Newcastle University

Background

BSc and PhD from London University. Based in Newcastle from 1993 to 1998 and from 2003 to present and in Edinburgh from 1998 to 2003.

Qualifications

BSc (London, 1982)
PhD (London, 1989)

Previous Positions

May 2003 - May 2006
Research Associate, NICR, Newcastle University.

Nov 1998 – Feb 2003
Senior Research Associate, Roslin Institute (Edinburgh).

Jan 1997 - Nov 1998
Senior Research Associate, Department of Biochemistry and Genetics, Newcastle University.

Jan 1993 - Jan 1997
Wellcome Postdoctoral Research Fellow, Department of Biochemistry and Genetics, Newcastle University.

Oct 1989 - Jan 1993
Postdoctoral Research Associate, Imperial Cancer Research Fund Molecular Oncology Unit, Hammersmith Hospital, London.

Jan 1986 Oct 1989
Research Assistant, Biochemistry Department, University College and Middlesex School of Medicine.

Jan 1983 Jan 1986
Research Technician, Immunology Department, St George's Hospital Medical School, University of London.

Informal Interests

Photography
Walking

Research Interests

My research interests fall into the areas of vertebrate gene regulation, nuclear organization and function and DNA repair. This is currently focussed on the following themes:

-Events leading to chromosomal translocation in leukaemia.
-Histone modifications including methylation and acetylation and changes in chromatin/nuclear organisation associated with DNA damage.
-Histone lysine methylation and the function of chromodomain proteins.
-Targeting DNA-repair proteins as a means on improving the efficacy of anti-cancer treatments.

Other Expertise

My areas of research expertise include:
- Fluorescence microscopy including quantitative and qualitative immunofluorescence, DNA FISH and 3D RNA FISH.
- Cell toxicity and growth inhibition assays (eg Clonogenic and XTT assays.
- Culture and manipulation of murine and human embryonic stem cells as well as other general cell biology techniques.
- Antibody purification and other protein biochemical techniques.
- Molecular cloning techniques including the design and assembly of expression and other DNA constructs.
- General bioinformatics and IT expertise.

Current Work

DNA topoisomerase poisons such as etoposide are commonly used anticancer drugs that introduce a type of DNA damage involving covalent topoisomerase DNA adducts. I am currently funded by the Leukaemia Research Fund to study the role of type II DNA topoisomerases in the aetiology of leukaemia. Specifically whether and how DNA topoisomerase II beta is involved in secondary leukaemias that sometimes occur after treatment with DNA-damaging cytotoxic anticancer drugs for a primary cancer. This project has involved the establishment of in-house high resolution interphase 3D FISH and chromatin immunoprecipitation techniques.

Interestingly, the cytotoxicity of topoisomerase poisons is poteintiated by another group of drugs known as histone deacetylase inhibitors. I am contributing to an Association for International Cancer Research (AICR)-funded project investigating the interactions between histone deacetylase inhibitors and DNA topoisomerase II with the aim of improving the therapy for lung cancer. These projects are part of the work of Prof. Caroline Austin’s laboratory in the Institute for Cell and Molecular Biosciences.

Research Roles

-Execution of ongoing research project/s from bench work to publication. This includes design of experiments, their execution and analysis and preparation and submission of manuscripts.
-Preparation of new research proposals. I have been a co-applicant on two recent successful grant proposals.
-Supervision of research student/s and less experienced members of the group.

Postgraduate Supervision

PhD student supervision:

Characterisation of DNA damage induced nuclear foci containing PML and TopBP1. 2004-2008. Student, Nicola Sunter

MSc research project supervision:
The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure (1992). Student, Sjak van der Saar. (In my previous post at the Roslin Institute.

