Institute of Cancer Sciences

Dr Mhairi Copland

  • Clinical Senior Lecturer (Paul O'Gorman Leukaemia Research Centre)

telephone: 01413017872
email: Mhairi.Copland@glasgow.ac.uk


The Leukaemia Stem Cell Self-Renewal group was established in 2008. Our research group is interested in the abnormalities of stem cell self-renewal and bone marrow microenvironment which develop in myeloid leukaemias. We have specific interests in the Hedgehog pathway in myeloid leukaemias, quiescence as a mechanism of drug resistance in leukaemia stem cells and interactions between leukaemia stem cells and their niche, in particular via the CXCL12/CXCR4 axis. An important aim of our work is the translation of basic laboratory research to clinical trials which we have achieved with the use of Hedgehog pathway inhibitors in chronic myeloid leukaemia.

Research interests


Aberrant leukaemia stem cell self-renewal and altered bone marrow microenvironment or “niche” allows the leukaemia stem cells to survive the most effective chemotherapeutic strategies available today, resulting in refractory leukaemia or relapse. Small molecule inhibitors are increasingly becoming available to target these essential stem cell pathways and assessing these novel compounds forms a very important part of our research.

We use a combination of immunomagentic cell separation and multi-parameter fluorescence activated cell sorting (FACS) to isolate the most primitive haemopoietic stem cells from the progenitor cells in both normal and leukaemic primary samples. We then use a combination of long and short-term culture techniques, together with a number of gene expression (microarray, Taqman qRT-PCR, Fluidigm) and protein expression/activity (Western blotting, flow cytometry, immunofluorescence) approaches to assess the differences between normal and leukaemic cells and the effects of small molecule inhibitors. In addition, we are currently involved with extending the leukaemia Biobank to include samples from patients with acute leukaemia and myelodysplastic syndrome.

We work with several academic collaborators including Professor Jon Cooper (Glasgow), Professor Peter Adams (Glasgow), Dr David Vetrie (Glasgow), Dr Kathryn Ball (Edinburgh), Professor Junia Melo (Adelaide) and Dr Ravi Bhatia (Duarte). We currently have industrial collaborations with Novartis, Genzyme and Bristol-Myers Squibb.

Individual projects:


• An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cell
• Phase 1 clinical trial “Dasatinib (BMS-354825) combined with SMO inhibitor (BMS-833923; XL139) in CML either resistant to imatinib or nilotinib or with suboptimal response to any prior TKI
• Development of a biomarker assay for the assessment of Hedgehog pathway activity in hematological malignancies
• Hedgehog signalling as a leukaemia stem cell self-renewal pathway in CML.
• Antagonising the CXCR4/SDF-1 interaction in chronic myeloid leukaemia for sensitisation to tyrosine kinase inhibitors

As a clinical senior lecturer, my clinical areas of interest/expertise are stem cell transplantation and myeloid leukaemias. I have an active role as a Principal Investigator for clinical trials at the Beatson West of Scotland Cancer Centre and I am PI for the Leukaemia and Lymphoma Research therapy Acceleration Programme here in Glasgow.

Group Members


• Dr Ross Kinstrie (PDRA)
• Dr David Irvine (Clinical Research Fellow)
• Miss Jennifer Richmond (RA)
• Miss Heather Morrison (RA)
• Dr Mark Moore (PDRA - part time)
• Dr Kirstin Lund (Clinical Research Fellow – jointly with Professor Peter Adams)

Jump to: 2012 | 2011 | 2009 | 2008 | 2007 | 2006 | 2005 | 2004 | 2003 | 2001
Number of items: 28.

2012

Faley, S., Copland, M. , Reboud, J., and Cooper, J. (2012) Intracellular protein trafficking kinetics in chronic myeloid leukemia stem cells using a microfluidic platform. Integrative Biology, 4 (4). p. 368. ISSN 1757-9694 (doi:10.1039/c2ib00086e)

Irvine, D.A., and Copland, M. (2012) Targeting hedgehog in hematologic malignancy. Blood, 119 (10). pp. 2196-2204. ISSN 0006-4971 (doi:10.1182/blood-2011-10-383752)

2011

Lucas, C.M., Harris, R.J., Giannoudis, A., Copland, M. , Slupsky, J.R., and Clark, R.E. (2011) Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression. Blood, 117 (24). pp. 6660-6668. ISSN 0006-4971 (doi:10.1182/blood-2010-08-304477)

Faley, S.L., Copland, M. , Reboud, J. , and Cooper, J.M. (2011) Cell chip array for microfluidic proteomics enabling rapid in situ assessment of intracellular protein phosphorylation. Biomicrofluidics, 5 (2). 024106. ISSN 1932-1058 (doi:10.1063/1.3587095)

