A5045441519- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Telomeres, Telomerase, and Senescence
- Genomics and Chromatin Dynamics
- Gene Regulatory Network Analysis
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Chromosomal and Genetic Variations
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Molecular Biology Techniques and Applications
- Chronic Lymphocytic Leukemia Research
- Advanced biosensing and bioanalysis techniques
- Lymphoma Diagnosis and Treatment
- Cancer-related gene regulation
- Circular RNAs in diseases
- Muscle Physiology and Disorders
- Advanced Nanomaterials in Catalysis
- Calcium signaling and nucleotide metabolism
- Chromatin Remodeling and Cancer
- RNA and protein synthesis mechanisms
Goethe University Frankfurt
2022-2025
University of Würzburg
2022-2023
University of Colorado Boulder
2019-2022
Institute of Predictive and Personalized Medicine of Cancer
2014-2022
Howard Hughes Medical Institute
2019
Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
2016-2017
Abstract Background Several long noncoding RNAs (lncRNAs) have been shown to function as components of molecular machines that play fundamental roles in biology. While the number annotated lncRNAs mammalian genomes has greatly expanded, studying lncRNA a challenge due their diverse biological and because loci can contain multiple modes may exert function. Results We previously generated characterized cohort 20 knockout mice. Here, we extend this initial study provide more detailed analysis...
The human endogenous retrovirus type-H (HERVH) family is expressed in the preimplantation embryo. A subset of these elements are specifically transcribed pluripotent stem cells where they appear to exert regulatory activities promoting self-renewal and pluripotency. How HERVH achieve such transcriptional specificity remains poorly understood. To uncover sequence features underlying activity, we performed a phyloregulatory analysis long terminal repeats (LTR7) family, which harbor its...
Abstract The spatial partitioning of the transcriptome in cell is an important form gene-expression regulation. Here, we address how intron retention influences spatio-temporal dynamics transcripts from two clinically relevant genes: TERT (Telomerase Reverse Transcriptase) pre-mRNA and TUG1 (Taurine-Upregulated Gene 1) lncRNA. Single molecule RNA FISH reveals that nuclear uniformly robustly retain specific introns. Our data suggest splicing retained introns occurs during mitosis. In...
Abstract Variability of gene expression due to stochasticity transcription or variation extrinsic signals, termed biological noise, is a potential driving force cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification noise at resolution. reveals enhanced nuclear versus cytoplasmic and distinct regulatory modes stratified by correlation between expression, chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells...
Telomerase is pathologically reactivated in most human cancers, where it maintains chromosomal telomeres and allows immortalization. Because telomerase reverse transcriptase (TERT) usually the limiting component for activation, numerous studies have measured TERT mRNA levels populations of cells or tissues. In comparison, little known about expression at single-cell single-molecule level. To address this, we analyzed across 10 cancer lines using RNA fluorescent situ hybridization (FISH) made...
A growing number of long noncoding RNAs (lncRNAs) have emerged as vital metabolic regulators. However, most human lncRNAs are nonconserved and highly tissue specific, vastly limiting our ability to identify lncRNA regulators (hLMRs). In this study, we established a pipeline putative hLMRs that metabolically sensitive, disease relevant, population applicable. We first progressively processed multilevel transcriptome data select liver exhibit dynamic expression in the general population, show...
BACKGROUND: Advanced age is unequivocally linked to the development of cardiovascular disease; however, mechanisms resulting in reduced endothelial cell regeneration remain poorly understood. Here, we investigated novel involved senescence that impact transcription and vascular repair after injury. METHODS: Native cells were isolated from young (20±3.4 years) aged (80±2.3 individuals subjected molecular analyses assess global transcriptional metabolic changes. In vitro studies conducted...
Primate-specific NBL2 macrosatellite is hypomethylated in several types of tumors, yet the consequences this DNA hypomethylation remain unknown. We show that conserved repeats are close to centromeres most acrocentric chromosomes. associates with perinucleolar region and undergoes severe demethylation a subset colorectal cancer (CRC). Upon histone acetylation, transcribed tumor cell lines primary CRCs. monomers exhibit promoter activity, contained within novel, non-polyA antisense lncRNAs,...
DNA hypomethylation at repetitive elements accounts for the genome-wide common in cancer, including colorectal cancer (CRC). We identified a pericentromeric repeat element called SST1 frequently hypomethylated (>5% demethylation compared with matched normal tissue) several cancers, 28 of 128 (22%) CRCs. somatic associated genome damage, especially tumors wild-type TP53. Seven percent CRCs exhibited higher ("severe") level (≥10%) that co-occurred TP53 mutations. correlated distinct histone...
Long noncoding RNAs (lncRNAs) are rapidly evolving and thus typically poorly conserved in their sequences. How these sequence differences affect the characteristics potential functions of lncRNAs with shared synteny remains unclear. Here we show that syntenically lncRNA Firre displays distinct expression localization patterns human mouse. Single molecule RNA FISH reveals a range cell lines, mouse ( mFirre ) is predominantly nuclear, while FIRRE hFIRRE distributed between cytoplasm nucleus....
