A5032047330- Neonatal Respiratory Health Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Medical Imaging and Pathology Studies
- Congenital Diaphragmatic Hernia Studies
- Pulmonary Hypertension Research and Treatments
- Tissue Engineering and Regenerative Medicine
- Extracellular vesicles in disease
- Respiratory Support and Mechanisms
- Inhalation and Respiratory Drug Delivery
- Occupational and environmental lung diseases
- Wnt/β-catenin signaling in development and cancer
- IL-33, ST2, and ILC Pathways
- Pediatric health and respiratory diseases
- Mesenchymal stem cell research
- Respiratory viral infections research
- Antibiotic Resistance in Bacteria
- Occupational exposure and asthma
- Epigenetics and DNA Methylation
- Telomeres, Telomerase, and Senescence
- Hippo pathway signaling and YAP/TAZ
- Immune Cell Function and Interaction
- Inflammasome and immune disorders
- Bacterial Infections and Vaccines
- Bariatric Surgery and Outcomes
German Center for Lung Research
2016-2025
Helmholtz Zentrum München
2016-2025
Institut für Lungenforschung
2025
Philipps University of Marburg
2023-2025
Universities of Giessen and Marburg Lung Center
2023-2025
Dermatology Research Center
2024
Kyoto University
2023
Ludwig-Maximilians-Universität München
2016-2023
Comprehensive Urology
2020-2021
Ruhr University Bochum
2020
Abstract The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single RNA-seq the bleomycin injury model, we resolved dynamics for 28 types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional state regeneration. These squamous morphology, feature p53 NFkB activation display features cellular senescence. Krt8+ appears in several...
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases age, ageing-related mechanisms such as cellular senescence have been proposed pathogenic drivers. alveolar epithelium represents major site tissue injury in this cell population probably detrimental to repair. However, the potential pathomechanisms epithelial impact senolytic drugs on senescent cells remain unknown. Here we demonstrate that...
Idiopathic pulmonary fibrosis (IPF) is a devastating chronic interstitial lung disease (ILD) characterized by tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, deranged repair are believed to be key processes involved in onset progression, but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown slow treatments that halt or reverse progression not identified. Ex vivo models of human proposed for drug discovery, one which...
Rationale: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterized by epithelial cell injury, increased (myo)fibroblast activation, and extracellular matrix deposition. Extracellular vesicles (EVs) regulate intercellular communication carrying variety of signaling mediators, including WNT (wingless/integrated) proteins. The relevance EVs in their potential contribution to pathogenesis, however, remain unexplored.Objectives: To characterize study the role EV-bound...
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Repetitive injury and reprogramming of the epithelium are thought to be critical drivers disease progression, contributing fibroblast activation, extracellular matrix remodeling, subsequently loss architecture function. To date, Pirfenidone Nintedanib only approved drugs known decelerate however, if how these affect epithelial cell function, remains largely unexplored.We treated murine human 3D ex vivo tissue cultures...
Chronic obstructive pulmonary disease (COPD), in particular emphysema, is characterized by loss of parenchymal alveolar tissue and impaired repair. Wingless INT-1 (WNT)/β-catenin signaling reduced COPD; however, the mechanisms thereof, specifically role frizzled (FZD) family WNT receptors, remain unexplored.To identify functionally characterize specific FZD receptors that control downstream lung repair COPD.FZD expression was analyzed homogenates epithelial type II (ATII) cells...
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...
Abstract The immunoproteasome is a specialized type of proteasome involved in MHC class I antigen presentation, antiviral adaptive immunity, autoimmunity, and also part broader response to stress. Whether the regulated by DNA stress, however, not known. We here demonstrate that mitochondrial stress upregulates presentation pathway via cGAS/STING/type interferon signaling resulting cell autonomous activation CD8 + T cells. cGAS/STING‐induced immune observed genomic conserved epithelial...
Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease, characterized by damage of epithelial cells, excessive deposition extracellular matrix in the interstitium and enhanced activation proliferation fibroblasts. S100a4, also termed FSP-1 (fibroblast-specific protein-1), was previously considered as marker fibroblasts but recent findings renal liver indicated that M2 macrophages are an important cellular source S100a4. Thus, we hypothesized fibrosis, produce secrete...
Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. IPF characterized by epithelial cell injury reprogramming, increases in (myo)fibroblasts altered deposition of extracellular matrix. The Wnt1-inducible signaling protein 1 (WISP1) involved impaired epithelial-mesenchymal crosstalk fibrosis. Here, we aimed to further investigate WISP1 regulation function primary human fibroblasts (phLFs). We demonstrate that directly upregulated Transforming...
The acquisition of mesenchymal traits is considered a hallmark breast cancer progression. However, the functional relevance epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial populations from human metastatic biopsies assess their potential in vivo. Strikingly, progressively decreasing cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, find that persistent EPCAM expression marks...
Interstitial lung disease (ILD) is a heterogenous group of disorders where destruction and incomplete regeneration the parenchyma often results in persistent architectural distortion pulmonary scaffold. Continuous mesenchyme-centered, disease-relevant signaling likely initiates perpetuates fibrotic remodeling process, specifically targeting epithelial cell compartment, thereby destroying gas exchange area.
PPARγ-dependent gene expression during adipogenesis is facilitated by ADP-ribosyltransferase D-type 1 (ARTD1; PARP1)-catalyzed poly-ADP-ribose (PAR) formation. Adipogenesis accompanied a dynamic modulation of the chromatin landscape at PPARγ target genes ligand-dependent co-factor exchange. However, how endogenous ligands, which have low affinity for receptor and are present levels in cell, can induce sufficient exchange unknown. Moreover, significance PAR formation PPARγ-regulated adipose...
Abstract Mechanisms of injury and repair in alveolar epithelial cells (AECs) are critically involved the progression various lung diseases including idiopathic pulmonary fibrosis (IPF). Homeobox only protein x (HOPX) contributes to formation distal during development. In adult lung, type (AT) I express HOPX lineage-labeled Hopx + give rise both ATI ATII after pneumonectomy. However, cell function HOPX-expressing fibrotic has not been investigated. this study, we have established a flow...
Abstract We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern lung function decline consistent hypothesis anti-aging effects metformin. Patients GOLD grades 1–4 COSYCONET cohort follow-up data up 4.5 y were included. The annual (FEV 1 , FVC) and CO diffusing capacity (KCO, TLCO) %predicted at baseline evaluated associations age, sex, BMI, pack-years, smoking status, function, exacerbation risk, respiratory symptoms, cardiac disease, as...
The continuous emergence of multidrug-resistant bacterial pathogens poses a major global healthcare challenge, with Klebsiella pneumoniae being prominent threat. We conducted comprehensive study on K. pneumoniae's antibiotic resistance mechanisms, focusing outer membrane vesicles (OMVs) and polymyxin, last-resort antibiotic. Our research demonstrates that OMVs protect bacteria from polymyxins. derived Polymyxin B (PB)-stressed exhibited heightened protective efficacy due to increased...
Idiopathic pulmonary fibrosis (IPF) is a lethal chronic lung disease characterized by aberrant intercellular communication, extracellular matrix deposition, and destruction of functional tissue. While vesicles (EVs) accumulate in the IPF lung, their cargo biological effects remain unclear. We interrogated proteome EV non-EV fractions during contribution to fibrosis. EVs accumulated 14 days after bleomycin challenge, correlating with decreased function initiated fibrogenesis healthy...
The urgent need for effective treatments acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. 2023 ATS Workshop on Precision Cut Lung Slices (PCLS) brought together 35 experts to discuss address role tissue-derived PCLS as a unique tool target drug discovery validation in pulmonary medicine. With increasing interest usage, along with advancements methods technology, there is growing consensus methodology readouts. current...
Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade CCL2 failed improve clinical course patients with lung fibrosis. However, as levels CCR2+CD4+ T cells in paediatric fibrosis had previously been found be increased, correlating symptoms, we hypothesised distinct CCR2+ cell populations might either increase or decrease disease depending on their subtype.To investigate role experimental and idiopathic other...
Lung injury activates quiescent stem and progenitor cells to regenerate alveolar structures. The sequence coordination of transcriptional programs during this process has largely remained elusive. Using single cell RNA-seq, we first generated a whole-organ bird’s-eye view on cellular dynamics cell-cell communication networks mouse lung regeneration from ∼30,000 at six timepoints. We discovered an injury-specific state characterized by Krt8 in flat epithelial covering surfaces. number these...