Chronic inflammatory responses have been shown to promote cancer development at multiple stages.90% ofperipheral T cell lymphoma (PTCL)show overexpression of the membrane proximal kinase SYKandin 17% of human PTCL, the recurrent translocation t(5;9)(q33;q22) generates a fusion protein containing the ITK and SYK kinases. This ITK-SYK fusion protein induces antigen-independent TCR signalling that is directly associated with lymphoma formation[11, 12]. In metabolic active malignant cells tight regulation of ROS-detoxifying pathways is required. The PhD candidate will investigatethe function of the antioxidant GSH-GCL complex in a clinical relevant model of PTCL in vivo.In a transgenic mouse model we will express the only known recurrent translocation found inPTCL patients (ITK-SYK). Thus, we are in the position to model the molecular events of human PTCL in a genetic mouse model. Elucidation of signaling and metabolic changes (caused by GCL-deficiency) in the context of PTCL might revealspecific targets for a therapeutic intervention, since currently, treatment options for PTCL are very limited
|Acronym||NEXTIMMUNE (Luana Guerra)|
|Effective start/end date||9/01/17 → 8/01/21|
- FNR - Fonds National de la Recherche: €169,500.00
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