Descrizione del progetto
Approfondimento sulla formazione di linfomi in pazienti affetti da celiachia
La celiachia è una malattia autoimmune caratterizzata dall’intolleranza al glutine, una proteina presente in alcuni cereali. I linfomi che complicano la celiachia derivano da un sottogruppo di linfociti innati intestinali che hanno sviluppato mutazioni in JAK1 e/o STAT3. Il blocco mirato di JAK1-STAT3 emerge quindi come una possibile opzione terapeutica per eliminare le cellule tumorali. Tuttavia, le cellule maligne, anche nella fase iniziale della linfoproliferazione, presentano ulteriori mutazioni. L’obiettivo del progetto SingCelCD, finanziato dall’UE, è esaminare in che modo le terapie mirate possano essere controproducenti a causa della presenza di sottopopolazioni tumorali refrattarie e possano interferire con la risposta antitumorale. I risultati aiuteranno a comprendere l’insorgenza del linfoma e apriranno la strada all’identificazione di bersagli terapeutici.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF-EF-RI - RI – Reintegration panelCoordinatore
75015 Paris
Francia