Research Groups

Kurt Anderson
Tumour Cell Migration
Jeff Evans
Translational Cancer Therapeutics
David Gillespie
Checkpoints and Cell Cycle Control
Eyal Gottlieb
Apoptosis and Tumour Metabolism
Danny Huang
Ubiquitin Signalling
Robert Insall
Cell Movement and Chemotaxis
Hing Leung
Urology Research
Laura Machesky
Actin in Cell Migration, Invasion and Metastasis
Jim Norman
Integrin Cell Biology
Michael Olson
Molecular Cell Biology
Kevin Ryan
Understanding Cell Death in Tumour Cells
Owen Sansom
Colorectal Cancer and WNT Signalling
Marcos Vidal
Drosophila Approaches to Cancer
Karen Vousden
Tumour Suppression
Robert J White
Transcription and Cancer
Sara Zanivan
Vascular Proteomics
University of Glasgow
David Gillespie - Checkpoints and Cell Cycle Control

Introduction

David GillepsieCancer is caused by loss of the normal controls that regulate cell proliferation and differentiation, yet it is commonly treated with radiation and genotoxic drugs that damage or inhibit the replication of DNA.

Our research focuses on understanding the molecular mechanisms that enable tumour cells to respond to and survive genotoxic stress.

By understanding how these processes are controlled and how they interact with those that regulate normal cell growth and division, we hope to find ways of exploiting the mutations that occur in cancer cells to make anti-cancer therapies more effective.

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Lab Report
icon Scientific Report 2010 Gillespie (135.34 kB)

Key Publications

Zachos G, Black EJ, Walker M, Scott MT, Vagnarelli P, Earnshaw WC, Gillespie DA (2007). Chk1 is required for spindle checkpoint function. Dev Cell 12, 247-60.

Robinson HM, Jones R, Walker M, Zachos G, Brown R, Cassidy J, Gillespie DA (2006). Chk1-dependent slowing of S-phase progression protects DT40 B-lymphoma cells against killing by the nucleoside analogue 5-fluorouracil. Oncogene 25, 5359-69.

Zachos G, Rainey MD, Gillespie DA (2005). Chk1-dependent S-M checkpoint delay in vertebrate cells is linked to maintenance of viable replication structures. Mole Cell Biol. 25, 563-74.

Black EJ, Clair T, Delrow J, Neiman P, Gillespie DAF (2004). Microarray analysis identifies Autotaxin, a tumour cell motility and angiogenic factor with lysophospholipase D activity, as a specific target of cell transformation by v-Jun. Oncogene 23, 2353-62.

MacLaren A, Black EJ, Clark W, Gillespie DA (2004). Jun-deficient cells undergo premature senescence as a result of spontaneous DNA damage accumulation. Mol Cell Biol. 24, 9006-18.

Zachos G, Gillespie DAF (2003). Chk1-deficient vertebrate somatic cells are viable but exhibit multiple checkpoint and survival defects in response to ionising radiation and inhibition of DNA replication. EMBO J. 22, 713-23.

Biography
Education and qualifications
1982: PhD, Biochemistry, University of Aberdeen
1978: BSc, Genetics (First Class Honours), University of Glasgow

Appointments
2000-present: Group Leader, Beatson Institute for Cancer Research and Professor of Cell & Molecular Biology, University of Glasgow
1993-2000: Group Leader, Beatson Institute for Cancer Research
1988-1993: Staff Scientist, Beatson Institute for Cancer Research
1985-1988: EMBO Fellow, Fred Hutchinson Cancer Research Center, Seattle, USA
1982-1985: Postdoctoral Fellow, Imperial Cancer Research Fund, London

Committee membership
2007-present: Science Foundation Ireland Grants Committee
2003-present: University of Glasgow Tenovus Medal Committee

Honours and awards
Fellow of the Royal Society of Edinburgh, 2007

Recent Publications
2011
Tho LM, Libertini S, Rampling R, Sansom O, Gillespie DA (2011). Chk1 is essential for chemical carcinogen-induced mouse skin tumorigenesis. Oncogene 2011 Aug 1. doi: 10.1038/onc.2011.326. [Epub ahead of print].

