Group Leaders and Projects

Professor Mark Meuth, Head of Institute

DNA damage response and the regulation of cell death in tumour and stem cells

• Gagou, M.E., Ganesh, A., Thompson, R., Phear, G., Sanders, C. and Meuth, M. (2011)
  The human Pif1 helicase suppresses apoptosis in response to DNA replication inhibitors in tumor cells.
  Cancer Res. In press.
• Myers, K., Gagou, M.E., Zuazua-Villar, P., Rodriguez, R., and Meuth M. (2009)
  ATR and Chk1 suppress a Caspase-3 apoptotic response following DNA replication stress.
  PLoS Genetics, 5(1):e1000324.

Professor Angela Cox

The role of common variants of genes involved in the DNA damage response and apoptosis pathways in susceptibility to common cancers

• Camp NJ*, Parry P*, Knight S, Abo R, Elliott G, Rigas S, Balasubramanian SP, Reed MWR, McBurney H, Latif A, Newman WG, Cannon-Albright LA, Evans DG, Cox A.
  Fine-mapping CASP8 risk variants in Breast Cancer.
  Cancer Epidemiology, Biomarkers and Prevention 2012 21, 176-81.
• Lin WY, Camp NJ, Cannon-Albright LA, Allen-Brady K, Balasubramanian S, Reed MW, Hopper JL, Apicella C, Giles GG, Southey MC, Milne RL, Arias-Pérez JI, Menéndez-Rodríguez P, Benítez J, Grundmann M, Dubrowinskaja N, Park-Simon TW, Dörk T, Garcia-Closas M, Figueroa J, Sherman M, Lissowska J, Easton DF, Dunning AM, Rajaraman P, Sigurdson AJ, Doody MM, Linet MS, Pharoah PD, Schmidt MK, Cox A.
  A role for XRCC2 gene polymorphisms in breast cancer risk and survival.
  J Med Genet. 2011 Jul;48(7):477-484

Dr. Cyril Sanders

Early events in DNA replication (initiation) using papillomavirus (bovine papillomavirus) as a model system

• Sanders C. (2010)
  Human Pif1 helicase is a G-quadruplex DNA binding protein with G-quadruplex DNA unwinding activity.
  Biochem. J. 430, 119-128.
• George T, Wen Q, Griffiths R, Ganesh A, Meuth M, Sanders CM. (2009)
  Human Pif-1 helicase unwinds synthetic DNA structures resembling stalled DNA replication forks.
  Nucleic Acids Res., 37, 6419-6502.

Dr. Jim Catto

Translational epigenomics in bladder and prostate cancer: Discovery of prognostic epigenetic molecular detail for application in clinical care. Epigenetic instability in cancer

• Dudziec E et al.
  Hypermethylation of CpG Islands and Shores adjacent to mirtron and microRNA genes in bladder cancer.
  Clin Cancer Res. 2011 Jan 28
• Owen HC, et al.
  Low frequency of epigenetic events in urothelial tumors from young patients.
  J Urol. 2010 Aug;184(2):459-63

Dr. Thierry Nouspikel

Regulation of Nucleotide Excision Repair in terminally differentiated and quiescent cells: consequences for mutagenesis (e.g. cancer) and cell survival (e.g. neurodegeneration)

• Nouspikel, T., and Hanawalt, P. C. (2006) Impaired nucleotide excision repair upon macrophage differentiation is corrected by E1 ubiquitin-activating enzyme. Proc Natl Acad Sci USA. 103, 188-193.
• Nouspikel, T., Hyka-Nouspikel.,N., and Hanawalt, P. C. (2006) Transcription Domain-Associated Repair in Human Cells. Molecular & Cellular Biology, 26,8722-8730.

Dr. Helen Bryant

Response of tumour cells to DNA replication stress. Exploitation of alterations in these responses to develop new therapies

• Gravells P, Hoh L, Canovas D, Rennie IG, Sisley K, Bryant H.
  Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R.
  Br J Cancer. 2011 Mar 29;104(7):1098-105
• Hoh L, Gravells P, Canovas D, Ul-Hassan A, Rennie IG, Bryant H, Sisley K.
  Atypically low spontaneous sister chromatid exchange formation in uveal melanoma.
  Genes Chromosomes Cancer. 2011 Jan;50(1):34-42.

Dr. Pat Eyers

The regulation and function of therapeutically important protein kinases

My laboratory uses state-of-the-art approaches to answer two critical biological questions. Firstly, we employ biochemical and biophysical techniques to understand how distinct members of the human kinome are regulated. Secondly, we use small molecule inhibitors of protein kinases to investigate the cell biology of this protein superfamily. By coupling mechanistic insights with drug resistance profiles, we have discovered that these compounds represent powerful mechanistic probes for understanding proliferative diseases such as cancer.

• Scutt PJ, Chu, MLH, Sloane DA, Cherry M, Bignell CR, Williams DH and Eyers PA. Discovery and exploitation of inhibitor-resistant Aurora and Polo kinase mutants for the analysis of mitotic networks. Journal of Biological Chemistry (2009) 284: 15880-15893
• Chu MLH, Lang Z, Chavas LMG, Neres J, Federova OS, Tabernero L, Cherry M, Williams DH, Douglas KT and Eyers PA. Biophysical and X-ray crystallographic analysis of Mps1 kinase inhibitor complexes. Biochemistry (2010) 49: 1689-1701

Dr. Spencer Collis

The identification and characterisation of novel genome maintenance factors and their involvement in genetically unstable human disorders

The work of the lab aims to understand the complex mechanisms of DNA repair pathways in order to expand our knowledge of cancer development and progression. We are discovering new proteins that are involved in the detection and subsequent repair of DNA damage, and we are particularly interested in determining if mutations in these proteins lead to the development of genetically unstable human diseases such as cancer. The study of such proteins will not only give us insight into how these DNA repair pathways work, but also tell us how they go wrong in the development of human disease. It is hoped that this work could lead to the development of new or improved anti-cancer treatments and/or clinically useful biomarkers.

• Staples CJ, Myers KN, Beveridge RD, Patil AA, Lee AJ, Swanton C, Howell M, Boulton SJ & Collis SJ.
The centriolar satellite protein Cep131 is important for genome stability.
J Cell Sci. Advance Online Publication July 13, 2012, doi:10.1242/jcs.104059
• Adamo A*, Collis SJ*, Adelman CA, Silva N, Ward JD, Martinez-Perez E, Boulton SJ & La Volpe A. *co-first authorship
  Preventing Non-Homologous End Joining Suppresses DNA repair defects of Fanconi Anemia.
  Molecular Cell 39(1), 25-35 2010