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Professor Jan Frayne

Biography

Jan Frayne obtained her first degree from Nottingham University and PhD from Bristol University before commencing research in developmental biology, specifically molecular aspects of spermatogenesis and sperm function. She moved to the Department of Biochemistry at the University of Bristol on a post-doctoral position within this area, obtaining a lectureship here in 2000. Although still maintaining an active interest in this area, in 2004 Jans interests diversified to study of erythropoiesis. 

Blood shortage is an important healthcare problem globally, with much interest in generating red blood cells in vitro as an alternative to donor blood, with the additional advantage of a safer transfusion product especially for many developing countries. In addition, transfusion requirements for some patients with rare blood group phenotypes cannot be met with present resources.

Jans research initially focussed on the development and utilization of in vitro systems to generate human erythroid cells from different stem cell sources (adult, cord blood, induced pluripotent and embryonic stem cells), and the molecular analysis of these cells. She implemented innovative comparative proteomic approaches for these studies, including targeted proteome-wide profiling and identification of transcription factor networks. Data from such studies has provided the most comprehensive insight and catalog to date of the RBC proteome, as well as identifying defects in PSC derived erythroid cells which are presently being targeted. Cord blood stem cells are an attractive progenitor source for the production of RBCs in vitro for transfusion. Extensive studies from the Frayne lab addressed the suitability of such cells, reassuring no detectable barrier to their use for adult therapeutics. She also developed a forward programming strategy to induce the switch to, and expression of adult globin by these cells at levels commensurate with normal adult RBCs.

Jan is also interested in the transcription factor regulation of erythropoiesis, identifying novel factors involved in erythropoiesis and lineage fate determination. KLF1 is a key regulator of erythropoiesis, and along with collaborators at NHSBT Bristol, she was the first to identify a mutation in KLF1 that results in a severe human disease phenotype, and demonstrated how this and other mutations in KLF1 can impede function.

Recently, Jan has taken an alternative approach, developing methodology and pioneering creation of the first human immortalised adult erythroid cell line (BEL-A), demonstrating for the first time a feasible approach to the manufacture of red cells for clinical use. The line is also the first erythroid line to recapitulate normal erythropoiesis. Extensive characterization has not revealed any differences between BEL-A reticulocytes and normal adult reticulocytes functionally, or at the molecular level. Genome editing approaches are now being used to create sub lines with specific gene edits as proof of principal for diagnostics and therapeutics. In addition, of particular interest is the use of the methodologies to generate model celular systems of RBC diseases to study the underlying molecular mechanisms and as drug screening platforms.

Jan Frayne is presently a principal investigator for the Bristol Institute of Transfusion Sciences (BITS), for the NIHR Blood and Transplant Research Unit (BTRU) in red blood cell products and for the Wellcome Trust funded BloodPharma (Novosang) consortia to generate RBCs in vitro from pluripotent stem cells for therapeutics.

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School of Biochemistry

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School of Biochemistry staff