Dr Sarah McClelland

Dr Sarah McClelland

BSc, PhD
Centre: Molecular Oncology
Lecturer
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QMUL Directory


Cancer cells near-ubiquitously display abnormal numbers and structures of chromosomes, termed Chromosomal Instability (CIN). CIN can promote tumour evolution and chemotherapy resistance. This means an important goal is to understand the processes generating CIN in cancer, and to develop new ways in which to target this tumour-specific feature.

Mclelland 111

To do this we run several projects in the lab to investigate how cancer cells from a panel of different cancer types (Ovarian, Pancreatic, Prostate and Colorectal) generate chromosomal instability. We also work to understand better the fundamental process of chromosome segregation during mitosis, specifically in the context of how chromosome identity can dictate behaviour during normal, and unperturbed conditions.

 Mclelland lab twitter logo

 

 

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. Understanding the relationship between replication stress and chromosomal instability.
We previously 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.

3. Investigating the phenomenon of non-random chromosome mis-segregation
We recently discovered that during perturbed cell division particular chromosomes are prone to mis-segregate and become aneuploid (Worrall and Tamura et al, Cell Reports 2018). E are now investigating this phenomenon further with additional approaches to disrupt accurate genome replication and segregation.

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

2018 - 2020 CRUK Pioneer award £200,000
2017 - 2018 WHRI Marie Curie COFUND £42,000
2018 - 2020 Wellbeing of Women £132,000
2017 - 2020 MRC DTP-funded studentship  
2017 - 2020 Barry Reed PhD studentship  
2017 - 2020 Pancreatic Cancer Research Fund Project grant
£180,000
2017 - 2019 Kay Kendall Leukaemia Fund Project Grant
£132,914

Key Publications

* equal contribution authors

Worrall JT, Tamura N, Mazzagatti A, Shaikh N, van Lingen T, Bakker B, Spierings DJC, Vladimirou E, Foijer F, McClelland SE. Non-Random Mis-Segregation of Human Chromosomes. Cell Reports (2018) 23, 3366–3380.

McClelland SE. Role of chromosomal instability in cancer progression. Endocr Relat Cancer (2017); 24(9): T23-T31. doi: 10.1530/ERC-17-0187. Epub. Review. PMID: 28696210

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), 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


Cancer cells near-ubiquitously display abnormal numbers and structures of chromosomes, termed Chromosomal Instability (CIN). CIN can promote tumour evolution and chemotherapy resistance. This means an important goal is to understand the processes generating CIN in cancer, and to develop new ways in which to target this tumour-specific feature.

Mclelland 111

To do this we run several projects in the lab to investigate how cancer cells from a panel of different cancer types (Ovarian, Pancreatic, Prostate and Colorectal) generate chromosomal instability. We also work to understand better the fundamental process of chromosome segregation during mitosis, specifically in the context of how chromosome identity can dictate behaviour during normal, and unperturbed conditions.

 Mclelland lab twitter logo

 

 

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

Speaking engagements

  • Invited talk: EMBO Chromoploidy workshop, Lisbon 2019
  • Invited talk: Roscoff Cell Cycle Meeting, Brittany, 2019
  • Invited talk: London Cell Cycle Club, Trieste, 2019
  • Selected talk, Genome Stability Network day, Cambridge, Jan 2018
  • Selected talk Roscoff Cell Cycle Meeting, Brittany, Sept 2017
  • Selected talk London Cell Cycle Club (LCCC), September 2017
  • Selected talk British Society for Cell Biology (BSCB), Warwick April 2017
  • Selected talk American Society for Cell Biology (ASCB), San Francisco, December 2016
  • Selected talk International Chromosome Conference, Brazil, July 2016
  • Selected talk EMBO aneuploidy workshop, Ireland, June 2016

Seminars 2016-2018

  • ERIBA, Netherlands, Sept 2018
  • University of Bristol, Nov 2018
  • University of Porto, Nov 2018
  • University of Kent, Jan 2017
  • Gulbenkian Research Institute (IGC), Lisbon, Feb 2017
  • Institut Curie, Paris, April 2017
  • 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

News

See other researchers working on:

Leukaemia Ovarian Cancer Pancreas
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