A5071456827- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Genetic Neurodegenerative Diseases
- Adenosine and Purinergic Signaling
- Congenital heart defects research
- RNA regulation and disease
- Pancreatic function and diabetes
- Neonatal and fetal brain pathology
- Neuroscience and Neuropharmacology Research
- Drug Transport and Resistance Mechanisms
- Mitochondrial Function and Pathology
- Down syndrome and intellectual disability research
- Adipose Tissue and Metabolism
- Tissue Engineering and Regenerative Medicine
- Retinal Development and Disorders
- Parkinson's Disease Mechanisms and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Neuroscience of respiration and sleep
- DNA Repair Mechanisms
- MicroRNA in disease regulation
Centro de Biología Molecular Severo Ochoa
2018-2024
University of Lausanne
2020-2024
Universidad Autónoma de Madrid
2018-2023
Biomedical Research Networking Center on Neurodegenerative Diseases
2019-2023
Instituto de Salud Carlos III
2019-2023
Royal College of Surgeons in Ireland
2019-2023
Consejo Superior de Investigaciones Científicas
2023
The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown be increased in the brain, including both microglia neurons, experimental models of epilepsy patients. To date, cell type-specific downstream effects P2X7Rs during seizures remain, however, incompletely understood.
Neonatal seizures represent a clinical emergency. However, current anti-seizure medications fail to resolve in ~50% of infants. The P2X7 receptor (P2X7R) is an important driver inflammation, and evidence suggests that P2X7R contributes epilepsy adults. no genetic proof has yet been provided determine what contribution makes neonatal seizures, its effects on inflammatory signalling during the therapeutic potential P2X7R-based treatments long-lasting brain excitability.Neonatal were induced by...
Schizophrenia (SCZ) is caused by an interplay of polygenic risk and environmental factors, which may alter regulators gene expression leading to pathogenic misexpression SCZ genes. The CPEB family RNA-binding proteins (CPEB1-4) regulates translation target RNAs (approximately 40% overall genes). We previously identified CPEB4 as a key dysregulated translational regulator in autism spectrum disorder (ASD) because its neuronal-specific microexon (exon 4) mis-spliced ASD brains, causing...
Autism spectrum disorders are early onset neurodevelopmental characterized by deficits in social communication and restricted repetitive behaviors, yet they quite heterogeneous terms of their genetic basis phenotypic manifestations. Recently, de novo pathogenic mutations DYRK1A, a chromosome 21 gene associated to neuropathological traits Down syndrome, have been identified patients presenting recognizable syndrome included the autism spectrum. These produce DYRK1A kinases with partial or...
Aging is the major risk factor for most human diseases and represents a socio-economical challenge modern societies. Despite its importance, process of aging remains poorly understood. Epigenetic dysregulation has been proposed as key driver process. Modifications in transcriptional networks chromatin structure might be central to age-related functional decline. A prevalent feature described during overall reduction heterochromatin, specifically marked by loss repressive histone...
Abstract Objective Pharmacoresistance and the lack of disease‐modifying actions current antiseizure drugs persist as major challenges in treatment epilepsy. Experimental models chemoconvulsant‐induced status epilepticus remain choice to discover potential antiepileptogenic drugs, but doubts extent which they model human pathophysiology. The aim present study was compare molecular landscape intra‐amygdala kainic acid mice with findings resected brain tissue from patients drug‐resistant...
Altered CPEBs and mRNA polyadenylation lead to thiamine deficiency in the brains of patients mice with Huntington’s disease.
Unlike aged somatic cells, which exhibit a decline in molecular fidelity and eventually reach state of replicative senescence, pluripotent stem cells can indefinitely replenish themselves while retaining full homeostatic capacity. The conferment beneficial-pluripotency related traits via
Abstract Several premature aging mouse models have been developed to study and identify interventions that can delay age‐related diseases. Yet, it is still unclear whether these truly recapitulate natural aging. Here, we analyzed DNA methylation in multiple tissues of four previously reported ( Ercc1 , LAKI Polg Xpg ). We estimated (DNAm) age samples using the Horvath clock. The most pronounced increase DNAm could be observed mice, a strain which exhibits deficit nucleotide excision repair....
Abstract Temporal lobe epilepsy is the most common and refractory form of in adults. Gene expression within affected structures such as hippocampus displays extensive dysregulation implicated a central pathomechanism. Post-transcriptional mechanisms are increasingly recognized determinants gene landscape, but key remain unexplored. Here we show, for first time, that cytoplasmic mRNA polyadenylation, one post-transcriptional regulating expression, undergoes widespread reorganization temporal...
Summary In vivo reprogramming through the forced expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) has demonstrated great potential for reversing age-associated phenotypes, as combination these transcription factors actively promote cell regeneration rejuvenation in various tissues organs. However, continuous OSKM raised safety concerns due to loss identity, decrease body weight, premature death. Although cyclic short-term or targeted can mitigate some detrimental effects mice, systemic wild...
