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 Chrissie Thirlwell

Chrissie Thirlwell

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

Overview

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.

Qualifications

  • BSc Immunology
  • MBBS
  • PhD Cancer genetics
  • FRCP
  • SFHEA

Grants/Funding:

  • 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.

Research

Research interests

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.

Research projects

Current Projects:

  • 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.

Collaborators

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.

Collaborators

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.

Collaborators

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.

Collaborators

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.

Collaborators

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.

Collaborators

Prof. Trevor Graham – Barts Cancer Institute, QMUL

Prof. John Bridgewater – University College London

Publications

Key publications | Publications by category | Publications by year

Publications by category


Journal articles

Pennycuick A, Teixeira VH, AbdulJabbar K, Raza SEA, Lund T, Akarca AU, Rosenthal R, Kalinke L, Chandrasekharan DP, Pipinikas CP, et al (2020). Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer. Cancer Discov, 10(10), 1489-1499. Abstract.  Author URL.  Full text.
Rizzo FM, Vesely C, Childs A, Marafioti T, Khan MS, Mandair D, Cives M, Ensell L, Lowe H, Akarca AU, et al (2019). Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours. Br J Cancer, 120(3), 294-300. Abstract.  Author URL.
Teixeira VH, Pipinikas CP, Pennycuick A, Lee-Six H, Chandrasekharan D, Beane J, Morris TJ, Karpathakis A, Feber A, Breeze CE, et al (2019). Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions. Nat Med, 25(3), 517-525. Abstract.  Author URL.
Pipinikas CP, Berner AM, Sposito T, Thirlwell C (2019). The evolving (epi)genetic landscape of pancreatic neuroendocrine tumours. Endocr Relat Cancer, 26(9), R519-R544. Abstract.  Author URL.
Pericleous M, Karpathakis A, Toumpanakis C, Lumgair H, Reiner J, Marelli L, Thirlwell C, Caplin ME (2018). Well-differentiated bronchial neuroendocrine tumors: Clinical management and outcomes in 105 patients. Clin Respir J, 12(3), 904-914. Abstract.  Author URL.
Laskaratos F-M, Rombouts K, Caplin M, Toumpanakis C, Thirlwell C, Mandair D (2017). Neuroendocrine tumors and fibrosis: an unsolved mystery?. Cancer, 123(24), 4770-4790. Abstract.  Author URL.
Karpathakis A, Dibra H, Pipinikas C, Feber A, Morris T, Francis J, Oukrif D, Mandair D, Pericleous M, Mohmaduvesh M, et al (2017). Progressive epigenetic dysregulation in neuroendocrine tumour liver metastases. Endocrine-Related Cancer, 24(2), L21-L25.
Childs A, Vesely C, Ensell L, Lowe H, Luong TV, Caplin ME, Toumpanakis C, Thirlwell C, Hartley JA, Meyer T, et al (2016). Expression of somatostatin receptors 2 and 5 in circulating tumour cells from patients with neuroendocrine tumours. Br J Cancer, 115(12), 1540-1547. Abstract.  Author URL.
StÃ¥lberg P, Westin G, Thirlwell C (2016). Genetics and epigenetics in small intestinal neuroendocrine tumours. J Intern Med, 280(6), 584-594. Abstract.  Author URL.
Karpathakis A, Dibra H, Pipinikas C, Feber A, Morris T, Francis J, Oukrif D, Mandair D, Pericleous M, Mohmaduvesh M, et al (2016). Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor. Clin Cancer Res, 22(1), 250-258. Abstract.  Author URL.
Rossi RE, Garcia-Hernandez J, Meyer T, Thirlwell C, Watkins J, Martin NG, Caplin ME, Toumpanakis C (2015). Chromogranin a as a predictor of radiological disease progression in neuroendocrine tumours. Ann Transl Med, 3(9). Abstract.  Author URL.
Teschendorff AE, Yang Z, Wong A, Pipinikas CP, Jiao Y, Jones A, Anjum S, Hardy R, Salvesen HB, Thirlwell C, et al (2015). Correlation of Smoking-Associated DNA Methylation Changes in Buccal Cells with DNA Methylation Changes in Epithelial Cancer. JAMA Oncol, 1(4), 476-485. Abstract.  Author URL.
Pipinikas CP, Dibra H, Karpathakis A, Feber A, Novelli M, Oukrif D, Fusai G, Valente R, Caplin M, Meyer T, et al (2015). Epigenetic dysregulation and poorer prognosis in DAXX-deficient pancreatic neuroendocrine tumours. Endocr Relat Cancer, 22(3), L13-L18. Author URL.
Rossi RE, Luong T-V, Caplin ME, Thirlwell C, Meyer T, Garcia-Hernandez J, Baneke A, Conte D, Toumpanakis C (2015). Goblet cell appendiceal tumors--management dilemmas and long-term outcomes. Surg Oncol, 24(1), 47-53. Abstract.  Author URL.
Partelli S, Inama M, Rinke A, Begum N, Valente R, Fendrich V, Tamburrino D, Keck T, Caplin ME, Bartsch D, et al (2015). Long-term outcomes of surgical management of pancreatic neuroendocrine tumors with synchronous liver metastases. Neuroendocrinology, 102, 68-76. Abstract.
Paul DS, Guilhamon P, Karpathakis A, Butcher LM, Thirlwell C, Feber A, Beck S (2014). Assessment of RainDrop BS-seq as a method for large-scale, targeted bisulfite sequencing. Epigenetics, 9(5), 678-684. Abstract.  Author URL.
Toumpanakis C, Kim MK, Rinke A, Bergestuen DS, Thirlwell C, Khan MS, Salazar R, Oberg K (2014). Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors. Neuroendocrinology, 99(2), 63-74. Abstract.  Author URL.
Goldstein R, Yu D, Gillmore R, Thirlwell C, O'Donoghue P, Mayer A, Meyer T (2014). Oxaliplatin/5-fluorouracil in advanced hepatocellular carcinoma: case report and single-center retrospective review. Future Oncol, 10(13), 2007-2014. Abstract.  Author URL.
Feber A, Guilhamon P, Lechner M, Fenton T, Wilson GA, Thirlwell C, Morris TJ, Flanagan AM, Teschendorff AE, Kelly JD, et al (2014). Using high-density DNA methylation arrays to profile copy number alterations. Genome Biology, 15(2). Abstract.
Pericleous M, Lumgair H, Baneke A, Morgan-Rowe L, Caplin ME, Luong TV, Thirlwell C, Gillmore R, Toumpanakis C (2012). Appendiceal goblet cell carcinoid tumour: a case of unexpected lung metastasis. Case Reports in Oncology, 5(2), 332-338. Abstract.
Jones AM, Thirlwell C, Howarth KM, Graham T, Chambers W, Segditsas S, Page KM, Phillips RKS, Thomas HJW, Sieber OM, et al (2007). Analysis of copy number changes suggests chromosomal instability in a minority of large colorectal adenomas. J Pathol, 213(3), 249-256. Abstract.  Author URL.

