A5103041984- RNA modifications and cancer
- Lung Cancer Research Studies
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
- Muscle Physiology and Disorders
- Genetic factors in colorectal cancer
- Cancer-related molecular mechanisms research
- Lymphoma Diagnosis and Treatment
- MicroRNA in disease regulation
- DNA Repair Mechanisms
- Sirtuins and Resveratrol in Medicine
- Chronic Lymphocytic Leukemia Research
- BRCA gene mutations in cancer
- Acute Ischemic Stroke Management
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
- Cerebrovascular and Carotid Artery Diseases
- PARP inhibition in cancer therapy
- RNA and protein synthesis mechanisms
- Calcium signaling and nucleotide metabolism
- Meat and Animal Product Quality
- Protein Hydrolysis and Bioactive Peptides
- Endoplasmic Reticulum Stress and Disease
Heidelberg University
2023-2025
University Hospital Heidelberg
2025
Institut Català d'Oncologia
2004-2025
Institut d'Investigació Biomédica de Bellvitge
2014-2025
Josep Carreras Leukaemia Research Institute
2019-2025
Medizinische Fakultät Mannheim
2024
Danbury Hospital
2022
Hospital Universitario La Paz
2016-2020
Institute of Molecular Genetics
2020
Bellvitge University Hospital
2020
Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence RNA modification landscapes in so-called epitranscriptome. Here, we report human glioma cells undergo DNA methylation-associated epigenetic silencing NSUN5, a candidate methyltransferase for 5-methylcytosine. In setting, NSUN5 exhibits tumor-suppressor characteristics vivo models. We also found loss generates an unmethylated status at...
RNA modifications are important regulators of transcript activity and an increasingly emerging body data suggests that the epitranscriptome its associated enzymes altered in human tumors.
Plitidepsin is an antitumoral compound safe for treating COVID-19 that targets the translation elongation factor eEF1A. Here we detect plitidepsin decreases de novo cap-dependent of SARS-CoV-2 and non-viral RNAs but affects less than 13% host proteome, thus preserving cellular viability. In response to plitidepsin, cells upregulate EIF2AK3 proteins reduce translation, also support proteostasis via ribosome synthesis cap-independent by eIF4G2 IGF2BP2. While inhibits cap- or internal entry...
Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder caused by mutations in the NF1 gene. In this paper we report our experience using cDNA-SSCP/HD analysis as mutational screening approach and double characterization of all at DNA RNA levels. Two hundred eighty-two different (in 374 independent patients) were identified, 140 which novel population. Most these are unique distributed along However, also detected 37 recurrent mutations. Our limited with respect to...
Recent efforts to sequence human cancer genomes have highlighted that point mutations in genes involved the epigenetic setting occur tumor cells. Small cell lung (SCLC) is an aggressive with poor prognosis, where little known about genetic events related its development. Herein, we identified presence of homozygous deletions candidate histone acetyltransferase KAT6B, and loss corresponding transcript, SCLC lines primary tumors. Furthermore, show, vitro vivo, depletion KAT6B expression...
Aging-related tau astrogliopathy (ARTAG) is defined by the presence of two types tau-bearing astrocytes: thorn-shaped astrocytes (TSAs) and granular/fuzzy in brain old-aged individuals. The present study focused on TSAs rare forms ARTAG with no neuronal pathology or restricted to entorhinal transentorhinal cortices, avoid bias from associated tauopathies. show 4Rtau phosphorylation at several specific sites abnormal conformation, but they lack ubiquitin are not immunostained tau-C3...
Sphingolipids function as membrane constituents and signaling molecules, with crucial roles in human diseases, from neurodevelopmental disorders to cancer, best exemplified the inborn errors of sphingolipid metabolism lysosomes. The dihydroceramide desaturase Δ4-dihydroceramide 1 (DEGS1) acts last step a sector pathway, de novo ceramide biosynthesis. Defects DEGS1 cause recently described hypomyelinating leukodystrophy-18 (HLD18) (OMIM #618404). Here, we reveal that is...
Mutations in dysferlin cause a type of muscular dystrophy known as dysferlinopathy. Dysferlin may be involved muscle repair and differentiation. We compared normal human skeletal cultures expressing with from dysferlinopathy patients. quantified the fusion index myoblasts measure development conducted optic electronic microscopy, immunofluorescence, Western blot, flow cytometry, real-time PCR at different developmental stages. Short interference RNA was used to corroborate results obtained...
Introduction— Apolipoprotein (apo) A-II is the second most abundant high-density lipoprotein (HDL) apolipoprotein. We assessed mechanism involved in altered postprandial triglyceride-rich metabolism of female human apoA-II-transgenic mice (hapoA-II-Tg mice), which results up to an 11-fold increase plasma triglyceride concentration. The relationships between apoA-II, HDL composition, and lipase (LPL) activity were also analyzed a group normolipidemic women. Methods Results— Triglyceride-rich...
Sirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, whose loss induces an accelerated aging phenotype directly linked to hyperactivation of the NF-κB pathway. Here we show SirT6 binds H3K9me3-specific histone methyltransferase Suv39h1 monoubiquitination conserved cysteines in PRE-SET domain Suv39h1. Following activation signaling is released from IκBα...
Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono-adenosine 5'-diphosphate (ADP)-ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a dual sirtuin, it features auto-mADPRT mADPRT occurs at previously undefined active site, and its abrogation alters chromatin distribution. identify an epigenetic pathway by which ADP-ribosyl-SirT7 recognized ADP-ribose reader mH2A1.1 under...
The Sirtuin family of NAD+-dependent enzymes plays an important role in maintaining genome stability upon stress. Several mammalian Sirtuins have been linked directly or indirectly to the regulation DNA damage during replication through Homologous recombination (HR). one them, SIRT1, is intriguing as it seems a general regulatory response (DDR) that has not yet addressed. SIRT1-deficient cells show impaired DDR reflected decrease repair capacity, increased instability and decreased levels...
Abstract Background The lack of dystrophin expression in Duchenne muscular dystrophy (DMD) induces muscle fibre and replacement by fibro‐adipose tissue. Although the role some growth factors process fibrogenesis has been studied, pathways activated PDGF‐AA have not described so far. Our aim was to study molecular fibrotic DMD. Methods Skeletal fibro‐adipogenic progenitor cells (FAPs) from three DMD treated with at 50 ng/mL were analysed quantitative mass spectrometry‐based proteomics....
Lynch syndrome is associated with germline mutations in DNA mismatch repair (MMR) genes. Up to 30% of changes found are variants unknown significance (VUS). Our aim was assess the pathogenicity eight MLH1 VUS identified patients suspected syndrome. All them novel or not previously characterized. For their classification, we followed a strategy that integrates family history, tumor pathology, and control frequency data variety silico vitro analyses at RNA protein level, such as MMR assay,...
The indexed individual, from now on termed M116, was the world's oldest verified living person January 17th 2023 until her passing August 19th 2024, reaching age of 117 years and 168 days (https://www.supercentenarian.com/records.html). She a Caucasian woman born March 4th 1907 in San Francisco, USA, Spanish parents settled Spain since she 8. Although centenarians are becoming more common demographics human populations, so-called supercentenarians (over 110 old) still rarity. In Catalonia,...
Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Calpain plays different roles cells, but little known about its functions or vivo substrates. The aim of this study was to identify the genes showing an altered expression LGMD2A patients and possible pathways they are implicated in. Ten muscle samples from with which molecular diagnosis ascertained were investigated using array technology analyze gene profiling as...