Mireille Gillings Professor of Cancer Genomics
+44 (0)1392 408301
RILD Building Level 4
University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK
Chrissie was recently appointed as the Mireille Gillings Professor of Cancer Genomics, joining the College of Medicine and Health and Institute of Biomedical and Clinical Science in August 2019. She graduated in Medicine from University College London Medical School, taking an intercalated BSc in Immunology. Her PhD in colorectal cancer genetics was funded by the Medical Research Council and undertaken at the Cancer Research UK London Research Institute. Whilst completing her Medical Oncology specialist training she held a National Institute of Health Research Clinical Lecturer post until her Consultant appointment in 2010.
Until moving to Exeter she was a Senior Lecturer and Consultant Medical Oncologist at the UCL Cancer Institute and Royal Free Hospital and lead Consultant in the multi-disciplinary neuroendocrine tumour and hepatocellular cancer teams. Chrissie has a national and international reputation for research in to and the management of neuroendocrine tumours and integrated genomic analysis of cancer.
Chrissie leads the Neuroendocrine tumour 100,000 genomes GeCIP and is the Cancer arm representative on the 100,000 genomes GeCIP board.
She is also a member of a Genomics England working group working towards the delivery and impact of the next 5 million genomes.
With her background in cancer epigenetics and genomics and the wealth of world-class experience in diabetes research at Exeter, her move here has enabled collaborations in order to investigate the increased risk of certain cancers seen in individuals with type 2 diabetes – tackling two of the biggest health challenges to society.
- BSc Immunology
- PhD Cancer genetics
- 2017 – 2021: NETRF Accelerator grant (Co-PI) $1.95 million “Finding the causes of SI-NETs” Co-PI with Prof Matthew Meyerson (Harvard / BROAD) and Asst Prof. Eric Nakakura (UCSF).
- 2018 – 2020: Cancer Research UK Clinical PhD Fellowship for Dr Alison Berner (Co-Supervisor) £220,000
- 2017 – 2020: Bowel and Cancer Research grant. PI “Epigenetic determinants of exceptional survival in metastatic colon cancer”. £50,000.
- 2015 – 2019: BRC (PI) £100,000 Utilising epigenomic analyses to determine tumour heterogeneity in mutationally quiet cancers.
- 2016—2018: NETRF (Co-Investigator) IMMUNET $100,000. Evaluating the immune landscape across a range and grade of Neuroendocrine tumours.. (PI – Prof. Tim Meyer)
- 2016-2020: Cancer Research UK PhD Fellowship for Ms Teresa Sposito. PhD Fellowship (Co-Supervisor). £220,000.
Chrissie’s research group has focused on integrated genomic and circulating free DNA analysis in neuroendocrine (NET) and other solid tumours. NETs have a very low background mutation rate and commonly harbor mutations in epigenetic machinery, her group has therefore focused on epigenetic analyses integrated with sequencing and transcriptome data. This work has led to a number of collaborations within the UK , the BROAD Institute and at Harvard, UCSF, Bern, Verona, Madrid and Uppsala Universities. Chrissie chairs and sits on national and international NET research and clinical committees.
To date, her group has successfully identified molecularly distinct sub-groups of NETs which have poorer clinical outcome, enabling stratification and personalized treatment. Alongside this, her group has also successfully isolated and sequenced DNA from NET circulating tumour cells.
Chrissie’s group has also collaboratively been developing a mouse model of pancreatic NETs through knocking out DAXX in pancreatic islets.
Through collaborative research bringing epigenetic expertise from her group to lung cancer research she has identified DNA methylation signatures associated with smoking in lung and buccal mucosa samples and also a discriminative signature which informs whether a pre-invasive lung lesion progresses to invasive cancer.
Chrissie’s move to Exeter has enabled the opportunity to bring together her experience of cancer genomics and epigenetics with the wealth of experience in diabetes research.
One in two people born after 1960 will be diagnosed with cancer. It is known that there is an increased risk of developing certain cancers including bowel and uterine in individuals with type 2 diabetes and obesity. Through forming collaborations between type 2 diabetes, obesity and colorectal cancer researchers and utilizing existing data and new data created through the 100,000 genomes project she plans to investigate the biological processes linking these conditions., ultimately leading to cancer prevention, earlier diagnosis, novel treatment strategies and improved outcomes.
- Why is there an increased risk of cancer in type 2 diabetes and obesity?
One in two people born after 1960 will be diagnosed with cancer. Around four and a half million people in the UK are diabetic (~90% have type 2 diabetes) with 7 million living with pre-diabetes. This project sets out to determine why there is a higher risk of developing certain types of cancer (including colorectal, endometrial, breast and liver cancer) in type 2 diabetes and obesity. Previously, genome wide association studies (GWAS) have successfully identified loci associated with certain cancers, type 2 diabetes and obesity. By studying the epigenetics of these conditions we can determine the effects of lifestyle and environment. By integrating existing GWAS and epigenomic data with new data created through the 100,000 genomes project we plan to determine the underlying cause(s) of this increased risk ultimately leading to cancer prevention, earlier diagnosis, novel treatment strategies and improved outcomes.
