicles. Furthermore, EVs...

AAA⁺ proteases (ATPases associated with various cellular activities) shape the cellular protein pool in response to environmental conditions. A prerequisite for understanding the underlying recognition and degradation principles is the identification of as many protease substrates as possible. Most previous studies made use of inactive protease var...

DOI: 10.1002/pmic.201800080 Regulated proteolysis of active and natively folded proteins is a universal strategy to shape the cellular proteome. In article number 1800080, Arends et al. use a combination of quantitative comparative proteomics and trapping experiments with a proteolytically inactive protease variant to investigate the substrate repe...

Controlling the cellular abundance and proper function of proteins by proteolysis is a universal process in all living organisms. In Escherichia coli, the ATP‐dependent Lon protease is crucial for protein quality control and regulatory processes. To understand how diverse substrates are selected and degraded, unbiased global approaches are needed....

Extracellular vesicles (EV) are secreted by most cells and are present in every body fluid. They can be seen as major players in the regulation and communication of cells. They are adressed as therapeutic and diagnostic tool for many disorders including neurodegenerative diseases. Distinct subpopulations of platelet derived EVs have been shown to c...

The mitochondrial outer membrane is essential for communication between mitochondria and the rest of the cell and facilitates the transport of metabolites, ions, and proteins. All mitochondrial outer membrane channels known to date are β-barrel membrane proteins, including the abundant voltage-dependent anion channel and the cation-preferring prote...

Background: Human hippocampal area CA1 is one of the first fields in the human telencephalon showing Alzheimer disease-specific neuropathological changes. In contrast, CA2 and CA3 are far later affected pointing to functional differences, which may be accompanied by differences in proteome endowment and changes. Methods: Human pyramidal cell lay...

Lipocalin-2 (LCN2) is a secreted adipokine that transports small hydrophobic molecules such as fatty acids and steroids. LCN2 limits bacterial growth by sequestering iron-containing siderophores and in mammalian liver protects against inflammation, infection, injury and other stressors. Because LCN2 modulates hepatic fat metabolism and homeostasis,...

Quantitative mass spectrometry approaches are used for absolute and relative quantification in global proteome studies. Up to date different relative and absolute quantification techniques are available that differ in quantification accuracy, proteome coverage, complexity and robustness. This review focuses on most common relative or absolute quant...

Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a technique to visualize molecular features of tissues based on mass detection. This chapter focuses on MALDI MSI of peptides and provides detailed operational instructions for sample preparation of cryoconserved and formalin- fixed paraffin-embedded (FFPE) tissue....

Methylglyoxal (MG), an arginine-directed glycating agent, is implicated in diabetic late complications. MG is detoxified by glyoxalase 1 (GLO1) of the cytosolic glyoxalase system. The aim was to investigate the effects of MG accumulation by GLO1-knockdown under hyperglycaemic conditions in human aortic endothelial cells (HAECs) hypothesizing that t...

Determination of the specific type of thyroid cancer is crucial for the prognosis and selection of treatment this malignancy. However, in some cases appropriate classification is not possible based on histopathological features only, and it might be supported by molecular biomarkers. Here we aimed to characterize molecular profiles of different thy...

The majority of poorly differentiated hepatocellular carcinomas (HCCs) develop from well-differentiated tumors. Endocytosis is a cellular function which is likely to take part in this development due to its important role in regulating the abundances of vital signaling receptors. Here, we aimed to investigate the abundance of endocytosis-associated...

Context and objective: Human hepatocellular carcinoma (HCC) is a severe malignant disease, and accurate and reliable diagnostic markers are still needed. This study was aimed for the discovery of novel marker candidates by quantitative proteomics. Methods and results: Proteomic differences between HCC and nontumorous liver tissue were studied by...

Background: The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of...

MYCN and HDAC2 jointly repress the transcription of tumor suppressive miR-183 in neuroblastoma. Enforced miR-183 expression induces neuroblastoma cell death and inhibits xenograft growth in mice. Here we aimed to focus more closely on the miR-183 signaling network using a label-free mass spectrometric approach. Analysis of neuroblastoma cells trans...

Introduction: MYCN and HDAC2 jointly repress the transcription of tumor suppressive miR-183 in neuroblastoma. Enforced miR-183 expression induces neuroblastoma cell death and inhibits xenograft growth in mice. Methods: Here we aimed to focus more closely on the miR-183 signaling network using a label-free mass spectrometric approach. Results: Analy...

