A5040855011- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Genetic Neurodegenerative Diseases
- Endometrial and Cervical Cancer Treatments
- Cancer-related gene regulation
- Reproductive System and Pregnancy
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Gynecological conditions and treatments
- Protein Degradation and Inhibitors
- Plant Molecular Biology Research
- CAR-T cell therapy research
- Acute Myeloid Leukemia Research
- RNA regulation and disease
- Plant Gene Expression Analysis
- Nerve injury and regeneration
- Autism Spectrum Disorder Research
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Drug Transport and Resistance Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
Saarland University
2022-2024
University of Tübingen
2009-2023
Universitätsklinikum Tübingen
2021
University of British Columbia
2007-2012
Simon Fraser University
2009-2012
Child and Family Research Institute
2011-2012
St. Paul's Hospital
2007
In this paper, we describe an application, PubCloud that uses tagclouds for the summarization of results from queries over thePubMed database biomedical literature. responds toqueries with tag clouds generated wordsextracted abstracts returned by query. The ofa user study comparing tag-cloud ofquery standard result list provided PubMedindicated cloud interface is advantageous in presenting descriptive information and reducing frustrationbut it less effective at task enabling users to...
Monoubiquitination of H2BK123 (H2BK123ub), catalyzed by Rad6/Bre1, is a transient histone modification with roles in transcription and essential for establishing H3K4 H3K79 trimethylations (H3K4me3 H3K79me3). Here, we investigated the chromatin network around H2BK123ub examining its localization co-occurrence dependent marks as well elongation mark H3K36me3 across genome Saccharomyces cerevisiae. In yeast, removed deubiquitinases Ubp8 Ubp10, but their genomic target regions remain to be...
Histone H3 lysine 36 methylation is a ubiquitous hallmark of productive transcription elongation. Despite the prevalence this histone posttranslational modification, however, downstream functions triggered by mark are not well understood. In study, we showed that H3K36 promoted chromatin interaction Isw1b chromatin-remodeling complex in Saccharomyces cerevisiae. Similar to methylation, was found at mid- and 3' regions transcribed genes genome wide, its presence active dependent on PWWP...
Histone H3 lysine 4 trimethylation (H3K4me3) is a hallmark of transcription initiation, but how H3K4me3 demethylated during gene repression poorly understood. Jhd2, JmjC domain protein, was recently identified as the major histone demethylase (HDM) in Saccharomyces cerevisiae . Although JHD2 required for removal methylation upon repression, deletion does not result increased levels bulk histones, indicating that this HDM unable to demethylate histones steady-state conditions. In study, we...
The impact of the genetic background on lipidome yeast strains remains underexplored. This study systematically compares lipidomes five commonly used laboratory strains: BY4741, W303, D273-10B, RM11-1a, and CEN.PK2-1c. Shotgun lipidomics reveals significant variations in lipid class acyl chain composition down to level molecular species. Notably, most abundant differed between phosphatidylinositol (PI) lipids are predominant while phosphatidylethanolamine (PE) D273. Ergosterol esters, which...
Spinocerebellar ataxia type 3 is the most common autosomal dominant inherited worldwide, caused by a CAG repeat expansion in Ataxin-3 gene resulting polyglutamine (polyQ)-expansion corresponding protein. The disease characterized neuropathological, phenotypical, and specific transcriptional changes affected brain regions. So far, there no mouse model available representing all different aspects of disease, yet highly needed for better understanding pathomechanisms. Here, we novel knock-in...
Onset and progression of neurodegenerative disorders, including synucleinopathies such as Parkinson's disease, have been associated with various environmental factors. A highly compelling association from a therapeutic point view has found between physically active lifestyle significantly reduced risk for disease. Mimicking conditions in animal models by promoting physical activity, social interactions, novel surroundings yields so-called enriched environment known to enhance adult...
Social anxiety disorder (SAD) is a psychiatric characterized by severe fear in social situations and avoidance of these. Multiple genetic as well environmental factors contribute to the etiopathology SAD. One main risk for SAD stress, especially during early periods life (early adversity; ELA). ELA leads structural regulatory alterations contributing disease vulnerability. This includes dysregulation immune response. However, molecular link between adulthood remains largely unclear. Evidence...