Publications by year


2020

Pennycuick A, Teixeira VH, AbdulJabbar K, Raza SEA, Lund T, Akarca AU, Rosenthal R, Kalinke L, Chandrasekharan DP, Pipinikas CP, et al (2020). Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer. Cancer Discov, 10(10), 1489-1499. Abstract.  Author URL.  Full text.

2019

Rizzo FM, Vesely C, Childs A, Marafioti T, Khan MS, Mandair D, Cives M, Ensell L, Lowe H, Akarca AU, et al (2019). Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours. Br J Cancer, 120(3), 294-300. Abstract.  Author URL.
Teixeira VH, Pipinikas CP, Pennycuick A, Lee-Six H, Chandrasekharan D, Beane J, Morris TJ, Karpathakis A, Feber A, Breeze CE, et al (2019). Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions. Nat Med, 25(3), 517-525. Abstract.  Author URL.
Pipinikas CP, Berner AM, Sposito T, Thirlwell C (2019). The evolving (epi)genetic landscape of pancreatic neuroendocrine tumours. Endocr Relat Cancer, 26(9), R519-R544. Abstract.  Author URL.

2018

Pericleous M, Karpathakis A, Toumpanakis C, Lumgair H, Reiner J, Marelli L, Thirlwell C, Caplin ME (2018). Well-differentiated bronchial neuroendocrine tumors: Clinical management and outcomes in 105 patients. Clin Respir J, 12(3), 904-914. Abstract.  Author URL.

2017

Laskaratos F-M, Rombouts K, Caplin M, Toumpanakis C, Thirlwell C, Mandair D (2017). Neuroendocrine tumors and fibrosis: an unsolved mystery?. Cancer, 123(24), 4770-4790. Abstract.  Author URL.
Karpathakis A, Dibra H, Pipinikas C, Feber A, Morris T, Francis J, Oukrif D, Mandair D, Pericleous M, Mohmaduvesh M, et al (2017). Progressive epigenetic dysregulation in neuroendocrine tumour liver metastases. Endocrine-Related Cancer, 24(2), L21-L25.

