The University of Southampton
Medicine
Phone:
07845 361124
Email:
G.Thomas@soton.ac.uk

Professor Gareth Thomas BDS, MScD, PhD, FDSRCS, FRCPath

Professor of Experimental Pathology, Consultant in Histopathology

Professor Gareth Thomas's photo
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Professor Thomas was appointed to the Chair of Experimental Pathology in 2009. He trained in Oral and Maxillofacial Pathology at University College Hospital, London, gaining his FDSRCS in 1994, MRCPath in 2004 and FRCPath in 2008. He undertook his PhD as an MRC Clinical Fellow at University College London and the Richard Dimblebey Department of Cancer Research, studying the functional role of alphav integrins in keratinocytes (1996-1999). In 2004 he was awarded a 5-year Clinician Scientist Fellowship from the Heath Foundation/Royal College of Pathologists to develop novel tumour therapies based on alphavbeta6 integrin expression in head and neck cancer. He was appointed Professor of Oral Pathology and Consultant in Oral and Maxillofacial Pathology at Barts and the London in 2007.

As a clinical pathologist I spend a lot of time looking down a microscope at cancers. My research focuses on understanding how the different cells within a tumour interact to affect patient survival, and particularly how cancers spread. My goal is to translate this research into clinical trials, and ultimately to help patients by improving diagnosis and treatment’

Professor Thomas leads a group that investigates how the tumour microenvironment promotes tumour progression, particularly the regulation of cancer cell motility. The translational element of this work, including biomarker studies and clinical trials, is focused on head and neck cancer. His research group is based within the Faculty of Medicine campus and comprises both clinical and non-clinical scientists. Potential students, post-doctoral scientists or clinician scientists who are interested in joining her group are encouraged to contact Professor Thomas.

He is a Consultant Pathologist in University Hospital Southampton NHS Foundation Trust.

Qualifications

BDS, University of Wales College of Medicine 1989
MScD, University of Wales College of Medicine 1995
PhD, University College London 2000

Fellowships

FDSRCS, Royal College of Surgeons (Eng) 1994
MRCPath, Royal College of Pathologists 2004
FRCPath, Royal College of Pathologists 2008
FRSB, Royal Society of Biology 2013

Appointments held

MRC Clinical Training Fellow, Eastman Dental Institute, University College London 1996-1999

Specialist Registrar and Honorary Lecturer, University College London Hospital 2000-2004

Health Foundation/Royal College of Pathologists Senior Research Fellow, Institute of Cancer, Barts and the London 2004-2007

Professor of Oral and Maxillofacial Pathology, Barts and the London, 2007-2009

Research

Responsibilities

Publications

Contact

Research interests

Professor Thomas’ research focuses on the tumour microenvironment, particularly how it in regulates mechanisms that promote tumour cell invasion/metastasis and immune evasion. Group members have been awarded a number of national and international prizes for this work.

The role of the tumour microenvironment

The ‘normal’ components of the tumour stroma (including fibroblasts, inflammatory cells, endothelial cells) play an important role in promoting tumour progression. This was emphasised strikingly in large studies on oral, oesophageal and colorectal cancer survival, where we described the prognostic significance of myofibroblastic cancer-associated fibroblast (CAF).

Our recent work has focused on mechanisms regulating myofibroblast differentiation and function; trying to understand why cancers containing these cells behave aggressively and also studying the signalling pathways that cause the accumulation of myofibroblasts in certain patients. Our recent studies have focused on the role of reactive oxygen species and DNA damage in this process. For this work we use a broad range of techniques, ranging through ‘omic’ analyses and imaging of human tissues, in vitro 3D tumour models and in vivo models of tumour growth and metastases. This has led to a better understanding of myofibroblast subtypes in cancers and also identification of potentially therapeutic stromal targets, which we are studying in the context of tumour invasion/metastasis and immune evasion.

The regulation of tumour invasion

The ability of tumour cells to invade into the surrounding tissues is a defining feature of cancer and metastatis is responsible for over 90% of cancer-related deaths. Most forms of cancer cell movement are dependent on a family of extracellular matrix receptors called integrins. We have extensive experience in studying integrin biology, particularly the integrin alphavbeta6, which is upregulated in many cancer types. We have shown previously that alphavbeta6 promotes tumour cell invasion and also regulates stromal myofibroblast differentiation through its ability to activate the cytokine TGF-beta1. We have described some of the key signalling pathways involved in these processes, including a novel link between alphavbeta6, cyclo-oxygenase enzymes and the prostaglandin E2 receptor, EP4. We also found that alphavbeta6 function can be biased towards either motility or TGF-beta activation through an adaptor protein, eps8, which act to ‘switch’ activity of small GTPases. More recently our studies have focused on how tumour cell metabolism affects cell movement, where we identified a novel mechanism by which aerobic glycolysis (the Warburg Effect) regulates integrin adhesion to make tumour cells more invasive.

