A5102839095- Cancer-related molecular mechanisms research
- Psoriasis: Treatment and Pathogenesis
- Circular RNAs in diseases
- Asthma and respiratory diseases
- MicroRNA in disease regulation
- Dermatology and Skin Diseases
- Autoimmune Bullous Skin Diseases
- RNA Research and Splicing
- RNA modifications and cancer
- RNA regulation and disease
- Pharmaceutical studies and practices
- Lipid metabolism and disorders
- Epigenetics and DNA Methylation
- Telomeres, Telomerase, and Senescence
- Immune cells in cancer
- Electron Spin Resonance Studies
- Redox biology and oxidative stress
- Cellular Mechanics and Interactions
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Urticaria and Related Conditions
- CRISPR and Genetic Engineering
- Various Chemistry Research Topics
- Health Systems, Economic Evaluations, Quality of Life
- Aortic aneurysm repair treatments
Boehringer Ingelheim (Germany)
2023-2025
Boehringer Ingelheim (China)
2024-2025
Boehringer Ingelheim (India)
2024
Goethe University Frankfurt
2014-2022
German Centre for Cardiovascular Research
2017-2020
Amsterdam University Medical Centers
2020
Amsterdam UMC Location Vrije Universiteit Amsterdam
2018-2020
University Hospital Leipzig
2020
University Hospital Frankfurt
2018
Technical University of Darmstadt
2013
The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important lncRNAs.Epigenetically controlled lncRNAs in human umbilical vein were searched exon-array analysis after knockdown histone demethylase JARID1B. Molecular mechanisms investigated RNA pulldown immunoprecipitation, mass spectrometry, microarray, several approaches, CRISPR-Cas9, assay for...
Background: Long noncoding RNAs have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify functionally characterize long potential mediators abdominal aortic aneurysm development. Methods: We profiled RNA transcript expression 2 murine models, Angiotensin II (ANGII) infusion apolipoprotein E–deficient ( ApoE −/− ) mice (n=8) porcine pancreatic elastase instillation C57BL/6 wild-type (n=12). The H19 was identified 1 of the most...
Abstract Aims Long non-coding RNAs (lncRNAs) have been shown to regulate numerous processes in the human genome, but function of these transcripts vascular aging is largely unknown. We aim characterize expression lncRNAs endothelial and analyse highly conserved lncRNA H19. Methods results H19 was downregulated endothelium aged mice. In human, atherosclerotic plaques mainly expressed by cells significantly reduced comparison healthy carotid artery biopsies. Loss led an upregulation p16 p21,...
Abstract Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report identification of aging-regulated lncRNA Sarrah (ENSMUST00000140003) that anti-apoptotic in cardiomyocytes. Importantly, loss SARRAH ( OXCT1-AS1 ) human engineered heart tissue results impaired contractile force development. directly binds promoters genes downregulated after silencing...
Endothelial cells play an important role in maintenance of the vascular system and repair after injury. Under proinflammatory conditions, endothelial can acquire a mesenchymal phenotype by process named endothelial-to-mesenchymal transition (EndMT), which affects functional properties cells. Here, we investigated epigenetic control EndMT. We show that histone demethylase JMJD2B is induced EndMT-promoting, proinflammatory, hypoxic conditions. Silencing reduced TGF-β2-induced expression genes,...
Abstract Blood vessels are constantly exposed to shear stress, a biomechanical force generated by blood flow. Normal stress sensing and barrier function crucial for vascular homeostasis controlled adherens junctions (AJs). Here we show that AJs stabilized the stress-induced long non-coding RNA LASSIE (linc00520). Silencing of in endothelial cells impairs cell survival, cell-cell contacts alignment direction associates with junction proteins (e.g. PECAM-1) intermediate filament protein...
