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We aim to discover the developmentally-regulated, molecular and biological properties of fetal haematopoietic stem and progenitor cells (HSPC) that provide the permissive cellular context for leukaemia and anemia in early childhood and to investigate the mechanisms which drive these changes.

A longitudinal section of fetal femur with multiplex immunofluorescent staining, showing CD34 in red and VEGFR2 in green.
Abnormal megakaryocytes from a trisomy 21 megakaryocyte progenitor colony, x100

We study three types of early childhood leukaemia where the first steps in the development of leukaemia (leukaemia initiation) happen before birth: Down Syndrome (DS)-leukaemias, infant acute lymphoblastic leukaemia (ALL) and Juvenile Myelomonocytic Leukaemia (JMML). We are also interested in how developmental changes in red blood cells and their progenitors are affected by mutations in ribosomal protein (RP) genes as found in most cases of Diamond Blackfan Anaemia, a rare congenital anaemia that typically manifests in fetal or neonatal life. 

I have a particular interest in the haematological problems of neonates, especially in Down syndrome. My group was the first to show that trisomy 21 causes global disruption to fetal HSPC development and that somatic mutations in the transcription factor GATA1 are present at very high frequency in Down syndrome at birth. My current work aims at identifying specific mechanisms by which trisomy 21 perturbs the functional, transcriptomic and epigenetic landscape of human fetal HSPC and how this causes abnormalities in blood and immune cell development in Down syndrome. I collaborate closely with Paresh Vyas in studies on Myeloid Preleukaemia and Leukaemia of Down Syndrome and with Andi Roy  in Acute Lymphoblastic Leukaemia in children with Down syndrome and Infant Leukaemia (with Tom Milne).  I also work in collaboration with Adam Mead on Juvenile Myelomonocytic Leukaemia, a rare disorder of early childhood and with the Diamond Blackfan Group at Imperial College London (Anastasios Karadimitris, Deena Iskander and Josu de la Fuente) on rare inherited anaemias in neonates and young children. I have a longstanding interest in neonatal haematology and work closely with Marella de Bruijn on fetal and neonatal neutrophil development.

Previous lab members

Neha Bhatnagar

Georg Bohn

Gemma Buck

Amelie Chaussade

Gillian Cowan

Josu de la Fuente

Natalina Elliott

Nick Fordham

Catherine Garnett

Katerina Goudevenou

Peng Hua

Deena Iskander

Binbin Liu

Eleni Louka

Laure Nizery

Sorcha O'Byrne

David O'Connor

Bethan Psaila

Helen Richmond

Andi Roy

Ollie Tunstall

Group Lead and Current DPhil Students

Selected publications