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PROTEOmAb
PROTEOmAb provides a service for quantitative analysis of energy metabolism proteins and oxidative stress in biological samples in a simple and repeatable manner, using high- affinity and high-specificity monoclonal antibodies (mAbs) developed by the service itself. This service is provided through the Centro de Biología Molecular Severo Ochoa.
The most noteworthy achievements of 2016 involve the following activities:
Identification of new diagnostic biomarkers and progression of pathology in biopsies of patients affected by rare diseases.
• Peripheral neuropathies: In the framework of the TREAT-CMT project and in cooperation with U732 (Dr. Palau) and U763 (Dr. Vilchez) it has been identified in skin biopsies of patients with Charcot-Marie- Tooth (CMT) 1A that proteins of the OXPHOS system and of the antioxidant system provide new early biomarkers of the progression of the disease. We have also developed a non-oriented and high- performance metabolomic approach which has enabled identifying non-invasive plasma biomarkers which are correlated with the stages in the progression of the disease and which can thus facilitate diagnosis and prognosis of patients with Charcot-Marie-Tooth 1A.
• Inflammatory myopathies: in cooperation with group U722 (Dr. Cardellach) new biomarkers for differential diagnosis of DM and sIBM have been identified in biopsies of patients affected by Polymyositis (PM), Dermatomyositis (DM) and Sporadic Inclusion Body Myositis (sIBM). We should stress PKM2 and IF1 as potential markers of development of cancer in DM.
• Pathologies with effect on the OXPHOS system: in cooperation with units U723 (Dr. Martín) and U701 (Dr. Martí) we are proceeding to analyse the markers of metabolism in biopsies of muscle of patients with progressive external ophthalmoplegia (PEO) with single or multiple deletion of the mitochondrial DNA (mtDNA). A cohort of patients with mitochondrial encephalomyopathy with lactic acidosis (MELAS) is also being studied, with healthy individuals to identify markers of differential diagnosis
of these diseases using the reverse phase protein array platform (ProteomAb). The project is in the implementation phase.
Phenotyping of animal models of rare diseases.
• Phenotyping of the model of Propionic Acidemia (2015-2016): In cooperation with group U746
(Dr. Pérez) an analysis has been made of the metabolic phenotype of different tissues of hypomorphic model of mouse Pcca-/-(A138T) of Propionic Acidemia disease at different ages. The analysis of the experimental model has enabled identifying alterations in the expression of specific proteins of energy metabolism of the tissue. The metabolic changes identified are maintained in each tissue regardless of the age, except for the brain, whose alterations proved to be less pronounced in older mice. The study led to the following publication:
In vivo evidence of mitochondrial dysfunction and altered redox homeostasis in a genetic mouse model of propionic acidemia: Implications for the pathophysiology of this disorder. L. Gallego-Villar, A. Rivera- Barahona, C. Cuevas-Martín, A. Guenzel, B. Pérez, M.A. Barry, M.P. Murphy, A. Logan, A. Gonzalez- Quintana, M.A. Martín, S. Medina, A. Gil-Izquierdo, J.M. Cuezva, E. Richard, L.R. Desviat. Free Radical Biology and Medicine, 2016 Jul;96:1-12.
• Metabolic phenotyping of Mouse Embryonic Fibroblasts. In cooperation with Dr. José M Torres’ group of the Universitat de Valéncia an analysis was made of the metabolic phenotype of mouse embryonic fibroblasts (MEFs), embryonic stem cells (ESCs) and of induced pluripotent stem cells (iPSCs) during reprogramming induced by different cell reprogramming factors.
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