A5071397390- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Acute Myeloid Leukemia Research
- Gene Regulatory Network Analysis
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Bioinformatics and Genomic Networks
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- Gene expression and cancer classification
- Semantic Web and Ontologies
- Glioma Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Prenatal Screening and Diagnostics
- Neuroscience and Neuropharmacology Research
- Microbial Metabolic Engineering and Bioproduction
- Hemoglobinopathies and Related Disorders
- Extracellular vesicles in disease
- Systemic Lupus Erythematosus Research
- Genomics and Phylogenetic Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Cancer-related molecular mechanisms research
- Biomedical Text Mining and Ontologies
Universidade Estadual de Campinas (UNICAMP)
2022-2025
Brazilian Institute of Neuroscience and Neurotechnology
2022-2025
Jackson Laboratory
2018-2022
Institute for Research in Immunology and Cancer
2014-2022
Université de Montréal
2014-2022
Center for Genomic Science
2019
The University of Texas MD Anderson Cancer Center
2008-2012
Laboratório Nacional de Computação Científica
2007-2008
Universidade Federal de Pernambuco
2006
Intracellular pathogens such as Mycobacterium tuberculosis have evolved strategies for coping with the pressures encountered inside host cells. The ability to coordinate global gene expression in response environmental and internal cues is one key their success. Prolonged survival replication within macrophages, a virulence trait of M. tuberculosis, requires dynamic adaptation diverse changing conditions its phagosomal niche. However, physiological adaptations during different phases this...
Tumors display widespread transcriptome alterations, but the full repertoire of isoform-level alternative splicing in cancer is unknown. We developed a long-read (LR) RNA sequencing and analytical platform that identifies annotates full-length isoforms infers tumor-specific events. Application this to breast samples thousands previously unannotated isoforms; ~30% affect protein coding exons are predicted alter localization function. performed extensive cross-validation with -omics datasets...
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for cell survival and demonstrate direct relationship between , elevated OxPhos gene expression, acquired chemoresistance pre-leukemic leukemic models. Disrupting with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction...
Only few small RNAs (sRNAs) have been characterized in Mycobacterium tuberculosis and their role regulatory networks is still poorly understood. Here we report a genome-wide characterization of sRNAs M. integrating experimental computational analyses. Global RNA-seq analysis exponentially growing cultures H37Rv had previously identified 1373 sRNA species. In the present show that 258 (19%) these were also by microarray expression. This set included 22 intergenic sRNAs, 84 mapping within...
The molecular determinants that render specific populations of normal cells susceptible to oncogenic reprogramming into self-renewing cancer stem are poorly understood. Here, we exploit T-cell acute lymphoblastic leukemia (T-ALL) as a model define the critical initiating events in this disease. First, thymocytes reprogrammed by SCL and LMO1 transcription factors pre-leukemic (pre-LSCs) remain non-malignant, evidenced their capacities generate functional T cells. Second, provide strong...
Current chemotherapies for T cell acute lymphoblastic leukemia (T-ALL) efficiently reduce tumor mass. Nonetheless, disease relapse attributed to survival of preleukemic stem cells (pre-LSCs) is associated with poor prognosis. Herein, we provide direct evidence that pre-LSCs are much less chemosensitive existing chemotherapy drugs than leukemic blasts because a distinctive lower proliferative state. Improving therapies T-ALL requires the development strategies target absolutely dependent on...
Significance Understanding how cell cycle and differentiation are coordinated during normal hematopoiesis will reveal molecular insights in leukemogenesis. LIM-only 2 (LMO2) is a transcriptional regulator that controls the erythroid lineage via activation of an erythroid-specific gene expression program. Here, we uncover unexpected function for LMO2 controlling DNA replication protein–protein interactions with essential enzymes. To our knowledge, this work provides first evidence...
Abstract Mesial temporal lobe epilepsy (MTLE) is a chronic neurological disorder characterized by the occurrence of seizures, and histopathological abnormalities in mesial structures, mainly hippocampal sclerosis (HS). We used multi‐omics approach to determine profile transcript protein expression dorsal ventral dentate gyrus (DG) Cornu Ammonis 3 (CA3) an animal model MTLE induced pilocarpine. performed label‐free proteomics RNAseq from laser‐microdissected tissue isolated...
