Genomic Instability
Recent successes:
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Fusion
of short telomeres in human cells is characterized by extensive
deletion and microhomology, and can result in complex rearrangements.
Letsolo BT, Rowson J, Baird DM, Nucleic Acids Res , Volume 38 , 6 (April 2010) pp.1841-1852
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Silenced yeast chromatin is maintained by Sir2 in preference to permitting histone acetylations for efficient NER.
Irizar A, Yu Y, Reed SH, Louis EJ, Waters R, Nucleic Acids Res (April 2010)
Our objectives in this area are to:
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Determine how chromosomal
domains are remodelled to permit DNA repair.
Prof Raymond Waters and Dr Simon Reed, Pathology dept
- Examine potential
inter-individual DNA repair capacity.
Prof Jeremy Cheadle, Prof Raymond Waters and Dr Simon Reed,Medical Genetics dept and Pathology dept
- Elucidate the role of telomere erosion during early-stage neoplasia and pre-neoplastic conditions.
Dr Duncan Baird, Pathology dept
- Understand how the loss of Werners helicate relates to invivo ageing and the cancer phenotypes of WRN individuals and exploit this for therapeutic benefit.
Dr Terence Davis and Prof David Kipling, Pathology dept
- Identify the causes of colorectal cancer (with particular analysis of the DNA repair pathways) and develop new diagnostic test.
Prof Julian Sampson and Prof Jeremy Cheadle, Medical Genetics dept, Colorectal Cancer
- Capitalize further on the potential of the Human Gene Mutation Database
to provide in silico highlights into the pathogenesis of human mutation.
Prof David Cooper, Medical Genetics dept, Human Gene Mutation Group
Publications
- Extreme telomere erosion in ATM-mutated and 11q-deleted CLL patients is independent of disease stage.
Britt-Compton B, Lin TT, Ahmed G, Weston V, Jones RE, Fegan C, Oscier DG, Stankovic T, Pepper C, Baird DM, Leukemia, Volume 26, 4 (April 2012) pp.826-830 - Expression of CD200 on AML blasts directly suppresses memory T-cell function.
Coles SJ, Hills RK, Wang EC, Burnett AK, Man S, Darley RL, Tonks A, Leukemia (March 2012) - Increased CD200 expression in acute myeloid leukemia is linked with an increased frequency of FoxP3(+) regulatory T cells.
Coles SJ, Hills RK, Wang EC, Burnett AK, Man S, Darley RL, Tonks A, Leukemia (March 2012) - Expansion of a CD8(+)PD-1(+) replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression.
Nunes C, Wong R, Mason M, Fegan C, Man S, Pepper C, Clin Cancer Res, Volume 18, 3 (February 2012) pp.678-687 - Assessing the malignant potential of ovarian inclusion cysts in postmenopausal women within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a prospective cohort study.
Sharma A, Gentry-Maharaj A, Burnell M, Fourkala EO, Campbell S, Amso N, Seif MW, Ryan A, Parmar M, Jacobs I, Menon U, UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) None, Bjog, Volume 119, 2 (January 2012) pp.207-219