A5039552731- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Cancer-related gene regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Syndromes and Imprinting
- Alzheimer's disease research and treatments
- Tuberous Sclerosis Complex Research
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Autism Spectrum Disorder Research
- Chromatin Remodeling and Cancer
- Ubiquitin and proteasome pathways
- Neural dynamics and brain function
- Receptor Mechanisms and Signaling
- Cancer Cells and Metastasis
- Parkinson's Disease Mechanisms and Treatments
- Genomics and Chromatin Dynamics
- Orbital Angular Momentum in Optics
- Genetic Associations and Epidemiology
- Single-cell and spatial transcriptomics
- Folate and B Vitamins Research
- Advanced Fluorescence Microscopy Techniques
- MXene and MAX Phase Materials
- PI3K/AKT/mTOR signaling in cancer
Instituto de Neurociencias
2021-2024
Consejo Superior de Investigaciones Científicas
2024
École Polytechnique Fédérale de Lausanne
2015-2022
Institut d'Investigació Biomédica de Bellvitge
2009-2016
Bellvitge University Hospital
2012-2016
Institut Català d'Oncologia
2016
Duran i Reynals Hospital
2014
Manufacturas Serviplast (Spain)
2012
Instituto de Biomedicina de Valencia
2006-2011
Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) newborn and centenarian genomes. The DNA had a lower methylation content reduced correlation status neighboring cytosine--phosphate--guanine (CpGs) throughout genome comparison with more homogeneously methylated DNA. hypomethylated CpGs observed compared...
Most of the studies characterizing DNA methylation patterns have been restricted to particular genomic loci in a limited number human samples and pathological conditions. Herein, we present compromise between an extremely comprehensive study sample population with intermediate level resolution CpGs at level. We obtained fingerprint 1628 which interrogated 1505 CpG sites. The revealed show this epigenetic mark be critical tissue-type definition stemness, particularly around transcription...
Differential methylation between the two alleles of a gene has been observed in imprinted regions, where one allele occurs on parent-of-origin basis, inactive X-chromosome females, and at those loci whose is driven by genetic variants. We have extensively characterized substantial range normal human tissues, reciprocal genome-wide uniparental disomies, hydatidiform moles, using combination whole-genome bisulfite sequencing high-density microarrays. This approach allowed us to define profiles...
One of the hallmarks cancer is disruption gene expression patterns. Many molecular lesions contribute to this phenotype, and importance aberrant DNA methylation profiles increasingly recognized. Much research effort in area has examined proximal promoter regions epigenetic alterations at other loci are not well characterized. Using whole genome bisulfite sequencing examine uncharted epigenome, we identify a type far-reaching alteration cells distal regulatory sequences described as...
Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, those affecting DNA methylation, might also exist. studied samples were gray matter from prefrontal cortex control disease-associated cases. We performed methylation analyses Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease...
The central nervous system has a pattern of gene expression that is closely regulated with respect to functional and anatomical regions. DNA methylation major regulator transcriptional activity, aberrations in the distribution this epigenetic mark may be involved many neurological disorders, such as Alzheimer's disease. Herein, we have analysed 12 distinct mouse brain regions according their CpG 5'-end patterns observed unique landscapes. methylomes obtained from cerebral cortex were used...
ABSTRACT Genetic screening in Alzheimer's disease (AD) has identified only a handful of genes that are mutated the disorder. Thus, for very large proportion patients, biology their is poorly understood. Epigenetic alterations may provide an explanation these cases. Using DNA methylation profiles human hippocampus from controls and we have presence promoter hypermethylation dual‐specificity phosphatase 22 (DUSP22) gene AD. DUSP22 likely candidate involvement pathogenesis disorder since, as...
Abstract The role of the plasma level homocysteine (Hcy), as a primary outcome, and effect silent cerebrovascular lesions genetic variants related to Hcy metabolism, secondary outcomes, in cognitive decline dementia Parkinson's disease (PD) were studied. This case–control study focused on 89 PD patients minimum 10 years evolution older than 60 years, who neuropsychologically classified either cognitively normal (n = 37), having mild impairment (Petersen criteria) 22), or suffering from...
Epigenetic regulation and, in particular, DNA methylation have been linked to the underlying genetic sequence.DNA quantitative trait loci (meQTL) identified through significant associations between and epigenetic codes physiological pathological contexts.We propose that interrogating interplay polymorphic alleles is a powerful method for improving our interpretation of risk genome-wide association studies otherwise lack mechanistic explanation.We integrated patient cancer genotype data...
