Detecting Cancer, Cancer Genetics, Cancer, Cancer Bioinformatics, Prostate Cancer

Video: Prostate Cancer: UEA Researchers Make Breakthrough

I am a group leader within the Cancer Genetics Team, Norwich Medical School, with over a decade of experience in applying and developing novel analyses of large-scale ‘omics datasets from human tumour samples to answer clinically relevant questions in translational cancer research. My focus is improving clinical outcomes in prostate cancer.

After completing my first degree in Physics (MSci) at Imperial College London, I went on to study for an MRes in Biological Complexity and PhD in Computational Biology at University College London.  My PhD focused on mathematical modelling of the p53 gene regulatory network and in particular integrating models and experiment data. I was employed as a Bioinformatics Officer at the Institute of Cancer Research (ICR) in Sutton for over six years before moving to the University of East Anglia to lead the bioinformatics team within the Cancer Genetics group in September 2013. In June 2016 I begun a senior lecturer role in the faculty of Norwich Medical School and in August 2021 I was promoted to Professor of Medical Bioinformatics and Genomics.

My main research interests lie in applying and developing novel analytic techniques to large-scale ‘omic datasets from human tumour samples to answer clinically relevant questions in translational cancer research, with a particular focus on prostate cancer.

Sequencing Studies

I am chair of the bioinformatics committee and PI of the CRUK-ICGC Prostate UK group, a multi-centre project that collects and analyses the whole genome sequences, transcriptomes and methylomes of 250 prostate cancer samples. We have successfully produced results that have impacted knowledge, research strategy and clinical strategy in the field of prostate cancer and have yielded ten publications including one in Nature, one in Science, three in Nature Genetics, and one in Lancet Oncology, with more to come. I was an essential driver in expanding this project to become the Pan-Prostate Cancer Group (PPCG; http://panprostate.org), a collaboration of multiple major prostate cancer centres across the world, and I am currently a member of the technology working group and lead of the non-genomic analysis working group. 

Subtypes in cancer

Within a single cancer disease type, sub classification is important to accurately determine prognosis, optimise treatment pathways, and help develop targeted drugs. A plethora of ‘omic datasets now exist that can be used to characterise individual samples and group cancers into subtypes. For transcriptome datasets, traditional unsupervised clustering approaches have largely been unsuccessful in determining subtypes due to the implicit assumption of sample assignment to a single cluster or group. Such analyses are in complete contrast to the well documented highly heterogeneous composition of many cancers.

One approach that is better suited to this structure is the Bayesian clustering method latent process decomposition (LPD). We have successfully applied LPD to prostate cancer and have found that different cancer subtypes can be identified in a single tumour sample, including a subtype called DESNT associated with poor prognosis. We are in the process of translating DESNT for use in a clinical setting.

We are applying LPD to transcriptome data from The Cancer Genome Atlas, a large US project that has generated comprehensive, multi-dimensional maps of the key ‘omic changes in a large number of cancer types. These studies are expected to detect and characterise novel stratifications for many cancer types. We will also develop a world-class scientist at the key interface between cancer and bioinformatics.

We are also involved in a Prostate Cancer Research project in collaboration wil the University of Oxford that will perform a comprehensive characterisation of prostate cancer subtypes using the PanProstate Cancer Group dataset to inform precision medicine.

Biomarker development

I was involved in the Movember GAP1 Urine Biomarker Project that led to the discover of Prostate Urine Risk (PUR) score that has a significant association with the aggressiveness of prostate cancer and can be used to predict how long men remain on active surveillance before they progress. We are currently being funded by Prostate Cancer UK and Movember in a study designed to provide information that will progress the future implementation of the PUR test in the clinic as an aid in shared decision making between patients and clinicians.

Cancer and bacteria

I have a growing interest in the role that bacteria plays in cancer and have developed an analytic pipeline (SEPATH) that identifies infectious agents in whole genome sequencing data. This pipeline has been further developed and applied to the whole genome sequence data of 40,000 cancer genomes from Genomics England’s 100,000 Genome project, 1000 prostate cancer genomes from the ICGC PanProstate project and 2500 geneomes from the ICGC PanCancer project.

