Postdoctoral Research Scientist
I did my PhD in France in Prof William Vainchenker’s lab (Institute of Gustave Roussy, Villejuif, Paris) under the supervision of Dr Francoise Wendling. I was interested in understanding the role of TGFb1 and megakaryocytes in the development of myelofibrosis in a mouse model. In 2003, as a postdoctoral researcher, I joined Prof Catherine Porcher’s lab whose main interest was to understand blood development and maturation through the function of the haematopoietic transcriptional regulator SCL/Tal-1. Having a strong background in megakaryopoiesis, my first project was to characterise SCL’s role in the development of the megakaryocytic lineage. This work showed that SCL critically controls megakaryocytic terminal differentiation through the transcriptional regulation of the cell-cycle regulator p21. After completion of this work, I focused on the role of SCL in early mouse blood development.
How a given transcription factor imposes a specific fate to multipotent progenitors is still a matter of debate. My project focuses on the emergence of the blood programme from mesodermal precursors through characterisation of the molecular mechanisms engaged by SCL, the earliest regulator of blood specification. Our cellular model is the mouse ES cell/embryoid body (EB) differentiation system that faithfully recapitulates the early events of embryogenesis. To identify the SCL-driven regulatory networks governing blood specification, I have used ATAC-, ChIP- and RNA-sequencing analyses in parallel with functional studies.
Establishment of an ES cell-derived murine megakaryocytic cell line, MKD1, with features of primary megakaryocyte progenitors.
Chagraoui H. and Porcher C., (2012), PLoS One, 7
SCL-mediated regulation of the cell-cycle regulator p21 is critical for murine megakaryopoiesis.
Chagraoui H. et al, (2011), Blood, 118, 723 - 735
A major role of TGF-beta1 in the homing capacities of murine hematopoietic stem cell/progenitors.
Capron C. et al, (2010), Blood, 116, 1244 - 1253
Differential use of SCL/TAL-1 DNA-binding domain in developmental hematopoiesis.
Kassouf MT. et al, (2008), Blood, 112, 1056 - 1067
Adenoviral-mediated TGF-beta1 inhibition in a mouse model of myelofibrosis inhibit bone marrow fibrosis development.
Gastinne T. et al, (2007), Exp Hematol, 35, 64 - 74