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UK Cilia Network

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Dr Susana Godinho

Department  Barts Cancer Institute
  Queen Mary University of London
Homepage  http://www.bci.qmul.ac.uk/staff/item/godinho

Research Interests

Cancer cells often contain extra centrosomes. The centrosome is the main microtubule-organizing centre in animal cells, an essential component of the cytoskeleton. In normal cells, centrosome number is tightly regulated, however, cancer cells tend to have too many centrosomes, a characteristic associated with tumour aggressiveness. Yet little is known about the role of centrosome amplification in tumour progression.

We currently focus on breast cancer to investigate how centrosome amplification impacts tumourigenesis in a variety of model systems, including 2-D and 3-D cell culture, and mouse models. We also collaborate with clinical scientists to use primary human tissue samples from patients in order to validate our findings.

Current Projects:

1. How cancer cells ‘adapt’ to centrosome amplification

In order to avoid cell death, cancer cells need to cluster extra centrosomes into two poles during mitosis, enabling quasi-normal bipolar cell division. This observation has generated an enormous interest as it provides the basis for using the presence of extra centrosomes as a target for cancer therapies. We are currently developing novel strategies to assess how different cell types cope with extra centrosomes, allowing them to survive. We expect to use this knowledge to develop novel therapeutic strategies that specifically target cancer cells.

2. Impact of centrosome amplification in cancer cell physiology

Unlike normal cells that are very intolerant to centrosome amplification, cancer cells frequently maintain extra centrosomes. This observation suggests that centrosome amplification is advantageous for the tumour. To address this question we use a variety of model systems to investigate how extra centrosomes affect cell physiology. Since our work suggests that centrosome amplification promotes invasive behaviour, we are currently investigating signalling pathways that are important in invasion/metastasis.

3. Developing mouse models to study the impact of centrosome amplification in tumour progression in vivo.

We are collaborating with experts in mouse genetics to develop new model systems to investigate the impact of extra centrosomes in tumour progression in vivo.

Key Publications

Ganem NJ, Godinho SA and Pellman D (2009). A mechanism linking extra centrosomes to chromosomal instability. Nature  vol. 460, (7252) 278-282. 10.1038/nature08136

Kwon M, Godinho SA, Chandhok NS, Ganem NJ, Azioune A, Thery M and Pellman D (2008). Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev  vol. 22, (16) 2189-2203. 10.1101/gad.1700908

2018

Monteiro P and Godinho SA (2018). Structural Centrosomal Abnormalities Push Cells toward Invasion. Dev Cell  vol. 45, (3) 286-288. 10.1016/j.devcel.2018.04.016

2017

Rhys AD, Monteiro P, Smith C, Vaghela M, Arnandis T, Kato T, Leitinger B, Sahai E, McAinsh A, Charras G and Godinho SA (2017). Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells. Rockefeller University Press  J Cell Biol  vol. 217, (1) 195-209. 10.1083/jcb.201704102

Godinho S (2017). Centrosomes: PIDDosome Joins the Counting Game. Curr Biol  vol. 27, (6) R237-R239. 10.1016/j.cub.2017.02.001

Rhys AD and Godinho SA (2017). Dividing with Extra Centrosomes: A Double Edged Sword for Cancer Cells. Adv Exp Med Biol  vol. 1002, 47-67. 10.1007/978-3-319-57127-0_3

2015

Gibbons JG, Branco AT, Godinho SA, Yu S and Lemos B (2015). Concerted copy number variation balances ribosomal DNA dosage in human and mouse genomes. Proc Natl Acad Sci U S A  vol. 112, (8) 2485-2490. 10.1073/pnas.1416878112

Arnandis T and Godinho SA (2015). Studying centrosome function using three-dimensional cell cultures. Methods Cell Biol  vol. 129, 37-50. 10.1016/bs.mcb.2015.03.010

2014

Godinho SA and Pellman D (2014). Causes and consequences of centrosome abnormalities in cancer. Philos Trans R Soc Lond B Biol Sci  vol. 369, (1650) 10.1098/rstb.2013.0467

Godinho SA, Picone R, Burute M, Dagher R, Su Y, Leung CT, Polyak K, Brugge JS, Théry M and Pellman D (2014). Oncogene-like induction of cellular invasion from centrosome amplification. Nature  vol. 510, (7503) 167-171. 10.1038/nature13277

2012

Calado DP, Sasaki Y, Godinho SA, Pellerin A, Köchert K, Sleckman BP, de Alborán IM, Janz M, Rodig S and Rajewsky K (2012). The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers. Nat Immunol  vol. 13, (11) 1092-1100. 10.1038/ni.2418

2011

Bettencourt-Dias M, Hildebrandt F, Pellman D, Woods G and Godinho SA (2011). Centrosomes and cilia in human disease. Trends Genet  vol. 27, (8) 307-315. 10.1016/j.tig.2011.05.004

2010

Vinciguerra P, Godinho SA, Parmar K, Pellman D and D'Andrea AD (2010). Cytokinesis failure occurs in Fanconi anemia pathway-deficient murine and human bone marrow hematopoietic cells. J Clin Invest  vol. 120, (11) 3834-3842. 10.1172/JCI43391

2009

Ganem NJ, Godinho SA and Pellman D (2009). A mechanism linking extra centrosomes to chromosomal instability. Nature  vol. 460, (7252) 278-282. 10.1038/nature08136

Godinho SA, Kwon M and Pellman D (2009). Centrosomes and cancer: how cancer cells divide with too many centrosomes. Cancer Metastasis Rev  vol. 28, (1-2) 85-98. 10.1007/s10555-008-9163-6

2008

Godinho S and Tavares AA (2008). A role for Drosophila Polo protein in chromosome resolution and segregation during mitosis. Cell Cycle  vol. 7, (16) 2529-2534. 10.4161/cc.7.16.6439

Kwon M, Godinho SA, Chandhok NS, Ganem NJ, Azioune A, Thery M and Pellman D (2008). Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev  vol. 22, (16) 2189-2203. 10.1101/gad.1700908

2007

Schüller U, Zhao Q, Godinho SA, Heine VM, Medema RH, Pellman D and Rowitch DH (2007). Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors. Mol Cell Biol  vol. 27, (23) 8259-8270. 10.1128/MCB.00707-07

2006

Pearson J, Godinho SA, Tavares A and Glover DM (2006). Heterologous expression of mammalian Plk1 in Drosophila reveals divergence from Polo during late mitosis. Exp Cell Res  vol. 312, (6) 770-781. 10.1016/j.yexcr.2005.11.031

Alves PS, Godinho SA and Tavares AA (2006). The Drosophila orthologue of xPlkk1 is not essential for Polo activation and is necessary for proper contractile ring formation. Exp Cell Res  vol. 312, (3) 308-321. 10.1016/j.yexcr.2005.10.033

TBC

TBC

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