Regulating The Self Renewal and Differentiation of Haematopoietic Stem and Progenitor Cells

Our research focuses on improving treatment outcomes for severely ill patients suffering from blood diseases by understanding basic mechanisms and applying this to graft engineering. Haematopoietic stem cells (HSCs) give rise to all blood lineages and are critical to life. However, HSC disorders exist, with haematological malignancies representing a significant cause of mortality and the inherited haemoglobin disorders being the most common monogenic diseases worldwide. Such diseases can potentially be cured by haematopoietic stem cell transplantation (HSCT), the most successful regenerative medicine therapy to date with the year 2013 marking the one millionth HSCT worldwide. Combining stem cell and novel targeted genome editing technologies provides powerful tools for correcting inherited gene disorders in autologous HSCs before transplanting them into the affected individual to correct the disease. Controlling the self-renewal and differentiation in HSCs ex vivo prior to transplantation is critical to their success in correcting a genetic defect, requiring an understanding of the transcriptional regulatory networks and cues that control the balance between human HSC self-renewal and commitment. This project aims to examine specific regulatory networks in HSC/HPC subsets at the single cell level performed using such techniques as Dynamic Array integrated fluidics chips on the BioMark HD platform combined with specific environmental cues from the bone marrow niche affect their fate and ahead of gene editing using CRISPR technology. In this way, it will be possible to regulate the balance between human HSC self-renewal and their lineage commitment and to optimise human HSCs for gene editing.