A5058583468- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Acute Myeloid Leukemia Research
- Zebrafish Biomedical Research Applications
- Epigenetics and DNA Methylation
- Neonatal Respiratory Health Research
- Genetic Syndromes and Imprinting
- Pluripotent Stem Cells Research
- Prenatal Screening and Diagnostics
- Autism Spectrum Disorder Research
- RNA modifications and cancer
- Growth Hormone and Insulin-like Growth Factors
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Single-cell and spatial transcriptomics
- Genomic variations and chromosomal abnormalities
- Multiple Myeloma Research and Treatments
- Neuroscience and Neural Engineering
- Protein Degradation and Inhibitors
- Cognitive Abilities and Testing
Josep Carreras Leukaemia Research Institute
2019-2024
Instituto de Salud Carlos III
2021-2024
Universitat de Barcelona
2020-2023
Centro de Investigación Biomédica en Red de Cáncer
2021
Institut d'Investigació Biomédica de Bellvitge
2011-2020
Leukemia Research Foundation
2018
Duran i Reynals Hospital
2014-2016
Abstract Fusion oncogenes (FOs) are common in many cancer types and powerful drivers of tumor development. Because their expression is exclusive to cells elimination induces cell apoptosis FO-driven cancers, FOs attractive therapeutic targets. However, specifically targeting the resulting chimeric products challenging. Based on CRISPR/Cas9 technology, here we devise a simple, efficient non-patient-specific gene-editing strategy through two introns genes involved rearrangement, allowing for...
Genomic imprinting is the epigenetic process that results in monoallelic expression of genes depending on parental origin. These are known to be critical for placental development and fetal growth mammals. Aberrant profiles at imprinted loci, such as DNA methylation defects, surprisingly rare pregnancies with compromised growth, while variations transcriptional output from expressed alleles more commonly reported complicated intrauterine restriction (IUGR). To determine if PLAGL1 HYMAI, two...
Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML) and is driven by rare therapy-resistant stem cells (LSCs) that reside specific bone marrow niches. Hypoxia signaling maintains quiescent metabolically relaxed state, desensitizing them to chemotherapy. This suggests hypothesis hypoxia contributes chemoresistance AML-LSCs may represent therapeutic target sensitize Here, we identify HIF
Mecp2 is a transcriptional repressor protein that mutated in Rett syndrome, neurodevelopmental disorder the second most common cause of mental retardation women. It has been shown loss syndrome cells alters silencing coding genes and microRNAs. Herein, we have studied impact impairment mouse model on global patterns long non-coding RNAs (lncRNAs). Using microarray platform assesses 41,232 unique lncRNA transcripts, identified aberrant transcriptome present brain mice. The study relevant...
Rett syndrome (RTT) is the second leading cause of mental impairment in girls and currently untreatable. RTT caused, more than 95% cases, by loss-of-function mutations methyl CpG-binding protein 2 gene (MeCP2). We propose here a molecular target involved RTT: glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity deregulated Mecp2-knockout (KO) mice models, SB216763, specific inhibitor, able to alleviate clinical symptoms with consequences at cellular levels. In vivo, inhibition...
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...
CD19-directed chimeric antigen receptor (CAR) T cells have yielded impressive response rates in refractory/relapse B cell acute lymphoblastic leukemia (B-ALL); however, most patients ultimately relapse due to poor CAR persistence or resistance of either CD19+ CD19- B-ALL clones. CD22 is a pan-B marker whose expression maintained both and relapses. CD22-CAR been clinically used patients, although also occurs. engineered with tandem (Tan-CAR) containing single construct CD19 scFvs may be...
B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. As predicted by its prenatal origin, infant B-ALL (iB-ALL) shows an exceptionally silent DNA mutational landscape, suggesting that alternative epigenetic mechanisms may substantially contribute to leukemogenesis. Here, we have integrated genome-wide methylome and transcriptome data from 69 patients with de novo MLL-rearranged (MLLr) non-MLLr iB-ALL uniformly treated according Interfant-99/06 protocol. signatures...
Rett syndrome (RTT) is a severe neurodevelopmental disease caused almost exclusively by mutations to the MeCP2 gene. This may be regarded as synaptopathy, with impairments affecting synaptic plasticity, inhibitory and excitatory transmission network excitability. The complete understanding of mechanisms behind how transcription factor so profoundly affects mammalian brain are yet determined. What known, that involvement in activity-dependent expression programs critical link between this...
