- COVID-19 diagnosis using AI
- Radiomics and Machine Learning in Medical Imaging
- Long-Term Effects of COVID-19
- Neuroinflammation and Neurodegeneration Mechanisms
- COVID-19 Clinical Research Studies
- Multiple Sclerosis Research Studies
- Olfactory and Sensory Function Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Cell Image Analysis Techniques
- Systemic Lupus Erythematosus Research
- Immune responses and vaccinations
- Innovations in Medical Education
- Immune cells in cancer
- Advanced Fluorescence Microscopy Techniques
- Extracellular vesicles in disease
- Lung Cancer Diagnosis and Treatment
- Infectious Encephalopathies and Encephalitis
- Health and Medical Research Impacts
- Interprofessional Education and Collaboration
- Immunotherapy and Immune Responses
- Respiratory Support and Mechanisms
- RNA Interference and Gene Delivery
- Retinal and Optic Conditions
- Advanced Nanomaterials in Catalysis
Humboldt-Universität zu Berlin
2018-2025
Charité - Universitätsmedizin Berlin
2016-2025
Freie Universität Berlin
2019-2025
German Rheumatism Research Centre
2015-2025
Leibniz Association
2020-2025
Inserm
2019
Sorbonne Université
2019
German Centre for Cardiovascular Research
2019
Institute for Neurodegenerative Disorders
2019
The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic disease. Moreover, thromboembolic events throughout the body, including in CNS, have been described. Given neurological symptoms observed large majority of individuals with SARS-CoV-2 penetrance CNS is likely. By various means, we demonstrate presence RNA and protein anatomically distinct regions nasopharynx brain. Furthermore, describe morphological changes associated infection such...
The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into blood study dynamics adaptive response in patients requiring intensive care. Before seroconversion SARS-CoV-2 spike protein, peripheral display a type 1 interferon-induced gene expression signature; however, following seroconversion, lose this signature, express instead signatures induced by IL-21 and TGF-β, produce mostly IgG1 IgA1....
Abstract The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic disease presenting with fever, cough, and often pneumonia. Moreover, thromboembolic events throughout the body including central nervous system (CNS) have been described. Given first indication for viral RNA presence in brain cerebrospinal fluid light of neurological symptoms large majority COVID-19 patients, SARS-CoV-2-penetrance CNS is likely. By precisely investigating...
The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due the lack appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging detect NADPH oxidases (NOX enzymes) in vivo identify inflammatory monocytes, activated microglia, astrocytes expressing NOX1 as major nervous system mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function vivo,...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis still elusive.Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied infected human lung...
Abstract Prolonged lung pathology has been associated with COVID-19, yet the cellular and molecular mechanisms behind this chronic inflammatory disease are poorly understood. In study, we combine advanced imaging spatial transcriptomics to shed light on local immune response in severe COVID-19. We show that activated adventitial niches crucial microenvironments contributing orchestration of prolonged immunopathology. Up-regulation chemokines CCL21 CCL18 associates endothelial-to-mesenchymal...
Although oligoclonal bands in the cerebrospinal fluid have been a hallmark of multiple sclerosis diagnosis for over three decades, role antibody-secreting cells remains unclear. T and B are critical pathogenesis, but increasing evidence suggests that plasma also contribute, through secretion autoantibodies. Long-lived known to drive various chronic inflammatory conditions as e.g. systemic lupus erythematosus, however, what extent they present autoimmune central nervous system inflammation...
<h3>Objective</h3> To investigate the relevance of dysfunctional T cells in immune-mediated myopathies. We analyzed T-cell exhaustion and senescence, context programmed cell death protein 1 (PD1)-related immunity skeletal muscle biopsies from patients with necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), induced by immune checkpoint inhibitors (irMyositis). <h3>Methods</h3> Skeletal 12 IMNM, 7 sIBM, 8 irMyositis were immunostaining immunofluorescence as well quantitative...
Abstract Innate lymphoid cells (ILCs) emerge in the last few years as important regulators of immune responses and biological processes. Although ILCs are mainly known tissue-resident cells, their precise localization interactions with microenvironment still unclear. Here we combine a multiplexed immunofluorescence technique customized computational, open-source analysis pipeline to unambiguously identify CD127 + situ characterize these microenvironments. Moreover, reveal transcription...
Myasthenia gravis (MG) is an autoimmune disease most frequently caused by autoantibodies (auto-Abs) against the acetylcholine receptor (AChR) located at neuromuscular junction. Thymic follicular hyperplasia present in of patients with early-onset AChR-Ab+ MG (EOMG), but its cellular and molecular drivers development remain poorly understood. We constructed a single cell-based transcriptional profile lymphoid cell types thymi from 11 immunotherapy-naïve EOMG. Multiplex histology ELISA were...
