Dr Allison Blair

Welcome to the Cancer Stem Cell Laboratory

The Blair Lab is interested in understanding understanding of the differences between stem cells that can initiate leukaemias and haemopoietic stem cells that produce normal blood cells.  The group studies the characteristics of leukaemia stem cells with the aim of developing new therapeutic strategies that are effective against all leukaemia cells.  The group also investigates expansion of normal blood cells to produce therapeutic quantities of red blood cells, platelets and neutrophils for use in transfusion and transplantation.

Vision

Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer with survival rates of 80-85%. Unfortunately for some patients the treatment is ineffective, usually due to the persistence of resistant cancer cells.  Our work is focused on understanding the biology of childhood leukaemia to help develop more effective therapies.  We and others have identified populations of leukaemia cells, known as leukaemia stem cells, that are resistant to current therapies.  These leukaemia stem cells can initiate and maintain leukaemia in model systems and may be responsible for causing relapse.  By increasing our understanding of the characteristics of these leukaemia stem cells, including how they grow and resist treatment, it may be possible to develop therapeutics that target these cells, with minimal damage to normal cells.

Not all blood diseases are cancerous, patients with blood disorders such as sickle cell disease or  b thalassaemia require blood transfusions regularly.  For many of these patients it can be difficult to obtain suitably matched blood.  We have shown that normal stem cells can be directed to mature into specific blood cells, such as red blood cells. These cultured red blood cells survive longer than normal blood cells.  It may be possible to grow red blood cells for patients with rare blood groups and to reduce the amount of harmful reactions in patients whose lives depend on receiving regular blood transfusions.

 

Mission and Impact

Our research aims to better understand the development of normal and malignant blood cells in order to develop novel therapeutic approaches for patients with blood diseases.

Approach

Our lab uses primary human cells, both malignant and normal haemopoietic cells.  We combine a variety of approaches and technologies, including developmental, molecular biology, imaging and functional assays.

Currently our team is addressing a number of questions:

1) Characterising leukaemia stem cells. We are continuing our previous work comparing stem cells characteristics in normal and leukaemia samples to identify differences that could be exploited for therapy.  We are also investigating the impact of some new targeted therapies on leukaemia stem cell populations.

2) Improved drug delivery.  We are developing systems that allow improved delivery of drugs to target areas without use of harmful solvents.

3) Survival of cultured blood cells. Using transfusion models, we are assessing the functional capacity of cultured blood cells as a resource for patients that depend on regular transfusions and those with rare blood groups.

4) Tolerance to blood group antigens. We are investigating differences in vesicles shed by red blood cells from healthy individuals and those with sickle cell disease as a means of inducing tolerance to blood cells and preventing transfusion complications.

Funding

Our lab is funded by the NIHR Blood and Transplant Research Unit Programmes in haemopoietic stem cell transplantation and immune therapies and red blood cell products, MRC and Dept. of Health.

Qualifications and History

  • 1994: Ph.D. University of St Andrews, UK
  • 2005: Certificate in First Line Management, Institute of Leadership and Management
  • 1994-1998: Research Fellow, Terry Fox Laboratory, Vancouver, Canada
  • 1998-2010: Senior Clinical Scientist, Bristol Institute for Transfusion Sciences, NHS Blood and Transplant
  • 2010-2015: Principal Clinical Scientist, University of Bristol
  • 2015-: Reader in Experimental Haematology, Lead Tissue Engineering and Stem Cell Therapies, University of Bristol

 Awards:

  • 1995-1997: Research Fellowship of the Leukemia Research Fund of Canada

Selected Publications

  1. Ede BC, Asmaro RR, Moppett JP, Diamanti P, Blair A. Investigating chemoresistance to improve sensitivity of childhood T-cell acute lymphoblastic leukemia to parthenolide. Haematologica. 2018;103(9):1493-1501. doi: 10.3324/haematol.2017.186700.
  2. Ridolfo R, Ede BC, Diamanti P, Perriman AW, van Hest JCM, Blair A and Willams DS. Biodegradable, Drug-Loaded Nanovectors via Direct Hydration as a New Platform for Cancer Therapeutics. Small. 2018;14(32):e1703774. doi: 10.1002/smll.201703774.
  3. Trakarnsanga K, Griffiths RE, Wilson MC, Blair A, Satchwell TJ, Meinders M, Cogan N Kupzig S Kurita R, Nakamura Y, Toye AM Anstee DJ Frayne J. An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells. Nat Comm. 2017; 8:14750. doi: 10.1038/ncomms14750.
  4. Kupzig S, Parsons SF, Curnow E, Anstee DJ, Blair A. Superior survival of ex vivo cultured human reticulocytes following transfusion into mice. Haematologica. 2017; 102(3):476-483. doi: 10.3324/haematol.2016.154443.
  5. Diamanti P, Cox CV, Moppett JP, Blair A.  Parthenolide eliminates leukemia-initiating cell populations and improves survival in xenografts of childhood acute lymphoblastic leukemia.  Blood. 2013; 121:1384-1393. doi: 10.1182/blood-2012-08-448852.

 

Dr Allison Blair
Leukaemia stem cells have high expression of NF-KB (green).  These cells can be targeted using inhibitors of this transcription factor.
Leukaemia stem cells have high expression of NF-kB (green). These cells can be targeted using inhibitors of this transcription factor.
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