Pellicano, F., Simara, P., Sinclair, A., Helgason, G.V., Copland, M. , Grant, S., and Holyoake, T.L. (2011) The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells. Leukemia, 25 (7). pp. 1159-67. ISSN 0887-6924 (doi:10.1038/leu.2011.67)

2009

Pellicano, F., Copland, M. , Jorgensen, H.G. , Mountford, J. , Leber, B., and Holyoake, T. (2009) BMS-214662 induces mitochondrial apoptosis in chronic myeloid leukemia (CML) stem/progenitor cells, including CD34+38- cells, through activation of protein kinase Cβ. Blood, 114 (19). pp. 4186-4196. ISSN 0006-4971 (doi:10.1182/blood-2009-05-219550)

Copland, M (2009) Ikaros deletions are associated with poor prognosis in acute lymphoblastic leukemia. Future Oncology, 5 (4). pp. 455-458. ISSN 1479-6694 (doi:10.2217/FON.09.16)

Faley, S.L., Copland, M. , Wlodkovic, D., Kolch, W. , Seale, K.T., Wikswo, J.P., and Cooper, J. (2009) Pachinko Biology: Gambling on Single Cells. In: 2009 35th Annual Northeast Bioengineering Conference. IEEE, New York, pp. 15-17. ISBN 978-1-4244-4362-8

Faley, S.L., Copland, M. , Wlodkowic, D., Kolch, W. , Seale, K.T., Wikswo, J.P., and Cooper, J.M. (2009) Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells. Lab On a Chip, 9 (18). pp. 2659-2664. ISSN 1473-0197 (doi:10.1039/b902083g)

2008

Konig, H, Copland, M , Chu, S, Jove, R, Holyoake, T, and Bhatia, R (2008) Effects of Dasatinib on Src Kinase Activity and Downstream Intracellular Signaling in Primitive Chronic Myelogenous Leukemia Hematopoietic Cells. Cancer Research, 68 (23). pp. 9624-9633. ISSN 0008-5472 (doi:10.1158/0008-5472.CAN-08-1131)

Heaney, NB, Copland, M , Stewart, K, Godden, J, Parker, AN, McQuaker, IG, Smith, GM, Crawley, C, Shepherd, P, and Holyoake, TL (2008) Complete molecular responses are achieved after reduced intensity stem cell transplantation and donor lymphocyte infusion in chronic myeloid leukemia. Blood, 111 (10). pp. 5252-5255. ISSN 0006-4971 (doi:10.1182/blood-2007-10-118141)

Copland, M, Pellicano, F , Richmond, L, Allan, EK, Hamilton, A , Lee, FY, Weinmann, R, and Holyoake, TL (2008) BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors. Blood, 111 (5). pp. 2843-2853. ISSN 0006-4971 (doi:10.1182/blood-2007-09-112573)

2007

Holyoake, T, and Copland, M (2007) LSC defenses breached by chemical arsenal. Blood, 110 (13). pp. 4138-4139. ISSN 0006-4971

Balabanov, S et al. (2007) Hypusination of eukaryotic initiation factor 5A (eIF5A): a novel therapeutic target in BCR-ABL-positive leukemias identified by a proteomics approach. Blood, 109 (4). pp. 1701-1711. ISSN 0006-4971 (doi:10.1182/blood-2005-03-037648)

Copland, M, Hamilton, Ashley , and Holyoake, TL (2007) Conventional Western blotting techniques will not reliably quantify p210 BCR-ABL - Response. Blood, 109 (3). p. 1336. ISSN 0006-4971

Konig, H, Copland, M , Jove, R, Holyoake, TL, and Bhatia, R (2007) Effect of dasatinib on BCR-ABL and Src mediated growth signaling in primary CML hematopoietic progenitors. Blood, 110 (11). 865A-865A.

2006

Copland, M, Hamilton, A, Eirick, LJ, Baird, JW, Allan, EK, Jordanides, N, Barow, M, Mountford, JC , and Holyoake, TL (2006) Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood, 107 (11). pp. 4532-4539. ISSN 0006-4971 (doi:10.1182/blood-2005-07-2947)

Hamilton, A., Elrick, L., Myssina, S., Copland, M. , Jorgensen, H.G. , Melo, J.V., and Holyoake, T.L. (2006) BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry. Leukemia, 20 (6). pp. 1035-1039. ISSN 0887-6924 (doi:10.1038/sj.leu.2404189)