Funding

1993-1996
Wellcome Postdoctoral Research Fellowship (3 years). Value ~ £100K

1996-1997
One year extension to the above Value ~ £30K

2004-2008
Gordon Piller Studentship (LRF) Value £76K
(Applicants CA Austin – grant holder, IG Cowell & BW Durkacz – co applicants)

2006-2009
LRF Project grant (RA1A (3 years). Value £131K
(Applicants Dr E Willmore (NICR), Dr B Durkacz (NICR), Dr G Summerfield & Dr I Cowell (ICaMB))

2008-2012
Gordon Piller Studentship (LRF)
(Applicants CA Austin – grant holder, IG Cowell– co applicant)

Undergraduate Teaching

I contribute to 3rd year modules BMS3012 "Cancer Biology and Therapy" and BGM3024 "The Molecular Basis of Cancer", delivering lectures on carcinogenesis, apoptosis, DNA repair mechanisms and genome instability in cancer.

Postgraduate Teaching

PhD student supervision:
2008-2012 .Student, Kayleigh Smith

2004-2007 Characterisation of DNA damage induced nuclear foci containing PML and TopBP1. Student, Nicola Sunter.

MSc research project supervision:
The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure (1992). Student, Sjak van der Saar(In my previous post at the Roslin Institute).

