PRISCILA IAMASHITA HIGAKI

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LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: FERNANDA BERNARDI BERTONHA ×

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  • article 13 Citação(ões) na Scopus
    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-Tzu
    Age 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.
  • article 6 Citação(ões) na Scopus
    Dynamic Gene Network Analysis of Caco-2 Cell Response to Shiga Toxin-Producing Escherichia coli-Associated Hemolytic-Uremic Syndrome
    (2019) BANDO, Silvia Y.; IAMASHITA, Priscila; SILVA, Filipi N.; COSTA, Luciano da F.; ABE, Cecilia M.; BERTONHA, Fernanda B.; GUTH, Beatriz E. C.; FUJITA, Andre; MOREIRA-FILHO, Carlos A.
    Shiga toxin-producing Escherichia coli (STEC) O113:H21 strains are associated with human diarrhea and some strains may cause hemolytic-uremic syndrome (HUS). In Brazil, these strains are commonly found in cattle but, so far, were not isolated from HUS patients. Here, a system biology approach was used to investigate the differential transcriptomic and phenotypic responses of enterocyte-like Caco-2 cells to two STEC O113:H21 strains with similar virulence factor profiles (i.e., expressing stx2, ehxA, epeA, espA, iha, saa, sab, and subA): EH41 (Caco-2/EH41), isolated from a HUS patient in Australia, and Ec472/01 (Caco-2/Ec472), isolated from bovine feces in Brazil, during a 3 h period of bacteria-enterocyte interaction. Gene co-expression network analysis for Caco-2/EH41 revealed a quite abrupt pattern of topological variation along 3 h of enterocyte-bacteria interaction when compared with networks obtained for Caco-2/Ec472. Transcriptional module characterization revealed that EH41 induces inflammatory and apoptotic responses in Caco-2 cells just after the first hour of enterocyte-bacteria interaction, whereas the response to Ec472/01 is associated with cytoskeleton organization at the first hour, followed by the expression of immune response modulators. Scanning electron microscopy showed more intense microvilli destruction in Caco-2 cells exposed to EH41 when compared to those exposed to Ec472/01. Altogether, these results show that EH41 expresses virulence genes, inducing a distinctive host cell response, and is likely associated with severe pathogenicity.