Established in 1996
Research focus on cellular and molecular basis of abnormal blood cell production in babies and children
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.
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