What we do all day and why
In the post-genomic era, the ongoing discovery of transcriptional products from non-coding regions of the genome continues to raise fundamental questions of biology. Long non-coding RNAs are a versatile class of transcripts, which add a new layer of complexity to the regulatory networks behind normal and malignant hematopoiesis.
MicroRNAs are short, non-coding, master post-transcriptional regulators of gene expression. They have been established as key players in developmental and physiological processes, as well as in pathological ones such as cancer. We have long been interested in the roles of microRNAs during both leukemic transformation and normal blood formation.
Children with Down syndrome (trisomy 21) have a 20-fold greater risk of developing myeloid leukemia. Of neonates with Down syndrome, 10% are diagnosed with transient leukemia, of which 30% develop full-blown leukemia within three years. We are investigating the additional genetic hits that co-operate with GATA1s to drive this progression.
The discovery and application of CRISPR-Cas9 has enhanced genome editing, overcoming a number of the limitations seen with previous genome editing tools. The system is efficient and simple, and acts at the endogenous locus on cellular DNA – both a major advance and advantage, with respect to achieving more physiological conditions.