Postdoctoral Fellow

Manon Tifenn Sarah Durand

Profile

I hold a PhD in Biochemistry, Cellular and Molecular Biology from the University of Burgundy, France, where I specialized in B-cell lymphomas and the role of heat shock proteins in survival signaling and targeted therapy. My research gave me expertise in biomarker validation, including the analysis of exosomes as potential biomarkers, and I developed the CAM (chorioallantoic membrane) assay for lymphoma xenografts, enabling the evaluation of novel therapeutic strategies. With a strong foundation in lymphoma biology and translational research, I am eager to apply these methodologies to the IJC postdoctoral project focused on identifying diagnostic and therapeutic biomarkers in T-cell lymphomas.

Project description

Angioimmunoblastic T-cell lymphoma (AITL) is a lymphoid neoplasm affecting elderly people, characterized by a sudden onset of symptoms and extended disease with a 5-years survival rate of 32%. It is originated by permanently active T follicular helper cells (Tfh) and constantly stimulates massive GC B cell division. Recently, identification of a group mutations in genes involved in epigenetic regulation (RHOA, TET2, IDH2, DNMT3A) has led to new drugs development with no significant improvement in patients’ outcome yet. We have characterized two animal models: plck-GAPDH and Apaf-1+/- showing similar lymphoproliferative disorder at late stages of life with striking similarities to human AITL. Besides, a new subpopulation of Tfh presenting two T cell receptors (TCRs) on their surface was identified. We hypothesize AITL origin could be in these abnormal T cells, opening a new diagnostic and disease progression monitoring biomarkers based on the expression of the different TCR chains. To prove our hypothesis, we will study thymopoiesis potential role in disease appearance using Apaf- 1 deficient mouse models. Defective TCRs activation response will be also analyzed to discard tumor origin during post-thymic events. Systematic study of the presence of these two TCRs by immunofluorescence analysis in AITL and other T cell lymphoma samples will be done to quantify the potential efficacy of the treatments and proper diagnosis. Finally, making use of the chicken chorioallantoic membrane model injected with tumoral Apaf-1 deficient cells and AITL patients’ biopsies, we will evaluate the therapeutic impact of blocking antibodies and CAR-T cell targeting one of these TCRs. Tumor size measurements and tumoral cells phenotypical characterization by flow cytometry and immunofluorescence will be done during and after the treatment.