Epigenetic dysregulation plays a pivotal role in mixed-lineage leukemia (MLL) pathogenesis, therefore serving as suitable therapeutic target. S-adenosylmethionine (SAM) is the universal methyl donor human cells and synthesized by methionine adenosyltransferase 2A (MAT2A), which deregulated different cancer types. Here, we used our CRISPR/Cas9-MLL-rearranged (CRISPR/Cas9-MLLr) model, faithfully mimicking MLLr patients’ pathology with indefinite growth potential vitro, to evaluate unknown of...
Mixed lineage leukemia (MLL) (KMT2A) rearrangements (KMT2Ar) play a crucial role in leukemogenesis. Dependent on age, major differences exist regarding disease frequency, main fusion partners and prognosis. In infants, up to 80% of acute lymphoid (ALL) bear MLL translocation half them are t(4;11), resulting poor contrast, adults only 10% myeloid (AML) t(9;11) with an intermediate The reasons for these poorly understood. Recently, we established efficient CRISPR/Cas9-based KMT2Ar model...
The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is characterized by agenesis of the uterus and upper part vagina in females with normal ovarian function.While genetic causes have been identified for a small subset patients epigenetic mechanisms presumably contribute to pathogenic unfolding, too, etiology has remained largely enigmatic. A comprehensive understanding gene activity context disease crucial identify etiological components their potential interplay.So far, this...
To identify potential genetic causes for Mayer-Rokitansky-Küster-Hauser syndrome (MRKH), we analyzed blood and rudimentary uterine tissue of 5 MRKH discordant monozygotic twin pairs. Assuming that a variant solely identified in the affected or could cause phenotype, mosaic ACTR3B with high allele frequency tissue, low twin, almost absent unaffected twin. Focusing on candidate genes, detected pathogenic GREB1L one pair their mother showing reduced phenotypic penetrance. Furthermore, two...
MLL rearranged (MLLr) leukemias are associated with a poor prognosis and limited response to conventional therapies. Moreover, chemotherapies result in severe side effects significant impairment of the immune system. Therefore, identification novel treatment strategies is mandatory. Recently, we developed human MLLr leukemia model by inducing chromosomal rearrangements CD34+ cells using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9. This authentically mimics patient...
Parkinson's disease (PD) is an age-dependent neurodegenerative disorder. Besides characteristic motor symptoms, patients suffer from cognitive impairments linked to pathology in cortical areas. Due obvious challenges tracing the underlying molecular perturbations human brain over time, we took advantage of a well-characterized PD rat model. Using RNA sequencing, profiled frontocortical transcriptome post-mortem patient samples and aligned expression changes with perturbation patterns...
Abstract Mutations in THAP1 (THAP domain-containing apoptosis-associated protein 1) are responsible for DYT6 dystonia. Until now, more than eighty different mutations gene have been found patients with primary dystonia, and two third of them missense mutations. The potential pathogeneses these human largely elusive. In the present study, we generated stable transfected neuronal cell lines expressing wild-type or mutated proteins patients. Transcriptional profiling using microarrays revealed...
Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and substantial cell migration activity (follicular trafficking). Recently, in situ follicular neoplasia (ISFN), accumulations immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers reactive lymph nodes, has been identified as precursor lesion FL with low risk progression manifest FL. The extent ongoing...
Abstract Parkinson’s disease (PD) is a neurological disorder with complex interindividual etiology that becoming increasingly prevalent worldwide. Elevated alpha-synuclein levels can increase risk of PD and may influence epigenetic regulation pathways. Here, we report genome-wide DNA methylation hydroxymethylation alterations associated overexpression two PD-linked variants (wild-type A30P) in LUHMES cells differentiated to dopaminergic neurons. Alpha-synuclein altered at thousands CpGs...
Abstract Dysregulated cholesterol homeostasis promotes tumorigenesis and progression. Therefore, metabolic reprogramming constitutes a new hallmark of cancer. However, until today, only few therapeutic approaches exist to target this pathway due the often-observed negative feedback induced by agents like statins leading controversially increased synthesis upon inhibition. Sterol regulatory element-binding proteins (SREBPs) are key transcription factors regulating fatty acids. Since SREBP2 is...