- Consultant Physician
The regulation of gene expression during erythropoiesis
Our laboratory is interested in the general question of how mammalian genes are switched on and off during lineage commitment and differentiation. We study genes (e.g. globin) in detail and also study gene expression using genome wide analyses. We study all aspects of gene expression including the key cis-regulatory elements (enhancers, promoters and insulators), the transcription factors and co-factors that bind them, the epigenetic modifications of chromatin and DNA and the role of associated phenomena such as chromosome conformation and nuclear sub-compartmentalisation using imaging techniques. These studies are performed both in cell systems and in model organisms as well as in human patients with various inherited and acquired genetic and epigenetic abnormalities. The translational goal of this work is to develop new ways to modify gene expression during blood formation with the aim of manipulating gene expression and ameliorating the clinical phenotypes of patients with a variety of blood disorders.
Ancient genomic linkage couples metabolism with erythroid development.
Preston AE. et al, (2023), bioRxiv
Loop extrusion by cohesin plays a key role in enhancer-activated gene expression during differentiation
Stolper RJ. et al, (2023)
RNA polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation.
Martell DJ. et al, (2023), Developmental cell
Understanding fundamental principles of enhancer biology at a model locus: Analysing the structure and function of an enhancer cluster at the α-globin locus.
Kassouf M. et al, (2023), Bioessays
Direct correction of haemoglobin E β-thalassaemia using base editors.
Badat M. et al, (2023), Nat Commun, 14