2011 - 2015
Programme: Wellcome Trust PhD Programme for Clinicians
Supervisor: Dr Katrin Ottersbach (co-supervisor: Brian Huntly)
Start year: Dec 2011
PhD Subject: A study of the developmental biology of infantile leukaemia in a mouse model
PhD Project Overview: In my research, I focus on a known leukaemia promoting mutation in the special context of the developing haematopoetic system - and how this origin may affect evolution of a pre-leukaemic clone into clinical disease.
A core doctrine in clinical paediatrics is that children are not “small adults” – that disease onset, progression, outcome and sequelae are dependent on aspects of growth and development from before birth through to adolescence. This can be readily demonstrated in the distinct spectra of cancers that are seen in children – which often have definite ages of peak incidence, with age often dictating the cancer’s biology, natural history and outcome. In the case of acute leukaemia, the most common malignancy of childhood, evidence from retrospective neonatal blood spot analysis suggests that pre-leukaemic clones are present at birth in many forms of childhood leukaemia, including seemingly highly penetrant forms of infantile leukaemia. This is a strong indication that these cancers have their origins during in utero development. Concurrently there has been increasing recognition of the differences between foetal and adult haematopoietic niches - these differences might have profound effects on a cells ability to undergo malignant transformation and its subsequent properties.