School of Biosciences

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About

Tim joined the School of Biosciences from UCL Cancer Institute in April 2017. He obtained his BSc in Molecular Biology and Biochemistry from the University of Durham in 2001, followed by a PhD at the Ludwig Institute for Cancer Research, UCL with Prof Ivan Gout, studying the ribosomal S6 kinases (enzymes involved in the control of cell growth in response to nutrient and growth factor signals). In 2005 Tim took up a postdoctoral position in Prof Webster Cavenee’s lab at the University of California San Diego LICR branch, where he continued to work on growth factor signalling in cancer, uncovering a molecular mechanism that renders brain tumour cells resistant to drugs targeting the Epidermal Growth Factor Receptor. In 2011 Tim moved back to UCL, joining Prof Chris Boshoff’s Cancer Research UK Viral Oncology Lab, before gaining funding from Rosetrees Trust to establish his independent research.

Tim’s research interests are in understanding the molecular changes that occur as cancers develop and evade destruction by our immune system. His goal is to apply these findings to enable earlier diagnosis and more effective therapy.

ORCID ID: http://orcid.org/0000-0002-4737-8233

Contact Information

Address

Stacey G.23 (ground floor)

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Publications

Also view these in the Kent Academic Repository

Article
Holme, H. et al. (2018). Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness. Scientific Reports [Online] 8. Available at: https://doi.org/10.1038/s41598-018-29043-z.
Lechner, M. et al. (2018). A cross-sectional survey of awareness of human papillomavirus-associated oropharyngeal cancers among general practitioners in the UK. BMJ Open [Online] 8:e023339. Available at: https://doi.org/10.1136/bmjopen-2018-023339.
Chakravarthy, A. et al. (2018). Pan-cancer deconvolution of tumour composition using DNA methylation. Nature Communications [Online] 9. Available at: https://doi.org/10.1038/s41467-018-05570-1.
Lechner, M. et al. (2018). Frequent HPV-independent p16/INK4A overexpression in head and neck cancer. Oral Oncology [Online] 83:32-37. Available at: https://doi.org/10.1016/j.oraloncology.2018.06.006.
Periyasamy, M. et al. (2017). p53 controls expression of the DNA deaminase APOBEC3B to limit its potential mutagenic activity in cancer cells. Nucleic Acids Research [Online] 45:11056-11069. Available at: http://dx.doi.org/10.1093/nar/gkx721.
Masterson, L. et al. (2016). CD8+ T cell response to human papillomavirus 16 E7 is able to predict survival outcome in oropharyngeal cancer. European Journal of Cancer [Online] 67:141-151. Available at: http://doi.org/10.1016/j.ejca.2016.08.012.
Campbell, J. et al. (2016). Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines. Cell Reports [Online] 14:2490-2501. Available at: http://dx.doi.org/10.1016/j.celrep.2016.02.023.
Chakravarthy, A. et al. (2016). Human Papillomavirus Drives Tumor Development Throughout the Head and Neck: Improved Prognosis Is Associated With an Immune Response Largely Restricted to the Oropharynx. Journal Of Clinical Oncology [Online] 34:4132-4141. Available at: http://dx.doi.org/10.1200/JCO.2016.68.2955.
Feber, A. et al. (2016). CSN1 Somatic Mutations in Penile Squamous Cell Carcinoma. Cancer Research [Online] 76:4720-4727. Available at: http://dx.doi.org/10.1158/0008-5472.CAN-15-3134.
Henderson, S. and Fenton, T. (2015). APOBEC3 genes: retroviral restriction factors to cancer drivers. Trends in Molecular Medicine [Online] 21:274-284. Available at: http://dx.doi.org/10.1016/j.molmed.2015.02.007.
Feber, A. et al. (2014). Using high-density DNA methylation arrays to profile copy number alterations. Genome Biology [Online] 15. Available at: http://dx.doi.org/10.1186/gb-2014-15-2-r30.
Chakravarthy, A., Henderson, S. and Fenton, T. (2014). When defense turns into attack: Antiviral cytidine deaminases linked to somatic mutagenesis in HPV-associated cancer. Molecular & Cellular Oncology [Online] 1:e29914 - e29914. Available at: http://dx.doi.org/10.4161/mco.29914.
Henderson, S. et al. (2014). APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development. Cell reports [Online] 7:1833-1841. Available at: http://doi.org/10.1016/j.celrep.2014.05.012.
Read, R. et al. (2013). A Kinome-Wide RNAi Screen in Drosophila Glia Reveals That the RIO Kinases Mediate Cell Proliferation and Survival through TORC2-Akt Signaling in Glioblastoma. PLoS Genetics [Online] 9:1-19. Available at: https://doi.org/10.1371/journal.pgen.1003253.
Lechner, M. et al. (2013). Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma. Genome Medicine [Online] 5. Available at: http://dx.doi.org/10.1186/gm419.
Wilson, G. et al. (2013). Integrated virus-host methylome analysis in head and neck squamous cell carcinoma. Epigenetics [Online] 8:953-961. Available at: http://dx.doi.org/10.4161/epi.25614.
Lechner, M. et al. (2013). Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors. Genome Medicine [Online] 5. Available at: http://dx.doi.org/10.1186/gm453.
Feng, H. et al. (2012). Phosphorylation of dedicator of cytokinesis 1 (Dock180) at tyrosine residue Y722 by Src family kinases mediates EGFRvIII-driven glioblastoma tumorigenesis. Proceedings of the National Academy of Sciences [Online] 109:3018-3023. Available at: http://dx.doi.org/10.1073/pnas.1121457109.
Fenton, T. et al. (2012). Resistance to EGF receptor inhibitors in glioblastoma mediated by phosphorylation of the PTEN tumor suppressor at tyrosine 240. Proceedings of the National Academy of Sciences [Online] 109:14164 - 14169. Available at: http://dx.doi.org/10.1073/pnas.1211962109.
Feng, H. et al. (2011). Activation of Rac1 by Src-dependent phosphorylation of Dock180(Y1811) mediates PDGFR\ensuremathα-stimulated glioma tumorigenesis in mice and humans. Journal of Clinical Investigation [Online] 121:4670-4684. Available at: https://doi.org/10.1172/JCI58559.
Fenton, T. and Gout, I. (2010). Functions and regulation of the 70 kDa ribosomal S6 kinases. International Journal of Biochemistry and Cell Biology [Online] 43:47-59. Available at: http://dx.doi.org/10.1016/j.biocel.2010.09.018.
Fenton, T. et al. (2009). Histone acetyltransferases interact with and acetylate p70 ribosomal S6 kinases in vitro and in vivo. The International Journal of Biochemistry & Cell Biology [Online] 42:359 - 366. Available at: http://dx.doi.org/10.1016/j.biocel.2009.11.022.
Book section
Lechner, M. and Fenton, T. (2016). Chapter One - The Genomics, Epigenomics, and Transcriptomics of HPV-Associated Oropharyngeal Cancer - Understanding the Basis of a Rapidly Evolving Disease. in: Advances in Genetics. Elsevier, pp. 1-56. Available at: http://discovery.ucl.ac.uk/1476690/.
Showing 23 of 24 total publications in KAR. [See all in KAR]
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Research Interests

