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Home » Proyectos de investigación » Metabolomic, proteomic and transcriptomic study of exosomes and extracellular DNA isolated from plasma of Paroxysmal Nocturnal Hemoglobinuria disease patients.
Título: Metabolomic, proteomic and transcriptomic study of exosomes and extracellular DNA isolated from plasma of Paroxysmal Nocturnal Hemoglobinuria disease patients.
IP: Dra. Irene Martínez Martínez / Dr. Constantino Martínez
Resumen del proyecto: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disease of the blood caused by the acquired mutation of the PIG-A gene. In consequence, there is an intrinsic defect in the cell membrane caused by the deficiency of GPI leading to the absence of protective proteins on the membrane. This causes the destruction of red blood cells by the complement system. The clinical manifestation of PNH is an intravascular hemolytic anemia with a high incidence of thrombosis, not totally understood. It may also develop in the context of other bone marrow disorders. Eculizumab is an effective treatment antibody that blocks complement component C5, impairing the the hemolysis and reducing the risk of thrombosis. Lately, there is an increasing interest in the study of exosomes since it has been demonstrated that the number of circulating exosomes increases in patients with inflammatory manifestations. Exosomes are 40-100 nm Ř membrane vesicles that can be detected in body fluids such as serum and plasma. The biological function of exosomes in vivo remains unclear. However, they seem to be involved in cell–cell communication, activating signaling pathways and transferring genetic information to other cells (mRNAs and miRNAs). On the other hand, plasma DNA has been associated to an increased thrombotic risk. In the PNH disease, where there is a higher sensitivity to cell lysis, it is expected that high levels of plasma DNA may contribute to the thrombotic risk. In this project, we aim to study the metabolome, proteome and transcriptome of exosomes from patients diagnosed of PNH. We also aim to investigate circulating levels of extracellular DNA and to find a correlation with the thrombotic risk and the treatment with Eculizumab. In summary, we aim to deepen into the thrombotic risk and hypercoagulability underlying PNH and to try to identify prothrombotic biomarkers in these patients.
Entidad financiadora: Instituto de Salud Carlos III
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University of Salamanca
Nucleus
PRB2
Biobanks Network
Institute Carlos III
Junta de Castilla y León
European Union
Banco Nacional de ADN
Edificio Multiusos I+D+i (Universidad de Salamanca)
C/ Espejo s/n. 37007 Salamanca
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