Projects per year
The generation of RBCs in vitro for transfusion therapy is a major goal of health services globally. My research is focussed on the development of in vitro systems to generate human erythroid cells from different stem cell sources, including adult, cord and iPSCs, and the molecular analysis of these cells. We utilise innovative proteomic approaches to qualitatively and quantitatively compare the differential proteome of erythroblasts from the different stem cells, along with genetic engineering to alter the behaviour and phenotype. I am also interested in the regulation of erythropoiesis by transcription factors and our studies have revealed both novel transcription factors, and factors differentially expressed in erythroid cells differentiated from some stem cell sources which we are continuing to investigate, alongside downstream effectors. I am particularly interested in the transcritpion factor KLF1 and, in collaboration with Prof Anstee of NHSBT, we were the first to identify and report a mutation in KLF1 that results in a severe human disease phenotype, and to demonstrate how this and other mutations in KLF1 affect DNA binding affinity. More recently an increasing number of individuals with a variety of mutations in KLF1 and varying disease severity have been identified. To study the effect and mechanisms by which these mutations result in disease we are presently developing a human ex vivo model system. In addition, we have generated the first human immortalised adult erythroid cell lines, that recapitulate normal erythropoiesis, express normal levels of adult globin and enucleate to form functonal reticulocytes, providing a sustainable supply of red cells. We are now generating further lines and utilising geneome editing approaches to creat sublines with selected genotypes/phenotypes, both for study and as proof of principal for future diagnostics and therapeutics.
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Developing human model cellular systems for the study of red blood cell diseases and as drug screening platforms
1/12/19 → 30/11/22
Internal ODA budget - Developing human model cellular systems for studying Red Blood Cell diseases and as screening platforms
1/12/22 → 31/03/23
Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturationHeil, J., Olsavszky, V., Daniels, D., Frayne, J. & Koch, P-S., 29 Nov 2021, In: Nature Communications. 12, 1, 6963.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile23 Downloads (Pure)
Deen, D., Daniels, D. E., Ferrer-Vicens, I., Ferguson, D. C. J., Frayne, J., Vernimmen, D. & al., E., 10 Aug 2021, In: Blood Advances. 5, 15, p. 3002-3015 14 p.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile28 Downloads (Pure)
Ferguson, D. C. J., MacInnes, K., Daniels, D. & Frayne, J., 26 Feb 2021, (E-pub ahead of print) Recent Advances in iPSC-Derived Cell Types. Elsevier Limited, Vol. 4. 1 p. (Advances in Stem Cell Biology; vol. 4).
Research output: Chapter in Book/Report/Conference proceeding › Chapter in a book