Transposable elements (TEs) drive genome evolution and can affect gene expression through diverse mechanisms. In breast cancer, disrupted regulation of TE sequences may facilitate tumor-specific transcriptomic alterations. We examine 142,514 full-length isoforms derived from long-read RNA sequencing (LR-seq) 30 samples to investigate the effects TEs on cancer transcriptome. Approximately half these contain sequences, contribute novel annotated splice junctions. quantify splicing LR-seq in...
Abstract Objective Mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) are brain lesions associated focal and characterized by increased density, heterotopic neurons, hypomyelination the white matter. Although previous studies have implicated somatic mutations SLC35A2 gene, cellular molecular mechanisms underlying MOGHE pathogenesis remain elusive. To address this gap, study aimed to systematically characterize cell type composition alterations at...
Background Data, data everywhere. The diversity and magnitude of the generated in Life Sciences defies automated articulation among complementary efforts. additional need this field for managing property access permissions compounds difficulty very significantly. This is particularly case when integration involves multiple domains disciplines, even more so it includes clinical high throughput molecular data. Methodology/Principal Findings emergence Semantic Web technologies brings promise...
Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anemia and 5q– syndrome, mutations RP genes lead to a defect erythroid translation cause anemia. Little is known about the molecular mechanisms selective mRNA involvement ribosomal-associated factors this process. Ribonuclease inhibitor 1 (RNH1) ubiquitously expressed protein that binds inhibits pancreatic-type ribonucleases. Here, we report RNH1 ribosomes...
Over 95% of human genes undergo alternative splicing (AS) in a developmental, tissue-specific, or signal transduction-dependent manner. Here, we present large-scale survey sex-biased differential (DAS) across 7027 samples 39 tissues from 532 individuals (351 males and 181 females) the Genotype-Tissue Expression project. We detected total 1278 statistically significant DAS events affecting 888 different 4417 gene expression (DGE) 3221 genes. Only 267 (29.3%) differentially spliced were also...
Focal cortical dysplasia (FCD) is a neurodevelopmental condition characterized by malformations of the cerebral cortex that often cause drug-resistant epilepsy. In this study, we performed multi-omics single-nuclei profiling to map chromatin accessibility and transcriptome landscapes FCD type II, generating comprehensive multimodal dataset comprising 61,525 cells from 11 clinical samples lesions controls. Our findings revealed profound chromatin, transcriptomic, cellular alterations...
Abstract Objectives We compared the proteomic signatures of hippocampal lesion induced in three different animal models mesial temporal lobe epilepsy with sclerosis (MTLE+HS): systemic pilocarpine model (PILO), intracerebroventricular kainic acid (KA), and perforant pathway stimulation (PPS). Methods used shotgun proteomics to analyze proteomes find enriched biological pathways dorsal ventral dentate gyrus (DG) isolated from hippocampi models. also obtained that DG patients pharmacoresistant...
Focal cortical dysplasia (FCD) is a brain malformation that causes medically refractory epilepsy. FCD classified into three categories based on structural and cellular abnormalities, with type II being the most common characterized by disrupted organization of cortex abnormal neuronal development. In this study, we employed cell-type deconvolution single-cell signatures to analyze bulk RNA-seq from multiple transcriptomic studies, aiming characterize composition lesions in patients IIa IIb...
Abstract We present Hierarchical Bayesian Analysis of Differential Expression and ALternative Splicing (HBA-DEALS), which simultaneously characterizes differential expression splicing in cohorts. HBA-DEALS attains state the art or better performance for both allows genes to be characterized as having gene expression, alternative splicing, both, neither. analysis GTEx data demonstrated sets that show predominant DGE DAST across multiple tissue types. These have pervasive differences with...
Abstract Background Little is known about bacterial transcriptional regulatory networks (TRNs). In Escherichia coli , which the organism with largest wet-lab validated TRN, its set of interactions involves only ~50% repertoire transcription factors currently known, and ~25% genes. Of those, a small proportion describes regulation processes that are clinically relevant, such as drug resistance mechanisms. Results We designed feed-forward (FF) bi-fan (BF) motif predictors for E. using...
Early T-cell development is precisely controlled by E proteins, that indistinguishably include HEB/TCF12 and E2A/TCF3 transcription factors, together with NOTCH1 pre-T cell receptor (TCR) signalling. Importantly, perturbations of early regulatory networks are implicated in leukemogenesis. gain function mutations invariably lead to acute lymphoblastic leukemia (T-ALL), whereas inhibition proteins accelerates Thus, NOTCH1, pre-TCR, E2A HEB functions intertwined, but how these pathways...