Development of systems for the generation of red blood cells (RBCs) from stem cells sources (adult peripheral blood, cord blood and pluripotent stem cells) in vitro is of great interest to health services globally, as such a product could overcome many of the problems associated with donor blood, in particular the availability for certain rare blood groups and for patients requiring repeat transfusions. Pluropotent stem cells (PSCs) have advantages for such systems as they have the potential to provide an inexhaustible source of progenitors for the generation of large numbers of RBCs, however further research is required before mature RBCs can be generated from these cells. We are utilising innovative proteomic approaches to analyse the differential proteome, phosphoproteome and transcription factor profile of erythroblasts from such stem cells as they progress down the erythroid pathway to determine why the cells have terminal differentiation defects, along with genetic manipulation to obtain the required adult phenotype.
An alternative and highly desirable approach to PSCs is to generate immortalized adult erythroid cell lines. We have recently created the first such cell lines, which now need to undergo extensive analysis using genomic, transcriptomic and proteomic approaches with the aim of making lines suitable for therapeutics. In addition we will be generating further lines under modified conditions, lines for selected blood groups and will use genome editing to create designer lines with selected rare blood groups. All cells will undergo the same extensive analysis as above along with a range of functional analysis.
We are also interested in the regulation of erythropoiesis, in particular transcription factors such as KLF1. KLF1 is essential for erythropoiesis and mutations in this transcription factor can result in severe red blood cell disorders. We are investigating how such mutations cause disease using genome editing techniques to create human immortalised erythroid lines carrying the selected mutations, and genomic, transcriptomic, proteomic and biochemical approaches to determine the underlying molecular mechanisms. We are part of the recently formed NIHR Blood and Transplant Research Unit (BTRU) to advance research on the manufacture of red blood cells from stem cells and their translation from the lab to human trails, and collaborate with Prof Dave Anstee and Dr Ash Toye at NHSBT, Bristol and within the University.
Projects are available in all areas of our research.