THAIS FERNANDA DE ALMEIDA GALATRO
Projetos de Pesquisa
Unidades Organizacionais
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
- Transcriptomic analysis of purified human cortical microglia reveals age-associated changes(2017) GALATRO, Thais F.; HOLTMAN, Inge R.; LERARIO, Antonio M.; VAINCHTEIN, Ilia D.; BROUWER, Nieske; SOLA, Paula R.; VERAS, Mariana M.; PEREIRA, Tulio F.; LEITE, Renata E. P.; MOLLER, Thomas; WES, Paul D.; SOGAYAR, Mari C.; LAMAN, Jon D.; DUNNEN, Wilfred den; PASQUALUCCI, Carlos A.; OBA-SHINJO, Sueli M.; BODDEKE, Erik W. G. M.; MARIE, Suely K. N.; EGGEN, Bart J. L.Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, F-c gamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.
conferenceObject Expression of CXCR7 and CXCR4 in diffuse astrocytomas and its interaction with HIF1 alpha expression and IDH1 mutation(2014) OBA-SHINJO, S. M.; MARIE, S. K. N.; BIANCO, A.; CLARA, C.; GALATRO, T.; ROSEMBERG, S.; TEIXEIRA, M. J.; UNO, M.conferenceObject Microglia exhibits proliferative and ECM modulating profiles in human gliomas(2017) GALATRO, T. F. de Almeida; LERARIO, A.; MORETTI, I.; SOLA, P.; BERTOLDI, E. R.; FREITAS, V. G.; PEREIRA, T.; MARTINEZ, R. C.; MALDAUN, M. V.; EGGEN, B. J. L.; MARIE, S. K.- Toll-like receptors 1, 2, 4 and 6 expression levels in diffusely infiltrative astrocytomas(2016) MORETTI, Isabele F.; FRANCO, Daiane Gil; SILVA, Roseli; GALATRO, Thais F.; OBA-SHINJO, Sueli M.; MARIE, Suely K. N.
conferenceObject Human microglia transcriptome and cross-species analysis(2015) GALATRO, T. F. de A.; HOLTMAN, I. R.; BROUWER, N.; SOLA, P.; REIS, G. N.; VAINCHTEIN, I. D.; VERAS, M.; PEREIRA, T.; PASQUALUCCI, C.; SOGAYAR, M. C.; BODDEKE, E. W. G.; MARIE, S. K. N.; EGGEN, B. J. L.- CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1 alpha Expression and IDH1 Mutation(2015) BIANCO, Andre Macedo; UNO, Miyuki; OBA-SHINJO, Sueli Mieko; CLARA, Carlos Afonso; GALATRO, Thais Fernanda de Almeida; ROSEMBERG, Sergio; TEIXEIRA, Manoel Jacobsen; MARIE, Suely Kazue NagahashiThe CXCR7, a new receptor for CXCL12 with higher affinity than CXCR4 has raised key issues on glioma cell migration. The aim of this study is to investigate the CXCR7 mRNA expression in diffuse astrocytomas tissues and to evaluate its interactions with CXCR4 and HIF1 alpha expression and IDH1 mutation. CXCR7, CXCR4 and HIF1 alpha mRNA expression were evaluated in 129 frozen samples of astrocytomas. IDH1 mutation status was analyzed with gene expressions, matched with clinicopathological parameters and overall survival time. Protein expression was analyzed by immunohistochemistry in different grades of astrocytoma and in glioma cell line (U87MG) by confocal microscopy. There was significant difference in the expression levels of the genes studied between astrocytomas and non-neoplasic (NN) controls (p < 0.001). AGII showed no significant correlation between CXCR7/HIF1 alpha (p = 0.548); there was significant correlation between CXCR7/CXCR4 (p = 0.042) and CXCR7/IDH1 (p = 0.008). GBM showed significant correlations between CXCR7/CXCR4 (p = 0.002), CXCR7/IDH1 (p < 0.001) and CXCR7/HIF1 alpha (p = 0.008). HIF1 alpha overexpression was associated with higher expressions of CXCR7 (p = 0.01) and CXCR4 (p < 0.0001), while IDH1 mutation was associated with lower CXCR7 (p = 0.009) and CXCR4 (p = 0.0005) mRNA expressions. Protein expression increased with malignancy and in U87MG cell line was mainly localized in the cellular membrane. CXCR7 was overexpressed in astrocytoma and correlates with CXCR4 and IDH1 in AGII and CXCR4, IDH1 and HIF1 alpha in GBM. Overexpression HIF1 alpha was related with higher expressions of CXCR7 and CXCR4, otherwise IDH1 mutation related with lower expression of both genes. No association between CXCR7 and CXCR4 expression and survival data was related.
