Publications

• Chagraoui H, Kassouf M, Banerjee S, Goardon N, Clark K, Atzberger A, Pearce A C, Skoda R C, Ferguson D J, Watson S P, Vyas P, and Porcher C (2011) SCL-mediated regulation of the cell cycle regulator p21 is critical for murine megakaryopoiesis. Blood, 118(3):723-35.

• El Omari Kamel, Hoosdally Sarah J, Tuladhar Kapil, Karia Dimple, Vyas Paresh, Patient Roger, Porcher Catherine, and Mancini Erika J (2011) Structure of the leukemia oncogene LMO2: implications for the assembly of a hematopoietic transcription factor complex. Blood, 117(7):2146-56.

• Kassouf M T, Hughes J R, Taylor S, McGowan S J, Soneji S, Green A L, Vyas P, and Porcher C (2010) Genome-wide identification of TAL1's functional targets: Insights into its mechanisms of action in primary erythroid cells. Genome Res, 20(8):1064-83.

• Kassouf Mira T, Chagraoui Hedia, Vyas Paresh, and Porcher Catherine (2008) Differential use of SCL/TAL-1 DNA-binding domain in developmental hematopoiesis. Blood, 112(4):1056-67.

• Hamlett Isla, Draper Julia, Strouboulis John, Iborra Francisco, Porcher Catherine, and Vyas Paresh (2008) Characterization of megakaryocyte GATA1-interacting proteins: the corepressor ETO2 and GATA1 interact to regulate terminal megakaryocyte maturation. Blood, 112(7):2738-49.

Understanding how stem cells are specified during embryonic development and how lineages differentiate to produce mature and specialised cells are central questions in biology and are of crucial interest to elucidate pathways involved in diseases.

Our research interests revolve around the molecular mechanisms involved in haematopoietic stem cell (HSC) specification from mesodermal precursors during development and in lineage maturation. The oncoprotein SCL/Tal-1 is a transcriptional regulator playing essential roles in HSC specification, terminal maturation of important blood lineages and leukaemogenesis (T-ALL, T-cell acute lymphoblastic leukaemia). Therefore, SCL is a molecular tool of choice to address the above questions in normal and malignant haematopoiesis.

Our goal is to identify regulatory protein complexes nucleated by SCL and their nuclear targets to get insight into the transcriptional networks engaged at the earliest stages of haemopoiesis as well as in erythroid and megakaryocytic development.

A large part of our work uses in vitro assays of embryonic stem (ES) cell differentiation. This culture system allows access to mesodermal/ immature haematopoietic precursors as well as to all types of differentiated haematopoietic lineages. In parallel, we have developed complementary and synergistic experimental strategies through the use of different genetic systems. Large-scale gene expression, ChIP-on-chip and proteomic approaches have also been set up.

Deciphering the molecular pathways required for HSC development and lineage differentiation is not only important for understanding normal blood development but also the pathogenesis of leukaemias.