A5045810254- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Cardiovascular Function and Risk Factors
- MicroRNA in disease regulation
- Cardiac electrophysiology and arrhythmias
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Molecular Biology Techniques and Applications
- Cardiovascular Effects of Exercise
- Circular RNAs in diseases
- Advanced biosensing and bioanalysis techniques
- Viral Infections and Immunology Research
- Cardiac Valve Diseases and Treatments
- Mitochondrial Function and Pathology
- Cancer-related gene regulation
- Zebrafish Biomedical Research Applications
- Histone Deacetylase Inhibitors Research
- Neuroblastoma Research and Treatments
- Cardiac Structural Anomalies and Repair
- Genetics and Neurodevelopmental Disorders
- Heart Failure Treatment and Management
- BRCA gene mutations in cancer
- Cardiac Fibrosis and Remodeling
Heidelberg University
2013-2023
German Centre for Cardiovascular Research
2013-2022
University Hospital Heidelberg
2012-2021
Siemens Healthcare (Germany)
2017
DKFZ-ZMBH Alliance
2017
German Cancer Research Center
2017
Epigenomics (Germany)
2017
Siemens (Austria)
2017
Statistics Austria
2017
Medical University of Vienna
2017
Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution all clinically relevant disease DCM phenotypes in larger cohorts. We utilized next-generation sequencing overcome these and screened a large cohort. In this multi-centre, multi-national study, we enrolled 639 patients with sporadic or familial DCM. To samples, applied standardized protocol for ultra-high coverage 84 genes, leading 99.1%...
Abstract Background Alzheimer disease (AD) is the most common form of dementia but identification reliable, early and non-invasive biomarkers remains a major challenge. We present novel miRNA-based signature for detecting AD from blood samples. Results apply next-generation sequencing to miRNAs samples 48 patients 22 unaffected controls, yielding total 140 unique mature with significantly changed expression levels. Of these, 82 have higher 58 lower abundance in patient selected panel 12 an...
Research Article22 January 2013Open Access Alterations in cardiac DNA methylation human dilated cardiomyopathy Jan Haas Department of Internal Medicine III, University Heidelberg, Germany Search for more papers by this author Karen S. Frese Yoon Jung Park Division Epigenomics and Cancer Risk Factors, German Center (DKFZ), Nutritional Science Food Management, Ewha Womans University, Seoul, South Korea Andreas Keller Human Genetics, Saarland Britta Vogel Anders M. Lindroth Dieter Weichenhan...
In this study, we aimed to clinically and genetically characterize LVNC patients investigate the prevalence of variants in known novel disease genes.Left ventricular non-compaction cardiomyopathy (LVNC) is an increasingly recognized cause heart failure, arrhythmia, thromboembolism, sudden cardiac death. We sought here dissect its genetic causes, phenotypic presentation outcome.In our registry with follow-up median 61 months, analysed 95 (68 unrelated index 27 affected relatives; definite...
Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions novel biomarkers linked to myocardial dysfunction heart failure, we performed first multi-omics study in tissue blood of patients with dilated cardiomyopathy controls.Infinium human methylation 450 was used for high-density epigenome-wide mapping left-ventricular biopsies whole peripheral living probands. RNA...
Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts up to one-third all heart failure cases. Since extrinsic monogenic explain only a fraction cases, common genetic variants are suspected contribute pathogenesis DCM, its age onset, clinical progression. By large-scale case-control genome-wide association study we aimed here identify novel risk loci DCM.Applying three-staged design, analysed more than 4100 DCM cases 7600 controls. We identified...
AimsNon-ischaemic heart failure is one of the today's most prevalent cardiovascular disorders. Since modern pharmacotherapy has proved to be very effective in delaying disease progression and preventing death, imaging modalities molecular biomarkers play an important role early identification clinical management as well risk assessment patients. The present study evaluated for first time whole peripheral blood miRNAs novel biomarker candidates non-ischaemic with reduced ejection fraction (HF-REF).
MicroRNAs (miRNAs) measured from blood samples are promising minimally invasive biomarker candidates that have been extensively studied in several case-control studies. However, the influence of age and sex as confounding variables remains largely unknown.We systematically explored impact on miRNAs a cohort 109 physiologically unaffected individuals whose was characterized by microarray technology (stage 1). We also investigated an independent different institution consisting 58 having...
Despite modern pharmacotherapy and advanced implantable cardiac devices, overall prognosis quality of life HF patients remain poor. This is in part due to insufficient patient stratification lack individualized therapy planning, resulting less effective treatments a significant number non-responders.State-of-the-art clinical phenotyping was acquired, including magnetic resonance imaging (MRI) biomarker assessment. An individualized, multi-scale model heart function covering anatomy,...