• Cowell IG, Tilby MJ, Austin CA. An overview of the visualisation and quantitation of low and high MW DNA adducts using the trapped in agarose DNA immunostaining (TARDIS) assay. Mutagenesis 2011. GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND: OXFORD UNIV PRESS, 26(2), 253-260.
• Cowell IG, Papageorgiou N, Padget K, Watters GP, Austin CA. Histone deacetylase inhibition redistributes topoisomerase IIβ from heterochromatin to euchromatin. Nucleus 2011, 2(1), 61-71.
• Toyoda E, Kagaya S, Cowell IG, Kurosawa A, Kamoshita K, Nishikawa K, Iiizumi S, Koyama H, Austin CA, Adachi N. NK₃₁₄, a topoisomerase II inhibitor that specifically targets the alpha isoform. Journal of Biological Chemistry 2008,283 35 23711-23720.
• Willmore E, Elliott SL, Mainou-Fowler T, Summerfield GP, Jackson GH, O'Neill F, Lowe C, Carter A, Harris R, Pettitt AR, Cano-Soumillac C, Griffin RJ, Cowell IG, Austin CA, Durkacz BW. DNA-dependent protein kinase is a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia. Clinical Cancer Research 2008,14 12 3984-3992.
• Cowell I, Sunter NJ, Singh PB, Austin CA, Durkacz BW, Tilby MJ. γH2AX foci form preferentially in euchromatin after ionising-radiation. PLoS ONE 2007, 2(10), e1057.
• Leontiou C, Watters GP, Gilroy KL, Heslop P, Cowell IG, Craig K, Lightowlers RN, Lakey JH, Austin CA. Differential selection of acridine resistance mutations in human DNA topoisomerase II beta is dependent on the acridine structure. Molecular Pharmacology 2007, 71(4), 1006-1014.
• Zhao Y, Thomas HD, Batey M, Cowell I, Richardson C, Griffin RJ, Calvert AH, Newell DR, Smith G, Curtin NJ. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Research 2006, 66(10), 5354-5362.
• Cowell, I.G., Durkacz, B.W., Tilby, M.J. Sensitization of breast carcinoma cells to ionizing radiation by small molecule inhibitors of DNA-dependent protein kinase and ataxia telangiectsia mutated. Biochemical Pharmacology 2005, 71(1-2), 13-20.
• Brown JP, Singh PB, Cowell IG. Composite cis-acting epigenetic switches in eukaryotes: lessons from Drosophila Fab-7 for the Igf2-H19 imprinted domain. Genetica 2003, 117(2/3), 199-207.
• Cowell IG. E4BP4/NFIL3, a PAR-related bZIP factor with many roles. BioEssays 2002, 24(11), 1023-1029.
• Cowell IG, Aucott R, Mahadevaiah SK, Burgoyne PS, Huskisson NS, Bongiorni S, Prantera G, Fanti L, Pimpinelli S, Wu R, Gilbert D, Shi W, Fundele R, Morrison H, Jeppesen P, Singh PB. Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals. Chromosoma 2002, 111(1), 22-36.
• Filesi I, Cardinale A, van der Sar S, Cowell IG, Singh PB, Biocca S. Loss of Heterochromatin Protein 1 (HP1) chromodomain function in mammalian cells by intracellular antibodies causes cell death. Journal of Cell Science 2002, 115(9), 1803-1813.
• Scholzen T, Endl E, Wohlenberg C, Sar SvanDer, Cowell IG, Gerdes J, Singh PB. The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure. Journal of Pathology 2002, 196(2), 135-144.
• Jones DO, Mattei MG, Horsley D, Cowell IG, Singh PB. The gene and pseudogenes of Cbx3/mHP1 gamma. DNA sequence 2001, 12(3), 147-160.
• Wang G, Ma A, Chow CM, Horsley D, Brown NR, Cowell IG, Singh PB. Conservation of heterochromatin protein 1 function. Molecular & Cellular Biology 2000, 20(18), 6970-6983.
• Kourmouli N, Theodoropoulos PA, Dialynas G, Bakou A, Politou AS, Cowell IG, Singh PB, Georgatos SD. Dynamic associations of heterochromatin protein 1 with the nuclear envelope. The EMBO Journal 2000, 19(23), 6558-6568.
• Jones DO, Cowell IG, Singh PB. Mammalian chromodomain proteins: their role in genome organisation and expression. BioEssays 2000, 22(2), 124-137.
• Cowell IG, Willmore E, Chalton DA, Marsh KL, Jazrawi E, Fisher LM, Austin CA. Nuclear distribution of human DNA topoisomerase IIβ: A nuclear targeting signal resides in the 116-residue C-terminal tail. Experimental Cell Research 1998, 243(2), 232-240.
• Cowell IG, Austin CA. Self-association of chromo domain peptides. Biochimica et Biophysica Acta: Protein Structure and Molecular Enzymology 1997, 1337(2), 198-206.
• Cowell IG, Hurst HC. Protein-protein interaction between the transcriptional repressor E4BP4 and the TBP-binding protein Dr1. Nucleic Acids Research 1996, 24(18), 3607-3613.
• Cowell IG. Repression versus activation in the control of gene transcription. Trends in Biochemical Sciences 1994. , 19(1), 38-42.
• Cowell IG, Hurst HC. Transcriptional repression by the human bZIP factor E4BP4: Definition of a minimal repression domain. Nucleic Acids Research 1994, 22(1), 59-65.
• Spencer SR, Taylor JB, Cowell IG, Xia CL, Pemble SE, Ketterer B. The human mitochondrial NADH: Ubiquinone oxidoreductase 51-kDa subunit maps adjacent to the glutathione S-transferase p1-1 gene on chromosome 11q13. Genomics 1992, 14(4), 1116-1118.
• Xia CL, Cowell IG, Dixon KH, Pemble SE, Ketterer B, Taylor JB. Glutathione transferase pi its minimal promoter and downstream cis- acting element. Biochemical and Biophysical Research Communications 1991, 176(1), 233-240.
• Dixon KH, Cowell IG, Xia CL, Pemble SE, Ketterer B, Taylor JB. Control of expression of the human glutathione S-transferase Pi gene differs from its rat homologue. Biochemical and Biophysical Research Communications 1989, 163(2), 815-822.
• Cowell IG, Dixon KH, Pemble SE, Ketterer B, Taylor JB. The structure of the human glutathione-Pi gene. Biochemical Journal 1988, 255(1), 79-83.
• Taylor JB, Pemble SE, Cowell IG, Dixon KH, Ketterer B. Molecular biology of the glutathione transferases. Biochemical Society Transactions 1986, 15, 578-579.
• Cowell IG, Sondka Z, Smith K, Lee KC, Manville CM, Sidorczuk Lesthuruge M, Rance HA, Padget K, Jackson GH, Adachi N, Austin CA. A model for MLL translocations in therapy-related leukemia involving topoisomerase IIB mediated DNA strand breaks and gene proximity. Proceedings of the National Academy of Sciences 2012. In Press.