A5080829856- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Pneumonia and Respiratory Infections
- Inflammasome and immune disorders
- Bacterial Infections and Vaccines
- Respiratory viral infections research
- Immune cells in cancer
- Tryptophan and brain disorders
- Microbial infections and disease research
- Galectins and Cancer Biology
- S100 Proteins and Annexins
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- Macrophage Migration Inhibitory Factor
- Neuroscience and Neuropharmacology Research
- Autoimmune and Inflammatory Disorders Research
- Amoebic Infections and Treatments
- Peroxisome Proliferator-Activated Receptors
- Neurogenetic and Muscular Disorders Research
- Cancer Cells and Metastasis
- Poxvirus research and outbreaks
- Nicotinic Acetylcholine Receptors Study
- Chronic Lymphocytic Leukemia Research
- Protein Tyrosine Phosphatases
- Cancer survivorship and care
University Hospital Bonn
2019-2025
University of Bonn
2005-2023
German Center for Neurodegenerative Diseases
2019-2022
Centers for Disease Control and Prevention
2002-2021
National Center for Immunization and Respiratory Diseases
2016-2021
Novartis (United States)
2020
Centre de Recherche Médicale et Sanitaire
2016
Agence de Médecine Préventive
2016
World Health Organization
2016
Institut Pasteur
2016
Microglia jointly degrade fibrillar
Abstract Despite the increasing interest in targeting stromal elements of tumor microenvironment, we still face tremendous challenges developing adequate therapeutics to modify landscape. A major obstacle this is our poor understanding phenotypic and functional heterogeneity cells tumors. Herein, perform an unbiased interrogation mesenchymal cells, delineating co-existence distinct subsets cancer-associated fibroblasts (CAFs) microenvironment murine carcinomas, each endowed with unique...
Microglia are crucial for maintaining brain health and neuron function. Here, we report that microglia establish connections with neurons using tunneling nanotubes (TNTs) in both physiological pathological conditions. These TNTs facilitate the rapid exchange of organelles, vesicles, proteins. In neurodegenerative diseases like Parkinson's Alzheimer's disease, toxic aggregates alpha-synuclein (α-syn) tau accumulate within neurons. Our research demonstrates use to extract from these...
Abstract The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted need for a sensitive, reproducible, and specific laboratory test confirmatory diagnosis anthrax. Centers Disease Control Prevention developed, optimized, rapidly qualified an enzyme-linked immunosorbent assay (ELISA) immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) serum. ELISA had minimum detection limit 0.06 µg/mL, reliable lower 0.09 quantification undiluted serum...
Mycoplasma pneumoniae is a significant cause of community-acquired pneumonia, which often empirically treated with macrolides or azalides such as erythromycin azithromycin. Recent studies have discovered the existence macrolide-resistant strains within population that been mapped to mutations domain V region 23S rRNA gene. Currently, identification these resistant relies on time-consuming and labor-intensive procedures restriction fragment length polymorphism, MIC studies, sequence analysis....
Abstract Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder causing memory loss, language problems and behavioural disturbances. AD associated with accumulation of fibrillar amyloid‐β (Aβ) formation neurofibrillary tau tangles. Fibrillar Aβ itself represents a danger‐associated molecular pattern, which recognized by specific microglial receptors. One key players NOD‐, LRR‐ pyrin domain‐containing 3 (NLRP3) inflammasome, whose activation has been demonstrated in patient...
Article26 November 2021Open Access Transparent process Microglial PD-1 stimulation by astrocytic PD-L1 suppresses neuroinflammation and Alzheimer's disease pathology Markus P Kummer Corresponding Author [email protected] orcid.org/0000-0002-0993-2918 Department of Neurodegenerative Diseases Geriatric Psychiatry, University Bonn Medical Faculty, Bonn, Germany These authors contributed equally to this work Search for more papers author Christina Ising orcid.org/0000-0002-7267-3488 German...