Tim combines wet lab and computational approaches, focusing on human papillomavirus (HPV)-driven carcinogenesis as a paradigm for understanding tumour development. A major focus of his research is on a family of cytosine deaminase (APOBEC) enzymes, whose main physiological function is thought to be as part of the innate immune response to viruses via their ability to mutate viral DNA. However, recent cancer genome sequencing efforts have revealed a significant off-target activity of APOBEC enzymes against the cellular genome. Indeed, in many cancers, the majority of somatic mutations are attributable to this activity. Tim’s team discovered that APOBECs generate specific oncogenic mutations, implicating them as key drivers of tumour development. Following this discovery, he has used CRISPR-Cas9 genome editing to generate cellular models for detailed study of APOBEC regulation, with the aim of determining how and why these enzymes turn against our own genomes during cancer development.

In tandem with studying these cellular models, Tim is using whole exome and viral genome sequencing, together with genome-wide DNA methylation analysis of patient samples from HPV-associated head and neck cancers, to understand how these tumours evolve and the changes that occur as they become metastatic. His team have recently developed a method to determine the nature and extent of immune cell infiltration into tumours using DNA methylation data, which he is now using to help build a picture of how tumours adapt and evade our immune responses.

Finally, while prophylactic vaccination holds great potential to eradicate HPV-driven cancer in the coming decades, this will not benefit those already infected, or those who do not have access to vaccination. There is therefore an urgent need to develop more effective therapies for the over 95% of cervical cancers, several other anogenital cancers and a rapidly increasing fraction of head and neck cancers that are caused by HPV. To this end, in collaboration with researchers at the Institute for Cancer Research, Tim and his team have used siRNA screening to identify protein kinases that are required for the growth of HPV-positive cancer cell lines. They are currently pursuing detailed study of one such kinase, which they now know controls expression of the viral oncogenes, as a potential drug target for these cancers.

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Enquiries: Phone: +44 (0)1227 823743

School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ

Last Updated: 21/04/2017