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Research areas

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        The laboratory focuses on a systemic perspective of the etiology and potential treatments of metabolic diseases (system biology approach). For this purpose, functional parameters, metabolic/metabolomics, genetics, epigenetics and proteomics platforms are being used and a wide range of bioinformatics tools are being implemented for the mapping, combination and integration of datasets.

 

        In addition, cancer and diabetes-induced metabolic alterations in the liver using gene delivery and silencing (siRNA) approaches of key metabolic and signal-transduction proteins in vivo. The initial onset of metabolic changes associated with the disease is characterized by resistance to insulin action and inflammation, together with gene expression remodeling and significant changes in the metabolome of the hepatocyte. Insights into these adaptations have been obtained from gene-altered mice (KO, Transgenic, etc.), although important aspects related to this organ metabolic zonation, energetics and mitochondrial function have not been dealt with appropriately. Through a combination of cell culture and experimental gene therapy approaches in vivo, such as receptor-mediated and hydrodynamic gene transfer, we are uncovering novel information on the integration of intracellular signaling pathways and the mitochondria, responsible for the regulation of metabolic stress response through the balance of energy production and consumption. High resolution respirometer allows us to evaluate the contribution of each element of the respiratory chain to the overall mitochondrial function and relate the observed alterations to the integrated metabolome.

In addition, we and our collaborators are developing and characterizing novel, chemically-modified siRNA for specific delivery into target organs to inhibit macrophage-mediated tumor survival and inflammation.

        The group is integrated in the IDIBELL program for “Diabetes and Metabolism” that studies: a) molecular and cellular biology of pancreatic islet, and in particular, the mechanisms of regeneration of b-cells for its use in the treatment of diabetes, b) the role of adipose tissue in the metabolic and hormonal alterations that link obesity and diabetes, and c) the regulation and metabolic integration of chronic processes associated to obesity-related type-2 diabetes, cancer and neurodegenerative disease, together with the signaling implicated in the control of cellular metabolism through the mitochondria.