Michaela Fontenay’s team – Normal and pathological hematopoiesis

Identification and functional characterization of anomalies in RNA splicing, translation and decay in AML and myelodysplastic neoplasms. Post-transcriptional regulations of gene expression contribute to leukemic cell reprogramming and resistance to treatments. The objectives of this axis are (i) to identify neo-antigens generated by splicing aberrancies and characterize the lymphocyte T CD8 immune response, and (ii) to identify protein expression bias due to RNA selective translation or decay and draw the consequences on leukemic cell biology and sensitivity to treatments.

Study of functional interactions between leukemic cells and their microenvironment. Mesenchymal stroma cells of the microenvironment are implicated in the maintenance of an inflammatory state of the bone marrow facilitating the emergence and progression of myelodysplastic neoplasms including VEXAS syndrome and AML. The contribution of immune cells still remains elusive. The objectives of this axis are (i) to study metabolic interactions between leukemic and stromal cells conferring resistances to treatments both in vitro and in vivo via ossicles mimicking humanized bone marrow niche in mice and (ii) to decipher the pro-inflammatory role of T CD8 lymphocytes.