SUMMARY The induction of cellular reprogramming by forced expression the transcription factors OCT4, SOX2, KLF4, and C-MYC (OSKM) has been shown to allow dedifferentiation somatic cells ameliorate age-associated phenotypes in multiple tissues organs. Yet date, benefits vivo are limited occurrence detrimental side-effects. Here, using complementary genetic approaches, we demonstrated that continuous leads hepatic intestinal dysfunction resulting decreased body weight premature death. By...
Abstract Unlike aged somatic cells, which exhibit a decline in molecular fidelity and eventually reach state of replicative senescence, pluripotent stem cells can indefinitely replenish themselves while retaining full homeostatic capacity. The conferment beneficial-pluripotency related traits via vivo partial cellular reprogramming (IVPR) significantly extends lifespan restores aging phenotypes mouse models. Although the phases are well characterized, details rejuvenation processes poorly...
Abstract Objective Posttranscriptional mechanisms are increasingly recognized as important contributors to the formation of hyperexcitable networks in epilepsy. Messenger RNA (mRNA) polyadenylation is a key regulatory mechanism governing protein expression by enhancing mRNA stability and translation. Previous studies have shown large‐scale changes hippocampus mice during epilepsy development. The cytoplasmic element‐binding CPEB4 was found drive epilepsy‐induced poly(A) tail changes, lacking...
ABSTRACT Over the last decades, several premature aging mouse models have been developed to study and identify interventions that can delay age-related diseases. Yet, it is still unclear whether these truly recapitulate natural aging. Here, we analyzed DNA methylation in multiple tissues of four previously reported (ERCC1, LAKI, POLG XPG). We estimated (DNAm) age samples using Horvath clock. The most pronounced increase DNAm could be observed ERCC1 mice, a strain which exhibits deficit...
Abstract Age-associated neurodegenerative disorders represent significant challenges due to progressive neuronal decline and limited treatments. In aged mice, partial reprogramming, characterized by pulsed expression of reprogramming factors, has shown promise in improving function various tissues, but its impact on the aging brain remains poorly understood. Here we investigated vivo mature neurons dentate gyrus young mice. Using two different approaches – a neuron-specific transgenic...
Abstract RNA mis-splicing correction therapies have been developed for neurological disorders like spinal muscular atrophy and neuronal ceroid lipofuscinosis. In Huntington’s disease (HD), pathogenic was initially observed in genes linked to neurodegeneration, such as HTT itself, MAPT , TAF1 . Later, genome-wide analyses identified a broader signature HD brains, involving additional neurodegeneration-related genes. Correcting each mis-spliced gene individually would be unfeasible,...
<title>Abstract</title> Aging is the major risk factor for most human diseases and represents a socio-economical challenge modern societies. Despite its importance, process of aging remains poorly understood. Epigenetic dysregulation has been proposed as key driver process. Alterations in transcriptional networks chromatin structure might be central to age-related functional decline. A prevalent feature described during overall reduction heterochromatin, specifically marked by loss...
ABSTRACT Autism spectrum disorders are early onset neurodevelopmental characterized by deficits in social communication and restricted repetitive behaviors, yet they quite heterogeneous terms of their genetic basis phenotypic manifestations. Recently, de novo pathogenic mutations DYRK1A , a chromosome 21 gene associated to neuropathological traits Down syndrome, have been identified patients presenting recognizable syndrome included the autism spectrum. These produce kinases with partial or...
ABSTRACT Schizophrenia (SCZ) is caused by a complex interplay of polygenic risk and environmental factors, which might alter regulators gene expression leading to pathogenic mis-expression SCZ genes. The RNA binding protein family CPEB (CPEB1, CPEB2, CPEB3, CPEB4) regulates the translation target RNAs bearing CPE sequences in their 3’UTR (approximately 40% overall genes). We previously identified CPEB4 as key dysregulated translational regulator autism spectrum disorder (ASD), proving that...
Background and Purpose Neonatal seizures are a clinical emergency. Current anti-seizure medications, however, fail to resolve in ~50% of infants. The P2X7 receptor (P2X7R) is an important driver inflammation evidence suggest P2X7R contributing epilepsy adults. To date, no genetic proof has been provided determine the contribution neonatal seizures, its effects on inflammatory signalling during therapeutic potential P2X7R-based treatments long-lasting brain excitability. Experimental Approach...
Abstract The molecular mechanisms that shape the gene expression landscape during development and maintenance of chronic states brain hyperexcitability are incompletely understood. Here we show cytoplasmic mRNA polyadenylation, a posttranscriptional mechanism for regulating expression, undergoes widespread reorganisation in temporal lobe epilepsy. Specifically, over 25% hippocampal transcriptome displayed changes their poly(A) tail mouse models epilepsy, particular evident phase....
Abstract Objective Pharmacoresistance and the lack of disease-modifying actions current anti-seizure drugs persist as major challenges in treatment epilepsy. Experimental models chemoconvulsant-induced status epilepticus remain choice to discover potential anti-epileptogenic but doubts extent which they model human pathophysiology. The aim present study was compare molecular landscape intraamygdala kainic acid mice with findings resected brain tissue from patients drug-resistant temporal...