1. PBL Tutor

I am a Problem Based Learning (PBL) tutor for a weekly group consisting of ten year 3 MBBS degree students covering the themes Digestion & Nutrition, Senses, and Homeostasis / Hormones. The role of a PBL tutor is to be a facilitator and not a knowledge bank. MBBS degree is a well-structured course based on the “constructive alignment” learning theory. Arguably the defining feature of the degree and the core of the programme are these sessions. PBL, as implemented at the Norwich Medical School, proceeds as follows:

• Patient-specific scenarios are used to explore clinical understanding of the week’s topic, identify the limit of knowledge of the group and identify further knowledge required to completely understand the scenario and plot a course forward (“brainstorming”).
• The group’s learning objectives for the week are set using the areas of knowledge identified in the discussion along with the course-provided learning objectives.
• Each student is assigned two learning objectives and studies them in detail during the week: a piece of written work is produced on one and a “presentation” for the other.
• In the session the following week the knowledge gained is shared with the rest of the group through various teaching methods (presentations to quizzes) and discussion.

2. PhD Supervisor

I am currently a PhD supervisor for six PhD students, primary supervisor for four. These students are investigating topics across the spectrum of our research. This involves weekly formal meetings where progress is assessed, problems are discussed, and goals are set. Informal meetings occur throughout the week. In the first year of study in particular there is more direct teaching on skills and techniques that are required to perform independent research. As the goal is to produce an independent researcher this is a very different learning space to undergraduate teaching.

 3. SSS Tutor

Since 2016, I have been the tutor for the year three Student Selected Studies Genetics topic as part pf the MBBS degree at Norwich Medical School. The students have to do independent research on a self-selected question and produce a scientific abstract, poster and presentation.

4. Lecturer

I am a part of the genetics theme of the Norwich Medical School MBBS and have lectured as part of the MSc Genomic Medicine at Imperial College London.

5. Lead of the grant writing part of the Tranferable Skills in Research module

This is part of the MRes in Clinical Science and other master courses.

Deputy Director Metabolic Health Research Centre (Dec 2023 - )

Research roles

I am chair of the bioinformatics committee and PI of the CRUK-ICGC Prostate UK group, a multi-centre project that collects and analyses the whole genome sequences, transcriptomes and methylomes of 250 prostate cancer samples. We have successfully produced results that have impacted knowledge, research strategy and clinical strategy in the field of prostate cancer and have yielded ten publications including one in Nature, one in Science, three in Nature Genetics, and one in Lancet Oncology, with more to come. I was an essential driver in expanding this project to become the Pan-Prostate Cancer Group (PPCG; http://panprostate.org), a collaboration of multiple major prostate cancer centres across the world, and I am currently a member of the executive committee, technology working group and lead of the non-genomic analysis working group. I am also an active member of other large consortia, including Genomics England 100,000 genome project, the Movember GAP1 Urine project (in which I am Lead Bioinformatician), and ICGC PanCancer Analysis of Whole Genomes project.

Norwich Cancer Research Network

In 2020, I played a vital role in setting up the Norwich Cancer Research Network (NCRN) whose aim it to increase the profile and reputation of UEA and other research institutes in Norwich for cancer research. I have led the development of the NCRN virtual seminar series which has been popular, with on average 30-40 people attending talks in a diverse range of topics. I have also been the key figure in organising the NCRN symposium 2020 which has had over 120 delegates, with 56 people contributing to talks or poster sessions. I am part of the NCRN exec committee.

Grant review committees

Other roles

I am a member of the FMH ethics committee (Feb 2020 -), which plays the vital role of ensuring that research conducted across the range of health disciplines meets accepted ethical principles and legal requirements. I am also the Norwich Medical School library representative (Jan 2019 -) and work closely with the library service to make sure our students are getting the best from the library.