Generalized pustular psoriasis (GPP) is a chronic inflammatory disease with an unpredictable course. Long-term treatment goals include sustained resolution of skin symptoms, prevention new flares, and improvement in quality life (QoL). To compare the effect interleukin-36 receptor monoclonal antibody spesolimab 600 mg subcutaneous (SC) loading dose (LD) followed by 300 SC every 4 weeks (q4w) versus placebo on symptoms QoL burden patients GPP. A post hoc analysis EFFISAYIL 2 trial...
Generalized pustular psoriasis (GPP) is a rare, chronic, systemic inflammatory disease with heterogeneous clinical course. GPP imposes substantial emotional burden on patients, including feelings of fear and anxiety.1 A post hoc analysis cross-sectional study was conducted via web-based survey qualitative telephone interviews adults from China, Japan, the UK USA. Those who completed could choose to participate in interview. Twenty-one participants (mean age: 41 years; female: 57.1%) survey;...
Leukocytes follow the well-defined steps of rolling, spreading, and crawling prior to diapedesis through endothelial cells (ECs). We found increased expression DLC-1 in stiffness-associated diseases like atherosclerosis pulmonary arterial hypertension. Depletion ECs cultured on stiff substrates drastically reduced cell stiffness mimicked leukocyte transmigration kinetics observed for soft substrates. Mechanistic studies revealed that DLC-1-depleted or failed recruit actin-adaptor proteins...
Introduction: Generalized pustular psoriasis (GPP) is a chronic, rare disease characterized by flares of widespread skin pustulation. Intravenous (IV) spesolimab, an anti-interleukin-36 receptor monoclonal antibody, approved for GPP flare treatment; however, the optimal dosing and long-term efficacy subcutaneous (SC) spesolimab treatment in patients with has not yet been reported. We report effect SC on achieving sustained remission Effisayil 2 (NCT04399837), 48-week trial that evaluated...
Introduction: Generalized pustular psoriasis (GPP) is characterized by flares of widespread pustulation and erythema that may be fatal. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, approved to treat GPP flares. Effisayil 2 trial (NCT04399837) assessed efficacy safety spesolimab for prevention over 48 weeks. Here we show the high-dose subcutaneous (SC) flare in prespecified subgroups 2.
 Methods: Eligible patients were randomized 1:1:1:1 receive placebo, or low- (300...
Introduction & Objectives: Generalized pustular psoriasis (GPP) is a chronic, rare and potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, effective approved treatment for GPP in adults. Effisayil 2 (NCT04399837) was pivotal, randomized controlled trial that evaluated the efficacy safety subcutaneous spesolimab preventing flares. Here, we report effect high-dose versus placebo on...
Introduction Generalized pustular psoriasis (GPP) is a chronic and potentially life-threatening disease characterized by flares of widespread skin pustulation. In Effisayil 2 (NCT04399837), high‑dose spesolimab was superior to placebo in GPP flare prevention numerically reduced the risk Dermatology Life Quality Index (DLQI) worsening (≥4-point increase total score from baseline; secondary endpoint), up Week 48. Methods Here, we further analyze effect high-dose versus on DLQI 2. Results...
Generalized pustular psoriasis (GPP) is a rare chronic skin disease characterized by recurrent, acute, and often life-threatening flares of widespread neutrophilic sterile pustules systemic inflammation. Spesolimab, an anti-interleukin-36 receptor antibody, approved in adults pediatric patients 12 years age older weighing at least 40 kg, as subcutaneous dosage for treatment GPP when not experiencing flare, intravenous flare treatment. In Effisayil 2, randomized, placebo-controlled trial...
Introduction: Generalized pustular psoriasis (GPP) is a chronic, rare and potentially life-threatening disease characterized by flares of widespread skin pustulation. Sustained clearance key treatment objective. Intravenous (IV) spesolimab, an anti-interleukin-36 receptor monoclonal antibody, approved for GPP flare treatment; however, the optimal dosing long-term efficacy subcutaneous (SC) spesolimab in patients with has not yet been reported. We report effect SC on achieving sustained...