Abstract SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered novel modulatory function of SHP2. Targeting protein with allosteric inhibitors promoted anti-tumor immunity, including enhancing T cytotoxic immune-mediated regression. Knockout using CRISPR/Cas9 gene editing showed that targeting cancer cells contributes to response. Inhibition activity augmented intrinsic IFNγ signaling resulting enhanced...
Neuroinflammation is a common feature of many neurodegenerative diseases. It fosters dysfunctional neuron-microglia-astrocyte crosstalk that, in turn, maintains microglial cells perniciously reactive state that often enhances neuronal damage. The molecular components mediate this critical communication are not fully explored. Here, we show secreted frizzled-related protein 1 (SFRP1), multifunctional regulator cell-to-cell communication, part the cellular underlying neuroinflammation. In...
Sabatolimab is a humanized monoclonal antibody (hIgG4, S228P) directed against human T-cell immunoglobulin domain and mucin domain-3 (TIM-3). Herein, we describe the development characterization of sabatolimab.Sabatolimab was tested for binding to its target TIM-3 blocking properties. The functional effects sabatolimab were in killing myeloid cell cytokine assays. Antibody-mediated phagocytosis (ADCP) by also assessed.Sabatolimab shown (i) enhance inflammatory production dendritic cells...
The highest risk factor for the development of neurodegenerative diseases like tauopathies is aging. Many physiological decrements underlying aging are linked to cellular senescence. Senescent cells characterized by an irreversible growth arrest and formation a senescence-associated secretory phenotype (SASP), proinflammatory secretome that modifies microenvironment contributes tissue deterioration. Microglia, innate immune in brain, can enter senescent state during In addition, microglia...
To assess the consequences of locus ceruleus (LC) degeneration and subsequent noradrenaline (NA) deficiency in early Alzheimer's disease (AD), mice overexpressing mutant amyloid precursor protein presenilin-1 (APP/PS1) were crossed with Ear2(-/-) that have a severe loss LC neurons projecting to hippocampus neocortex. Testing spatial memory hippocampal long-term potentiation revealed an impairment APP/PS1 mice, whereas or showed only minor changes. These deficits associated distinct synaptic...
In 2015, Niger reported the largest epidemic of Neisseria meningitidis serogroup C (NmC) meningitis in sub-Saharan Africa. The NmC coincided with W (NmW) cases during season, resulting a total 9,367 meningococcal through June 2015. To clarify phylogenetic association, genetic evolution, and antibiotic determinants strains Niger, we sequenced genomes 102 isolates from this epidemic, comprising 81 21 NmW isolates. 82 were completed, all included analysis. All had sequence type 10217, which...
The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. network was established strengthen surveillance laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis.
Mycoplasma pneumoniae is an important etiologic agent of primary atypical pneumonia in children and adults. The diagnosis M. infection commonly confirmed through serologic testing. In this study, we used paired sera from 51 patients (all with positive complement fixation [CF] titers) to compare the results eight enzyme immunoassays (EIAs) available commercially United States. We compared two single-use EIAs six plate-type EIAs. Results acute-phase ranged only 7 (14%) by ImmunoWELL (GenBio)...
Alzheimer's disease (AD) is a neurodegenerative condition that leads to neuronal death and memory dysfunction. In the past, specific peroxisome proliferator-activated receptor (PPAR)γ-agonists, such as pioglitazone, have been tested with limited success improve AD pathology. Here, we investigated therapeutic efficacy of GFT1803, novel potent PPAR agonist activates all three isoforms (α/δ/γ) in APP/PS1 mouse model comparison selective PPARγ-agonist pioglitazone. Both compounds showed similar...
Abstract Increasing evidence suggests that both synaptic loss and neuroinflammation constitute early pathologic hallmarks of Alzheimer’s disease. A downstream event during inflammatory activation microglia astrocytes is the induction nitric oxide synthase type 2, resulting in an increased release post‐translational S‐nitrosylation protein cysteine residues. Both events, inflammation dysfunction, could be connected if this excess nitrosylation occurs on proteins. In long term, such changes...