Medicine

Tim Underwood

BSc (Hons), MBBS, PhD, FRCS (Gen. Surg)

Primary position:
MRC Clinician Scientist and Senior Lecturer

Background

The University of Southampton

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).

Qualifications

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)

Appointments held

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- )

Mr Tim Underwood's photo

Publications

The University of Southampton's electronic library (e-prints)

Article

Underwood, Timothy J., Hayden, Annette L., Derouet, Mathieu, Garcia, Edwin, Noble, Fergus, White, Michael J., Thirdborough, Steve, Mead, Abbie, Clemons, Nicholas, Mellone, Massimiliano, Uzoho, Chudy, Primrose, John N, Blaydes, Jeremy P and Thomas, Gareth J (2014) Cancer associated fibroblasts predict for poor outcome and promote periostin-dependent invasion in oesophageal adenocarcinoma. The Journal of Pathology (doi:10.1002/path.4467). (PMID:25345775).
Weaver, Jamie M.J., Ross-Innes, Caryn S., Shannon, Nicholas, Lynch, Andy G., Forshew, Tim, Barbera, Mariagnese, Murtaza, Muhammed, Ong, Chin-Ann J., Lao-Sirieix, Pierre, Dunning, Mark J., Smith, Laura, Smith, Mike L., Anderson, Charlotte L., Carvalho, Benilton, O'Donovan, Maria, Underwood, Timothy J., May, Andrew P., Grehan, Nicola, Hardwick, Richard, Davies, Jim, Oloumi, Arusha, Aparicio, Sam, Caldas, Carlos, Eldridge, Matthew D., Edwards, Paul A.W., Rosenfeld, Nitzan, Tavaré, Simon and Fitzgerald, Rebecca C. (2014) Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nature Genetics, 46, (8), 837-843. (doi:10.1038/ng.3013 ). (PMID:24952744).
Cowie, Andrew, Noble, Fergus and Underwood, Timothy (2014) Strategies to improve outcomes in esophageal adenocarcinoma. Expert Review of Anticancer Therapy, 14, (6), 677-687. (doi:10.1586/14737140.2014.895668). (PMID:24621143 ).
Langley, Ruth E., Wilson, Richard H., Ring, Alistair E., Kynaston , Howard Gordon, Cameron, David A., Coyle, Christopher, Gilbert, Duncan Charles, Patrono, Carlo, Rowley, Sam, Murphy, Claire, Adlam, David, Hubner, Richard, Iveson, Tim, Steele, Robert J., Thomas, Anne L., Underwood, Timothy J., Jankowski, Janusz, Gupta, Sudeep and Pramesh, Conjeevaram S. (2014) Add-aspirin trial: a phase III, double blind, placebo-controlled, randomized trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common nonmetastatic solid tumors. Journal of Clinical Oncology, 32, (15), supplement 2014 ASCO Annual Meeting Abstracts, TPS1617.
Curtis, Nathan J., Noble, Fergus, Bailey, Ian S., Kelly, Jamie J., Byrne, James P. and Underwood, Timothy J. (2014) The relevance of the Siewert classification in the era of multimodal therapy for adenocarcinoma of the gastro-oesophageal junction. Journal of Surgical Oncology, 109, (3), 202-207. (doi:10.1002/jso.23484). (PMID:24243140).
Lavery, Danielle L., Nicholson, Anna M., Poulsom, Richard, Jeffery, Rosemary, Hussain, Alia, Gay, Laura J., Jankowski, Janusz A., Zeki, Sebastian S., Barr, Hugh, Harrison, Rebecca, Going, James, Kadirkamanathan, Sritharan, Davis, Peter, Underwood, Timothy, Novelli, Marco R., Rodriguez-Justo, Manuel, Shepherd, Neil, Jansen, Marnix, Wright, Nicholas A. and McDonald, Stuart A.C. (2014) The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands. Gut, 1-10. (doi:10.1136/gutjnl-2013-306508). (PMID:24550372).
