Coeliac disease is a chronic autoimmune-like enteropathy induced by dietary gluten in 0.5-2% Europeans. A rare but specific complication is the onset of invasive enteropathy-associated lymphomas. The host laboratory has demonstrated that in approximately 70% of CD patients, invasive lymphomas are preceded by a clonal low-grade intraepithelial lymphoproliferation, usually called type II refractory CD (RCDII).
I intend to take advantage of my experience in cellular immunology and single-cell analyses: 1- to analyse the peri-tumor microenvironment and search for anti-tumoral T cell response in RCDII; and 2- to analyse the functional intra-clonal heterogeneity among RCDII malignant cells. The results should provide further insight into the mechanisms, which control disease progression and will help us to assess therapeutic strategies. This project will complete and extend the on-going genomic analysis of lymphomas complicating CD. It will notably help to assess if the JAK1/STAT3 pathway is a pertinent therapeutic target and the possible interest of checkpoint inhibitors.
To achieve the aims of the innovative translational project, I will integrate one of the European leader research center in genetic diseases, giving me the opportunity to gain experience in translational immunology and human genetics, as well as to reinforce my expertise in cutting-edge single cell technologies and bioinformatics. Overall this project represents a unique stepping-stone to complete my training in pathophysiology and establish collaborations, which should put me in excellent position to establish as an independent researcher.
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