Duhagon Serrat, María Ana


Grado y Servicio

Grado 3 / Facultad de Medicina / Departamento de Genética


Email: mduhagon@fcien.edu.uy / Teléfono: 098763245

Área disciplinar


Disciplina / Subdisciplina

Biología Molecular / Parasitología molecular / Genética Molecular Humana

Mayor nivel académico

Doctorado, PEDECIBA (año 2007)

Link a web personal

Link a CVUY

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Pertenece al SNI

Si pertenece / Nivel I

Pertenece al PEDECIBA

Si pertenece / Grado 3


Título del Plan de Actividades

Biología Molecular básica en T.cruzi y aplicada en enfermedades genéticas humanas

Palabras clave

cancer, prostata, microARN, cruzi, genoma, transcriptoma, madre,ARN, expresion, genes

Resumen Publicable

A CONTINUACION SE RESUMEN LAS DOS LINEAS DE TRABAJO ACTUAL.1.PROSTATE CANCER (PCa) is the second most frequently diagnosed cancer and cause of cancer death among men in the US and Uruguay. Our work focuses on the understanding of the role of cancer stem cells (CSC) in PCa initiation and progression. CSCs are a minor subpopulation of cells with stem cell like characteristics which have been shown to be responsible for the initiation, maintenance and evolution of the tumor. These attributes are due to their multipotency, self-renewal ability and phenotypic plasticity, and have fundamental implications in treatment resistance and metastasis. For this reason CSCs are viewed as the remaining seed responsible for relapse and metastasis after treatment. We have developed a model for PCSC differentiation and we have identified genes that may be driven the process. Most of our current studies are on three microARNs (miRs) identified by this approach. MiRs are extensively deregulated in cancers and can be used for disease stratification, follow up, prognosis and therapeutics. We seek for the elucidation of their effect in the neoplasic phenotype, the discovery of their protein targets and the validations of the candidate gene-target pairs in the clinical set. We will finally assess the potential of the selected miRs to predict the clinical presentation and outcome of the disease. The characterization of miRs associated to the origin and progression of PCa and the validation of their relevance in the clinical set would be a significant achievement for the future use of these molecules in the clinical management of the disease.2. TRYPANOSOMA CRUZI (T. cruzi) is the causative agent of Chagas disease, a neglected parasitosis that affects Latin American shantytowns, representing the highest parasitic economic burden. The therapeutic drugs currently used to treat the disease have low efficacy and are highly toxic for the patient, so the development of new drugs with improved efficacy, higher specificity for the parasite and less toxicity for the host is imperative. Although little is known about the global mechanisms governing proliferation and differentiation of trypanosomatids, genomic studies have revealed that they greatly diverge from those of the human host, which makes them particulate suitable targets for the development of parasite specific pharmacological therapies. Our project aims to uncover new molecules responsible for the control and progression of the proliferative cycle of T. cruzi through the high throughput, comprehensive and quantitative identification of genes deferentially expressed in the various parasite stages. We will perform RNA-seq studies from total RNA (transcriptome) and Ribo-seq studies of actively translated mRNA (translatome). The latter is obtained from polysomes after a nuclease digestion that generates ribosome footprints (Ingolia et al., 2009), whose abundance represents the rate of the mRNA translation for each gene. Since trypanosomatids exert a poor control of gene expression at the level of transcription, mRNA stability and translatability are proposed to represent major regulatory points. There is in fact mounting evidence of the global regulation at RNA stability obtained by microarrays or RNA-seq in trypanosomatids, but we still lack any assessment of the importance of translation regulation in these organisms. “Ribo-seq” or global ribosome footprint analysis has emerged as a new tool to address this question. It also has the advantage to provide a more realistic picture of the gene expression profiles in the cell than the obtained by the transcriptome.We isolate total mRNA and ribosome footprints from each stage to generate adapted libraries sequence with high throughput sequence them. The data is analyzed bioinformatically to identify genes differentially expressed. We also study the patterns of gene regulation at the level of stability and translatability of the mRNAs. We this data we will be able to assess the characteristics of the global translation regulation of the mRNA for the first time in trypanosomatids. We will also study the differentially regulated proteins specific for the parasite, with no ortologous in the human host, in order to select those which meet the criteria for a desirable drug target. Overall, our study would help to further understand the mechanisms that determine parasite replication and differentiation and to discover new targets for the design of more specific drug therapy.

Grado y Fecha de Ingreso al RDT

Grado 2 / Desde: 2010-04-01

Programa: Científico Proveniente del Exterior

El cargo NO se enmarca en este programa

Participa de Grupo Autoidentificado

No participa de ningún grupo autoidentificado



Curriculum Vitae

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Producción Académica

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