Noble, Fergus, Nolan, Luke, Bateman, Adrian C., Byrne, James, Kelly, Jamie, Bailey, Ian, Sharland, Donna, Rees, Charlotte, Iveson, T., Underwood, T.J. and Bateman, Andrew R. (2013) Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus. World Journal of Gastroenterology, 19, (48), 9282-9293. (doi:10.3748/wjg.v19.i48.9282).
Noble, Fergus, Hopkins, James, Curtis, Nathan, Kelly, Jamie, Bailey, Ian, Byrne, James, Bateman, Adrian C., Bateman, Andrew R. and Underwood, T.J. (2013) The role of systemic inflammatory and nutritional blood-borne markers in predicting response to neoadjuvant chemotherapy and survival in oesophagogastric cancer. Medical Oncology, 30, (3), 596-609. (doi:10.1007/s12032-013-0596-6). (PMID:23690267).
Noble, F., Kelly, J.J., Bailey, I.S., Byrne, J.P. and Underwood, T.J. (2013) A prospective comparison of totally minimally invasive versus open Ivor Lewis esophagectomy. Diseases of the Esophagus, 26, (3), 263-271. (doi:10.1111/j.1442-2050.2012.01356.x).
Noble, F., Curtis, N.J. and Underwood, T.J. (2013) C-reactive protein 2 days after laparoscopic gastric bypass surgery reliably indicates leaks and moderately predicts morbidity. Journal of Gastrointestinal Surgery, 17, (4), 844-845. (doi:10.1007/s11605-012-2082-4). (PMID:23225106).
Bateman, Adrian C., Sommerlad, Matthew and Underwood, Timothy J. (2012) Chronic gastric ulceration: a novel manifestation of IgG4-related disease? Journal of Clinical Pathology, 65, (6), 569-570. (doi:10.1136/jclinpath-2011-200565 ). (PMID:22259178).
Noble, Fergus, Curtis, Nathan, Harris, Scott, Kelly, Jamie J., Bailey, Ian S., Byrne, James P., Underwood, Timothy J. and South Coast Cancer Collaboration-Oesophago-Gastric (SG-OG) (2012) Risk assessment using a novel score to predict anastomotic leak and major complications after oesophageal resection. Journal of Gastrointestinal Surgery, 16, (6), 1083-1095. (doi:10.1007/s11605-012-1867-9).
Noble, Fergus, Curtis, Nathan, Hopkins, James, Botting, N., Ali, S., Kelly, Jamie, Bailey, Ian, Byrne, James and Underwood, Tim (2011) Pre-operative systemic inflammatory and nutritional markers predict long term outcome after oesophageal cancer resection. British Journal of Surgery, 98, (S7), 19-20. (doi:10.1002/bjs.7752).
Noble, Fergus, Curtis, Nathan, Sreekumar, Rahul, Uduko, C., Chande, S., Kelly, Jamie, Bailey, Ian, Byrne, James and Underwood, Tim (2011) Risk assessment using a novel scoring system (NUn score) to predict major complications after oesophageal resection. British Journal of Surgery, 98, (S7), 7. (doi:10.1002/bjs.7752).
Underwood, T.J., Derouet, Mathieu F., Noble, Fergus, Uzoho, Chudy, Kelly, Jamie, Byrne, James, Bailey, Ian, Primrose, J.N. and Blaydes, Jeremy P. (2011) Fibroblast secreted periostin plays a functional role in oesophageal tumour cell invasion and indicates resistance to chemotherapy and poor prognosis. British Journal of Surgery, 98, (S7), 28-29. (doi:10.1002/bjs.7752).
Noble, Fergus, Underwood, Tim, Allenby-Smith, Oliver, Davies, Nick, Kelly, Jamie and Byrne, James (2010) Introduction of minimally invasive oeosophagectomy with thoracoscopic oesophageal mobilisation into UK practice: outcome in 102 consecutive patients. British Journal of Surgery , 97 , (S5), 6. (doi:10.1002/bjs.7299).
Noble, Fergus, Underwood, Tim, Poirier, Veronique and Byrne, James SWCIS UGI Tumour Panel (2010) Impact of PET/CT on management of oesophageal cancer a multi-centre study 2 year follow-up. British Journal of Surgery , 97 , (S5), 56. (doi:10.1002/bjs.7299).
