A5042109083- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Systemic Sclerosis and Related Diseases
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- Medical Imaging and Pathology Studies
- Neonatal Respiratory Health Research
- Advanced X-ray and CT Imaging
- Extracellular vesicles in disease
- MRI in cancer diagnosis
- Cancer Cells and Metastasis
- Advanced Proteomics Techniques and Applications
- Cancer Diagnosis and Treatment
- Lung Cancer Diagnosis and Treatment
- Dermatologic Treatments and Research
- Molecular Biology Techniques and Applications
- Cell Image Analysis Techniques
- Inhalation and Respiratory Drug Delivery
- Tracheal and airway disorders
- Water-Energy-Food Nexus Studies
- Inflammatory Myopathies and Dermatomyositis
- Water resources management and optimization
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Mast cells and histamine
- Wound Healing and Treatments
- Gut microbiota and health
University Hospital of Bern
2022-2025
University of Bern
2022-2025
German Center for Lung Research
2020-2024
University Hospital of Zurich
2016-2024
Helmholtz Zentrum München
2020-2024
University of Zurich
2020-2024
Dermatology Research Center
2023-2024
Ludwig-Maximilians-Universität München
2022-2023
University Medical Center Groningen
2023
Abstract Computational trajectory inference enables the reconstruction of cell state dynamics from single-cell RNA sequencing experiments. However, requires that direction a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank ( https://cellrank.org ) for fate mapping diverse scenarios, including regeneration, reprogramming and disease, which unknown. Our approach combines robustness with directional...
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations individual the variability present in population. Here we integrated Human Lung Cell Atlas (HLCA), combining 49 respiratory system into single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents consensus re-annotation with...
Single-cell proteomics by mass spectrometry is emerging as a powerful and unbiased method for the characterization of biological heterogeneity. So far, it has been limited to cultured cells, whereas an expansion complex tissues would greatly enhance insights. Here we describe single-cell Deep Visual Proteomics (scDVP), technology that integrates high-content imaging, laser microdissection multiplexed spectrometry. scDVP resolves context-dependent, spatial proteome murine hepatocytes at...
ABSTRACT Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture variability present in population, these must include diverse demographics such as age ethnicity from both healthy diseased individuals. The growth size number single-cell datasets, combined with recent advances computational techniques, for first time makes it possible generate comprehensive large-scale through integration multiple datasets. Here, we integrated Human...
The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single-cell transcriptomic proteomic data from multiple large pulmonary fibrosis patient cohorts. Integration 233,638 transcriptomes (n = 61) across three independent cohorts enabled us derive shifts type proportions a robust core set genes altered lung for 45 types. Mass spectrometry analysis lavage fluid 124) plasma 141) proteomes identified...
Background Radiomic features calculated from routine medical images show great potential for personalised medicine in cancer. Patients with systemic sclerosis (SSc), a rare, multiorgan autoimmune disorder, have similarly poor prognosis due to interstitial lung disease (ILD). Here, our objectives were explore computed tomography (CT)-based high-dimensional image analysis (“radiomics”) characterisation, risk stratification and relaying information on pathophysiology SSc-ILD. Methods We...
Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms and fibrogenesis directly in human tissue has been hampered by the lack organotypic models analytical techniques. In this work, we coupled ex vivo cytokine drug perturbations precision-cut lung slices (hPCLS) with single-cell RNA sequencing induced multilineage circuit fibrogenic cell states hPCLS. We showed that these were highly similar to multicohort atlas from patients pulmonary...
TGF-β is a master regulator of fibrosis, driving the differentiation fibroblasts into apoptosis-resistant myofibroblasts and sustaining production extracellular matrix (ECM) components. Here, we identified nuclear long noncoding RNA (lncRNA) H19X as TGF-β-driven tissue fibrosis. was consistently upregulated in wide variety human fibrotic tissues diseases strongly induced by TGF-β, particularly fibroblast-related cells. Functional experiments following silencing revealed that an obligatory...