Background: Several comparable mechanisms have been identified for hepatic and pulmonary fibrosis. The human microfibrillar associated glycoprotein 4 (MFAP4), produced by activated myofibroblasts, is a ubiquitous protein playing a potential role in extracellular matrix (ECM) turnover and was recently identified as biomarker for hepatic fibrosis in...

The interferon-stimulated gene 15 (ISG15) plays an important role in the pathogenesis of hepatitis C virus (HCV) infection. ISG15-regulated proteins have previously been identified that putatively affect this proviral interaction. The present observational study aimed to elucidate the relation between ISG15 and these host factors during HCV infecti...

The 24th HBPP workshop of the HUPO Brain Proteome Project Initiative (HUPO BPP) was hosted during the 14th HUPO World Congress at the magnificent Vancouver Convention Centre in Canada. The HUPO BPP initiative is an open international project under the support of the Human Proteome Organization (HUPO) and aims to make research results of the human b...

Cholangiocellular carcinoma (CCC) and pancreatic ductal adenocarcinoma (PDAC) are two highly aggressive cancer types which arise from epithelial cells of the pancreatobiliary system. Owing to their histological and morphological similarity, differential diagnosis between CCC and metastasis of PDAC located in the liver frequently proves an unsolvabl...

Hepatocellular carcinoma (HCC) is one of the most aggressive tumors and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing for an accurate and early tumor diagnosis. To identify potential markers with such applications, we analyzed a patient cohort consisting of 50 pat...

Autophagy is an evolutionarily-conserved process that delivers diverse cytoplasmic components to the lysosomal compartment for either recycling or degradation. This involves the removal of protein aggregates, the turnover of organelles, as well as the elimination of intracellular pathogens. In this situation, when only specific cargoes should be ta...

The HUPO Brain Proteome Project (HUPO BPP) held its 23rd workshop in São Paulo, Brazil, April 16-17, 2015. The focus of the spring workshop was on strategies and predictive therapies concerning neurodegenerative diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The exact discrimination of lesions with true hepatocellular differentiation from secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary protein-biomarkers by using complementary proteomic techniques (2D-DIGE, label-free MS). The identified candid...

In personalized medicine, one major goal is the identification of yet unknown patient subgroups with specific gene or protein expression. Different subgroups can indicate different molecular subtypes of a disease. These subtypes might correlate with disease progression, prognosis or therapy response, and the subgroup-specific genes or proteins are...

In personalized medicine, one major goal is the identification of yet unknown patient subgroups with specific gene or protein expression. Different subgroups can indicate different molecular subtypes of a disease. These subtypes might correlate with disease progression, prognosis or therapy response, and the subgroup-specific genes or proteins are...

Stem cell transplantation is a promising therapeutic strategy to enhance axonal regeneration after spinal cord injury. Unrestricted somatic stem cells (USSC) isolated from human umbilical cord blood is an attractive stem cell population available at GMP grade without any ethical concerns. It has been shown that USSC transplantation into acute injur...

Unlabelled: Transcription of mouse cytomegalovirus (MCMV) immediate early ie1 and ie3 is controlled by the major immediate early promoter/enhancer (MIEP) and requires differential splicing. Based on complete loss of genome replication of an MCMV mutant carrying a deletion of the ie3-specific exon 5, the multifunctional IE3 protein (611 amino acids...

Protein inference connects the peptide-spectrum matches (PSMs) obtained from database search engines back to proteins, which are typically at the heart of most proteomics studies. Different search engines yield different PSMs and thus different protein lists. Analysis of results from one or multiple search engines is often hampered by different dat...

Hepatic fibrosis and cirrhosis are major health problems worldwide. Up to now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. In order to develop non-invasive diagnostic assays for the assessment of liver fibrosis it is urgently necessary to identify molecules which are robustly expressed in association with...

Mass spectrometry imaging (MSI) has become a powerful and successful tool in the context of biomarker detection especially in recent years. This emerging technique is based on the combination of histological information of a tissue and its corresponding spatial resolved mass spectrometric information. The identification of differentially expressed...

Nasal lavage fluid (NLF) becomes more and more important as a noninvasive patient sample serving as a new opportunity to discover new biomarkers in diverse human diseases comprising mainly respiratory disorders. This was supported by the observation that the protein profile of NLF differs from conventional samples of i.e. whole blood, hence being c...