After myocardial infarction in the adult heart remaining, non-infarcted tissue adapts to compensate loss of functional tissue. This adaptation requires changes gene expression networks, which are mostly controlled by transcription regulating proteins. Long non-coding transcripts (lncRNAs) taking part fine-tuning such programs. We describe and characterize cardiomyocyte specific lncRNA Sweetheart RNA (Swhtr), an approximately 10 kb long transcript divergently expressed from cardiac core...
Summary Variability of gene expression due to stochasticity transcription or variation extrinsic signals, termed biological noise, is a potential driving force cellular differentiation. While unicellular organisms exploit noise as bet-hedging strategy, its role during multilineage differentiation stem cells underexplored. Utilizing single-cell RNA-sequencing reconstruct cell state manifolds, we developed VarID2, method for the quantification at resolution. VarID2 reveals enhanced nuclear...
The incidence and prevalence of cardiovascular disease is highest among the elderly. There a need to further understand mechanisms behind endothelial cell aging in order achieve vascular rejuvenation minimize onset age-related diseases. Long non-coding RNAs (lncRNAs) have been proposed regulate numerous processes human genome, yet their function therapeutic potential remain largely unknown. This primarily because majority studies investigating impact on lncRNA expression heavily rely vitro...
ABSTRACT Background Several long noncoding RNAs (lncRNAs) have been shown to function as central components of molecular machines that play fundamental roles in biology. While the number annotated lncRNAs mammalian genomes has greatly expanded, their functions remain largely uncharacterized. This is compounded by fact identifying lncRNA loci robust and reproducible phenotypes when mutated a challenge. Results We previously generated cohort 20 knockout mice. Here, we extend our initial study...
Neurofibromatosis Type 1 (NF1) is a genetic condition affecting approximately 1:3500 persons worldwide. The NF1 gene codes for neurofibromin protein, GTPase activating protein (GAP) and negative regulator of RAS. undergoes alternative splicing exon 23a (E23a) that 21 amino acids placed at the center GAP related domain (GRD). E23a-containing type II exhibits weaker Ras-GAP activity compared to E23a-less I isoform. Exon E23a has been with cognitive impairment present in individuals. We...
Genome methylation profiles define naïve-like (n-CLL), memory-like (m-CLL), and intermediate (i-CLL) subsets of chronic lymphocytic leukaemia (CLL). The can be easily determined by the analysis five-CpG signature. m-CLL, i-CLL, n-CLL with good, intermediate, poor prognoses, respectively, differ somatic hypermutation status immunoglobulin heavy chain variable gene (IGHV), a widely used prognostic predictor in CLL. We have previously shown that expression WNT5A, encoding ROR1 ligand,...
Abstract The human endogenous retrovirus type-H (HERVH) family is expressed in the preimplantation embryo. A subset of these elements are specifically transcribed pluripotent stem cells where they appear to exert regulatory activities promoting self-renewal and pluripotency. How HERVH achieve such transcriptional specificity remains poorly understood. To uncover sequence features underlying activity, we performed a phyloregulatory analysis long terminal repeats (LTR7) family, which harbor...
Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL Gene Expression Noise Dynamics Unveil Functional Heterogeneity of Ageing Hematopoietic Stem Cells Cell 56 Pages Posted: 22 Aug 2022 Publication Status: Under Review See all articles by Reyna Edith Rosales-AlvarezReyna Rosales-AlvarezJulius-Maximilians-Universität - Würzburg Institute Systems ImmunologyJasmin RettkowskiMax Planck Immunobiology and...
Abstract Telomerase is pathologically reactivated in most human cancers, where it maintains chromosomal telomeres and allows immortalization. Because telomerase reverse transcriptase (TERT) usually the limiting component for activation, numerous studies have measured TERT mRNA levels populations of cells or tissues. However, little known about expression at single-cell single-molecule level. Here we analyzed across 10 cancer lines using RNA FISH made several unexpected findings. First, there...
The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled “Beyond Genomes” took place October 13th 14th 2016 in Barcelona. BCEC was the fourth edition of a series annual conferences coordinated by Marcus Buschbeck subsequently organized leading research centers together with B•DEBATE, joint initiative BIOCAT “La Caixa” Foundation. Salvador Aznar-Benitah, Eduard Batlle, Raúl Méndez from Institute for Research Biomedicine selected panel speakers. As title indicates, this year's...
Abstract Numerous global connections have been made between splicing and other layers of gene regulation, including the spatial partitioning transcriptome in cell. Yet, there has surprisingly little analysis spatio-temporal regulation individual protein-coding non-coding RNA molecules single cells. Here we address how intron retention influences dynamics transcripts from two clinically relevant genes: TERT (Telomerase Reverse Transcriptase) pre-mRNA TUG1 (Taurine-Upregulated Gene 1) lncRNA....