Pat McPherson Professor of Cancer Biology
Understanding the role of the DNA Damage Response in Cancer
Division of Cancer Research
Jacqui Wood Cancer Centre
University of Dundee
James Arrott Drive
Ninewells Hospital And Medical School
+(44) 01382 383360
Professor Kevin Hiom is currently the Pat McPherson Chair of Cancer Biology at the Biomedical Research Institute and Dundee Cancer Centre at the Ninewells Hospital and Medical School.
Professor Hiom received his BSc in Genetics from the University of Liverpool and carried out his PhD work at the MRC National Institute for Medical Research London, where he developed an interest in how cells are able to repair damage to their DNA. Post-doctoral fellowships followed at the Imperial Cancer Research Fund Laboratories (now Cancer Research UK) and the National Institutes of Health in the United States. In 1998 Professor Hiom started his own research group at the MRC Laboratory of Molecular Biology in Cambridge where his attention turned towards understanding the relationship between defects in DNA repair and cancer. In 2009 Professor Hiom relocated his group to the Biomedical Research Institute in Dundee.
In 1998 Professor Hiom was awarded the Pfizer award for Biology for his work on the mechanisms for generating antibody diversity in the immune response. In 2005 he was awarded the Discovery Award of the Fanconi Anaemia Research Fund for the identification of the FANCJ gene, defects in which cause the human chromosome instability syndrome Fanconi’s anaemia.
Cancer cells exhibit profound genomic instability resulting in the accumulation of mutations and DNA breaks, as well as gross chromosome rearrangements and aberrations. Loss of genome stability is commonly associated with defects in factors involved in the DNA damage response (DDR), which detect and signal the presence of DNA lesions and participate in their repair. Inherited defects in DDR factors are responsible for a broad range of human diseases and cancer-predisposing conditions, including Fanconi’s anaemia, Ataxia telangiectasia, Seckel syndrome and early onset breast and ovarian cancer. As well as being a driving force towards cancer, defects in the DDR sensitize cancer cells to agents that damage DNA and therefore can be exploited for therapy.
Our group is interested in understanding the fundamental molecular mechanisms used by cells to detect and repair DNA damage and using this information to stratify patients for treatment and discover new cancer therapies. One specific interest in our lab is the function of the breast cancer associated tumour suppressor BRCA1 and its associated proteins. We are investigating the role of the BRCA1 protein as an ubiquitin ligase in the repair of DNA breaks and in the regulation of transcription. This has developed into a broader interest in the ubiquitylation of histones in chromatin. BRCA1 also makes multiple interactions through its C-terminal BRCT domains. Using genetic biochemical and cell biological techniques we are studying how these interactions contribute to the tumour suppressor function of BRCA1 through regulation of the DNA damage response.
Recently we have initiated studies on the repair of DNA damage in whole tissues. In collaboration with Professor Inke Näthke at the College of Life Sciences in Dundee we are also looking at the cellular consequences of DNA damage in living gut tissue and the contribution made by the tumor suppressor APC in this process.
- Kitao H, Nanda I, Sugino RP, Kinomura A, Yamazoe M, Arakawa H, Schmid M, Innan H, Hiom K, Takata M. (2011) FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells. Genes Cells. 16 714-27
- Maertens G.N., El Messaoudi-Aubert S., Elderkin S., Hiom K. and Peters G. (2010) Ubiquitin specific proteases 7 and 11 modulate polycomb regulation of the INK4a timour suppressor. EMBO J. 29 2553-65
- Yun M.H. & Hiom K (2009) CtIP modulates the choice of DNA double strand break repair pathway throughout the cell cycle Nature 459, 460-463
- London T.B.C, Barber L.J., Mosedale G., Balasubramanian S., Hickson I.D., Boulton S.J. & Hiom K. FANCJ is a structure -specific DNA helicase associated with the maintenance of genomic G-C tracts. J Biol Chem. 283 36132-36139
- Elderkin S., Maertens G.N., Endoh M., Mallery D.L., Morrice N., Koseki H., Peters G., Brockdorff N. & Hiom K. (2007). A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin. Molecular Cell 28 107-120
- Bridge W.L., Vandenberg C.J., Franklin R.J. & Hiom K. (2005). The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair. Nat Genet. 37 953-957.
- Levitus M., Waisfisz Q., Godthelp B. C., de Vries Y., Hussain S., Wiegant W. W., Elghalbzouri-Maghrani E., Steltenpool J., Rooimans M A., Pals G., Arwert F., Mathew C.G, Zdzienicka M. Z., Hiom K., De Winter J.P. & Joenje H. (2005). The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J.Nat Genet. 37 934-935.
- Vandenberg C.J, Gergely F., Ong, C.Y.. Pace, P., Mallery, D.L., Hiom K*. & Patel K.J. (2003). BRCA1-Independent ubiquitination of FANCD2 Molecular Cell 12 247-254 * (joint communicating author)
- Mallery D.L., Vandenberg C.J. & K. Hiom (2002). Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains. EMBO J ,12 6755-6762
Jane Cuddihy, Dissecting the function of the APC tumour suppressor gene, 2013.
- 2012 A*Star symposium Singapore
- 2011 Meeting Chair. Abcam Meeting on Ubiquitin –like Molecules and Disease, Cambridge UK
- 2011 Speaker and Session Chair Gordon Research Conference
- Genetic Toxicology- Barga, Italy
- 2011 EMBO Meeting Speaker Ubiquitin & DNA Damage Responses. Croatia
- 2010 Speaker: Gordon Research Conference on Mutagenesis. Maine, USA.
- 2010 Speaker: Annual Association for Radiation Research Meeting. Oxford UK
- 2010 Faculty: EMBO Workshop on DT40. Galway, Ireland
- 2011 Seminar - Weatherall Institute Oxford
- 2011 Seminar - Institute of Cancer Research, Zurich
- 2010 Seminar - University of Wales medical School Cardif
- 2010 Seminar - Beatson Institute Glasgow