The HUPO Brain Proteome Project (HUPO BPP) held its 22nd workshop in Madrid, Spain, October 7, 2014. The focus of the autumn workshop was on the development of characterization tools for neurodegenerative diseases in proteomics

This study was designed to identify and validate potential new biomarkers for prostate cancer and to distinguish patients with and without biochemical relapse. Prostate tissue samples analyzed by 2D-DIGE (two-dimensional difference in gel electrophoresis) and mass spectrometry (MS) revealed downregulation of secernin-1 (P < 0.044) in prostate cance...

Identification and Validation of Potential New Biomarkers for Prostate Cancer Diagnosis and Prognosis Using 2D-DIGE and MS” by Cordelia Geisler, Nadine T. Gaisa, David Pfister, Susanne Fuessel, Glen Kristiansen, Till Braunschweig, Sonja Gostek, Birte Beine, Hanna C. Diehl, Angela Jackson, Christoph H. Borchers, Axel Heidenreich, Helmut E. Meyer, Ru...

The occurrence of cancer is often associated with a dysfunction in one of the three central membrane-involution processes—autophagy, endocytosis or cytokinesis. Interestingly, all three pathways are controlled by the same central signaling module: the class III phosphatidylinositol 3-kinase (PI3K-III) complex and its catalytic product, the phosphor...

The combined deletion of chromosomal arms 1p and 19q has been described as a prognostic marker for oligodendroglial tumors. These tumors show a better response to chemotherapy and radiotherapy. Recently, we found a lower abundance of peroxiredoxin 1 (PRDX1) in oligodendroglial tumors with 1p/19q deletion, suggesting a potential role of this enzyme...

BACKGROUND & PURPOSE: Hepatocellular carcinoma (HCC) is a major lethal cancer worldwide. Despite sophisticated diagnostic algorithms, the differential diagnosis of small liver nodules still is difficult. While imaging techniques have advanced, adjuvant protein-biomarkers as glypican3 (GPC3), glutamine-synthetase (GS) and heat-shock protein 70 (HSP...

Background Platelets (PLTs) in stored PLT concentrates (PLCs) release PLT extracellular vesicles (PL-EVs) induced by senescence and activation, resembling the PLT storage lesion. No comprehensive classification or molecular characterization of senescence-induced PL-EVs exists to understand PL-EV heterogeneity.Study Design and MethodsPL-EVs from 5-d...

We analyzed anex vivo model of in situ aged human dermal fibroblasts, obtained from 15 adult healthy donors from three different age groups using an unbiased quantitative proteome-wide approach applying label-free mass spectrometry. Thereby, we identified 2409 proteins, including 43 proteins with an age-associated abundance change. Most of the diff...

The prostate-specific G-protein-coupled receptor 1 (PSGR1) is an olfactory receptor specifically expressed in the prostate gland. PSGR1 expression is elevated both in benign prostatic hyperplasia tissue and in prostate cancer. Stimulation of PSGR1 by the odorant β-ionone leads to an increase in the intracellular Ca2 + concentration, activation of m...

Peroxisomal biogenesis is an ubiquitin-dependent process because the receptors required for the import of peroxisomal matrix proteins are controlled via their ubiquitination status. A key step is the monoubiquitination of the import receptor Pex5p by the ubiquitin-conjugating enzyme (E2) Pex4p. This monoubiquitination is supposed to take place afte...

The aim of this study was the identification of novel biomarker candidates for the diagnosis of cholangiocellular carcinoma (CCC) and its immunohistochemical differentiation from benign liver and bile duct cells. CCC is a primary cancer which arises from the epithelial cells of bile ducts and is characterised by high mortality rates due to its late...

Background: The intestinal peptide transporter PEPT-1 plays an important role in development, growth, reproduction and stress tolerance in C. elegans as revealed by the severe phenotype of the pept-1-deficient strain pept-1. The reduced number of offspring and increased stress resistance were shown to result from changes in the insulin/IGF-signalin...

The prognosis of pancreatic neuroendocrine tumors is related to size, histology and proliferation rate. However, this stratification needs to be refined further. We conducted a proteome study on insulinomas, a well-defined pancreatic neuroendocrine tumor entity, in order to identify proteins that can be used as biomarkers for malignancy. Based on a...

The HUPO Brain Proteome Project (HUPO BPP) held its 20th workshop in Yokohama, Japan, September 15, 2013. The focus of the autumn workshop was on new insights and prospects of neurodegenerative diseases.

