Developmental haematopoiesis and it’s impact on leukaemogenesis in infants

Seminar Synopsis

The overall aim of the research in the Ottersbach lab is to understand how blood is generated during development and how this process can go wrong during leukaemogenesis in infants. Both of these topics will be covered in the talk.  One focus is the emergence of the first haematopoietic stem cells (HSCs) and how this is regulated by the local microenvironment. Through our long-term work on the transcription factor Gata3 and the cell cycle regulator p57Kip2, we have uncovered a functional interplay between the developing haematopoietic and the sympathetic nervous system, with the latter providing the neurotransmitters catecholamines, which support the first HSCs. Gata3 and p57Kip2 also regulate the emergence of HSCs from the haemogenic endothelium in a more direct manner, and the next challenge will be to understand how these two functions are integrated. Our studies have further uncovered important differences between embryonic, foetal and adult HSCs and progenitors. This has evolved into the other main line of research in the lab, concerning the developmental origins of infant leukaemia. As a model, we are using infant leukaemia associated with the MLL-AF4 translocation. We have generated a pre-leukaemia model for this disease and have successfully used it for the discovery of factors, such as the miRNAs miR-130b and miR-128a, that can drive a full leukaemic phenotype. We are also further dissecting the unique properties of foetal progenitors that are essential contributors to leukaemia development in infants.

About Katrin Ottersbach

Katrin Ottersbach obtained her PhD in 2001 at the Beatson Institute for Cancer Research (Glasgow, UK) under the supervision of Prof. Gerard Graham working on the role of chemokines in haematopoietic progenitor regulation. She then joined the lab of Prof. Elaine Dzierzak (Erasmus MC, Rotterdam, Netherlands) as a postdoctoral fellow, where she started working on the generation of haematopoietic stem cells during mouse development. From there she moved to the University of Cambridge, UK, to start her own lab in 2006, still focusing on haematopoietic stem cell emergence, but with an interest in the niche. In recent years, her group has also started working on the developmental origins of infant leukaemia. In 2015, she moved her lab to the MRC Centre for Regenerative Medicine at the University of Edinburgh, Scotland.