Aim: Undergraduate medical education is currently in a fundamental transition towards competency-based programs around the globe. A major curriculum reform implies dual challenge: change of and delivering organization. Both are closely interwoven. In this article, we provide practical insights into our approach managing such large undergraduate program at Charité – Universitätsmedizin Berlin.Methods: Members project management team summarized key features process with reference to...
Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Methods: Blood samples were collected from 20 NMOSD and 17 MS, as well 15 Systemic Lupus Erythematosus (SLE) 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) density gradient separation stained the antibodies against CD14, CD15, CD16, CD45, analyzed by flow cytometry imaging...
The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: living organism. Only this way can biomedicine truly comprehend pathogenesis develop effective therapeutic strategies. Here we demonstrate discuss advantages pitfalls two strategies quantify FRET vivo—ratiometrically time-resolved by fluorescence lifetime imaging—and show their concrete application context neuroinflammation adult mice.
A hallmark of autoimmune retinal inflammation is the infiltration retina with cells innate and adaptive immune system, leading to detachment layers even complete loss photoreceptor layer. As only optical system in organism, eye enables non-invasive longitudinal imaging studies these local processes their effects on target tissue. Moreover, as a window central nervous (CNS), also reflects general neuroinflammatory taking place at various sites within CNS. Histological murine models, such...
Abstract In COVID-19 neurological alterations are noticed during the systemic viral infection. Various pathophysiological mechanisms on central nervous system (CNS) have been suggested in past two years, including neurotropism hypothesis. Nevertheless, complications can also occur independent of and at different stages disease may be persistent. Previous autopsy studies CNS from patients with severe show infiltration macrophages T lymphocytes, especially perivascular regions as well...
In aging individuals, both protective as well regulatory immune functions are declining, resulting in an increased susceptibility to infections autoimmunity. NADPH oxidase 2-deficiency cell subsets has been shown be associated with aging. Using intravital marker-free NAD(P)H fluorescence lifetime imaging, we have previously identified microglia/myeloid cells and astrocytes main cellular sources of oxidases (NOX) activity the CNS during neuroinflammation, due over-activation NOX). The...
Abstract Here we have analyzed the dynamics of adaptive immune response triggered by SARS-CoV-2 in severely affected COVID-19 patients, as reflected activated B cells egressing into blood, at single cell level. Early on, before seroconversion to spike protein, peripheral displayed a type 1 interferon-induced gene expression signature. After seroconversion, lost this signature, expressed IL-21- and TGF-β-induced signatures, mostly IgG1 IgA1. In sustained reaction until day 59, shifted IgA2,...
Abstract Post-acute lung sequelae of COVID-19 are challenging many survivors across the world, yet mechanisms behind poorly understood. Our results delineate an inflammatory cascade events occurring along disease progression within fibrovascular niches. It is initiated by endothelial dysfunction, followed heme scavenging CD163 + macrophages and production CCL18. This chemokine synergizes with local CCL21 upregulation to influence stromal composition favoring mesenchymal transition. The...
Fluorescence-lifetime imaging microscopy (FLIM) is a technique to generate images, in which the contrast obtained by excited-state lifetime of fluorescent molecules instead their intensity and emission spectrum. The ubiquitous coenzymes NADH NADPH, hereafter NAD(P)H, cells show short fluorescence ≈400 psec free-state longer when bound enzymes. NAD(P)H this state depends on binding-site specific enzyme. In case NADPH members oxidases family we measured 3650 as compared enzymes typically...
Abstract Objective To investigate whether low-density granulocytes (LDGs) are a immunophenotypic feature of patients with multiple sclerosis (MS) and/or neuromyelitis optica spectrum disorder (NMOSD). Methods Blood samples were collected from 26 NMOSD and 20 MS, as well 18 Systemic Lupus Erythematosus (SLE) 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) density gradient separation stained the antibodies against CD14, CD15, CD16, CD45, analysed by flow...
The multiple sclerosis therapeutic teriflunomide is known to block the de novo synthesis of pyrimidine in mitochondria by inhibiting enzyme dihydroorotate-dehydrogenase (DHODH). metabolic processes oxidative phosphorylation and glycolysis are further possible downstream targets. In healthy adult mice, high levels (DHODH) activity measured central nervous system (CNS), DHODH inhibition may cause indirect effects on reactive oxygen species production NADPH oxidase (NOX) mediated stress, be key...