Dr Sarah McClelland

Dr Sarah McClelland

BSc, PhD
Centre: Molecular Oncology
Lecturer
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We are interested in understanding mechanisms controlling genomic stability, and how these are deregulated in cancer.

Cancer cells frequently display abnormal numbers and structures of chromosomes, termed chromosomal instability (CIN).

CIN can promote tumour evolution and chemotherapy resistance, therefore understanding mechanisms contributing to CIN will aid design of novel therapeutic strategies to treat cancer.

Research Details

Cancer cells frequently exhibit abnormalities in the number and structure of their chromosomes. These abnormalities can be generated at every cell division, meaning that a population of cancer cells can contain cells that are very different to one another. This process is termed chromosomal instability, and is associated with chemotherapy resistance and poor patient prognosis.

My lab aims to understand the mechanisms that underlie numerical and structural chromosome aberrations in cancer at a molecular level, which also involves understanding how normal cells replicate and segregate their genomes. We are interested in how mechanisms generating chromosomal instability may vary between tumour types, and in using this information to understand chemotherapy resistance and create more accurate models of chromosomal instability. Ultimately we aim to improve cancer patient survival by advancing our knowledge of processes underlying tumour drug resistance, and using this to aid treatment stratification and chemotherapy design.

Current projects:

1. Mechanisms driving chromosomal instability in Ovarian cancer.

High-grade serous ovarian cancer (HGSOC) represents the major subtype of ovarian cancer and displays high levels of chromosomal instability. We are collaborating with the Balkwill and Lockley laboratories to investigate mechanisms driving chromosomal instability in HGSOC using cell lines, 3-D culture systems and human tissue samples.

2. Investigating the function of genes overexpressed in cancer in maintenance of genome stability.

In a recent screen of genes overexpressed in colorectal cancer we identified multiple genes with novel roles in accurate chromosome segregation. Using classical cell biology and microscopy techniques we aim to characterise their function to improve our understanding of mechanisms driving chromosomal instability in cancer and of mechanisms promoting genomic stability in general.

3. Understanding the relationship between replication stress and chromosomal instability.

We recently identified an important role for replication stress in promoting chromosome missegregation events in colorectal cancer. However the exact molecular mechanisms underlying the generation of chromosomal instability following replication stress are not clear. Using proof-of-principle experiments in diploid cells we aim to model these processes to better understand the link between replication stress and chromosomal instability.

Profile

Aug 2013: Established laboratory at the Barts Cancer Institute, Queen Mary University of London (UK).

Jan 2009 - Aug 2013: Post-doctoral Research Fellow with Professor Charles Swanton at the Cancer Research UK London Research Institute, UK. Integrating genomics and cell biological analysis to identify genes and mechanisms promoting chromosomal instability in cancer.

Mar 2005 – Jan 2009: Post-doctoral Research Fellow with Dr A. McAinsh at the Marie Curie Research Institute, Surrey, UK. Investigating the function of novel human kinetochore proteins.

Aug 2003 – May 2004: Post-doctoral Research Fellow with Dr P. Bianco at the Center for Single Molecule Biophysics, State University of New York (SUNY) at Buffalo, USA. Single molecule experiments with the human recombination protein hRad54 and investigating the properties of novel DNA dyes.

Oct 1999 – Aug 2003: PhD in Biochemistry with Dr M. Szczelkun at the University of Bristol, UK. Translocation by Type I Restriction Endonucleases

Funding

2017 - 2020 Pancreatic Cancer Research Fund Project grant
£180,000
2017 - 2019 Kay Kendall Leukaemia Fund Project Grant
£132,914
2014 - 2017 Barts and the London Charity Large Project Grant
£186,517
2014 CRUK development fund £10,408
     
  Barts Cancer Institute Early Career Researcher Fellowship

Key Publications

* equal contribution authors

Burrell RA*, McClelland SE*, Endesfelder D, Groth P, Weller MC, Shaikh N, Domingo E, Kanu N, Dewhurst SM, Gronroos E, Chew SK, Rowan AJ, Schenk A, Sheffer M, Howell M, Kschischo M, Behrens A, Helleday T, Bartek J, Tomlinson IP, Swanton C. Replication stress links structural and numerical chromosomal instability in colorectal cancer. Nature. 2013 Feb 28, 494:492-6. PMID: 23446422

Birkbak NJ, Eklund AC, Li Q, McClelland SE, Endesfelder D, Tan P, Tan IB, Richardson AL, Szallasi Z, Swanton C. Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer. Cancer Res., 2011. PMID: 21270108

McClelland SE*, Borusu S*, Amaro AC, Winter JR, Belwal M, McAinsh AD & Meraldi P. The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity. EMBO J., 2007. PMID: 18007590

Porter IM, McClelland SE, Khoudoli GA, Hunter CJ, Andersen JS, McAinsh AD, Blow J & Swedlow, J.R. Bod1, a novel kinetochore protein required for chromosome biorientation. J. Cell Biol., 2007. PMID: 17938248


Further Publications

For additional publications, please click here


We are interested in understanding mechanisms controlling genomic stability, and how these are deregulated in cancer.

Cancer cells frequently display abnormal numbers and structures of chromosomes, termed chromosomal instability (CIN).

CIN can promote tumour evolution and chemotherapy resistance, therefore understanding mechanisms contributing to CIN will aid design of novel therapeutic strategies to treat cancer.

External Activities

  • Member of the British Society for Cell Biology (BSCB)
  • 12-13th February 2017: Lecturing for the PhD course ’Inside the Cell' at the Gulbenkian Institute, Lisbon

News

Speaking engagements

  • 4th April 2017 Seminar at the Institut Curie, Paris
  • 8th February 2017 Seminar at University of Warwick
  • 24th January 2017 Seminar at University of Kent
  • 18th January 2017 Seminar at QMUL School of Biological Sciences
  • November 2016 Seminar at University of Birmingham
  • July 2016: "Determining the missegregation rates of individual human chromosomes.” The International Chromosome Conference, Foz do Igazu, Brazil (presenter: Joseph Worrall)
  • June 2016: "Mapping chromosome-specific determinants of recurrent aneuploidies in cancer and ageing." Chromo 2016 Aneuploidy Meeting, Galway, Ireland
  • June 2016: Warwich University seminar
  • Jan 2014: Replication stress and Chromosomal Instability student symposium, Amsterdam
  • March 2014: Seminar at University of Geneva
  • March 2014: Seminar at University of Bristol
  • May 2014: Seminar at Genome Damage and Stability Centre, Brighton
  • June 2014: Seminar at University of Birmingham
  • July 2014: Seminar at University of Oxford
  • November 2013: Invited speaker at the NCRI conference

See other researchers working on:

Ovarian Cancer
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