Caracterização funcional de fatores de transcrição envolvidos na regulação do metabolismo de glicogênio de Neurospora crassa

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Identificação de proteínas ligantes de CRABP2, proteína envolvida na via de sinalização celular por ácido retinóico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Mapeamento fino de qtls e polimorfismos de genes candidatos associados ao crescimento no cromossomo 1 da galinha

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desempenho e concentrações de alguns componentes do metabolismo intermediário de frangos com potencial de crescimento diferenciado submetidos ao estresse por calor

Pós-graduação em Zootecnia - FCAV

Busca de parceiros físicos da proteína CRABP2, utilizando o sistema de duplo-híbrido em Saccharomyces cerevisae

A metilação de ilhas CpG em regiões regulatórias de vários genes tem sido descrita como um processo importante no silenciamento de genes supressores de tumor e diretamente envolvida no processo de carcinogênese de uma série de tumores. O estudo desses genes afetados pela metilação em tumores visa à procura de marcadores moleculares para o diagnóstico, prognóstico e tratamento de tumores, e também a caracterização do seu papel no processo biológico do câncer. O nosso grupo de pesquisa participou de um Projeto Temático que visa a identificação de genes metilados em tumores de cabeça e pescoço (processo 03/09497-3) e foi então proposta a utilização do sistema de duplo-híbrido de levedura como ferramenta no início da análise funcional destes genes. Dessa maneira, utilizando como isca o gene CRABP2 identificado como diferencialmente metilado em câncer de cabeça e pescoço, foi realizado o rastreamento de duplo-híbrido para a identificação de interações físicas proteína-proteína. Foram rastreados aproximadamente 2,1x105 transformantes neste sistema, dos quais 550 foram inicialmente positivos para His+. Desses, 182 transformantes confirmaram a marca His+ e foram testados para -galactosidase. Em seguida, 19 foram selecionados para passar pela etapa do “plasmid linkage”. Após esse teste, 9 clones confirmaram a ligação dos marcadores His+ e β-gal+ com a presença do plasmídeo LEU2 . Assim, após o sequenciamento dos insertos contidos nos clones identificados, ciclina D3 (CCND3), alfa-macroglobulina 2 (A2M) (2 clones), canal aniônico dependente de voltagem 2 (VDAC2), tubulina alfa 1 (TUBA1), tubulina alfa 2 (TUBA2), tubulina beta (TUBB), fator de ligação ao “enhancer” do gene interleucina 2 (ILF2) e desoxi-hipusina sintase (DHPS) emergiram como ligantes de CRABP2

Estudo das interações entre proteína NS1 do hRSV e flavonóides utilizando métodos biofísicos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeito protetor da proteína anti-inflamatória Galectina-1 sobre o processo de uveíte induzida pelo inflamógeno lipopolissacarídeo

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo do papel da proteína eIF5A na elongação da tradução em S. cerevisiae: análise da relação funcional com o trna de alanina e sua participação na síntese proteica geral da célula

Pós-graduação em Biotecnologia - IQ

Caracterização funcional do fator da tradução eIF5A por meio de interações genéticas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Caracterização biofísica da interação entre a proteína M2-1 do Vírus Sincicial Respiratório Humano (HRSV) com quercetina

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Correlação da imunoexpressão do fator de choque térmico 1 (hsf1) com aspectos clinicopatológicos em carcinomas de células escamosas de língua oral

Squamous cell carcinoma of oral tongue shows high rates of morbidity and mortality in the population, therefore, great efforts are being made to classify morphological changes and identify biomarkers that have prognostic value and that are able to group patients in individualized therapeutic options. From this perspective, there is the heat shock factor 1 (HSF1), which is a heat shock factor transcription protein (HSPs) that allows the cancer to deal with stressors associated with malignancy, acting differently in tumor progression. This research aimed to perform a clinico-pathological analysis of 70 cases of oral tongue squamous cell carcinoma (OTSCC) and immunohistochemical study of the expression of HSF1 protein in OTSCC, comparing it with 30 specimens of normal oral mucosa (NOM), and correlating this immunostaining with clinico-pathological aspects of OTSCC. To analyze the association between immunoexpression of HSF1 and clinicophatoloical aspects, the cases were categorized in minor and major overexpression, based in the median immunostaining score. Regarding the cases of OTSCC, 57.1% showed clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998) and 47.1% as high risk of malignancy according to Brandwein-Gensler et al., (2005). A disease free survival rate of 47.84% and overall survival rate of 68.20% was observed in the analyzed cases, and the high degree of malignancy according to Bryne’s system (1998) (p=0.05), tumor size T3 or T4 (p=0.04), local recurrence (p=0.02), and perineural invasion (p=0.02) determined negative impacts in survival time. We observed also a statistically significant result (p<0.01) when comparing the immunoreactivity of HSF1 between NOM and OTSCC. This significantly increased expression of HSF1 in cases of OTSCC suggests that this protein acts, indeed, in the pathogenesis of this disease. However, there were no statistically significant associations between this overexpression and the clinico-pathological parameters analyzed. This finding may reflect the influence of epigenetic events on HSF1 gene or a possible stability of this protein expression throughout disease progression.

Correlação da imunoexpressão do fator de choque térmico 1 (hsf1) com aspectos clinicopatológicos em carcinomas de células escamosas de língua oral

Squamous cell carcinoma of oral tongue shows high rates of morbidity and mortality in the population, therefore, great efforts are being made to classify morphological changes and identify biomarkers that have prognostic value and that are able to group patients in individualized therapeutic options. From this perspective, there is the heat shock factor 1 (HSF1), which is a heat shock factor transcription protein (HSPs) that allows the cancer to deal with stressors associated with malignancy, acting differently in tumor progression. This research aimed to perform a clinico-pathological analysis of 70 cases of oral tongue squamous cell carcinoma (OTSCC) and immunohistochemical study of the expression of HSF1 protein in OTSCC, comparing it with 30 specimens of normal oral mucosa (NOM), and correlating this immunostaining with clinico-pathological aspects of OTSCC. To analyze the association between immunoexpression of HSF1 and clinicophatoloical aspects, the cases were categorized in minor and major overexpression, based in the median immunostaining score. Regarding the cases of OTSCC, 57.1% showed clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998) and 47.1% as high risk of malignancy according to Brandwein-Gensler et al., (2005). A disease free survival rate of 47.84% and overall survival rate of 68.20% was observed in the analyzed cases, and the high degree of malignancy according to Bryne’s system (1998) (p=0.05), tumor size T3 or T4 (p=0.04), local recurrence (p=0.02), and perineural invasion (p=0.02) determined negative impacts in survival time. We observed also a statistically significant result (p<0.01) when comparing the immunoreactivity of HSF1 between NOM and OTSCC. This significantly increased expression of HSF1 in cases of OTSCC suggests that this protein acts, indeed, in the pathogenesis of this disease. However, there were no statistically significant associations between this overexpression and the clinico-pathological parameters analyzed. This finding may reflect the influence of epigenetic events on HSF1 gene or a possible stability of this protein expression throughout disease progression.

Estudo do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition

Efeito do nível de proteína da ração no crescimento de Tenca (Tinca tinca), no crescimento de manjerição (Ocimum basilicum) e no balanço de nutrientes num sistema de Aquaponia

Dissertação de mestrado, Aquacultura e Pescas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014

Development of gene therapy to deliver the receptor-specific rhTRAIL DHER variant to induce apoptosis in activated hepatic stellate cells for the treatment of liver fibrosis

Dissertação de Mestrado, Engenharia Biológica, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014