- 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.
Author Correction: Enhancer-promoter interactions and transcription.
Higgs DR., (2021), Nat Genet
Enhancers predominantly regulate gene expression during differentiation via transcription initiation.
Larke MSC. et al, (2021), Molecular cell
The relationship between genome structure and function.
Oudelaar AM. and Higgs DR., (2020), Nature reviews. Genetics
The mouse alpha-globin cluster: a paradigm for studying genome regulation and organization.
Oudelaar AM. et al, (2020), Current opinion in genetics & development, 67, 18 - 24
Loss of Extreme Long-Range Enhancers in Human Neural Crest Drives a Craniofacial Disorder.
Long HK. et al, (2020), Cell stem cell, 27, 765 - 783.e14