A5052641517- Atherosclerosis and Cardiovascular Diseases
- IL-33, ST2, and ILC Pathways
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- RNA Research and Splicing
- Angiogenesis and VEGF in Cancer
- Cutaneous lymphoproliferative disorders research
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Enzyme Catalysis and Immobilization
- Monoclonal and Polyclonal Antibodies Research
- Cardiac, Anesthesia and Surgical Outcomes
- Cancer-related molecular mechanisms research
- Systemic Lupus Erythematosus Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- Genetics and Neurodevelopmental Disorders
- Biomedical and Engineering Education
- Gene Regulatory Network Analysis
- Nutrition and Health in Aging
- Frailty in Older Adults
CeMM Research Center for Molecular Medicine
2020-2025
Austrian Academy of Sciences
2020-2025
Babraham Institute
2017-2022
University of Cambridge
2017-2022
Dynamique du noyau
2017
Heinrich Heine University Düsseldorf
2015
Abstract Vascular smooth muscle cells (VSMCs) show pronounced heterogeneity across and within vascular beds, with direct implications for their function in injury response atherosclerosis. Here we combine single-cell transcriptomics lineage tracing to examine VSMC healthy mouse vessels. The transcriptional profiles of single VSMCs consistently reflect region-specific developmental history heterogeneous expression disease-associated genes involved inflammation, adhesion migration. We detect a...
Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on from patients with sarcoidosis bioinformatically reconstructed the underlying gene regulatory networks. We discovered an stimulatory environment repurposes transcriptional programs associated organ development. Granuloma formation...
Abstract Aims Traditional markers of cell senescence including p16, Lamin B1, and senescence-associated beta galactosidase (SAβG) suggest very high frequencies senescent cells in atherosclerosis, while their removal via ‘senolysis’ has been reported to reduce atherogenesis. However, selective killing a variety different types can exacerbate atherosclerosis. We therefore examined the specificity vascular smooth muscle (VSMCs) effects genetic or pharmacological senolysis Methods results...
Abstract Aims Quiescent, differentiated adult vascular smooth muscle cells (VSMCs) can be induced to proliferate and switch phenotype. Such plasticity underlies blood vessel homeostasis contributes disease development. Oligoclonal VSMC contribution is a hallmark of end-stage disease. Here, we aim understand cellular mechanisms underpinning generation this oligoclonality. Methods results We investigate the dynamics clone formation using confocal microscopy single-cell transcriptomics in...
Vascular inflammation underlies cardiovascular disease. smooth muscle cells (VSMCs) upregulate selective genes, including MMPs (matrix metalloproteinases) and proinflammatory cytokines upon local inflammation, which directly contribute to vascular disease adverse clinical outcome. Identification of factors controlling VSMC responses is therefore considerable therapeutic importance. Here, we determine the role Histone H3 lysine 9 di-methylation (H3K9me2), a repressive epigenetic mark that...
Abstract Ene reductases from the Old Yellow Enzyme family are versatile biocatalysts useful for synthesis of optically active compounds. One disadvantage when compared to competing catalysts in chemical syntheses is that often only one stereoisomer product available. Another drawback can be lack activity certain enzyme–substrate combinations. We were able approach both these challenges rationally case enzymatic methyl 3‐hydroxy‐2‐methylpropanoate (commonly denoted as Roche ester) and...
Rheumatoid arthritis (RA) is characterized by immune dysregulation, including alterations in peripheral blood mononuclear cell (PBMC) populations and aberrant cytokine signaling. Methotrexate (MTX) the preferred first-line treatment for RA, yet its precise mechanisms of action remain incompletely understood. This study employed a multi-omics strategy-combining single-cell RNA sequencing (scRNA-seq) immunophenotyping-to identify key effector cells their cellular responses RA patients over 12...
Abstract Lung pathogenic T helper type 2 (pTh2) cells are important in mediating allergic asthma, but fundamental questions remain regarding their heterogeneity and epigenetic regulation. Here we investigate immune regulation asthma by single-cell RNA sequencing mice challenged with house dust mite, the presence absence of histone deacetylase 1 (HDAC1) function. Our analyses indicate two distinct highly proinflammatory subsets lung pTh2 pinpoint thymic stromal lymphopoietin (TSLP) Tumour...
The exploitation of synthetic lethality by small-molecule targeting pathways that maintain genomic stability is an attractive chemotherapeutic approach. Ctf4/AND-1 protein hub, which links DNA replication, repair, and chromosome segregation, represents a novel target for the Herein, we report design, optimization, validation double-click stapled peptides encoding Ctf4-interacting peptide (CIP) replicative helicase subunit Sld5. By screening stapling positions in Sld5 CIP, identified...
Human brain organoids are powerful in vitro models for development and disease. However, their variability can complicate use biomedical research drug discovery. Both the specific protocol as well pluripotent starting cell line influence organoid result incomplete representation of types an experiment. Here, we systematically analyze cellular transcriptional landscape grown from multiple lines using four different protocols recapitulating dorsal ventral forebrain, midbrain, striatum. We...
ABSTRACT Rationale Vascular smooth muscle cell (VSMC) dysregulation is a hallmark of vascular disease, including atherosclerosis. In particular, the majority cells within atherosclerotic lesions are generated from pre-existing VSMCs and clonal nature has been documented for VSMC-derived in multiple disease models. However, mechanisms underlying generation oligoclonal phenotype proliferating unknown. Objective To understand cellular VSMC expansion disease. Methods Results Here we analyse...
Abstract The exploitation of synthetic lethality by small‐molecule targeting pathways that maintain genomic stability is an attractive chemotherapeutic approach. Ctf4/AND‐1 protein hub, which links DNA replication, repair, and chromosome segregation, represents a novel target for the Herein, we report design, optimization, validation double‐click stapled peptides encoding Ctf4‐interacting peptide (CIP) replicative helicase subunit Sld5. By screening stapling positions in Sld5 CIP, identified...
Abstract Lung pathogenic T helper type 2 (pTh2) cells are important drivers of allergic asthma, but fundamental questions remain regarding their regulation and heterogeneity. The differentiation effector functions immune tightly regulated by epigenetic processes. Histone deacetylase 1 (HDAC1) is an regulator cells, however, its role in pTh2 yet to be determined. Here we investigate asthma single-cell RNA sequencing (scRNA-seq) mice challenged with house dust mite, the presence absence HDAC1...
<h3>Introduction</h3> Vascular smooth muscle cells (VSMCs) show inherent plasticity, enabling their phenotypic switch into a synthetic state for vascular repair and remodelling. Under inflammatory conditions, this contributes to atherosclerotic plaque development, with VSMCs demonstrated produce multiple plaque-resident cell types. However, only small fraction of participate in disease associated proliferation<sup>1</sup> it is unclear if defined subset within the heterogeneous population....
Aim: Vascular smooth muscle cell (VSMC) accumulation is implicated in vascular disease development and VSMCs have been shown to produce 40-90% of atherosclerotic plaque-resident cells. However, mouse models atherosclerosis injury, VSMC arises from clonal expansion very few medial Here we profiled transcriptional heterogeneity single VSMCs, which may underlie this selective response. Methods: We isolated aortic healthy mice HFD-induced plaques using VSMC-specific Myh11-CreERt2/Rosa26-Confetti...