Translational studies

Our work also has a strong translational component, attempting to address some of the important clinical questions in cancer, using our pathology expertise to identify potential prognostic biomarkers and therapeutic targets. Our recent study on HPV-positive oropharyngeal cancer has highlighted the important role of anti-tumour immunity in patient survival. This work led to funded immunotherapy trials in both HPV-positive and HPV–negative head and neck cancer. Currently we are using next generation sequencing and digital pathology/image analysis to profile the molecular characteristics of intratumoral immune and stromal cells. These types of study ensure that our laboratory-based research remains clinically relevant.

Clinical trials

Investigation of the molecular and genetic mechanisms promoting head and neck cancer development and progression 2010-2015 (UKCRN 8130; ISRCTN 71276356). Chief Investigator GJ Thomas.

Prospective evaluation of smooth muscle actin (SMA) expression in predicting oral cancer aggression. 2011-2014. Chief Investigator GJ Thomas. Cancer Research UK funded.

Molecular and genetic mechanisms regulating pancreatic cancer development and progression. 2012-2017 (UKCRN 10180). Chief Investigator GJ Thomas.

Immune response evaluation as a prognostic tool in HPV-positive oropharyngeal cancer. 2014-2015. Chief Investigators GJ Thomas and E King. Cancer Research UK funded

Investigating molecular and cellular mechanisms of head and neck skin malignancy. (UKCRN 10773). 2012-2017. Chief Investigator E King.

COAST Trial (Cisplatin Ototoxicity attenuated by ASpirin Trial): A phase II randomised controlled trial of aspirin in the preventative role of cisplatin induced ototoxicity. 2012 – 2015. Chief Investigator E King. Cancer Research UK funded.

p110delta PI3-kinase inhibition: overcoming immune suppression in head and neck cancer patients. 2015-2017. Chief Investigator C Ottensmeier/E King

Figure shows tumour cells invading an organotypic culture
Figure 1 Microenvironment projects
Figure shows a co-culture of alphavbeta6-expressing tumour cells (red) and smooth muscle actin-expressing myofibroblasts (green). Cell nuclei are shown in blue.
Figure 2 Microenvironment projects

Research group

Cancer Sciences Academic Unit

Affiliate research group

Cancer Sciences Research group

Current group

Dr Emma King Senior Clinical Lecturer/Consultant in ENT surgery

Dr Karwan Moutasim Clinical Lecturer in Cellular Pathology

Dr Jo Tod Clinical Lecturer in Gastroenterology

Dr Veronika Jenei: Senior Research Fellow

Dr Massimiliano Mellone: Research Fellow

Dr Chris Hanley: Research Fellow

Dr Hollie Robinson: Postdoctoral Researcher

Mrs Monette Lopez: Medical Laboratory Scientific Officer

Ms Maria Machado: Medical Laboratory Scientific Officer

Ms Marta Navio: Medical Laboratory Scientific Officer

Postgraduate student supervision

PhDs supervised to completion, 11

MDs supervised to completion, 1

Current

Steven Frampton (CRUK Clinical Fellow; PhD)

Jason Fleming (MRC Clinical Fellow; PhD)

Abbie Mead (CRUK/MRC Student; PhD)

Kirsty Ford (MRC Student; PhD

Adal Mirza (Clinical Fellow; MD)

Professor Thomas was awarded the Faculty Postgraduate Supervisor Prize in 2012.

Group members have been awarded 8 local, 11 national and 5 international research prizes.

Faculty of Medicine

DI Faculty of Medicine Tissue Bank

Academic Lead Research Governance

Clinical Lead Translational Sciences, Clinical Trials Unit

Academic Lead for Histopathology, UHS NHS Foundation Trust

Co-Director Southampton Experimental Cancer Medicine Centre

National responsibilities

NCRI Head and Neck Cancer Clinical Trials Group

NCRI Molecular Biomarkers Advisory Group

Cancer Research UK Experimental Medicine Expert Review Panel

The Pathological Society of Great Britain and Ireland Committee

ECMC Cellular and Molecular Pathology Network Group Steering Committee

Articles

Conferences

Professor Gareth Thomas
University of Southampton, Faculty of Medicine Cancer Sciences Unit, Somers Building, MP 824 Tremona Road Southampton SO16 6YD Tel: 07845 361124

Room Number:SGH//MP824

Telephone:07845 361124
Email:G.Thomas@soton.ac.uk

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