2016

Childs A, Vesely C, Ensell L, Lowe H, Luong TV, Caplin ME, Toumpanakis C, Thirlwell C, Hartley JA, Meyer T, et al (2016). Expression of somatostatin receptors 2 and 5 in circulating tumour cells from patients with neuroendocrine tumours. Br J Cancer, 115(12), 1540-1547. Abstract.  Author URL.
StÃ¥lberg P, Westin G, Thirlwell C (2016). Genetics and epigenetics in small intestinal neuroendocrine tumours. J Intern Med, 280(6), 584-594. Abstract.  Author URL.
Karpathakis A, Dibra H, Pipinikas C, Feber A, Morris T, Francis J, Oukrif D, Mandair D, Pericleous M, Mohmaduvesh M, et al (2016). Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor. Clin Cancer Res, 22(1), 250-258. Abstract.  Author URL.

2015

Rossi RE, Garcia-Hernandez J, Meyer T, Thirlwell C, Watkins J, Martin NG, Caplin ME, Toumpanakis C (2015). Chromogranin a as a predictor of radiological disease progression in neuroendocrine tumours. Ann Transl Med, 3(9). Abstract.  Author URL.
Teschendorff AE, Yang Z, Wong A, Pipinikas CP, Jiao Y, Jones A, Anjum S, Hardy R, Salvesen HB, Thirlwell C, et al (2015). Correlation of Smoking-Associated DNA Methylation Changes in Buccal Cells with DNA Methylation Changes in Epithelial Cancer. JAMA Oncol, 1(4), 476-485. Abstract.  Author URL.
Pipinikas CP, Dibra H, Karpathakis A, Feber A, Novelli M, Oukrif D, Fusai G, Valente R, Caplin M, Meyer T, et al (2015). Epigenetic dysregulation and poorer prognosis in DAXX-deficient pancreatic neuroendocrine tumours. Endocr Relat Cancer, 22(3), L13-L18. Author URL.
Rossi RE, Luong T-V, Caplin ME, Thirlwell C, Meyer T, Garcia-Hernandez J, Baneke A, Conte D, Toumpanakis C (2015). Goblet cell appendiceal tumors--management dilemmas and long-term outcomes. Surg Oncol, 24(1), 47-53. Abstract.  Author URL.
Partelli S, Inama M, Rinke A, Begum N, Valente R, Fendrich V, Tamburrino D, Keck T, Caplin ME, Bartsch D, et al (2015). Long-term outcomes of surgical management of pancreatic neuroendocrine tumors with synchronous liver metastases. Neuroendocrinology, 102, 68-76. Abstract.

2014

Paul DS, Guilhamon P, Karpathakis A, Butcher LM, Thirlwell C, Feber A, Beck S (2014). Assessment of RainDrop BS-seq as a method for large-scale, targeted bisulfite sequencing. Epigenetics, 9(5), 678-684. Abstract.  Author URL.
Toumpanakis C, Kim MK, Rinke A, Bergestuen DS, Thirlwell C, Khan MS, Salazar R, Oberg K (2014). Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors. Neuroendocrinology, 99(2), 63-74. Abstract.  Author URL.
Goldstein R, Yu D, Gillmore R, Thirlwell C, O'Donoghue P, Mayer A, Meyer T (2014). Oxaliplatin/5-fluorouracil in advanced hepatocellular carcinoma: case report and single-center retrospective review. Future Oncol, 10(13), 2007-2014. Abstract.  Author URL.
Feber A, Guilhamon P, Lechner M, Fenton T, Wilson GA, Thirlwell C, Morris TJ, Flanagan AM, Teschendorff AE, Kelly JD, et al (2014). Using high-density DNA methylation arrays to profile copy number alterations. Genome Biology, 15(2). Abstract.

2012

Pericleous M, Lumgair H, Baneke A, Morgan-Rowe L, Caplin ME, Luong TV, Thirlwell C, Gillmore R, Toumpanakis C (2012). Appendiceal goblet cell carcinoid tumour: a case of unexpected lung metastasis. Case Reports in Oncology, 5(2), 332-338. Abstract.

2007

Jones AM, Thirlwell C, Howarth KM, Graham T, Chambers W, Segditsas S, Page KM, Phillips RKS, Thomas HJW, Sieber OM, et al (2007). Analysis of copy number changes suggests chromosomal instability in a minority of large colorectal adenomas. J Pathol, 213(3), 249-256. Abstract.  Author URL.

Chrissie_Thirlwell Details from cache as at 2020-12-05 04:45:38

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External Engagement and Impact

Awards

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.


Committee/panel activities

  • 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.

 


Editorial responsibilities

  • 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

Teaching responsibilities: (Undergraduate, Postgraduate)

  • MSc Lecturing
  • Undergraduate and postgraduate student supervision

Supervision / Group

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