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Professor David Anstee


My group is based at the NHSBT Blood Centre in Filton, Bristol. The programme of research is focussed on two topics, red cell biologyand prion disease.

Our work on red cell biology seeks to improve understanding of the process whereby red cells are made (erythropoiesis) and how they function in health and disease. To this end we have developed in vitro methods for generating red cells from haemopoietic stem cells in culture with a view to generating sufficient quantities of cultured red cells for transfusion therapy. Optimising culture conditions to increase both cell numbers, and the enucleation and correct maturation of cultured red cells, requires an understanding of transcriptomics and proteomics of erythropoiesis. The study of the mutations involved in dyserythropoiesis, where cell division and enucleation are disrupted, can also help to unravel these processes. We have also identified the causative mutations for diseases of the red cell in several rare anaemias. Our knowledge of the structure and function of red cells is being used to further understanding of the changes occurring in donated red cells upon storage.

Our work on prion disease is focussed on the development of a blood test for variant CJD which is suitable for screening blood donations.

Recent Publications:

McGuire LI, Peden AH, Orrú CD, Wilham JM, Appleford NE, Mallinson G, Andrews M, Head MW, Caughey B, Will RG, Knight RS, Green AJ. Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease.
Ann Neurol. 2012 Aug;72(2):278-85.

Griffiths RE, Kupzig S, Cogan N, Mankelow TJ, Betin VMS, Trakarnsanga K, Massey EJ, Lane JD, Parsons SF, Anstee DJ
Maturing reticulocytes internalise plasma membrane in glycophorin A-containing vesicles which fuse with autophagosomes prior to exocytosis
Blood blood-2011-09-376475; published ahead of print April 6, 2012, doi:10.1182/blood-2011-09-376475

Peden AH, McGuire LI, Appleford NE, Mallinson G, Wilham JM, Orrú CD, Caughey B, Ironside JW, Knight RS, Will RG, Green AJ, Head MW.
Sensitive and specific detection of sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion.
J Gen Virol. 2012 Feb;93(Pt 2):438-49. Epub 2011 Oct 26. PubMed PMID: 22031526.

Flatt JF, Guizouarn H, Burton NM, Borgese F, Tomlinson RJ, Forsyth RJ, Baldwin SA, Levinson BE, Quittet P, Aguilar-Martinez P, Delaunay J, Stewart GW, Bruce LJ.
Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome.
Blood. 2011 Jul 26. [Epub ahead of print]

Giardine B, Borg J, Higgs DR, Peterson KR, Philipsen S, Maglott D, Singleton BK, Anstee DJ, Basak AN, Clark B, Costa FC, Faustino P, Fedosyuk H, Felice AE, Francina A, Galanello R, Gallivan MV, Georgitsi M, Gibbons RJ, Giordano PC, Harteveld CL, Hoyer JD, Jarvis M, Joly P, Kanavakis E, Kollia P, Menzel S, Miller W, Moradkhani K, Old J, Papachatzopoulou A, Papadakis MN, Papadopoulos P, Pavlovic S, Perseu L, Radmilovic M, Riemer C, Satta S, Schrijver I, Stojiljkovic M, Thein SL, Traeger-Synodinos J, Tully R, Wada T, Waye JS, Wiemann C, Zukic B, Chui DH, Wajcman H, Hardison RC, Patrinos GP.
Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach.
Nat Genet. 2011 Mar 20;43(4):295-301.

Singleton BK, Lau W, Fairweather VSS, Burton NM, Wilson MC, Parsons SF, Richardson BM, Trakarnsanga K, Brady RL, Anstee DJ, Frayne J
Mutations in the second zinc finger of human EKLF reduce promoter affinity but give rise to benign and disease phenotypes
Blood 2011 blood-2011-04-349985; published ahead of print July 21, 2011, doi:10.1182/blood-2011-04-349985

Bruce LJ, Guizouarn H, Burton NM, Gabillat N, Poole J, Flatt JF, Brady RL, Borgese F, Delaunay J, Stewart GW The monovalent cation leak in over-hydrated stomatocytic red blood cells results from amino acid substitutions in the Rh associated glycoprotein (RhAG)
Blood 113 (6):1350-7(2009)

Clewley JP, Kelly CM, Andrews N, Vogliqi K, Mallinson G, Kaisar M, Hilton DA, Ironside JW, Edwards P, McCardle LM, Ritchie DL, Dabaghian R, Ambrose HE, Gill ON.
Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey BMJ 2009;338:b1442

Singleton BK, Burton NM, Green C, Brady LR, Anstee DJ
Mutations in EKLF/KLF1 form the molecular basis of the rare blood group In(Lu) phenotype
Blood 112(5):2081-8 (2008)

Appleford NEJ, Wilson K, Houston F, Bruce LJ, Morrison A, Bishop M, Chalmers K, Miele G, Massey E, Prowse C, Manson J, Will RG, Clinton M, MacGregor I, Anstee DJ
Alpha-Hemoglobin stabilizing protein is not a suitable marker for a screening test for variant Creutzfeldt-Jakob disease
Transfusion. 48(8):1616-26 (2008)
Dr David Anstee

Director of the International Blood Group Reference Laboratory.

NHSBT Filton Blood Centre,
Northway,
Filton,
Bristol,
BS34 7QH

+44(0)117 921 7200
Email: david.anstee@nhsbt.nhs.uk

Lab members:
Erythropoiesis and production of cultured red cells.

Dr. Steve Parsons,
Dr Frances Spring,
Dr Rebecca Griffiths,
Dr Tosti Mankelow,
Dr Belinda Singleton,
Dr Sabine Taylor,
Dr Nicola Cogan,
Dr Vanya Crew,
Carole Green.

Structure and Function of human red cells in health, disease and storage.

Dr Lesley Bruce,
Dr Joanna Flatt,
Dr Nicholas Burton,
Dr Belinda Singleton,
Dr Tosti Mankelow.

Development of a Blood Test for vCJD

Dr Gary Mallinson,
Nigel Appleford,
Dr Dave Jackson,
Maria Kaisar.

Collaborators within NHSBT

Dr Ashley Toye
Dr Rebecca Cardigan
Dr Allison Blair
Dr Cedric Ghevaert
Prof. Dave Roberts

External Collaborators

Dept. Biochemistry, University of Bristol (Prof Leo Brady, Dr Jan Frayne, Dr Jon Lane).

Scottish Blood Transfusion Service (Prof Marc Turner, Dr Jo Mountford).

University of Edinburgh (Dr Lesley Forrester)

Roslin Cells, Edinburgh (Dr Aiden Courtney).

National CJD Research & Surveillance unit , Edinburgh (Prof Bob Will, Dr Alison Green)

Roslin Institute, Edinburgh (Prof Jean Manson).

Division of Medicine, University College London (Prof Gordon Stewart)

Laboratoire d'hématologie, CHU Bicêtre (Dr Véronique Picard)

New York Blood Center (Dr Joel Chasis, Prof Mohandas Narla)

Funding

Dept. Health (England)
NIHR
Wellcome Trust
Bio Rad