A5015029827- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- Cell death mechanisms and regulation
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Multiple Myeloma Research and Treatments
- Blood groups and transfusion
- Heparin-Induced Thrombocytopenia and Thrombosis
- Antimicrobial Resistance in Staphylococcus
- Acute Myeloid Leukemia Research
- Quinazolinone synthesis and applications
- Genetics and Neurodevelopmental Disorders
- Bacterial biofilms and quorum sensing
- Ion channel regulation and function
- Viral gastroenteritis research and epidemiology
- Retinal Diseases and Treatments
- NF-κB Signaling Pathways
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Melanoma and MAPK Pathways
- Protein Tyrosine Phosphatases
- Influenza Virus Research Studies
Friedrich-Loeffler-Institut
2017-2025
Universitätsmedizin Greifswald
2019-2024
Otto-von-Guericke University Magdeburg
2013-2022
Vector-based SARS-CoV-2 vaccines have been associated with vaccine- induced thrombosis thrombocytopenia syndrome (VITT/TTS), but the causative factors are still unresolved. We comprehensively analyzed ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Johnson Johnson) vaccines. contains significant amounts of host cell protein impurities, including functionally active proteasomes, adenoviral proteins. A much smaller amount impurities was found in Ad26.COV2.S. Platelet factor 4 formed complexes...
Antigenic stimulation of the T cell receptor (TCR) initiates a change from resting state into an activated one, which ultimately results in proliferation and acquisition effector functions. To accomplish this task, cells require dramatic changes metabolism. Therefore, we investigated metabolic intermediates indicating for crucial pathways reflecting status cells. Moreover analyzed possible regulatory molecules required initiation changes. We found that inducing conditions result increase key...
Treatment of acute leukemia is challenging and long-lasting remissions are difficult to induce. Innovative therapy approaches aim complement standard chemotherapy improve drug efficacy decrease toxicity. Promising new therapeutic targets in cancer include voltage-gated Kv1.3 potassium channels, but their role unclear. We reported that channels lymphocytes blocked by memantine, which known as an antagonist neuronal N-methyl-D-aspartate type glutamate receptors clinically applied advanced...
Abstract Staphylococcus aureus is a Gram-positive opportunistic pathogen that has colonized nearly 30% of the human population and can cause life-threatening infections. S. exports variety virulence factors, such as novel set extracellular serine protease-like proteins (Spls). Spls are expressed by most clinical isolates , but their pathophysiological substrates role during infection largely unknown. Here we characterized substrate cleavage specificity recombinantly SplA SplB proteins. We...
African swine fever virus (ASFV) is a large DNA of the Asfarviridae family that causes fatal hemorrhagic disease in domestic and wild boar. Infections with moderately virulent strains predominantly result milder clinical course lower lethality. As target cells ASFV, monocytes play crucial role triggering T-cell-mediated immune defense ASF pathogenesis. We compared effect highly "Armenia2008" (ASFV-A) strain naturally attenuated "Estonia2014" (ASFV-E) on cellular activation vivo primary ex...
Cell survival and function critically relies on the fine-tuned balance of protein synthesis degradation. In steady state, standard proteasome is sufficient to maintain this proteostasis. However, upon inflammation, sharp increase in production requires additional mechanisms limit protein-associated cellular stress. Under inflammatory conditions release interferons, immunoproteasome (IP) induced support processing recycling. antigen-presenting cells constitutively expressing IPs,...
Application of the proteasome inhibitor Bortezomib for treatment haematopoietic malignancies such as multiple myeloma significantly improves average overall survival patients. However, one most severe side effects is development peripheral neuropathies caused by neurotoxic limiting its therapeutic efficacy. With ONX-0914 a specific β5i (LMP7)-immunosubunit containing proteasomes was developed that targets exclusively subtypes mainly expressed in immune cells including B lymphocytes origin...
Background/Aim: Androgen receptor (AR) degradation is the primary regulator of androgen activity. This study was designed to investigate influence proteasome on AR protein stability after enzalutamide (Enz) treatment. Materials and Methods: Cell counting treatment utilized assess effect Enz cell proliferation. Changes in mRNA levels were evaluated using reverse transcription-polymerase chain reaction (RT-PCR). Proteasome activity assessed by measurement chymotrypsin-like beta-5 subunit...
Abstract Pharmacologic targeting of chromatin-associated protein complexes has shown significant responses in KMT2A -rearranged ( KMT2A-r ) acute myeloid leukemia (AML) but resistance frequently develops to single agents. This points a need for therapeutic combinations that target multiple mechanisms. To enhance our understanding functional dependencies AML, we have used proteomic approach identify the catalytic immunoproteasome subunit PSMB8 as specific vulnerability. Genetic and...