A certain degree of bias in high-throughput molecular technologies including microarrays and next-generation sequencing (NGS) is known. To quantify the actual impact biomarker discovery platform on miRNA profiles, we first performed a meta-analysis: raw data 1 539 705 NGS blood-borne miRNomes were statistically evaluated, suggesting substantial influence technology profiles. We observed highly significant dependency nucleotide composition expression level. Higher was discovered for...
With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play pivotal role in HF, we sought here identify key metabolic changes ischemic- and non-ischemic HF by using multi-OMICS approach. Serum metabolites mRNAseq epigenetic DNA methylation profiles were analyzed from blood left ventricular biopsy specimens of the same individuals. In total collected serum n = 82 patients with Dilated Cardiomyopathy (DCM) 51 controls...
The survival rate among children with relapsed tumors remains poor, due to tumor heterogeneity, lack of directly actionable drivers and multidrug resistance. Novel personalized medicine approaches tailored each are urgently needed improve cancer treatment. Current pediatric precision oncology platforms, such as the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) study, reveal that molecular profiling tissue identifies targets associated clinical benefit a subgroup...
BACKGROUND Alterations in microRNA (miRNA) expression patterns whole blood may be useful biomarkers of diverse cardiovascular disorders. We previously reported that miRNAs are significantly dysregulated acute myocardial infarction (AMI) and applied machine-learning techniques to define miRNA subsets with high diagnostic power for AMI diagnosis. However, the kinetics time-dependent sensitivity these novel remained unknown. METHODS To characterize temporal changes expressed human (miRNome), we...
Within just a few years, the new methods for high-throughput next-generation sequencing have generated completely novel insights into heritability and pathophysiology of human disease. In this review, we wish to highlight benefits current state-of-the-art technologies genetic epigenetic research. We illustrate how these help constantly improve our understanding mechanisms in biological systems summarize progress made so far. This can be exemplified by case heritable heart muscle diseases,...
Research Article14 November 2017Open Access Source DataTransparent process Genomic structural variations lead to dysregulation of important coding and non-coding RNA species in dilated cardiomyopathy Jan Haas Department Internal Medicine III, University Heidelberg, Germany DZHK (German Centre for Cardiovascular Research), Search more papers by this author Stefan Mester Alan Lai Karen S Frese Farbod Sedaghat-Hamedani Elham Kayvanpour Tobias Rausch EMBL (European Molecular Biology Laboratory),...
The molecular mechanisms that guide heart valve formation are not well understood. However, elucidation of the genetic basis congenital disease is one prerequisites for development tissue-engineered valves.We isolated here a mutation in zebrafish, bungee (bng(jh177)), which selectively perturbs embryonic by abrogating endocardial Notch signaling cardiac cushions. We found positional cloning bng phenotype caused missense (Y849N) zebrafish protein kinase D2 (pkd2). impairs PKD2 activity and...
Integrin-linked kinase (ILK) is an essential component of the cardiac mechanical stretch sensor and bound in a protein complex with parvin PINCH proteins, so-called ILK-PINCH-parvin (IPP) complex. We have recently shown that inactivation ILK or β-parvin activity leads to heart failure zebrafish via reduced B (PKB/Akt) activation. Here, we show proteins localize at sarcomeric Z disks costameres skeletal muscle. To investigate vivo role for IPP stability PKB signaling within vertebrate heart,...
Depending on context and tumor stage, deregulation of autophagy can either suppress tumorigenesis or promote chemoresistance survival. Histone deacetylases (HDACs) modulate autophagy; however, the exact mechanisms are not fully understood. Here, we analyze effects broad-spectrum HDAC inhibitors (HDACi) panobinostat vorinostat transcriptional regulation with respect to transcription factor activity (Transcription EB—TFEB, forkhead boxO—FOXO) autophagic flux in neuroblastoma cells. In...
Genome wide association studies (GWAS) are applied to identify genetic loci, which associated with complex traits and human diseases. Analogous the evolution of gene expression analyses, pathway analyses have emerged as important tools uncover functional networks genome-wide data. Usually, combine statistical methods a priori available biological knowledge. To determine significance thresholds for pathways, correction multiple testing over-representation permutation is applied. We...
Alternative splicing (AS) is one of the major mechanisms to warrant proteomic and functional diversity eukaryotes. However, complex nature machinery, its associated regulators implications alternatively spliced transcripts only poorly understood. We investigated here role regulator rbfox1 in vivo using zebrafish as a model system. find that loss-of leads progressive cardiac contractile dysfunction heart failure. By deep-transcriptome sequencing quantitative real-time PCR we show depletion...
Abstract Background and aims The cardiac societies of Europe the United States have established different risk models for preventing sudden death (SCD) in hypertrophic cardiomyopathy (HCM). aim this study is to validate current SCD prediction methods a German HCM cohort improve them by addition genotype information. Methods patients without prior or equivalent arrhythmic events ≥ 18 years age were enrolled an expert center Germany. primary endpoint was defined as SCD/-equivalent within 5...