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Sandra Irvine

Sandra Irvine, CSci, PhD, FHEA, FRCPath
Haematology Department,
Centre for Cancer Research and Cell Biology
Queen’s University Belfast
97, Lisburn Rd
Belfast BT9 7BL
Tel: +44(0) 28 90972794
Fax: +44(0) 28 9097 2776
Email: s.irvine@qub.ac.uk

Present Position:

  • Consultant Clinical Scientist/ Honorary Reader
  • Centre for Cancer Research and Cell Biology, Queen’s University Belfast.

Societies:

  • American Society for Haematology
  • European Haematology Association
  • British Society for Haematology
  • Association of Clinical Biochemists
  • Haematology Association of Ireland
  • Royal College of Pathologists
  • International CCN Society

Research Themes:

I am employed as a consultant clinical scientist at Belfast Health and Social Care Trust and work at the interface between basic and clinical research. I have strong collaborations with clinical colleagues providing a clear translational emphasis to my work. My group is focussed on Chronic Myeloid Leukaemia which is characterised by the presence of the BCR-ABL onco-protein in more than 95% of patients. In addition to primary cells from patients we have human and murine cell lines which reflect the full spectrum of the CML phenotype.
My research programme has developed from my clinical responsibilities and is studying the interaction between quiescent leukaemic stem cells and the bone marrow microenvironment in myeloid leukaemia. There are two main strands to our investigations:

  • 1) We were the first group to identify a role for CCN3 in leukaemia showing that it is down-regulated in Chronic Myeloid Leukaemia (CML). This discovery led to a major publication in Blood and we lodged a patent covering the use of CCN3 in patients with CML and other myeloproliferative disorders. Leukaemic progenitor cells characteristically evade growth regulation by overcoming normal inhibitory processes and alterations in adhesion leading to an accumulation of dysfunctional progenitors within the circulation. Using primary human CML cells and cell lines we have shown that CCN3 plays a central role in leukaemic transformation; transient and stable CCN3 overexpression studies were able to demonstrate reversal of key aspects of the malignant phenotype. Furthermore, both overexpression of CCN3 and treatment with recombinant CCN3 enhances sensitivity to the tyrosine kinase inhibitor imatinib suggesting an alternate mechanism to target CML stem cells resistant to current therapeutics. More recently we have shown a key role for CCN3 in regulating NOTCH1 signalling in CML. Our current focus is on understanding the role of CCN3 in mediating the stem cell- bone marrow microenvironment regulatory axis.
  • 2) We are also investigating the proteasome, a proteolytic complex, as a therapeutic target in malignant stem cells in collaboration with Professor Brian Walker, Department of Pharmacy, Queen’s University. We have developed highly sensitive methods to interrogate proteasome activity in small numbers of cells to facilitate clinical studies with Professor TCM Morris and Professor Mc Mullin (BCH Trust) and Professor Tessa Holyoake (Glasgow). This strategy is being used to screen new inhibitory compounds targeting upstream pathways in the Ubiquitin Proteasome System both synthesized ‘in house’ and by commercial collaborators. Combining these drugs with conventional tyrosine kinase inhibitors offers a potent means to target drug resistant leukaemic stem cells.

Recent Publications:

