FERNANDA BERNARDI BERTONHA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Pediatria, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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conferenceObject TRISOMY 21-DRIVEN GENE EXPRESSION DYSREGULATION IN HUMAN THYMUS: CONVERGING GENOMIC AND EPIGENOMIC MECHANISMS(2016) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; FEREIRA, Leandro Rodrigues; CARNEIRO-SAMPAIO, MagdaconferenceObject Complete Transcriptional Network Driven-View of Thymic Hypofunction in Down Syndrome(2014) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; FEREIRA, Leandro Rodrigues; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; GRASSI, Marcilia Sierro; CARNEIRO-SAMPAIO, Magdaarticle 16 Citação(ões) na Scopus Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants(2016) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; FERREIRA, Leandro Rodrigues; FURLANETTO, Glaucio; CHACUR, Paulo; ZERBINI, Maria Claudia Nogueira; CARNEIRO-SAMPAIO, MagdaTrisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue - obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT) - and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the ""canonical"" way of thymus functioning. Conversely, DS networks represent a ""non-canonical"" way, i. e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes.conferenceObject MODULAR TRANSCRIPTIONAL REPERTOIRE AND microRNA-TARGET ANALYSES IN THYMIC TISSUE OF DOWN SYNDROME INFANTS(2015) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; FEREIRA, Leandro Rodrigues; CARNEIRO-SAMPAIO, Magda- Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures(2015) MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; IAMASHITA, Priscila; SILVA, Filipi Nascimento; COSTA, Luciano da Fontoura; SILVA, Alexandre Valotta; CASTRO, Luiz Henrique Martins; WEN, Hung-TzuAge at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system's constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to generate adaptive mechanisms, what has implications for epilepsy management and drug discovery.