Epigenetic Factors in Normal and Malignant Hematopoiesis

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At a glance
Polycomb group proteins constitute a family of chromatin proteins which are important for the control of cell proliferation and carcinogenesis. The defective function of these proteins is directly associated with the uncontrolled proliferation of blood cells and some factors which interact with polycomb protein complexes are suspected regulators of their activity. Our team aims to characterize these interactions and assess their role in normal development and in leukemia.

Our work contributes to improve the current understanding of hematopoiesis and will allow us to propose  new therapeutic strategies.

Overview
We are interested in mechanisms involved in cell fate decision in hematopoietic stem cells, differentiated cells and leukemic cells.

Our main goal is to understand how sequence specific transcription factors interplays with the chromatin acting Polycomb complexes (PcG) and how this interplay can affect cell fate and cell transformation through the repression or the activation of a gene program.

Experimental approaches
Characterization of PcG protein recruitment to chromatin

By combining genomic large-scale approaches and KD strategies on mouse and human cells we are addressing the mechanism of PcG protein recruitment to chromatin.

Epigenetic signature and cell identity

We are developing KO mouse model to address the role of PcG proteins and their epigenetic marks in HSC function. We demonstrated that the PLZF transcription factor interacts and recruits the PcG complex PRC1 and we are developing assay to address how PLZF intervenes in the recruitment or displacement of PcG proteins to chromatin and how this dynamic process influence HSC properties.

Identification and characterisation of new molecular targets in AML

By using epigenetic and gene expression profiling on patient samples we are evaluating the importance of abnormal PcG protein function in Acute Myeloid Leukaemia (AML) pathology and we are identifying new PcG deregulated targets in AML.