A5014964900- Extracellular vesicles in disease
- Wnt/β-catenin signaling in development and cancer
- MicroRNA in disease regulation
- Mass Spectrometry Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- Cancer-related gene regulation
- Circular RNAs in diseases
- Neurobiology and Insect Physiology Research
- Cellular transport and secretion
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
- Lipid Membrane Structure and Behavior
- Pancreatic function and diabetes
- Heat shock proteins research
- Cell Adhesion Molecules Research
- RNA modifications and cancer
- Sphingolipid Metabolism and Signaling
- Complement system in diseases
- Analytical Chemistry and Chromatography
- RNA regulation and disease
- DNA and Nucleic Acid Chemistry
- Invertebrate Immune Response Mechanisms
- Microtubule and mitosis dynamics
- Ferroptosis and cancer prognosis
- Electromagnetic Fields and Biological Effects
University of Potsdam
2021-2025
Heidelberg University
2012-2024
German Centre for Cardiovascular Research
2018-2024
University Hospital Heidelberg
2012-2024
Centre Hospitalier Intercommunal de Poissy
2023
University of Bonn
2023
University of Göttingen
2017-2022
Nephrologisches Zentrum Goettingen
2022
University Medical Center
2014-2021
HMU Potsdam – Health and Medical University Potsdam
2020-2021
Abstract Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of vesicular nomenclatures and components, online searches for EV-related publications components currently challenging. Results: We present an improved version EVpedia, a public database EVs research. This community web portal contains identification orthologous bioinformatic tools personalized function. EVpedia includes 6879 publications, 172...
Degradation of host hemoglobin by the human malaria parasite Plasmodium falciparum is a massive metabolic process. What role this degradation plays and whether it essential for survival have not been established, nor roles various degradative enzymes clearly defined. We report that P. can grow in medium containing single amino acid (isoleucine, only missing from hemoglobin). In medium, growth hemoglobin-degrading enzyme gene knockout lines (missing falcipain-2 plasmepsins alone or...
Extracellular vesicles (EVs) are membrane particles secreted from cells into all body fluids. Several EV populations exist differing in size and cellular origin. Using differential centrifugation EVs pelleting at 14,000 g ("microvesicles" (MV)) 100,000 ("exosomes") distinguishable by protein markers. Neutral sphingomyelinase (nSMase) inhibition has been shown to inhibit exosome release since used study their functional implications. How nSMases (also known as SMPD2 SMPD3) affect the basal...
Insulin is both a hormone regulating energy metabolism and growth factor. We others have shown that physiological doses of insulin initiate complex signals in primary human mouse β-cells, but the functional significance insulin's effects on this cell type remains unclear. In present study, role β-cell apoptosis was examined. Exogenous completely prevented induced by serum withdrawal when given at picomolar or low nanomolar concentrations not higher concentrations, indicating are...
Background The Radical-Pair-Model postulates that the reception of magnetic compass directions in birds is based on spin-chemical reactions specialized photopigments eye, with cryptochromes discussed as candidate molecules. But so far, exact subcellular characterization these molecules retina remained unknown. Methodology/Principal Findings We here describe localization cryptochrome 1a (Cry1a) European robins, Erithacus rubecula, and domestic chickens, Gallus gallus, two species have been...
// Kerstin Menck 1,* , Florian Klemm Julia Christina Gross 2 Tobias Pukrop 1 Dirk Wenzel 3 Claudia Binder Dept of Hematology/Oncology, University Medicine, Göttingen, Germany Div. Signaling and Functional Genomics, German Cancer Research Center, Heidelberg, Max Planck Institute for Biophysical Chemistry, * These authors contributed equally to this work. Correspondence: Binder, email: Keywords : Breast cancer, exosomes, Evi, microvesicles, macrophages, Wnt 5a Received August 27, 2013...
During endosome maturation, neutral sphingomyelinase 2 (nSMase2, encoded by SMPD3) is involved in budding of intraluminal vesicles (ILVs) into late endosomes or multivesicular bodies (MVBs). Fusion these with the plasma membrane results secretion exosomes small extracellular (sEVs). Here, we report that nSMase2 activity controls sEV through modulation vacuolar H+-ATPase (V-ATPase) activity. Specifically, show inhibition induces V-ATPase complex assembly drives MVB lumen acidification and...
Standardized, comprehensive platforms for the discovery of protease substrates have been extremely difficult to create. Screens specificity are now frequently based on cleavage patterns peptide substrates, which contain small recognition motifs that required scissile bond within an active site. However, these studies do not identify in vivo nor can they lead definition macromolecular features account biological proteases. To use properly folded proteins a proteomic screen we used 2D...
The Haemophilus influenzae HMW1 adhesin is a high-molecular weight protein that secreted by the bacterial two-partner secretion pathway and mediates adherence to respiratory epithelium, an essential early step in pathogenesis of H. disease. In recent work, we discovered glycoprotein undergoes N-linked glycosylation at multiple asparagine residues with simple hexose units rather than N-acetylated units, revealing unusual N-glycosidic linkage suggesting new glycosyltransferase activity....