Underwood, Timothy J., Derouet, Mathieu F., White, Michael J., Noble, Fergus, Moutasim, Karwan A., Smith, Eric, Drew, Paul A., Thomas, Gareth J., Primrose, John N. and Blaydes, Jeremy P. (2010) A comparison of primary oesophageal squamous epithelial cells with HET-1A in organotypic culture. Biology of the Cell, 102, 635-644. (doi:10.1042/BC20100071). (PMID:20843300).
Abu Hilal, M., Underwood, T., Zuccaro, J., Primrose, J. and Pearce, N (2010) Short- and medium-term results of totally laparoscopic resection for colorectal liver metastases. British Journal of Surgery, 97, (6), 927-933. (DOI: 10.1002/bjs.7034).
Abu Hilal, Mohammad, Underwood, Tim, Taylor, Matthew G., Hamdan, Khaled, Elberm, Hassan and Pearce, Neil W. (2010) Bleeding and hemostasis in laparoscopic liver surgery. Surgical Endoscopy, 24, (3), 572-577. (doi:10.1007/s00464-009-0597-x).
Underwood, T. J., Brent, A. and Nash, G. J. (2010) Haemorrhoidal artery ligation operation (HALO) for the treatment of symptomatic anorectal varices. Colorectal Disease, 12, (2), 148-149. (doi:10.1111/j.1463-1318.2008.01725.x).
Underwood, Timothy J., Southgate, Jeremy, Talbot, Robert and Nash, Guy F. (2008) Perforated diverticulitis presenting as necrotising fasciitis of the leg. World Journal of Emergency Surgery, 3, (10), 3-[pp]. (doi:10.1186/1749-7922-3-10).
Underwood, Timothy J., Amin, Jay, Lillycrop, Karen A. and Blaydes, Jeremy P. (2007) Dissection of the functional interaction between p53 and the embryonic proto-oncoprotein PAX3. FEBS Letters, 581, (30), 5831-5835. (doi:10.1016/j.febslet.2007.11.056).
Underwood, T.J., Blaydes, J.P. and Lillycrop, K.A. (2005) Mechanisms of inhibition of p53 function in tumours that express the Pax3 proto-oncogene. British Journal of Surgery, 92, (10), p.1308. (doi:10.1002/bjs.5192).
Awasthi, Shally, Beardmore, Jil, Clark, Jocalyn, Hadridge, Philip, Madani, Hardi, Marusic, Ana, Purcell, Gretchen, Rhoads, Margaret, Sliwa-Hähnle, Karen, Smith, Richard, Edejer, Tessa Tan-Torres, Tugwell, Peter and Underwood, Tim (2005) Five futures for academic medicine. PLoS Medicine, 2, (7), e207-[8pp]. (doi:10.1371/journal.pmed.0020207).
Underwood, T.J. and ICRAM (The International Campaign to Revitalise Academic Medicine) (2004) Academic medicine: the evidence base. British Medical Journal, 329, (7469), 789-791. (doi:10.1136/bmj.329.7469.789).

Book

Underwood, T.J. and (ICRAM) International Campaign to Revitalise Academic Medicine (2005) The future of academic medicine - five scenarios to 2025, New York, USA, Milbank Memorial Fund, 50pp.

Book Section

Primrose, J.N. and Underwood, T.J. (2013) Stomach and duodenum. In, Williams, Norman, Bulstrode, Christopher and O'Connell, P. Ronan (eds.) Bailey & Love's Short Practice of Surgery, 26th edition. Boca Raton, US, CRC Press, 1023-1057.
Underwood, T.J. (2010) Gallbladder cancer: The rationale for aggressive resection. In, Johnson, Colin D. and Taylor, Irving (eds.) Recent Advances in Surgery 33. India, Republic of, IN, Jaypee Brothers Medical Publishers (P) Ltd, 62-72.
 

Research

Research Interests

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

Responsibilities

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

Teaching Responsibilities

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.

Contact

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
Email: T.J.Underwood@soton.ac.uk