Abstract: I am investigating the role of TGFbeta in the formation of haematopoietic stem cells (HSCs), a self-renewing multipotent progenitor population that generates and maintains all mature blood cells. HSCs arise during embryonic development from a subset of the arterial endothelium, t

he haemogenic endothelium, and supply blood cells throughout adult life. TGFbeta is required to programme the endothelium to become haemogenic and it does so by regulating endothelial expression of the Notch ligand Jag1a. The requirement for TGFbeta is two-fold and sequential: autocrine, via Tgfb1a and Tgfb1b produced in the endothelial cells themselves, followed by a paracrine input of Tgfb3 from the notochord, suggesting that the former programmes the haemogenic endothelium and the latter drives the process of endothelial to haematopoietic transition. This is the first instance where TGFbeta signalling is directly implicated as a positive input in the formation of HSCs.

Biography: I am a BHF Intermediate Basic Science Research Fellow, with a focus on the genetic programming of haemogenic endothelial cells by TGFbeta signalling. I am interested in learning how extrinsic signalling impinges on lineage fate decisions during embryonic development, and how cells carry out those decisions in vivo. Understanding the molecular mechanisms underpinning the differentiation of endothelial cells and of blood stem cells in the embryo will inform current unsuccessful attempts to generate blood cells in vitro for therapeutical use. I first ventured into developmental biology as a Biochemistry undergraduate, studying Notch target genes in chick embryos. After this, I went on to pursue a PhD in Developmental Biology at the Hubrecht Institute in Utrecht, The Netherlands. I started using zebrafish during my PhD and identified two zebrafish BMP receptors that were required for left-right asymmetry. Later I joined Roger Patient’s lab to do research on developmental haematopoiesis. In 2014 I became a Principal Investigator in the Radcliffe Department of Medicine at the University of Oxford, hosted in Prof. Patient’s lab.