Research

The central themes of my lab are:

1. Characterising intra-tumour heterogeneity and using it to predict prognosis
2. Understanding and predicting the evolution of premalignant disease.
3. Understanding how the clonal structure of tissues (particularly in the GI tract) shape patterns of somatic evolution.

The major tools of the lab are genomics, bioinformatics, histopathology and mathematical modelling.

Other Activities

• Faculty of gastrointestinal cancer section of  F1000.com
• Evolution lead for the colorectal cancer domain (GeCIP) of Genomics England
• Member of Critical Gaps in Bowel Cancer Research working group

Major Funding

• 2018-2023- NIH, Arizona Centre for Cancer Evolution (ACE) Cancer Systems Biology Centre, direct funding of ~$800k of $8M total
• 2018-2021- Cancer Research UK, Early detection of colorectal cancer risk in patients with inflammatory bowel disease ~£0.5M
• 2017-2019- Bowel and Cancer Research, The epigenetic basis of exceptional survival in metastatic colon cancer, £50k
• 2017-2022- Wellcome Trust, Evolutionary predictions in colorectal cancer (EPICC), ~£1.3m
• 2015-2018- Barts Charity, Large Project Grant: Derivation of evolutionary biomarkers for cancer risk prediction in Ulcerative Colitis, £465k
• 2015-2021- Cancer Research UK, Career Development Award: Quantification of human colorectal cancer evolution: initiation, progression, metastasis and response to treatment, £1M

Recent Publications

Author Correction: The effects of mutational processes and selection on driver mutations across cancer types (Nature Communications, (2018), 9, 1, (1857), 10.1038/s41467-018-04208-6) Temko D, Tomlinson IPM, Severini S et al. Nature Communications (2020) 11(7)

Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology Sequeira I, Rashid M, Tomás IM et al. Nature Communications (2020) 11(7)

Measuring single cell divisions in human tissues from multi-region sequencing data Werner B, Case J, Williams MJ et al. Nature Communications (2020) 11(7)

The MOBSTER R package for tumour subclonal deconvolution from bulk DNA whole-genome sequencing data Caravagna G, Sanguinetti G, Graham TA et al. BMC Bioinformatics (2020) 21(7)

Evolutionary dynamics of neoantigens in growing tumours Graham T, Eszter L, Marc W et al. Nature Genetics (2020) (1)
https://www.biorxiv.org/content/10.1101/536433v1

Subclonal reconstruction of tumors using machine learning and population genetics Graham T, Caravagna G, Heide T et al. Nature Genetics (2020) 52(1) 898-907
https://www.biorxiv.org/content/10.1101/586560v1

Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell–like phenotype Lupo B, Sassi F, Pinnelli M et al. Science Translational Medicine (2020) 12(7)

Navigating the path to distant metastasis Graham TA, Shibata D Nature genetics (2020) 52(7) 642-643

Genetic heterogeneity highlighted by differential FDG-PET response in diffuse large B-cell lymphoma Araf S, Korfi K, Bewicke-Copley F et al. Haematologica (2020) 105(7) E318-E321

Stabilising selection causes grossly altered but stable karyotypes in metastatic colorectal cancer Cross W, Mossner M, Nowinski S et al. (2020) (18)

Team

Postdoctoral Researchers
Dr Eszter Lakatos, Dr Maximilian Mossner, Dr Jacob Househam

PhD Students
Freddie Whiting, Calum Gabbutt

Clinical Research Fellows
Anisha Sukha, Ibrahim Al Bakir, Alison Berner

Biography

I originally trained as a mathematician (MSci Mathematics, Imperial College, 2002) before spending time in a cancer genetics lab as part of my interdisciplinary PhD (PhD Mathematical Biology, UCL, 2009). As a postdoc, I worked in Nick Wright's lab at the Cancer Research UK London Research Institute studying clonal expansions in human tissues (2008-2011), and Carlo Maley’s lab at UCSF looking at the pattern of clonal evolution in human cancers (2011-2013).

I joined BCI in September 2013.

Please contact me to discuss opportunities. Further information about my lab can be found here.