Thesis defense Angélique Blangy--Letheule

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  • Le 09 October 2023
    Amphi DE
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  • 13h30

Title of the thesis : Characterization of candidate biomarkers or therapeutic targets emerging from secretome analysis during septic shock: a translational approach

Equipe

Team II - Ion channels and cardiopathies


Directeur de thèse

Benjamin Lauzier


Co-directeur

Bertrand Rozec


Co-encadrante

Aurélia Leroux


Rapportrices

Hélène Amory, PU, Equine Clinical Department, Faculty of Veterinary Medicine, Fundamental and Applied Research for Animals & Health, Faculty of Veterinary Medicine, University of Liège

Anne-Claire Lukaszewicz, PU-PH, Hospices civiles de Lyon, EA 7426 "Pathophysiology of Injury-Induced Immunosuppression", Joint Research Unit HCL-bioMérieux


Examinateur

Paul Mulder, PU, INSERM EnVI UMR 1096, Univ Rouen Normandie

 

Abstract

Septic shock is a systemic inflammatory response syndrome associated with circulatory failure leading to organ dysfunction. It is associated with one death every 3 seconds worldwide. Currently, there is no early, sensitive and specific biomarker available to improve the management of patients in septic shock. The secretome is the set of proteins secreted by a cell, a tissue or an organism at a given time and under certain conditions. It is easily accessible from plasma and can be studied by a nontargeted proteomics approach. The objectives of my thesis were to study and identify biomarkers in the secretome of experimental and spontaneous models of sepsis as well as of patients with viral pneumonia. For this purpose, a rat model of endotoxemic shock was used to validate the enrichment of low abundance proteins. For this purpose, a rat model of endotoxemic shock was used to validate the enrichment of low abundance proteins in plasma by ProteoMiner® in order to identify deregulated proteins during the development of the pathology. The transfer to humans being complicated with regard to the model used, we used a model of equine spontaneous sepsis closer to the pathophysiology of humans. A diagnostic score for equine sepsis was developed to be able to accurately stratify patients and perform robust and reproducible studies. At the same time, horses with sepsis were selected and their plasma secretome analyzed to identify candidate biomarkers. This approach has also been used to identify biomarkers for viral pneumonia in humans, demonstrating that the plasma secretome can serve as a source of biomarkers for sepsis and other diseases.
Mis à jour le 02 October 2023 - Elise MARTINEAU.
https://umr1087.univ-nantes.fr/training/thesis-defense-angelique-blangy-letheule