Background: Local ablative techniques such as selective internal radiation therapy (SIRT) have become the mainstay of treating hepatocellular carcinoma (HCC) in the bridging-to-transplant and palliative setting. We recently demonstrated that epithelial circulating tumor cells (CTCs) correlate to an unfavorable outcome. We wanted to scrutinize whet...

The Baculoviral IAP repeat-containing protein 5 (BIRC5), also known as inhibitor of apoptosis protein survivin, is a member of the chromosomal passenger complex and a key player in mitosis. To investigate the function of BIRC5 in liver regeneration, we analyzed a hepatocyte-specific BIRC5-knockout mouse model using a quantitative label-free proteom...

The HUPO Brain Proteome Project (HUPO BPP) held its 21(st) workshop in Honolulu, Hawaii. During the 23-24 January 2014 the island became the center of the open workshop of the scientific community.

In the nasal cavity, the nonmotile cilium of olfactory sensory neurons (OSNs) constitutes the chemosensory interface between the ambient environment and the brain. The unique sensory organelle facilitates odor detection for which it comprises all necessary components of initial and downstream olfactory signal transduction. In addition to its functi...

Genetic and environmental factors mediate via different physiological and molecular processes a shifted energy balance leading to overweight and obesity. To get insights in the underlying processes involved in energy intake and weight gain, we compared hypothalamic tissue of mice kept on a high-fat or control diet for 10 days by a proteomic approac...

Proteomics has evolved into a powerful and widely used bioanalytical technique in the study of cancer, especially hepatocellular carcinoma (HCC). In this review, we provide an up to date overview of feasible proteome-analytical techniques for clinical questions. In addition, we present a broad summary of proteomic studies of HCC utilizing various t...

In recent years, knowledge about immune-related disorders has substantially increased, especially in the field of central nervous system (CNS) disorders. Recent innovations in protein-related microarray technology have enabled the analysis of interactions between numerous samples and up to 20,000 targets. Antibodies directed against ion channels, r...

Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disorder, is characterized by the progressive and selective loss of upper and lower motor neurons. Diagnosis of this disorder is based on clinical assessment, and the average survival time is less than 3 years. Injections of IgG from ALS patients into mice are known to sp...

Up to now the diagnosis of early stage cholangiocarcinoma (CC) has remained difficult, with low sensitivities reported for current diagnostic methods. Based on recent promising findings about circulating U2 small nuclear RNA fragments (RNU2-1f) as novel blood-based biomarkers for pancreatic and colorectal adenocarcinoma, we studied the utility of R...

In recent years, knowledge about immune-related disorders has substantially increased, especially in the field of central nervous system (CNS) disorders. Recent innovations in protein-related microarray technology have enabled the analysis of interactions between numerous samples and up to 20,000 targets. Antibodies directed against ion channels, r...

Over the past years, phosphoproteomics has advanced to a prime tool in signaling research. Since then, an enormous amount of information about in vivo protein phosphorylation events has been collected providing a treasure trove for gaining a better understanding of the molecular processes involved in cell signaling. Yet, we still face the problem o...

http://www2.kenes.com/wip2014/abstract/Documents/HIGH%20RES%20-%2020th%20World%20Congress%20on%20Parkinson%27s%20Disease%20and%20Related%20Disorders.pdf 559 Objectives: During the progress of Parkinson’s disease (PD) neuromelanin containing dopaminergic neurons of the substantia nigra pars compacta (Snpc) degenerate and synaptic processes are impa...

Abstract In previous studies we identified the interferon stimulated gene 15 (ISG15) as a pro-viral host factor in the pathogenesis of hepatitis C virus (HCV) infection. However, the functional link between ISG15 and the HCV replication cycle is not well understood. Aim of the present study was to functionally analyze the role of ISG15 and to ident...

FE65 is a cytosolic adapter protein and an important binding partner of the amyloid precursor protein (APP). Dependent on Thr668 phosphorylation in APP, which influences amyloidogenic APP processing, FE65 undergoes nuclear translocation, thereby transmitting a signal from the cell membrane to the nucleus. As this translocation may be relevant in Al...

Detection of yet unknown subgroups showing differential gene or protein expression is a frequent goal in the analysis of modern molecular data. Applications range from cancer biology over developmental biology to toxicology. Often a control and an experimental group are compared, and subgroups can be characterized by differential expression for onl...