Methyl CpG binding protein 2 (MeCP2) is a chromosomal of the brain, very abundant especially in neurons, where it plays an important role regulation gene expression. Hence has potential to be affected by mammalian circadian cycle. We performed expression analyses mice brain frontal cortices obtained at different time points and we found that levels MeCP2 are altered circadianly, affecting overall organization chromatin resulting circadian-dependent well-stablished target genes. Furthermore,...
Rett Syndrome is a neurodevelopmental autism spectrum disorder caused by mutations in the gene coding for methyl CpG-binding protein (MeCP2). The disease characterized abnormal motor, respiratory, cognitive impairment, and autistic-like behaviors. No effective treatment of available. Mecp2 knockout mice have range physiological neurological abnormalities that resemble human syndrome can be used as model to interrogate new therapies. Herein, we show combined administration Levodopa...
DNA methylation (5-methylcytosine, 5 mC) is involved in many cellular processes and an epigenetic mechanism primarily associated with transcriptional repression. The recent discovery that mC can be oxidized to 5-hydromethylcytosine (5hmC) by TET proteins has revealed the "sixth base" of provides additional complexity what was originally thought a stable repressive mark. However, our knowledge genome-wide distribution 5hmC different tissues currently limited. Here, we sought define loci...
Constitutive activation of the chemokine receptor CXCR4 has been associated with tumor progression, invasion, and chemotherapy resistance in different cancer subtypes. Although pathway recently suggested as an adverse prognostic marker diffuse large B-cell lymphoma, its biological relevance this disease remains underexplored. In a homogeneous set 52 biopsies from patients, antibody-based cytokine array showed that tissue levels CXCL12 correlated high microvessel density bone marrow...
A major challenge in the stem cell biology field is ability to produce fully functional cells from induced pluripotent (iPSCs) that are a valuable resource for therapy, drug screening and disease modelling. Here we developed novel inducible CRISPR-mediated activation strategy (iCRISPRa) drive expression of multiple endogenous transcription factors important vitro fate differentiation iPSCs haematopoietic progenitor cells. This work has identified key role IGFBP2 development hematopoietic...
Epigenetic mechanisms are fundamental for shaping the activity of central nervous system (CNS). Methyl-CpG binding protein 2 (MECP2) acts as a bridge between methylated DNA and transcriptional effectors responsible differentiation programs in neurons. The importance MECP2 dosage CNS is evident Rett Syndrome duplication syndrome, which neurodevelopmental diseases caused by loss-of-function mutations or gene, respectively. Although many studies have been performed on syndrome models, little...
Methyl CpG binding protein 2 (MeCP2) binds DNA, and has a preference for methylated CpGs and, hence, in cells, it accumulates heterochromatin. Even though is expressed ubiquitously MeCP2 particularly important during neuronal maturation. This underscored by the fact that Rett syndrome, neurological disease, 80% of patients carry mutation MECP2 gene. Since gene lies on X chromosome subjected to inactivation, affected are usually chimeric wild type mutant MeCP2. Here, we present generation...
Human pluripotent stem cells (hPSCs) and mesenchymal stromal/stem (hMSCs) are clinically relevant sources for cellular therapies modeling human development disease. Many cell-based applications rely on the ability to activate several endogenous genes simultaneously modify cell fate. However, genetic intervention of these remains challenging. Several catalytically dead Cas9 (dCas9) proteins fused distinct activation domains can modulate gene expression when directed their regulatory regions...
Although more and children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, could disturb the delicate step of implantation, trigger placenta-related adverse outcomes with potential long-term effects, through disrupted epigenetic regulation. We have previously demonstrated that placental DNA methylation was significantly lower after IVF/ICSI than following natural conception at two differentially methylated regions (DMRs) associated...
A major challenge in the stem cell biology field is ability to produce fully functional cells from induced pluripotent (iPSCs) that are a valuable resource for therapy, drug screening, and disease modelling. Here, we developed novel inducible CRISPR-mediated activation strategy (iCRISPRa) drive expression of multiple endogenous transcription factors (TFs) important vitro fate differentiation iPSCs haematopoietic progenitor cells. This work has identified key role IGFBP2 developing...
Background There are few therapeutic options available for patients with B-cell acute lymphoblastic leukemia (B-ALL) relapsing as CD19 – either after chemotherapy or CD19-targeted immunotherapies. CD22-chimeric antigen receptor (CAR) T cells represent an attractive addition to CD19-CAR cell therapy because they will target both CD22 + B-ALL relapses and preleukemic cells. However, the immune escape mechanisms from CD22-CAR cells, potential contribution of epitope binding anti-CD22...