Research

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 and pancreatic cancers to investigate how centrosome amplification impacts tumorigenesis 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:

• 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.

• 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.

• 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. We are particularly interested in understanding how cells with extra centrosomes communicate and influence the surrounding cells.

Other Activities

• Scientific committee member of the British Society of Cell Biology
• Member of the American Association for Cancer Research
• Associate faculty member of Faculty of 1000
• Member of the America Society for Cell Biology

Major Funding

• 2021-2027 - CRUK Programme Foundation Award, Investigating the impact of centrosome amplification in cancer, £1,489,237.76
• 2019-2021 - EU Horizon 2020 Marie Skłodowska-Curie Fellowship CentrosoTME (GA 839075), €212,933.76
• 2019-2022- Medical Research Council, Dissecting the role of supernumerary centrosomes-induced exosome secretion in PDAC microenvironment, £477,195
• 2018-2022- Cancer Research UK, Non-Clinical Training Award, 2018, £198,070
• 2016-2021- The Lister Institute of Preventive Medicine, Lister Institute Research Fellowship Prize, £199,974
• 2015-2018- Medical Research Council, Characterisation of the signalling pathways involved in cell invasion downstream of extra centrosomes, £466,417

Recent Publications

Centrosome amplification fine tunes tubulin acetylation to differentially control intracellular organization Monteiro P, Yeon B, Wallis SS et al. EMBO Journal (2023) 42(7)

Low HER2 expression in normal breast epithelium enables dedifferentiation and malignant transformation via chromatin opening Hayat A, Carter EP, King HW et al. DMM Disease Models and Mechanisms (2023) 16(7)

Too close for comfort? Endomembranes promote missegregation by enclosing lost chromosomes Donker L, Godinho SA Journal of Cell Biology (2022) 221(7)

Centrosome amplification mediates small extracellular vesicle secretion via lysosome disruption Adams SD, Csere J, D'angelo G et al. Current Biology (2021) 31(7) 1403-1416.e7

Centrosome amplification mediates small extracellular vesicles secretion via lysosome disruption Adams S, Csere J, D’angelo G et al. (2020) (18)

Macrophages induce malignant traits in mammary epithelium via IKKε/TBK1 kinases and the serine biosynthesis pathway Wilcz-Villega E, Carter E, Ironside A et al. EMBO Molecular Medicine (2020) 12(7)

Early Career Advisory Board. J Cell Biol (2019) 218(2) 2813-2814
https://www.ncbi.nlm.nih.gov/pubmed/31439635

Early Career Advisory Board: Q&A on career and publishing. Marat A J Cell Biol (2019) 218(2) 2815-2818
https://www.ncbi.nlm.nih.gov/pubmed/31439634

The principles of spindle bipolarity Godinho SA Nature Reviews Molecular Cell Biology (2019) 20(7) 325

Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation Marteil G, Guerrero A, Vieira AF et al. Nature Communications (2018) 9(7)

Team

Postdoctoral Researchers

• Dr Samuel Wallis
• Dr Maria Fankhaenel
• Dr Lisa Donker
• Dr Julia Frankenberg Garcia

PhD Students

• Mr Bongwhan Yeon
• Mr Robert Dryden

Clinical Research Fellows

• Dr Sarah Duncan
  

Research Technicians

• Claire Curel

Biography

• 1999: MSc in Biology, specialisation in Microbiology and Genetics, University of Lisbon (Portugal)
• 2006: PhD in Cellular Biology, Gulbenkian Institute of Science (Portugal) and Cambridge University (UK). Investigating the role of Polo kinase during mitosis.
• 2006: Postdoctoral Fellow, Dana-Farber Cancer institute and Harvard Medical School (USA). Studying how cancer cells cluster extra centrosomes during mitosis.
• 2010: Harvard-Portugal Programme Fellow, Dana-Farber Cancer institute and Harvard Medical School (USA). Investigating the role of centrosome amplification in cancer cell invasion using 3-D cell culture models.
• 2013: Established Lab at Barts Cancer Institute, Queen Mary University of London (UK).