BSc BM BCh DPhil FRCP
Professor of Medical Oncology
- Tumour Growth Group, Oxford Molecular Pathology Institute, Sir William Dunn School
- Honorary Consultant Medical Oncologist, Oxford Hospitals
- T. O. Ogunlesi Senior Research Fellow, Lincoln College
Cancer, tumour growth and translational oncology at the Dunn School
Basic mechanisms and targets of tumour growth control
Molecular and cell biology of sarcoma
Translational development of IGF2-TRAP
Adaptive and biomarker directed clinical trials
The work of the group at the Sir William Dunn school is directed at regulators of tumour growth. Initial focus has been on IGF2 and the structure and function of the M6P/IGF2 receptor. Through understanding the molecular evolution of domain 11 binding, we have identified key steps the acquisition of IGF2 binding during mammalian genomic imprinting evolution, and developed an IGF2-TRAP through forward and directed evolution in vitro. This work continues towards first-in-man clinical trials in human cancer patients, where detailed biomarker analysis will be be developed and tested in parallel model systems.
Continuing the theme of tumour growth control, functional genetic studies have focused on two regulatory genes associated with cancer invasion and metastasis. Using intestinal organoids, the functional impact of E-cadherin EC1 extra-cellular domain and Smad4 MH1 domains have been evaluated. Current work continues to explore novel discoveries, including the post-translational regulation of key regulatory differentiation genes.
Through the NIHR Musculoskeletal biomedical research unit and Biomedical research centre, we are investigating the molecular basis of sarcoma diagnostics, and functional implications of key regulatory genes in specific sarcoma subtypes, and the targeting of key pathways in biomarker adaptive bayesian clinical trials, where we combine and integrate analysis of endpoints using next generation sequencing analysis with radiological (PET-CT) and tissue biomarker data.
Church, D., Carter, E., Phillips, B., Stuckey, D., Buffa, F., Manek, S., Clarke, K., Harris, A.L., Hassan, A.B. Igf2 dependency of Pten (+/-) developmental and tumour phenotypes in the mouse. (2011) Oncogene, 31: 3635-46.
van Maldegem AM, Bhosale A, Gelderblom HJ, Hogendoorn PC, Hassan AB. Comprehensive analysis of published phase I/II clinical trials between 1990-2010 in osteosarcoma and Ewing sarcoma confirms limited outcomes and need for translational investment. Clin Sarcoma Res. (2012) Jan 27;2(1):5.
Haley, V.L., Barnes, D.J., Graham, C.F., Sandovici, I., Constancia, M. and Hassan, A.B. Synergistic and dependent genetic interactions between Igf2 and p53 during embryonic and tumour development, (2011) EMBO Molecular Medicine 4: 705-18.
Williams, C., Hoppe, H., Rezgui, D., Strickland, M., Frago, S., Forbes, B., Gutzner, F., Ellis, R.Z., Wattana-Amorn, P., Prince, S.N., Zaccheo, O.J., Jones, E.Y., Crump, M.C. and Hassan, A.B. An exon splice enhancer primes IGF2:IGF2R binding site for structure and functional evolution. (2012) Science 338; 1209-13.
Hughes, J., Frago, S., Bühnemann, C., Carter, E.J. and Hassan, A.B. Maternal transmission of a humanised Igf2r allele results in an Igf2 dependent hypomorphic and non-viable growth phenotype. (2013) PlosOne e57270.
Bühnemann, C., Li, S., Brandford-White, H., Yu, H., Hogendoorn, P.C., Llombart-Bosch, A., Picci, P., Noble, A., Hassan, A.B. Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis. PLoS One 2014 9(9):e107105.
Frago, S., Nicholls, R.D. Strickland, M., Hughes, J., Williams, C., Garner, L. Surakhy, M. Maclean, R., Rezgui, D., Prince, S.N., Zaccheo, O.J. Ebner, D., Sanegre, S., Yu, S., Buffa, F., Crump, M.P. and Hassan, A.B. Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist. Proc. Nat. Acad. Sci. 2016, E2766-E2775.
Julia Matheson*, Claudia Bühnemann*, Emma J. Carter, David Barnes, Hans-Jürgen Hoppe, Jennifer Hughes, Stephen Cobbold, James Harper, Hans Morreau, Marvat Shurakhy, A. Bassim Hassan. Epithelial-mesenchymal transition induced by conditional disruption of Cdh1 and Apc in intestinal adenoma organoids is E-cadherin EC1 domain dependent. Oncotarget 2016 in PRESS.
David Barnes, Edward Hookway, Udo Oppermann, Simon Hughes, Daniel Swan, Dietrich Lueerssen, Nick Athanasou, Andrew B. Hassan. Comprehensive genomic characterization of a rare melanotic neuroectodermal tumour presenting in a fibula of a 2 month old child. BMC Cancer, 2016, in PRESS.