Professor Sarah McClelland

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:

• 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.

• 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.

• 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). We are now investigating this phenomenon further with additional approaches to disrupt accurate genome replication and segregation.

• 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