The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is associated to mutations of the DNA methyl-transferase DNMT3B, resulting in a reduction enzyme activity. Aberrant expression immune system genes hypomethylation pericentromeric regions accompanied by chromosomal were determined as alterations driving disease phenotype. However, so far only technologies capable analyze single loci applied determine epigenetic ICF patients. In current study, we performed...
Epithelial-to-mesenchymal transition (EMT) is a plastic process in which fully differentiated epithelial cells are converted into poorly differentiated, migratory and invasive mesenchymal cells, it has been related to the metastasis potential of tumors. This reversible can also eventually undergo mesenchymal-to-epithelial transition. The existence dynamic EMT suggests involvement epigenetic shifts phenotype. Herein, we obtained DNA methylomes at single-base resolution Madin-Darby canine...
Abstract Background MeCP2—a chromatin-binding protein associated with Rett syndrome—has two main isoforms, MeCP2-E1 and MeCP2-E2, differing in a few N-terminal amino acid residues. Previous studies have shown brain region-specific expression of these isoforms which, addition to their different cellular localization differential during development, suggest that they may also non-overlapping molecular mechanisms. However, functions E2 remain largely unexplored. Results Here, we show the...
Abstract Aging involves the deterioration of organismal function, leading to emergence multiple pathologies. Environmental stimuli, including lifestyle, can influence trajectory this process and may be used as tools in pursuit healthy aging. To evaluate role epigenetic mechanisms context, we have generated bulk tissue single cell multi-omic maps male mouse dorsal hippocampus young old animals exposed environmental stimulation form enriched environments. We present a molecular atlas aging...
Abstract The recent discovery of mutations in Dardarin ( LRRK2 ) have been related to the appearance Parkinson's disease several families. Notably, one single mutation this gene (R1441G) not only appeared familial, but also apparently sporadic Parkinson (PD) patients Basque descent. A clinical population was ascertained, and subjects were classified into non‐Basque descent according their known ancestry. R1441G assayed using an allele‐specific polymerase chain reaction, nucleotide...
Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about need understand complex ways which nature nurture interact produce mental illness. We analyze epigenome several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450k) DNA methylation array. identified 159 differentially methylated CpG sites included known novel candidate sequences...
Significance Memory formation relies on a plethora of functions, including epigenetic modifications. Over recent years, multiple studies have indicated the potential HDAC inhibitors (HDACis) as cognitive enhancers, but their mode action is not fully understood. Here, we tested whether HDACi treatment improves memory via “cognitive priming,” stipulating that HDACis—without inherent target specificity—specifically enhance naturally occurring plasticity processes. We found combining HDACis with...
Autism spectrum disorders are associated with defects in social response and communication that often occur the context of intellectual disability. Rett syndrome is one example which epilepsy, motor impairment, disturbance may co-occur. Mutations histone demethylases known to several these syndromes. Herein, we aimed identify whether mutations candidate demethylase JMJD1C (jumonji domain containing 1C) implicated disorders.We performed mutational functional analysis 215 cases autism...
Abstract Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in adult brain. To explore Kdm1a’s function we develop inducible forebrain-restricted knockouts. By applying multi-omic transcriptome, epigenome chromatin conformation data, combined super-resolution microscopy, find elimination causes neuronal activation nonneuronal...
The N-methyl-D-aspartate receptor (NMDAr) hypofunction hypothesis suggests that excitatory-inhibitory (E-I) imbalance underlies cognitive deficits associated with neuropsychiatric disorders, such as schizophrenia (SCZ). In this study, we investigated the impact of NMDAr blockade on pyramidal neurons and interneurons in CA1 region hippocampus using vivo electrophysiological recordings during both spontaneous exploratory behaviors. Through administration MK-801, an antagonist, assessed changes...
Inhibitors of the mechanistic target rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis response inhibition. This feature driven by EVI1 SOX9. functionally cooperates with positively regulates SOX9, promotes...
Parkinson disease (PD) is the second most common neurodegenerative disorder and characterized by loss of dopaminergic neurons in substantia nigra. Mutations PINK1 were shown to cause recessive familial PD, today are proposed be associated with via mitochondrial dysfunction oxidative damage. The gene comprises eight exons, which encode a ubiquitously expressed 581 amino acid protein that contains an N-terminal targeting domain serine/threonine kinase. To better understand relationship between...