Le mercredi 2 octobre 2024, Monsieur Sébastien PIRSON, titulaire d’un Master en sciences biomédicales à finalité approfondie et d’un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques, sous la direction de Madame Agnès NOËL. 

Cette épreuve consistera en la défense publique d'une thèse intitulée :  "New partners of uPARAP involved in pathological lymphangiogenesis".

Le jury sera composé de :

Chantal HUMBLET (Présidente), Christophe DEROANNE (Secrétaire), Pascale HUBERT, Fabrice JOURNE (Inst. Bordet), Agnès NOËL, Sophie TARTARE DECKERT (Univ. Nice).

Résumé de la thèse :

Recently, the uPARAP/Endo180 protein was identified as a regulator of lymphangiogenesis.  Its genetic ablation in mice leads to excessive proliferation and hyperbranching of the lymphatic vasculature. In order to better understand the molecular mechanisms involved in this process, we searched for new binding partners and transcriptomic targets of uPARAP/Endo180. Among the proteins identified as being linked to uPARAP, we found VE-Cadherin and AXL. Using different variants, we identified the CTLD-3/4 domains of uPARAP/Endo180 as being responsible for the interaction with VE-Cadherin. Related to AXL, the transcriptomic approach in lymphatic endothelial cells (LECs) also identified the regulation of AXL by uPARAP/Endo180. Its role in lymphangiogenesis remained unknown until now. We have shown that this receptor is expressed in a specific population of LECs in lymph nodes, and that it is overexpressed in the metastatic state of lymph nodes. Its silencing or inhibition in LECs significantly reduced their migration and proliferation in vitro in 2D and 3D models. We also demonstrated that its activation was induced by VEGF-C and that it reinforced this pathway via PI3K/AKT signaling. Finally, its role, in vivo, in VEGF-C-induced lymph vessel budding was demonstrated by the use of inhibitors in a lymph node lymphangiogenesis model.