Tim Humphrey D.Phil

Chromosome Integrity Group
Understanding how genome stability is maintained in response to DNA double-strand breaks.

Dr. Tim Humphrey

Email 
Tel  +44 (0)1865 617327
Fax  +44 (0)1865 617318
Fax (PA)  123456
Contact address  Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ
Department  Department of Oncology
College No College

Research Summary

DNA double-strand breaks (DSBs) are highly genotoxic lesions, arising either through DNA metabolism or from exposure to DNA damaging agents such as ionizing radiation.  In addition to causing cell death, such lesions can cause chromosomal rearrangements, a hallmark of cancer cells, which can lead to oncogene activation or to loss of heterozygosity.  The objective of the laboratory is to understand how genome stability is maintained in response to DSB's.  We are examining the mechanisms and determinants of DSB repair, including the role of tumour suppressor genes, in suppressing break-induced chromosomal rearrangements in normal cells.  Further we are examining DSB misrepair and the fate of unrepaired broken chromosomes, to gain new insights into the mechanisms by which such lesions contribute to genome instability and tumorigenesis.  We are using the genetically amenable fission yeast Schizosaccharomyces pombe as our primary model system in which DNA damage responses are evolutionarily conserved.  Findings made in fission yeast are being analysed further in mammalian cells.  research techniques employed include genetics, molecular biology and biochemistry.

Collaborators

Group Members

  • Dr Chen-Chun Pai, Postdoctoral Researcher
  • Dr Sovan Sarkar, Postdoctoral Researcher
  • Carol Walker, Lab Manager
  • Elizabeth Blaikley, DPhil Student
  • Sara Ahrabi, DPhil Student
  • Sophia Pfister, DPhil Student

Collaborators

    Biography

    Appointments
    2007 Senior Group Leader, CRUK/MRC Oxford Institute for Radiation Oncology, Oxford  University  
    2003-2007 Senior Group Leader, MRC Radiation and Genome Stability Unit  
    1997-2003 Group Leader MRC, Radiation and Genome Stability Unit  
    1997 Director of Graduate Studies  
    1993-1997 Post-Doctoral Research Fellow, Harvard University
    1991-1993 Post-Doctoral Research Fellow, Oxford University   
    1985-1987 Research Assistant, Heidelberg University

    Awards Training and Qualifications

    • 2003, MRC Career Appointment,
    • 1996, Charles A. King Trust Post-Doctoral Fellowship Award,
    • 1994, Human Frontiers Science Programme Fellowship Award,
    • 1993, European Molecular Biology Long-Term Fellowship,
    • 1991, D. Phil. Molecular Biology, Oxford University
    • 1985, B.Sc. Hons. Brewing and Microbiology, Heriot-Watt University

    Publications

    Selected Publications:

    Moss J, Tinline-Purvis H, Walker C, Folkes L, Stratford M, Hayles J, Hoe K, Kim D, Park H, Kearsey S, Fleck O, Holmberg C, Nielsen O, and Humphrey T (2010). Break-induced ATR and Ddb1-Cul4Cdt2 ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. Genes Dev, 24(23):2705-16.

    McFarlane R, and Humphrey T (2010). A role for recombination in centromere function. Trends Genet, 26(5):209-213.

    Tinline-Purvis H, Savory A, Cullen J, Dave A, Moss J, Bridge W, Marguerat S, Bahler J, Ragoussis J, Mott R, Walker C, and Humphrey T (2009). Failed gene conversion leads to extensive end processing and chromosomal rearrangements in fission yeast. EMBO J, 28(21):3400-12.

    George V, Brooks G, and Humphrey T (2007). Regulation of cell cycle and stress responses to hydrostatic pressure in fission yeast. Mol Biol Cell, 18(10):4168-79.

    Cullen J, Hussey S, Walker C, Prudden J, Wee BY, Dave A, Findlay J, Savory A, and Humphrey T (2007). Break-induced loss of heterozygosity in fission yeast: dual roles for homologous recombination in promoting translocations and preventing de novo telomere addition. Mol Cell Biol, 27(21):7745-57.

    Humphrey T, and Pearce A (2005). Cell cycle molecules and mechanisms of the budding and fission yeasts. Methods Mol Biol, 296:3-29.

    Dunand-Sauthier I, Walker C, Narasimhan J, Pearce A, Wek R, and Humphrey T (2005).
    Stress-activated protein kinase pathway functions to support protein synthesis and translational adaptation in response to environmental stress in fission yeast. Eukaryot Cell, 4(11):1785-93.

    Humphrey T, and Brooks G (2005). Cell Cycle Control: Mechanisms and Protocols. Methods in Molecular Biology, Humana Press, Inc. Totowa NJ, USA, 206.

    Watson A, Mata J, Bahler J, Carr A, and Humphrey T (2004). Global gene expression responses of fission yeast to ionizing radiation. Mol Biol Cell, 15(2):851-60.

    Prudden J, Evans J, Hussey S, Deans B, O'Neill P, Thacker J, and Humphrey T (2003). Pathway utilization in response to a site-specific DNA double-strand break in fission yeast. EMBO J, 22(6):1419-30.