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Turner Group Picnic with a ginger cat

Our Research

In our lab, we investigate the pathogenesis and aetiology of paediatric cancers towards the development of biomarkers to facilitate kinder, less toxic and novel therapeutic approaches.

Current Projects

Mechanisms of Lymphomagenesis

Lymphoma is a heterogeneous disease class consisting of greater than 40 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.

Comparative analysis of endemic and sporadic Burkitt lymphoma

Our lab works together with Jackson Orem at the Uganda Cancer Institute in Kampala, Uganda in an effort to understand the aetiology and pathogenesis of Burkitt lymphoma with a particular emphasis on tumour clonal evolution with treatment. This aspect of our research is supported by Cambridge Africa.

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL)

The most recent addition to the family of ALCL is a form of cancer associated with the presence of textured breast implants. Given our 20 years of experience of working towards understanding the pathogenesis of ALCL, we have turned our attention to unraveling the mechanisms that drive this specific form of cancer.

Recent Publications

Garland, G.D*., Ducray, S.P*., Jahangiri, L.J., Pucci, P., Burke, G.A.A., Monahan, J., Lai, R., Merkel, O., Schiefer, A., Kenner, L., Bannister, A.J. and Turner, S.D. (2022) BRG1 and NPM-ALK are co-regulated in Anaplastic Large Cell Lymphoma; BRG1 is a potential therapeutic target in ALCL. Cancers, in press

Lucy Hare, G.A. Amos Burke and Suzanne D. Turner (2021) Resistance to Targeted Agents Used to Treat Paediatric ALK-Positive ALCL 13(23), 6003; https://doi.org/10.3390/cancers13236003

Karaca-Atabay, E., Wang, Q., Cheong, T., Ambrogio, C., Mota, I., Prokoph, N., Leonardi, N., Hossa, J., Patrucco, E., Pich, A., Mologni, L., Gambacorti-Passerini, C., Brugières, L., Geoerger, B., Turner, S.D., Voena, C., & Chiarle, R. (2021) Tyrosine phosphatases regulate resistance to ALK inhibitors in lymphoma. Blood, in press

Newman, A.M., Zaka, M., Zhou, P., Blain, A.E., Erhorn, A., Barnard, A., Crossland, R.E., Wilkinson, S., Enshaei, A., De Zordi, J., Harding, F., Taj, M., Wood, K., Televantou, D., Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma, Leukemia, in press

Gong, C., Krupka, J., Gao, J., Grigoropoulos, N.F., Screen, M., Cucco, F., Mohammed, M., Usheva, Z., Bornelöv, S., Ruiz De Los Mozos, I., Meng, W., Barrans, S., Bain, A., Burke, G.A., Forde, S., Matthews, J.D., Beer, P., Cooke, S., Burton, C., Campbell, P., Davies, A., Roman, E., Turner, S.D., Ule, J., Rand, V., Oellerich, T., Turner, M., Du, M., Samarajiwa, S. and Hodson, D.J. (2021) DDX3X and DDX3Y co-operate to facilitate MYC-driven B cell lymphomas. Molecular Cell, in press

 

Group Members from elsewhere

Leila Jahangiri - visiting research fellow

Gill Kortum, Manager of the CRUK Cambridge Centre Paediatric Programme