- CoGA: An R Package to Identify Differentially Co-Expressed Gene Sets by Analyzing the Graph Spectra(2015) SANTOS, Suzana de Siqueira; GALATRO, Thais Fernanda de Almeida; WATANABE, Rodrigo Akira; OBA-SHINJO, Sueli Mieko; MARIE, Suely Kazue Nagahashi; FUJITA, AndreGene set analysis aims to identify predefined sets of functionally related genes that are differentially expressed between two conditions. Although gene set analysis has been very successful, by incorporating biological knowledge about the gene sets and enhancing statistical power over gene-by-gene analyses, it does not take into account the correlation (association) structure among the genes. In this work, we present CoGA (Co-expression Graph Analyzer), an R package for the identification of groups of differentially associated genes between two phenotypes. The analysis is based on concepts of Information Theory applied to the spectral distributions of the gene co-expression graphs, such as the spectral entropy to measure the randomness of a graph structure and the Jensen-Shannon divergence to discriminate classes of graphs. The package also includes common measures to compare gene co-expression networks in terms of their structural properties, such as centrality, degree distribution, shortest path length, and clustering coefficient. Besides the structural analyses, CoGA also includes graphical interfaces for visual inspection of the networks, ranking of genes according to their ""importance"" in the network, and the standard differential expression analysis. We show by both simulation experiments and analyses of real data that the statistical tests performed by CoGA indeed control the rate of false positives and is able to identify differentially co-expressed genes that other methods failed.
- Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair(2019) MA, Jianhui; BENITE, Jorge A.; LI, Jie; MIKI, Shunichiro; ALBUQUERQU, Claudio Ponte de; GALATRO, Thais; ORELLANA, Laura; ZANCA, Ciro; REED, Rachel; BOYER, Antonia; KOGA, Tomoyuki; VARKI, Nissi M.; FENTON, Tim R.; MARIE, Suely Kazue Nagahashi; LINDAHL, Erik; GAHMAN, Timothy C.; SHIAU, Andrew K.; ZHOU, Huilin; DEGROOT, John; SULMAN, Erik P.; CAVENEE, Webster K.; KOLODNER, Richard D.; CHEN, Clark C.; FURNARI, Frank B.Ionizing radiation (IR) and chemotherapy are standard-of-care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. We identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2. pY240-PTEN is rapidly elevated and bound to chromatin through interaction with Ki-67 in response to IR treatment and facilitates the recruitment of RAD51 to promote DNA repair. Blocking Y240 phosphorylation confers radiation sensitivity to tumors and extends survival in GBM preclinical models. Y240F-Pten knockin mice showed radiation sensitivity. These results suggest that FGFR-mediated pY240-PTEN is a key mechanism of radiation resistance and is an actionable target for improving radiotherapy efficacy.
- Correlation between molecular features and genetic subtypes of Glioblastoma: critical analysis in 109 cases(2017) GALATRO, Thais F; SOLA, Paula; MORETTI, Isabele F; MIURA, Flavio K; OBA-SHINJO, Sueli M; MARIE, Suely KN; LERARIO, Antonio MOBJECTIVE: Glioblastoma, the most common and lethal brain tumor, is also one of the most defying forms of malignancies in terms of treatment. Integrated genomic analysis has searched deeper into the molecular architecture of GBM, revealing a new sub-classification and promising precision in the care for patients with specific alterations. METHOD: Here, we present the classification of a Brazilian glioblastoma cohort into its main molecular subtypes. Using a high-throughput DNA sequencing procedure, we have classified this cohort into proneural, classical and mesenchymal sub-types. Next, we tested the possible use of the overexpression of the EGFR and CHI3L1 genes, detected through immunohistochemistry, for the identification of the classical and mesenchymal subtypes, respectively. RESULTS: Our results demonstrate that genetic identification of the glioblastoma subtypes is not possible using single targeted mutations alone, particularly in the case of the Mesenchymal subtype. We also show that it is not possible to single out the mesenchymal cases through CHI3L1 expression. CONCLUSION: Our data indicate that the Mesenchymal subtype, the most malignant of the glioblastomas, needs further and more thorough research to be ensure adequate identification.
- Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair (vol 35, pg 504, 2019)(2019) MA, Jianhui; BENITEZ, Jorge A.; LI, Jie; MIKI, Shunichiro; ALBUQUERQUE, Claudio Ponte de; GALATRO, Thais; ORELLANA, Laura; ZANCA, Ciro; REED, Rachel; BOYER, Antonia; KOGA, Tomoyuki; VARKI, Nissi M.; FENTON, Tim R.; MARIE, Suely Kazue Nagahashi; LINDAHL, Erik; GAHMAN, Timothy C.; SHIAU, Andrew K.; ZHOU, Huilin; DEGROOT, John; SULMAN, Erik P.; CAVENEE, Webster K.; KOLODNER, Richard D.; CHEN, Clark C.; FURNARI, Frank B.