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Dr Suzanne D Turner

Dr Suzanne D Turner

Reader in Cellular and Molecular Tumour Biology

Division of Cellular and Molecular Pathology

Division of Cellular and Molecular Pathology
Lab Block Level 3
Box 231
Addenbrooke's Hospital
Cambridge
CB2 0QQ

Office Phone: +44 (0) 1223 762655

Research themes

Cancer:

Research Interests

Turner Research

Understanding the pathogenesis and aetiology of paediatric cancers towards the development of novel therapeutic approaches and biomarkers

Mechanisms of Lymphomagenesis

Lymphoma is a heterogeneous disease class consisting of greater than 30 different sub-types and the incidence of this disease has been increasing year on year. In our research we are making progress towards understanding how and why lymphoma develops and hence in the development of new treatments. We investigate a paradigm of lymphomageneis in which a chromosomal translocation leads to the generation of an oncogene and subsequent presumed transformation of T-cells. The oncogene we work with is Nucleophosmin-Anaplastic Lymphoma Kinase (NPM-ALK), a hyperactive tyrosine kinase generated as a result of a translocation between chromosomes 2 and 5. This event is associated with greater than 90% of cases diagnosed as anaplastic large cell lymphoma (ALCL), a mature T-cell malignancy mainly occurring in paediatric patients. Our research aims to unravel the events leading from the t(2;5) to lymphoma. We use a variety of experimental approaches to reach this goal.

Understanding drug resistance in paediatric cancers

We are also developing a resource of patient derived xenografts of paediatric lymphoma, specifically ALCL and Burkitt lymphoma as well as neuroblastoma. Applying these models, our lab is conducting research to experimentally-induce relapse in an effort to understand clonal evolution of tumour cell growth. With this knowledge in hand, our lab then applies high-throughput drug screens and sequencing approaches to develop novel therapeutic regimens. Alongside, this research activity, we also employ CRISPR/Cas9 screens for the identification of putative mechanisms of drug resistance employing cell lines.

  • Group Members:

    Hugo Larose
    Nina Prokoph
    Stephen Ducray
    Jamie Matthews
    Mun Liew
    Gill Currie

    We collaborate with Dr Amos Burke, a paediatric oncologist at Addenbrooke's hospital in Cambridge

Other responsibilities:

Organiser Part 1B Pathology
Fellow and Tutor Hughes Hall
Executive committee member and co-lead paediatric programme, Cambridge Cancer Centre
Coordinator ALKATRAS Marie Curie Innovative Training Network (www.alkatras.erialcl.net)
Biological studies lead, NCRI paediatric lymphoma clinical studies sub-group

Co-chair European Inter-group for Childhood Non-Hodgkin Lymphoma (EICNHL)

Key Publications

1. Malcolm, T*., Villarese, P*., Fairbairn, C., Lamant, L., Trinquand, A., Hook, C.E., Burke, G.A.A., Brugieres, L., Hughes K., Payet, D., Merkel, O., Schiefer, A., Ashankyty, I., Mian, S., Wasik, M., Turner, M., Kenner, L., Asnafi, V., Macintyre,E. and Turner, S.D. (2015) NPM-ALK mimics beta selection enabling thymic escape and peripheral lymphoma development. Nature Communications, 7, Article number: 10087 doi:10.1038/ncomms10087

2. Moti, N., Malcolm, T., Hamoudi, R., Mian, S., Garland, G., Hook, C.E., Burke, G.A.A., Wasik, M., Merkel, O., Kenner, L., Laurenti, E., Dick, J.E.and Turner, S.D. (2014) Anaplastic Large Cell Lymphoma stem cells possess a gene expression profile reflective of an early thymic progenitor pointing to a primitive cell of origin. Oncogene, doi:10.1038/onc.2014.112

3. McDuff, F.K.E., Lim, S-V., Dalbay, M. and Turner, S.D. (2013) Assessment of the transforming potential of novel Anaplastic Lymphoma Kinase point mutants. Molecular Carcinogenesis 52(1):79-83

4. Laimer, D., Dolznig, H., Kollmann, K., Vesely, P.W., Schlederer, M., Merkel, O., Schiefer, A., Hassler, M.R., Heider, S., Amenitsch, L., Thallinger, C., Staber, P.B., Simonitsch-Klupp, I., Artaker, M., Lagger, S., Turner, S.D., Pileri, S., Piccaluga, P.P., Valent, P., Messana, K., Landra, I., Weichhart, T., Knapp, S., Shehata, M., Todaro, M., Sexl, V., Höfler, G., Piva, R., Medico, E., Riggeri, B.A., Cheng, M., Eferl, R., Egger, G., Penninger, J.M., Jaeger, U., Moriggl, R., Inghirami, G.and Kenner, L. (2012) Identification of PDGFR blockade as a rational and highly effective therapy for NPM-ALK driven lymphomas. Nature Medicine 18(11):1699-704

5. Youssif, C., Goldenbogan J., Hamoudi R., Viskaduraki M., Bacon, CM, Burke, A.A and Turner S.D. (2009) Genomic profiling of pediatric ALK-positive Anaplastic Large Cell Lymphoma – a Children’s Cancer and Leukaemia Group study. Genes Chromosomes and Cancer 48(11):1018-26

6. Cui Y., Kerby A., McDuff F.K.E. and Turner S.D. (2009) NPM-ALK modulates the p53 tumour suppressor pathway in a JNK and PI 3-Kinase dependent manner: MDM-2 is a potential therapeutic target for the treatment of ALK-expressing malignancies. Blood. 113(21):5217-5227.

7. Turner S.D., Yeung D., Hadfield K., Cook S.J. and Alexander D.R. (2007) The NPM- ALK Tyrosine Kinase Mimics TCR Signalling Pathways Inducing NFAT and AP-1 by Ras-Dependent Mechanisms. Cellular Signaling. 19(4):740-47.

8. Turner S.D., Merz H., Yeung D., Alexander D.R. (2006) CD2 Promoter Regulated Nucleophosmin-Anaplastic Lymphoma Kinase in Transgenic Mice Causes B Lymphoid Malignancy. Anticancer Research 26(5A):3275-79.

9. Turner S.D., Tooze R.M., Macklennan K., Alexander D.R. (2003) Vav-promoter regulated oncogenic fusion protein NPM-ALK in transgenic mice causes B-cell lymphomas with hyperactive Jun kinase. Oncogene 22:7750-7761.