Prof Tim Frayling – University of Exeter
Prof Jon Mill – University of Exeter
Prof Ian Tomlinson – University of Edinburgh
Prof Stephan Beck – University College London
- Finding the causes of small intestinal neuroendocrine tumours (SINETs).
SINETs are mutationally quiet tumours, with only 8% of tumours harboring mutations in the tumour suppressor gene CDKN1B. The background mutation rate is lower than virtually all other solid tumours. This project is analysing multifocal (multiple tumours throughout the small bowel) SINET cases incorporating whole genome sequencing, transcriptome analysis, genome-wide DNA methylation analysis in order to determine the underlying genomic mechanisms driving tumour development. Single cell sequencing is also being undertaken to identify and validate the cell of origin of these intriguing tumours.
Prof. Matthew Meyerson – BROAD Institute / Harvard University
Prof. Eric Nakakura – University College of San Francisco
- Integrated genomic analysis of pancreatic and bronchial NETs
Through integrated genomic analyses my group has previously identified distinct molecular subgroups of small intestinal NETs in groups of tumours which have the same pathological classification. These molecular subgroups have differing clinical outcome and have the potential to improve prognostication and treatment selection. This approach is now being undertaken in pancreatic and bronchial NETs.
Prof. Aldo Scarpa – University of Verona
Prof. Aurel Perren – University of Bern
Prof. Rocio Garcia-Carbonero – University of Madrid
- Development of a pancreatic NET mouse model
There are very few reliable in vitro and in vivo models for use in neuroendocrine tumour research. Mutations in the chromatin remodellers ATRX and DAXX are implicated in the development of pancreatic NETs (PNET). This project is centered on knocking out DAXX in pancreatic islets in order to determine the role it plays in pancreatic homeostasis and PNET tumour development.
Prof. Paolo Salomoni – DZNE Bonn
- Integrated genomic analysis of pre-invasive lung cancer
Through studying DNA sequencing, methylation and transcriptome analysis in serial bronchial biopsy samples taken from high risk patients undergoing bronchoscopy our collaboration identified DNA methylation and transcriptome signatures which predict whether an individual lung biopsy progresses to invasive cancer or regresses in to normal epithelium. This work was led by Prof. Sam Janes at UCL and my group provided epigenetic expertise. Further work is ongoing to determine the role of immune surveillance in this process.
Project lead Prof. Sam Janes – University College London
- Colorectal cancer exceptional survivors
A subset of patients with metastatic colorectal cancer have an exceptionally good outcome and overall survival when compared with described survival data. The reason for this is not clear. This project is studying the DNA sequence, methylation and transcriptome in serial tumour samples resected from patients undergoing treatment and follow up for up to and over ten years. Through learning what makes these cases exceptional we plan to improve outcomes for all patients with colorectal cancer.
Prof. Trevor Graham – Barts Cancer Institute, QMUL
Prof. John Bridgewater – University College London
Publications by category
Publications by year
Chrissie_Thirlwell Details from cache as at 2020-07-11 05:05:26
External Engagement and Impact
2012: 2nd Young Researcher Prize for research in Basic Science of Neuroendocrine Tumours at 9th European NET Society meeting, Copenhagen.
2011: UK and Ireland Neuroendocrine Tumour Society annual meeting 1st prize for basic science research in NETs.
2011: 1st Young Researcher Prize for research in Basic Science of Neuroendocrine Tumours at 8th European NET Society meeting, Lisbon.
2010: 1st Young Researcher Prize for research in Basic Science of Neuroendocrine Tumours at 7th European NET Society meeting, Berlin.
2009: UK and Ireland Neuroendocrine Tumour Society annual meeting prize for oral presentation.
Chair of the UK and Ireland Neuroendocrine Tumour society (UKINETs) Research Committee 2016 – December 2019.
NET GeCIP Lead for 100,000 Genomes project 2017 – ongoing.
Genomics England – Cancer Arm representative on Genomics England Board 2018 - ongoing
UKINETs Executive committee member 2016 – December 2019.
European Neuroendocrine Tumour Society Advisory board member – basic and translational research 2019 - ongoing
European Society of Medical Oncology (ESMO) NET track Faculty member – 2018 – ongoing.
- Board of Scientific Advisors -NET Research Foundation (USA) – 2016 – ongoing.
Grant and abstract reviewer for the American Association of Cancer Research (AACR) and the European Neuroendocrine Tumour society – 2012 – ongoing.
- Neuroendocrinology 2019 - ongoing
Invited lectures 2019:
ENDO 2019 American Society of Endocrinology – “Breaking Bad – the genomics of NETs”
European Society of Medical Oncology 2019 – “The Genomic landscape of bronchial NETs”
NET masterclass Budapest – “The cost of funding NET and cancer therapies”
Teaching responsibilities: (Undergraduate, Postgraduate)
- MSc Lecturing
- Undergraduate and postgraduate student supervision