Background Systemic sclerosis (SSc) is an autoimmune disease characterized by overproduction of extracellular matrix (ECM) and multiorgan fibrosis. Animal studies pointed to bone marrow-derived cells as a potential source pathological ECM-producing in immunofibrotic disorders. So far, involvement monocytes macrophages the fibrogenesis SSc remains poorly understood. Methods Results Immunohistochemistry analysis showed accumulation CD14 + collagen-rich areas, well increased amount alpha smooth...
Abstract Computational trajectory inference enables the reconstruction of cell-state dynamics from single-cell RNA sequencing experiments. However, requires that direction a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank ( https://cellrank.org ) for mapping fate single cells diverse scenarios, including perturbations such as regeneration or disease, which unknown. Our approach combines robustness with...
Abstract Objective To retrospectively evaluate if texture-based radiomics features are able to detect interstitial lung disease (ILD) and distinguish between the different stages in patients with systemic sclerosis (SSc) comparison mere visual analysis of high-resolution computed tomography (HRCT). Methods Sixty (46 females, median age 56 years) SSc who underwent HRCT thorax were analyzed. Visual was performed by two radiologists for presence ILD features. Gender, age, pulmonary function...
Antifibrotic therapy with nintedanib is the clinical mainstay in treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital fingerprints. Here, we performed an integrative analysis radiomic and proteomic profiles (radioproteomics) to assess whether changes signatures can stratify degree antifibrotic response (experimental) ILD. Unsupervised...
Background: Interstitial lung disease (ILD) is a common and severe complication in rheumatic diseases. Folate receptor-β expressed on activated, but not resting macrophages which play key role dysregulated tissue repair including ILD. We therefore aimed to pre-clinically evaluate the potential of 18F-AzaFol-based PET/CT (positron emission computed tomography/computed tomography) for specific detection macrophage-driven pathophysiologic processes experimental Methods: The pulmonary expression...
In this study, we aimed to assess the impact of different CT reconstruction kernels on stability radiomic features and transferability between diseases tissue types. Three lung were evaluated, i.e. non-small cell cancer (NSCLC), malignant pleural mesothelioma (MPM) interstitial disease related systemic sclerosis (SSc-ILD) as well four types, primary tumor, largest involved lymph node ipsilateral contralateral lung.Pre-treatment non-contrast enhanced scans from 23 NSCLC, 10 MPM 12 SSc-ILD...
Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapidly evolving interstitial lung (ILD), driving its mortality. Specific imaging-based biomarkers the evolution of are needed to help predict and quantify ILD. We evaluated potential an automated ILD quantification system (icolung®) from chest CT scans, in prediction progression SSc-ILD. used retrospective cohort 75 SSc-ILD patients evaluate AI-based tool correlate image-based pulmonary function tests their over...
The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. expression membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by endothelial growth factor (VEGF), hypoxia, inflammation, acts as an antagonist. signalling also attenuated soluble (sTie2), the extracellular domain receptor, which shed upon stimulation with VEGF. Herein, we investigate role Ang/Tie2 in peripheral vasculopathy systemic sclerosis (SSc) including animal models. Ang-1/-2...
Abstract Computational trajectory inference enables the reconstruction of cell-state dynamics from single-cell RNA sequencing experiments. However, requires that direction a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank (https://cellrank.org) for mapping fate single cells diverse scenarios, including perturbations such as regeneration or disease, which unknown. Our approach combines robustness with...
Abstract Single-cell proteomics by mass spectrometry (MS) is emerging as a powerful and unbiased method for the characterization of biological heterogeneity. So far, it has been limited to cultured cells, whereas an expansion complex tissues would greatly enhance insights. Here we describe single-cell Deep Visual Proteomics (scDVP), technology that integrates high-content imaging, laser microdissection multiplexed MS. scDVP resolves context-dependent, spatial proteome murine hepatocytes at...