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Single Cell approaches for the study of oncogenic processes during coeliac disease.

Project description

Insight into lymphoma formation in patients with coeliac disease

Coeliac disease (CD) is an autoimmune disease characterised by intolerance to gluten, a protein found in some grains. Lymphomas complicating CD are derived from a subset of gut innate lymphocytes that have acquired mutations in JAK1 and/or STAT3. Targeted JAK1-STAT3 blockade therefore emerges as a possible therapeutic option to eliminate tumour cells. Yet malignant cells, even at the early stage of lymphoproliferation, display additional mutations. The scope of the EU-funded SingCelCD project is to investigate how targeted therapies may be counter-productive due to the presence of refractory tumour subpopulations and could interfere with anti-tumour response. Results will help understand the onset of lymphoma and pave the way towards the identification of therapeutic targets.

Objective

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.

Coordinator

IMAGINE INSTITUT DES MALADIES GENETIQUES NECKER ENFANTS MALADES FONDATION
Net EU contribution
€ 196 707,84
Address
24 BD DU MONTPARNASSE
75015 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
€ 196 707,84