Life-threatening toxic shock syndrome is often caused by the superantigen toxin-1 (TSST-1) produced Staphylococcus aureus . A well-known risk factor lack of neutralizing antibodies. To identify determinants anti-TSST-1 antibody response, we examined 976 participants German population-based epidemiological Study Health in Pomerania (SHIP-TREND-0). We measured levels, analyzed colonization with TSST-1-encoding S. strains, and performed a genome-wide association analysis genetic factors....
Abstract Background PAG/Cbp represents a ubiquitous mechanism for regulating Src family kinases by recruiting Csk to the plasma membrane, thereby controlling cellular activation. Since are known oncogenes, we used RNA interference in primary human T cells test whether loss of PAG resulted lymphocyte transformation. Results PAG-depletion enhanced kinase activity and augmented proximal T-cell receptor signaling; exactly phenotype expected this negative regulator. Surprisingly, rather than...
Epithelial cells are an important line of defense within the lung. Disruption epithelial barrier by pathogens enables systemic dissemination bacteria or viruses host leading to severe diseases with fatal outcomes. Thus, lung epithelium can be damaged seasonal and pandemic influenza A viruses. Influenza virus infection induced dysregulation immune system is beneficial for lower respiratory tract, causing bacterial viral co-infection. Host regulate protein homeostasis response different...
Upon antigen recognition by the T cell receptor (TCR), a complex signaling network orchestrated protein-tyrosine kinases (PTKs) and phosphatases (PTPs) regulates transmission of extracellular signal to nucleus. The role PTPs Src-homology 2 (SH2) domain-containing phosphatase 1 (SHP1, Ptpn6) (SHP2, Ptpn11) have been studied in various types including cells. Whereas SHP1 acts as an essential negative regulator proximal steps signalling, SHP2 activation is still matter debate. Here, we analyzed...
Proteolysis as mediated by one of the major cellular protein degradation pathways, ubiquitin-proteasome system (UPS), plays an essential role in learning and memory formation. However, functional relevance immunoproteasomes healthy brain especially their impact on normal function including processes has not been investigated so far. In present study, we analyzed phenotypic effects impaired immunoproteasome formation using a β5i/LMP7-deficient mouse model different behavioral paradigms...
Abstract Dissecting the different steps of processing and presentation tumor‐associated antigens is a key aspect immunotherapies enabling to tackle immune response evasion attempts cancer cells. The immunodominant glycoprotein gp100 209‐217 epitope, which liberated from melanoma differentiation antigen PMEL17 , part immunotherapy trials. By analyzing human cell lines, we here demonstrate that pool N‐terminal extended peptides sharing common minimal epitope generated by proteasome subtypes....
By changing the relative abundance of generated antigenic peptides through alterations in proteolytic activity, interferon (IFN)-γ-induced immunoproteasomes influence outcome CD8+ cytotoxic T lymphocyte responses. In present study, we investigated effects hepatitis C virus (HCV) infection on IFN-γ-induced immunoproteasome expression using a HCV cell culture system. We found that, although IFN-γ induced transcriptional mRNAs encoding β1i/LMP2, β2i/MECL-1 and β5i/LMP7 subunits, formation was...
Primary and acquired therapy resistance is a major problem in patients with BRAF-mutant melanomas being treated BRAF MEK inhibitors (BRAFI, MEKi). Therefore, development of alternative regimes still required. In this regard, new drug combinations targeting different pathways to induce apoptosis could offer promising approaches. Here, we investigated the combination proteasome Kv1.3 potassium channel inhibition on chemo-resistant, inhibitor-resistant as well sensitive human melanoma cells....
Antigenic stimulation of T cells initiates a change from the resting state into an activated one mediated by triggering cell receptor (TCR). This is characterized rapid proliferation, differentiation and acquisition effector functions. To maintain energetic needs accompanied this processes, are able to adapt their uptake utilization extracellular nutrients. Proliferation distinct subsets lymphocytes like effector-, regulatory-, memory antigens, various cytokines growth factors through...
Abstract Objectives Characterization of the proteasome and its stability in buffy‐coat derived platelet concentrates (PCs) during storage. Background The plays a key role cell homeostasis by processing misfolded or abnormal proteins regulating levels activities high number contributing to cycle, survival, proliferation. Controversial data exist, whether inhibition affects function. Little is known about function, expression, PCs storage, potential storage lesions. Study design methods were...
<title>Abstract</title> Vector-based SARS-CoV-2 vaccines have been associated with vaccine-induced thrombosis thrombocytopenia syndrome (VITT/TTS), but the causative factors are still unresolved. We comprehensively analyzed ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson). nCoV-19 contains significant amounts of host cell protein impurities, including functionally active proteasomes, adenoviral proteins. In much less impurities were found. Platelet-factor 4 (PF4) formed...