Professor Jan Frayne

B.Sc.(Nott.), Ph.D.(Bristol)

  • BS8 1TD

1992 …2020

Research output per year

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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

Research Output

  • 62 Article (Academic Journal)
  • 8 Conference Contribution (Conference Proceeding)
  • 1 Chapter in a book

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 journalArticle (Academic Journal)

Open Access
File
  • 20 Downloads (Pure)

    Comparing the two leading erythroid lines BEL-A and HUDEP-2

    Daniels, D. E., Downes, D., Ferrer Vicens, I., Ferguson, D. C. J., Singleton, B. K., Wilson, M. C., Trakarnsanga, K., Kurita, R., Nakamura, Y., Anstee, D. J. & Frayne, J., 21 Nov 2019, In : Haematologica. 105, 3, 11 p., 229211.

    Research output: Contribution to journalArticle (Academic Journal)

    Open Access
    File
    172 Downloads (Pure)

    Genetic manipulation of cell line derived reticulocytes enables dissection of host malaria invasion requirements

    Satchwell, T. J., Wright, K. E., Haydn-Smith, K. L., Sánchez-Román Terán, F., Moura, P. L., Hawksworth, J., Frayne, J., Toye, A. M. & Baum, J., 23 Aug 2019, In : Nature Communications. 10, 9 p., 3806 (2019).

    Research output: Contribution to journalArticle (Academic Journal)

    Open Access
    File
  • 115 Downloads (Pure)

    Supervised Work

    CRISPR-Cas9 gene editing in an immortalized erythroid cell line for production of engineered red blood cells

    Author: Hawksworth, J., 1 Oct 2019

    Supervisor: Spear, A. (Supervisor), Toye, A. (Supervisor) & Frayne, J. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

    Investigating the process of reticulocyte maturation to erythrocytes in vitro

    Author: Moura, P. L., 23 Jan 2020

    Supervisor: Toye, A. (Supervisor) & Frayne, J. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)