Cell Division

Cancer is a disease of excessive cell division, with cancer cells proliferating uncontrollably, leading to the disruption of normal tissue function and ultimately death. The focus of Dr Burgess' research and his laboratory is to understand exactly how cells divide, how this process is disrupted in cancer cells, and then use this information to target and specifically kill cancer cells. We hope to use this knowledge to provide new avenues for targeted treatment, and to help improve current treatments for patients.

Recently, we demonstrated that correct mitotic progression was dependent on maintaining a tightly regulated balance between the activities of the phosphatase PP2A, and kinase CDK1. Further, we identified the novel mitotic kinase Greatwall as the master regulator of this balance. These results dramatically altered our understanding of mitosis and opened up several new and exciting research pathways. The primary aim of the lab is to further explore and characterise these pathways, to identify new chemotherapeutic targets and improve the sensitivity and selectivity of existing cancer drugs. The group utilises cutting edge basic cell biology research, live cell imaging, and Mass Spectrometry, combined with the world-class translational cancer research facilities at the Garvan and The Kinghorn Cancer Centre.

 

Cell Division Group work: Images • Videos

Selected Publications

1.        McCloy RA, Shelley EJ, Roberts CG, Boslem E, Biden TJ, Nicholson RI, Gee JM, Sutherland RL, Musgrove EA, Burgess A, et al. (2013) Role of endoplasmic reticulum stress induction by the plant toxin, persin, in overcoming resistance to the apoptotic effects of tamoxifen in human breast cancer cells. Br J Cancer 109: 3034–3041.

2.        Caldon CE, Sergio CM, Burgess A, Deans AJ, Sutherland RL, Musgrove EA (2013) Cyclin E2 induces genomic instability by mechanisms distinct from cyclin E1. Cell Cycle 12: 606–617.

3.        Burgess A, Lorca T, Castro A (2012) Quantitative Live Imaging of Endogenous DNA Replication in Mammalian Cells. PLoS ONE 7: e45726.

4.        Wigan M, Pinder A, Giles N, Pavey S, Burgess A, Wong S, Sturm RA, Gabrielli B (2012) A UVR-Induced G2-Phase Checkpoint Response to ssDNA Gaps Produced by Replication Fork Bypass of Unrepaired Lesions Is Defective in Melanoma. J Invest Dermatol 132: 1681–1688.

5.        Vigneron S, Gharbi-Ayachi A, Raymond A-A, Burgess A, Labbé J-C, Labesse G, Monsarrat B, Lorca T, Castro A (2011) Characterization of the mechanisms controlling greatwall activity. Mol Cell Biol 31: 2262–2275.

6.        Gharbi-Ayachi A, Labbé J-C, Burgess A, Vigneron S, Strub J-M, Brioudes E, Van-Dorsselaer A, Castro A, Lorca T (2010) The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A. Science 330: 1673–1677.

7.        Burgess A, Vigneron S, Brioudes E, Labbé J-C, Lorca T, Castro A (2010) Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance. Proc Natl Acad Sci USA 107: 12564–12569.

8.        Lorca T, Bernis C, Vigneron S, Burgess A, Brioudes E, Labbé J-C, Castro A (2010) Constant regulation of both the MPF amplification loop and the Greatwall-PP2A pathway is required for metaphase II arrest and correct entry into the first embryonic cell cycle. J Cell Sci 123: 2281–2291.

9.        Vigneron S, Brioudes E, Burgess A, Labbé JC, Lorca T, Castro A (2010) RSK2 is a kinetochore-associated protein that participates in the spindle assembly checkpoint. Oncogene 29: 3566–3574.

10.     Vigneron S, Brioudes E, Burgess A, Labbé J-C, Lorca T, Castro A (2009) Greatwall maintains mitosis through regulation of PP2A. EMBO J 28: 2786–2793.

11.     Burgess A, Labbé JC, Vigneron S, Bonneaud N, Strub JM, van Dorsselaer A, Lorca T, Castro A (2008) Chfr interacts and colocalizes with TCTP to the mitotic spindle. Oncogene 27: 5554–5566.

12.     Bernis C, Vigneron S, Burgess A, Labbé J-C, Fesquet D, Castro A, Lorca T (2007) Pin1 stabilizes Emi1 during G2 phase by preventing its association with SCF(betatrcp). EMBO Rep 8: 91–98.

13.     Burgess A, Wigan M, Giles N, DePinto W, Gillespie P, Stevens F, Gabrielli BG (2006) Inhibition of S/G2 phase CDK4 reduces mitotic fidelity. J Biol Chem 281: 9987–9995.

14.     Burgess A, Ruefli A, Beamish H, Warrener R, Saunders N, Johnstone R, Gabrielli BG (2004) Histone deacetylase inhibitors specifically kill nonproliferating tumour cells. Oncogene 23: 6693–6701.

15.     Burgess AJ, Pavey S, Warrener R, Hunter LJ, Piva TJ, Musgrove EA, Saunders N, Parsons PG, Gabrielli BG (2001) Up-regulation of p21(WAF1/CIP1) by histone deacetylase inhibitors reduces their cytotoxicity. Mol Pharmacol 60: 828–837.


More Garvan Publications

Staff in the Group

Rachael McCloy

Research Assistant

Mina Rasouli

PhD Student

Samuel Rogers

Honours Student

Diseases We Research
Cancer - Breast

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