Xu N, Libertini S, Black EJ, Lao Y, Hegarat N, Walker M, Gillespie DA (2011). Cdk-mediated phosphorylation of Chk1 is required for efficient activation and full checkpoint proficiency in response to DNA damage. Oncogene 2011 Jul 18. doi: 10.1038/onc.2011.310. [Epub ahead of print].

2010
Xu N, Hegarat N, Black EJ, Scott MT, Hochegger H, Gillespie DA (2010). Akt/PKB suppresses DNA damage processing and checkpoint activation in late G2. J Cell Biol. 190, 297-305.

Mocciaro A, Berdougo E, Zeng K, Black E, Vagnarelli P, Earnshaw W, Gillespie D, Jallepalli P, Schiebel E (2010). Vertebrate cells genetically deficient for Cdc14A or Cdc14B retain DNA damage checkpoint proficiency but are impaired in DNA repair. J Cell Biol. 189, 631-9.

Smith J, Tho LM, Xu N, Gillespie DA (2010). The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res. 108, 73-112.

2009

Walker M, Black EJ, Oehler V, Gillespie DA, Scott MT (2009). Chk1 C-terminal regulatory phosphorylation mediates checkpoint activation by de-repression of Chk1 catalytic activity. Oncogene 28, 2314-23.

Muller PAJ, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S, Lukashchuk N, Gillespie DA, Ludwig RL, Gosselin P, Cromer A, Brugge JS, Sansom OJ, Norman JC, Vousden KH (2009). Mutant p53 drives invasion by promoting integrin recycling. Cell 139, 1327-41.

2008
Bennett LN, Larkin C, Gillespie DA, Clarke PR (2008). Claspin is phosphorylated in the Chk1-binding domain by a kinase distinct from Chk1. Biochem Biophys Res Commun. 369, 973-6.

Holmström T, Mialon A, Kallio M, Nymalm Y, Mannerma L, Holm T, Johansson H, Black E, Gillespie D, Salminen A, Langel U, Valdez B, Westermarck J (2008). c-Jun supports ribosomal RNA processing and nucleolar localisation of RNA helicase DDX21. J Biol Chem. 283, 7046-53.

Rainey MD, Black EJ, Zachos G, Gillespie DAF (2008). Chk2 is required for optimal mitotic delay in response to irradiation-induced DNA damage incurred in G2 phase. Oncogene 27, 896-906.

Scorah J, Dong MQ, Yates JR 3rd, Scott M, Gillespie D, McGowan CH (2008). A conserved PCNA-interacting sequence in Chk1 is required for checkpoint function. J Biol Chem. 283, 17250-9.

2007
Abdelmohsen K, Pullmann R, Jr., Lal A, Kim HH, Galban S, Yang X, Blethrow JD,Walker M, Shubert J, Gillespie DA, Furneaux H, Gorospe M (2007). Phosphorylation of HuR by Chk2 regulates SIRT1 expression. Mol Cell 25, 543-57.

Bourke E, Dodson H, Merdes A, Cuffe L, Zachos G,Walker M, Gillespie D, Morrison CG (2007). DNA damage induces Chk1-dependent centrosome amplification. EMBO Reports 8, 603-9.

Maya-Mendoza A, Petermann E, Gillespie DAF, Caldecott KW, Jackson DA (2007). Chk1 regulates the density of active replication origins during the vertebrate S phase. EMBO J. 26, 2719-31.

Ridpath JR, Nakamura A, Tano K, Luke AM, Sonoda E, Arakawa H, Buerstedde JM, Gillespie DA, Sale JE, Yamazoe M, Bishop DK, Takata M, Takeda S, Watanabe M, Swenberg JA, Nakamura J (2007). Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde. Cancer Res. 67, 11117-22.

Zachos G, Black EJ, Walker M, Scott MT, Vagnarelli P, Earnshaw WC, Gillespie DA (2007). Chk1 is required for spindle checkpoint function. Dev Cell 12, 247-60.

Zachos G, Gillespie DA (2007). Exercising restraints: Role of Chk1 in regulating the onset and progression of unperturbed mitosis in vertebrate cells. Cell Cycle 6, 810-3.

Images

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Lab Members

Post-docs: Silvana Libertini (Marie Curie Fellow), Elzbieta Wiernasz

Scientific Officers: Liz Black, Mark Walker

PhD Students: Desiree Piscitello, Joanne Smith

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