  • Crawford L and Irvine AE.
    Targeting the Ubiquitin Proteasome System In Haematological Malignancies.
    Blood Reviews 2013; 27: 297-304.
  • Suresh S, McCallum L, Crawford LJ, Sharpe D, Lu W, Irvine AE.
    The matricellular protein CCN3 regulates NOTCH1 signalling pathway in Chronic Myeloid Leukemia.
    J Pathol 2013; 231: 378-387.
  • Crawford L and Irvine AE
    Proteasome Inhibitors in the Treatment of Multiple Myeloma
    In: Multiple Myeloma: An Overview, Ed A Gupta, Pub In Tech 2012: 3-32.
  • McCallum L, Lu W, Lazar N, Perbal B, Irvine AE
    CCN3 suppresses mitogenic signalling and reinstates growth control mechanisms in Chronic Myeloid Leukaemia
    J Cell Commun Signal. 2012; 6: 27-35
  • Suresh S, McCallum L, Lu W, Lazar N, Perbal B, Irvine AE.
    MicroRNAs 130a/b are regulated by BCR-ABL and downregulate expression of CCN3 in CML.
    J Cell Commun Signal. 2011; 5: 183-191.
  • Stevenson R, Fatehullah A, Jagan I, Deevi RK, Bingham V, Irvine AE, Armstrong M, Morrison PJ, Dimmick I, Stewart R, Campbell FC.
    Enhanced lymphocyte interferon (IFN)-γ responses in a PTEN mutation-negative Cowden disease kindred
    Clin Exp Immunol. 2011; 164 (2); 202 -210.
  • Stephen M Twigg, Alexandra E Irvine, A Leask, B Perbal.
    Report on the Sixth International Workshop on the CCN Family of Genes.
    J Cell Commun Signal 2011;5:1-3
  • Lisa J Crawford, Brian Walker and Alexandra E Irvine.
    Proteasome Inhibitors in Cancer Therapy
    J Cell Commun Signal 2011; 5:101-110.
  • Letizia Foroni, Gill Wilson, Gareth Gerrard, Joanne Mason, David Grimwade, Helen E. White, David Gonzalez de Castro, Stephen Austin, Abida Awan, Emma Burt, Tim Clench, Jeremy Hancock Alexandra E Irvine, Aytug Kizilors, Stephen Langabeer, Benedict Milner J, Guillermina Nickless, Anna Schuh, Anne Sproul, Lihui Wang, Caroline Wickham,and Nicholas C.P Cross.
    Guidelines for the measurement of BCR-ABL1 transcripts
    in Chronic Myeloid Leukaemia. Br J Haematol 2011; 153:179-190
  • Mc Callum L & Irvine AE.
    CCN3:A NOVel Growth Factor in Leukaemia.
    In: CCN Proteins in Health and Disease.
    Pub Springer 2010; 115-124
  • Irvine AE, Yeger H and Perbal B.
    Report on the Fifth International Workshop on the CCN Family of Genes.
    In: CCN Proteins in Health and Disease.
    Pub Springer 2010; 5-13.
  • Crawford LJ, Peake R, Price S, Morris TCM, Irvine AE.
    Adiponectin is produced by lymphocytes and is a negative regulator of granulopoiesis.
    J Leuk Biol 2010 ; 88:807-811.
  • Liggett A, Crawford LJ, Walker B, Morris TCM, Irvine AE
    Methods for measuring Proteasome Activity: Current Limitations and Future Developments.
    Leukaemia Research 2010; 34:1403 -1409.
  • Heaney NB, Pellicano F, Zhang B, Crawford L, Kazmi SMA, Jorgensen HG, Irvine AE, Bhatia R, Holyoake TL.
    Bortezomib induces apoptosis in primitive chronic myeloid leukaemia stem cells and cells expressing T315I BCR-ABL mutation and synergises with dasatinib.
    Blood 2010; 115: 2241 - 2250.
  • Lynn McCallum, Wanhua Lu, Susan Price, Noureddine Lazar, Bernard Perbal, Alexandra E. Irvine
    CCN3: a key growth regulator in Chronic Myeloid Leukaemia
    J Cell Commun Signal 2009 ;3:115-124.
  • W Lu, L Mc Callum, AE Irvine.
    CCN3: a NOVel growth factor.
    In: Molecular Mechanisms of Neoplastic Transformation.
    Pub Transworld Research Network 2009; 75-92.
  • L Mc Callum & AE Irvine.
    CCN3- A Key Regulator of the Haemopoietic Compartment.
    Blood Reviews 2009; 23:79-85.
  • Amjad Hayat, Shaun R McCann, Stephen Langabeer, Sandra Irvine, Mary Frances McMullin, Eibhlin Conneally.
    Effective use of imatinib-mesylate in the treatment of relapsed CML after allogeneic transplantation.
    Haematologica 2009; 94:296-8.
  • Irvine AE, Perbal B, Yeger H.
    Report on the fifth international workshop on the CCN family of genes.
    J Cell Commun Signal. 2009; 2:95-100.
  • Wanhua Lu, Lynn McCallum, Alexandra E. Irvine.
    A Rapid And Sensitive Method For Measuring Cell Adhesion.
    J Cell Commun Signal 2009; 3:147-149.
  • LJ Crawford , P Windrum, L Magill, JV Melo, L Mc Callum, MF Mc Mullin, H Ovaa, B Walker, AE Irvine.
    Proteasome Proteolytic Activity is Linked to Bcr-Abl Expression.
    Exp Hematol 2008; 37:357-66.
  • OM Sheehy, AE Irvine, RJG Cuthbert, M Humphries, MF Mc Mullin.
    Use Of Imatinib In Elderly Patients In Northern Ireland: Evidence Of Comparable Haematological And Molecular Responses To Younger Patients.
    Hematology 2008;13:133-136.
  • SM Mc Closkey, P Windrum, MF Mc Mullin, B Walker, AE Irvine
    G-CSF increases proteasome activity in myeloid cells.
    Br J Haematol 2008; 143:593-604.
  • LJ Crawford, B Walker , AE Irvine
    Proteasome Inhibitors: A therapeutic strategy for haematological malignancy.
    Frontiers in BioSciences 2008; 13: 4285-4296.
  • S Mc Closkey, Mc Mullin MF, Walker B, Irvine AE.
    The therapeutic potential of the proteasome in leukaemia.
    Hematol Oncol. 2008; 26: 73-81 .