Projects per year
Personal profile
Research interests
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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Projects
- 3 Active
Developing human model cellular systems for the study of red blood cell diseases and as drug screening platforms
1/12/19 → 30/11/22
Project: Research
Research Output
Characterization and evolutionary origin of novel C2H2 zinc finger protein (ZNF648) required for both erythroid and megakaryocyte differentiation in humans
Ferguson, D. C. J., Haji Mokim, J., Meinders, M., Moody, E. R. R., Williams, T. A., Trakarnsanga, K., Daniels, D. E., Ferrer-Vicens, I., Shoemark, D., Tipgomut, C., Macinnes, K. A., Wilson, M. C., Singleton, B. K. & Frayne, J., 5 Oct 2020, In : Haematologica.Research output: Contribution to journal › Article (Academic Journal)
Expression and retention of thymidine phosphorylase in cultured reticulocytes as a novel treatment for MNGIE
Meinders, M., Shoemark, D. K., Dobbe, J. G. G., Streekstra, G. J., Frayne, J. & Toye, A. M., 12 Jun 2020, In : Molecular Therapy - Methods and Clinical Development. 17, p. 822-830 9 p.Research output: Contribution to journal › Article (Academic Journal)
Open Access
File
GENERATION OF AN IMMORTALISED ERYTHROID CELL LINE FROM HAEMATOPOIETIC STEM CELLS OF A HAEMOGLOBIN E/β-THALASSEMIA PATIENT
Trakarnsanga, K., Tipgomut, C., Metheetrairut, C., Wattanapanitch, M., Khuhapinant, A., Poldee, S., Kurita, R., Nakamura, Y., Srisawat, C. & Frayne, J., 17 Sep 2020, (Accepted/In press) In : Scientific Reports.Research output: Contribution to journal › Article (Academic Journal)