The Haemophilus influenzae HMW1 adhesin mediates adherence to respiratory epithelial cells, a critical early step in the pathogenesis of H. disease. In recent work, we demonstrated that undergoes glycosylation. addition, observed glycosylation is essential for tethering bacterial surface, prerequisite HMW1-mediated host epithelium. this study, examined proteolytic fragments by mass spectrometry, achieved 89% amino acid sequence coverage, and identified 31 novel modification sites. All...
Extracellular vesicles (EVs) are shed by many different cell types. Their nucleic acids content offers new opportunities for biomarker research in solid tumors. The role of EV RNA prostate cancer (PCa) is still largely unknown. EVs were isolated from benign and malignant lines blood plasma patients with PCa (n = 18) controls prostatic hyperplasia (BPH) 7). Nanoparticle tracking analysis (NTA), Western blot, electron microscopy, flow cytometry used the characterization EVs. Non-coding...
In prostate cancer and other malignancies sensitive robust biomarkers are lacking or have relevant limitations. Prostate specific antigen (PSA), the only biomarker widely used in cancer, is suffering from low specificity. Exosomes offer new perspectives discovery of blood-based biomarkers. Here we present a proof-of principle study for proteomics-based identification pipeline, implementing existing data sources, to exemplarily identify exosome-based candidates cancer.Exosomes malignant PC3...
Von Willebrand factor (VWF) dimerizes through C-terminal CK domains, and VWF dimers assemble into multimers in the Golgi by forming intersubunit disulfide bonds between D3 domains. This unusual oxidoreductase reaction requires propeptide (domains D1D2), which acts as an endogenous pH-dependent chaperone. The cysteines involved multimer assembly were characterized using a construct that encodes N-terminal D1D2D'D3 Modification with thiol-specific reagents demonstrated secreted D'D3 monomer...
Plakoglobin and β-catenin are homologous armadillo repeat proteins found in adherens junctions, where they interact with the cytoplasmic domain of classical cadherins α-catenin. Plakoglobin, but normally not β-catenin, is also a structural constituent desmosomes, it binds to domains desmosomal cadherins, desmogleins desmocollins. Here, we report structural, biophysical, biochemical studies aimed at understanding molecular basis selective exclusion α-catenin from desmosomes. The crystal...
Abstract Cryptochromes are a ubiquitous group of blue-light absorbing flavoproteins that in the mammalian retina have an important role circadian clock. In birds, cryptochrome 1a (Cry1a), localized UV/violet-sensitive S1 cone photoreceptors, is proposed to be retinal receptor molecule light-dependent magnetic compass. The localization Cry1, homologue avian Cry1a, unknown and it open whether Cry1 also involved field sensing. To constrain possible we immunohistochemically analysed 90 species...
Genome editing by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 is evolving rapidly. Recently, second-generation CRISPR/Cas9 activation systems based on nuclease inactive dead (d)Cas9 fused to transcriptional transactivation domains were developed for directing specific guide (g)RNAs regulatory regions of any gene interest, enhance transcription. The application dCas9 activate cardiomyocyte transcription in targeted genomic loci vivo has not been demonstrated so far.
Cancer metastasis is largely influenced by cell–cell communication, to which exosomes play a vital role. Exosomes are small extracellular vesicles (sEVs) that originate as intraluminal (ILVs) within multivesicular bodies (MVBs) during endosome maturation. ILV formation depends on several pathways, including of ceramide synthesis neutral sphingomyelinase 2 [nSMase2]. Colorectal cancer (CRC)‐derived sEVs reported carry diverse range metastatic cargo proteins; however, segregation them in the...
We used solution-phase hydrogen/deuterium (H/D) exchange and multistage tandem mass spectrometry (MS/MS) experiments in an electrospray ion-trap spectrometer operating the negative-ion mode to investigate consequences of loss a high proton-affinity (PA) base from T-rich tetra hexadeoxynucleotides. The oligodeoxynucleotides containing one or two other nucleobases take advantage spectral inertness T because fragmentation oligomer is simple, allowing tight focus on those processes interest....
The pathology of Alzheimer's disease (AD) begins years prior to clinical diagnosis. development antecedent biomarkers that indicate the presence AD and predict risk for decline in both cognitively normal mildly impaired individuals will be useful as effective therapies are developed. While cerebrospinal fluid (CSF) markers such amyloid-β (Aβ) 42 tau useful, additional needed. To identify new markers, we utilized 2-D difference gel electrophoresis (2-D DIGE) individual CSF samples from...
Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and role Wnt signaling this process is well described, contribution epidermal secretion homeostasis remains poorly understood. To analyze proteins process, we created a conditional knockout allele cargo receptor Evi/Gpr177/Wntless mice that lacked Evi expression epidermis. We found K14-Cre, Evi-LOF lost their hair during first cycle, showing...