Jorgensen, H.G., Copland, M. , Allan, E.K. , Jiang, X.Y., Eaves, A., Eaves, C., and Holyoake, T.L. (2006) Intermittent exposure of primitive quiescent chronic myeloid leukemia cells to granulocyte-colony stimulating factor in vitro promotes their elimination by imatinib mesylate. Clinical Cancer Research, 12 (2). pp. 626-633. ISSN 1078-0432 (doi:10.1158/1078-0432.CCR-05-0429)

2005

Copland, M., Jorgensen, H.G. , and Holyoake, T.L. (2005) Evolving molecular therapy for chronic myeloid leukaemia - are we on target? Hematology, 10 (5). pp. 349-359. ISSN 1024-5332 (doi:10.1080/10245330500234195)

Copland, M, Fraser, AR, Harrison, SJ, and Holyoake, TL (2005) Targeting the silent minority: emerging immunotherapeutic strategies for eradication of malignant stem cells in chronic myeloid leukaemia. Cancer Immunology Immunotherapy, 54 (4). pp. 297-306. ISSN 0340-7004 (doi:10.1007/s00262-004-0573-1)

Allan, EK, Jordanides, NE, McLintock, LA, Copland, M , Devaney, M, Stewart, K, Parker, A , Johnson, PRE, Holyoake, T, and Jones, BL (2005) Poor performance of galactomannan and mannan sandwich enzyme-linked immunosorbent assays in the diagnosis of invasive fungal infection. British Journal of Haematology, 128 (4). pp. 578-579. ISSN 0007-1048 (doi:10.1111/j.1365-2141.2004.05333.x)

Jordanides, NE, Allan, EK, McLintock, LA, Copland, M , Devaney, M, Stewart, K, Parker, AN, Johnson, PRE, Holyoake, TL, and Jones, BL (2005) A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients. Bone Marrow Transplantation, 35 (4). pp. 389-395. ISSN 0268-3369 (doi:10.1038/sj.bmt.1704768)

Jorgensen, H.G., Copland, M. , and Holyoake, T.L. (2005) Granulocyte-colony-stimulating factor (filgrastim) may overcome imatinib-induced neutropenia in patients with chronic-phase myelogenous leukemia. Cancer, 103 (1). pp. 210-211. ISSN 0008-543X (doi:10.1002/cncr.20742)

Copland, M, Hamilton, A, Baird, JW, Barow, M, Allan, EK, Elrick, LJ, and Holyoake, TL (2005) Dasatinib (BMS-354825) has increased activity against Bcr-Abl compared to imatinib in primary CML cells in vitro, but does not eradicate quiescent CML stem cells. Blood, 106 (11). 205A-205A.

2004

McLintock, LA, Jordanides, NE, Allan, EK, Copland, M , Stewart, K, Parker, A , Devaney, M, Holyoake, T, and Jones, BL (2004) The use of a risk group stratification in the management of invasive fungal infection: a prospective validation. British Journal of Haematology, 124 (3). pp. 403-404. ISSN 0007-1048 (doi:10.1046/j.1365-2141.2003.04794.x)

2003

Kilpatrick, DC et al. (2003) No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections. Clinical and experimental immunology, 134 (2). pp. 279-284. ISSN 0009-9104 (doi:10.1046/j.1365-2249.2003.02284.x)

2001

Copland, M., Walker, I.D., and Tait, R.C. (2001) Oral anticoagulation and hemorrhagic complications in an elderly population with atrial fibrillation. Archives of Internal Medicine, 161 (17). pp. 2125-2128. ISSN 0003-9926 (doi:10.1001/archinte.161.17.2125)

This list was generated on Sat May 26 15:39:46 2012 BST.
  • Leukaemia and Lymphoma Research Therapy Acceleration Programme
    Leukaemia & Lymphoma Research
    2012 - 2013
     
  • An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cells
    Leukaemia & Lymphoma Research
    2011 - 2014
     
  • Scottish Senior Clinical Fellowship Scheme
    Scottish Funding Council
    2009 - 2013
     
  • An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cells
    Scottish Executive Health Department
    2009 - 2010
     
  • Self-renewal pathway manipulation as a potential therapeutic strategy for the eradication of Chronic Myeloid Leukaemia (CML) Stem Cells
    Scottish Executive Health Department
    2009 - 2011
     
  • Novel drug combinations for eradication of Ph+/Bcr-Abl+ haemopoietic stem cells in chronic myeloid leukaemia (CML)
    MRC
    2003 - 2006
     
  • Novel drug combinations for eradication of Ph+/Bcr-Abl+ haemopoietic stem cells in chronic myeloid leukaemia (CML)
    Leukaemia Research Trust for Scotland
    2003 - 2006