A5062438964- Neonatal Respiratory Health Research
- Birth, Development, and Health
- Congenital Diaphragmatic Hernia Studies
- Respiratory Support and Mechanisms
- Pulmonary Hypertension Research and Treatments
- Asthma and respiratory diseases
- Adipose Tissue and Metabolism
- Cystic Fibrosis Research Advances
- Pregnancy and preeclampsia studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Kruppel-like factors research
- Adipokines, Inflammation, and Metabolic Diseases
- Regulation of Appetite and Obesity
- Tracheal and airway disorders
- Gestational Diabetes Research and Management
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- SARS-CoV-2 and COVID-19 Research
- Fatty Acid Research and Health
- Neuroscience of respiration and sleep
- Infant Nutrition and Health
- Immunotherapy and Immune Responses
- Allergic Rhinitis and Sensitization
- Growth Hormone and Insulin-like Growth Factors
- Connective tissue disorders research
- FOXO transcription factor regulation
University Hospital Cologne
2015-2025
University of Cologne
2016-2025
German Center for Lung Research
2019-2025
Universities of Giessen and Marburg Lung Center
2020-2025
Cardio-Pulmonary Institute
2022-2025
Justus-Liebig-Universität Gießen
2006-2025
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2021-2025
Klinik und Poliklinik für Kinder- und Jugendmedizin
2015-2024
Centrum für Integrierte Onkologie
2024
Institute of Experimental Endocrinology of the Slovak Academy of Sciences
2023
Prematurely born infants who require oxygen therapy often develop bronchopulmonary dysplasia (BPD), a debilitating disorder characterized by pronounced alveolar hypoplasia. Hyperoxic injury is believed to disrupt critical signaling pathways that direct lung development, causing BPD. We investigated the effects of normobaric hyperoxia on transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) in neonatal C57BL/6J mice exposed 21% or 85% O 2 between postnatal days P1 P28....
Rationale Premature infants exposed to oxygen are at risk for bronchopulmonary dysplasia (BPD), which is characterised by lung growth arrest. Inflammation important, but the mechanisms remain elusive. Here, we investigated inflammatory pathways and therapeutic targets in severe clinical experimental BPD. Methods results First, transcriptomic analysis with silico cellular deconvolution identified a lung-intrinsic M1-like-driven cytokine pattern newborn mice after hyperoxia. These findings...
Rationale In adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic phenotypes. It is unclear whether such classification achievable in children. Objectives To define T2-high easily accessible biomarkers compare resulting phenotypes across all ages. Methods the multicentre clinical All Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited followed for years (1 year adults). Extensive characterisation...
Abstract Although transforming growth factor‐beta (TGF‐β) signaling negatively regulates branching morphogenesis in early lung development, few studies to date have addressed the role of this family factors during late development. We describe here that expression, tissue localization, and activity components TGF‐β machinery are dynamically regulated development mouse human. Pronounced changes expression localization receptors Acvrl1, Tgfbr1, Tgfbr2, Tgfbr3, endoglin, intracellular...
Hypothalamic inflammation has been demonstrated to be an important mechanism in the pathogenesis of obesity-induced type 2 diabetes mellitus. Feeding pregnant and lactating rodents a diet rich saturated fatty acids consistently shown predispose offspring for development obesity impaired glucose metabolism. However, hypothalamic not addressed as potential underlying mechanism. In this study, virgin female C57BL/6 mice received high-fat feeding starting at conception until weaning postnatal d...
Abstract Preterm infants with oxygen supplementation are at high risk for bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease. Inflammation macrophage activation is central to the pathogenesis of BPD. CXCL10, chemotactic and pro-inflammatory chemokine, elevated in lungs evolving BPD hyperoxia-based mice. Here, we tested if CXCL10 deficiency preserves growth after hyperoxia by preventing activation. To this end, exposed Cxcl10 knockout ( −/− ) wild-type mice an experimental...
