BSc (Hons), MBBS, PhD, FRCS (Gen. Surg)
- Primary position:
- MRC Clinician Scientist and Senior Lecturer
Tim Underwood was appointed as an MRC Clinician Scientist in 2011. He graduated from the Royal Free Hospital School of Medicine (London) in 1998 with a first class BSc in Molecular Medicine and the Gant Medal for Surgery. He trained in General Surgery in London and Southampton before completing a PhD in the Blaydes laboratory in 2007. He has subsequently specialized in Upper Gastrointestinal Surgery with a special interest in oesophageal cancer and minimally invasive surgical techniques. He was awarded the Association of Surgeons of GB & I prize and medal for his outstanding performance in the final FRCS exams in February 2011.
Mr Underwood was appointed as an NIHR Clinical Lecturer in Surgery in 2008 and developed a research program to investigate stromal-epithelial interactions in the oesophagus. He has developed a 3D organotypic model of the human oesophagus and is currently using this to study the role of cancer associated fibroblasts in the development and maintenance of oesophageal cancer.
Mr Underwood is collaborating with Dr Rebecca Fitzgerald (MRC Cancer Cell Unit, Cambridge) on a CRUK funded project to sequence to oesophageal cancer genome as part of the International Cancer Genome Consortium (www.icgc.org).
BSc, Molecular Medicine, University of London (1997)
MBBS, University of London (1998)
MRCS, Royal College of Surgeons of England (2002)
PhD, University of Southampton (2007)
FRCS (Gen. Surg), Royal College of Surgeons of England (2011)
MRC/RCS Clinical Research Training Fellow, Cancer Sciences Division, University of Southampton (2003-2006)
Specialist Registrar, General Surgery, Wessex Deanery (2003-2008)
NIHR Clinical Lecturer in Surgery, Cancer Sciences Division, University of Southampton (2008-2011)
MRC Clinician Scientist, Cancer Sciences Division, University of Southampton (2011- )
The University of Southampton's electronic library (e-prints)
Mr Underwood’s research has a focus on the development and progression of upper GI cancer, in particular oesophageal cancer. His surgical science interests include minimally invasive surgery and pre and post-operative predictors of outcome after oesophagogastic surgery.
Stromal-epithelial interactions in oesophageal cancer
Oesophageal adenocarcinoma (EAC) is the fastest rising cancer in the UK; the incidence has doubled in men over the last 25 years. At presentation the majority of oesophageal tumours will have invaded through the wall of the oesophagus, meaning that only 20% of patients will be suitable for curative treatment. Early invasion leads to disseminated disease and an overall five year survival of only 7%, one of the lowest of any cancer.
Southampton offers a unique opportunity to perform research in oesophageal cancer. The surgical unit performs over 80 upper gastro-intestinal cancer resections per year and the biomedical research facility is a 2 minute walk from the operating theatre. This allows Mr Underwood’s team to exploit their access to primary tissue for laboratory research; furthermore:
• Mr Underwood has set up a comprehensive, ethically approved oesophageal tissue bank that contains over 200 patients’ samples including cell isolates, frozen tissue and matched blood from diagnostic endoscopy and oesophageal resections. The tissue bank is linked to a rigorously maintained prospective database that allows biological findings to be correlated with clinico-pathological patient outcomes.
• The team is able to culture oesophageal epithelial cells and fibroblasts directly from resected specimens.
Molecular studies of carcinogenesis have traditionally been conducted on cells that form the tumour i.e. – epithelial cells and less focus has been placed on the epithelial microenvironment (stroma). An emerging body of evidence suggests that the stroma is important in the initiation and progression of a range of epithelial cancers including skin, breast, prostate and ovary, but little is known about the role of the stroma in oesophageal carcinogenesis. The stroma contains a number of cell types, including fibroblasts, endothelial cells and immune cells, all of which may have a role in tumour progression. Mr Underwood’s research concentrates on cancer associated fibroblasts (CAF) as recent evidence suggests that CAF are fundamental to tumour biology. CAF differ in phenotype from normal fibroblasts, and functional studies indicate that fibroblasts play a role in cancer initiation, progression and metastasis. Information regarding the role of the tumour microenvironment in oesophageal cancer is limited. It is clear that the gene expression profile of stromal cells is altered in EAC and its precursor lesion Barrett’s oesophagus (BE). However, the events required for fibroblast activation, the timing of fibroblast activation in the BE-EAC sequence and the influence that CAF have on EAC progression are yet to be elucidated.
Using a 3D organotypic model developed in the Underwood laboratory the team have shown that primary oesophageal CAF promote invasion compared to normal oesophageal fibroblasts. Moreover, CAF promote the invasion of normal oesophageal squamous cells suggesting that invasion in this model is stromal cell dependent. The team has therefore begun an analysis of candidate molecules which may be responsible for this effect. They have identified several CAF associated candidates, including the TGF-β related gene periostin, on which they have begun a functional analysis.
Academic unit: Cancer Sciences Academic Unit
Affiliate academic units: Cancer Sciences Research group
University of Southampton
South Coast Cancer Collaboration - Oesophagogastric (SC3-OG), Lead
National and International responsibilities
NIHR cross disciplinary leadership group
Heartburn Cancer Awareness and Support, Trustee and Director
National Cancer Research Institute (NCRI) Upper GI Clinical Studies Group - Oesophagogastric subgroup – member
The OCCAMS collaboration – lead researcher for Southampton
BM4 and BM5. Ward based teaching for students during their surgical attachment. Developed and delivers trauma scenarios for year 1 BM4 students using the SIMMAN suite. Lectures on trauma and the clinical physiology of shock.
BMedSc Project Supervisor. Offers 2 clinically based projects per year and has supervised previous BMedSc project prize winner.
Mr Tim Underwood
Faculty of Medicine University of Southampton Southampton General Hospital Mailpoint 801 South Academic Block Tremona Road Southampton SO16 6YD or Faculty of Medicine University of Southampton Building 85 Life Sciences Building Highfield Campus Southampton SO171BJ
Room Number: SGH/AC67/MP816
Telephone: (023) 8120 5976
Facsimile: (023) 8120 4020