We determined in patients with pulmonary arterial (PA) hypertension (PAH) whether addition to increased production of elastase by PA smooth muscle cells previously reported, elastic fibers are susceptible degradation because their abnormal assembly.Fibrillin-1 and elastin the major components fibers, fibrillin-1 binds bone morphogenetic proteins (BMPs) large latent complex transforming growth factor-β1 (TGFβ1). Thus, we considered BMPs like TGFβ1 contribute fiber assembly this process is...
Exercise during pregnancy has beneficial effects on maternal and offspring’s health in humans mice. The underlying mechanisms remain unclear. This comparative study aimed to determine the long-term of an exercise program metabolism, weight gain, body composition changes hormones [insulin, leptin, brain-derived neurotrophic factor (BDNF)]. Pregnant women ( n =34) mouse dams =44) were subjected compared with matched controls (period I). Follow-up offspring was performed over 6 months humans,...
Abstract Maternal obesity determines and metabolic diseases in the offspring. The white adipose tissue (WAT) orchestrates pathways, its dysfunction contributes to disorders a sex-dependent manner. Here, we tested if sex differences influence molecular mechanisms of programming WAT offspring obese dams. To this end, maternal was induced with high-fat diet (HFD) were studied at an early phase [postnatal day 21 (P21)], late (P70) finally P120. In found sex-independent increase dams using...
Obesity is a pre-disposing condition for chronic obstructive pulmonary disease, asthma, and arterial hypertension. Accumulating evidence suggests that metabolic influences during development can determine lung diseases (CLD). We demonstrate maternal obesity causes early disorder in the offspring. Here, interleukin-6 induced bronchial microvascular smooth muscle cell (SMC) hyperproliferation increased airway vascular resistance. The key anti-proliferative transcription factor FoxO1 was...
Background Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about contribution B-cells this chronic inflammatory disease. In study we various B-cell populations specific clinical features Methods All Age Asthma Cohort (ALLIANCE), a subgroup 154 adult patients and 28 healthy controls were included for characterisation by flow cytometry. Questionnaires, lung function...
Rationale: The strongest genetic risk factor for childhood-onset asthma, the 17q21 locus, is associated with increased viral susceptibility and disease-promoting processes.Objectives: To identify biological targets underlying escalated clinical phenotype mediated by locus.Methods: Genome-wide transcriptome analysis of nasal brush samples from 261 children (78 healthy, 79 wheezing at preschool age, 104 asthmatic) within ALLIANCE (All-Age-Asthma) cohort, a median age 10.0 (range, 1.0–20.0)...
The right ventricle (RV) is at risk in patients with complex congenital heart disease involving right-sided obstructive lesions. We have shown that capillary rarefaction occurs early the pressure-loaded RV. Here we test hypothesis microRNA (miR)-34a, which induced RV hypertrophy and failure (RVF), blocks hypoxia-inducible factor-1α-vascular endothelial growth factor (VEGF) axis, leading to attenuated angiogenic response increased susceptibility failure.
Abstract Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation early-onset dysregulates pulmonary adipocytokine/insulin signaling, resulting in programming of asthma-like disease adult mice. Offspring with pHA showed at day 21 (P21): (1) obesity, greater...
Abstract The novel coronavirus pandemic, first reported in December 2019, was caused by the severe acute respiratory syndrome 2 (SARS-CoV-2). SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells, which can elicit distress (ARDS) characterized rapid onset widespread inflammation, so-called cytokine storm. In viral infections, monocytes are recruited into lung subsequently differentiate dendritic cells (DCs). DCs critical players development...
Despite improved neonatal intensive care, the risk of premature-born infants developing bronchopulmonary dysplasia (BPD) and encephalopathy prematurity (EoP) remains high. With hyperoxia being a major underlying factor, both preterm-birth-related complications are suggested to be closely interrelated. However, experimental models lacking for assessment potentially close interplay between organs. To establish model, suitable affected organs, Wistar rats were exposed 80% oxygen from postnatal...