Career History

Professional Qualifications and professional memberships

  • 1977 - B.A. (Hons) Cambridge, Medical Science 1980 M.B.B.S. London University 1983 M.R.C.P.
  • 1989 - M.D. Cambridge University
  • 1999 - F.R.C.P.
  • 2003 - F.R.C.P. Edinburgh

Research interests

  • Inflammatory Bowel Disease
  • Colorectal Cancer
  • Apoptosis
  • Epithelial barrier function and cell shedding

Career summary

Studied medicine at the Universities of Cambridge (Corpus Christi College) and London (St Thomas’ Hospital). Qualified in 1980. After junior posts in London, Edinburgh and Stoke on Trent became medical registrar in the King’s Liver Unit with Roger Williams. In 1985 became a research fellow with Michael Farthing in St Bartholomew’s hospital, London. In 1989 obtained a Medical Doctorate on the absorption of short chain fatty acids. Became a post-doctoral fellow with Mark Donowitz and Chip Montrose at Johns Hopkins Medical School (1988-90). In 1990 won a Senior Research Fellow Award from the American Gastroenterology Association and an award for outstanding accomplishment in Postdoctoral Research from the American Physiological Society. Returned to the University of Manchester in 1991 to work with Lord Turnberg on apoptosis in the GI epithelium. In 1992 was awarded The Sir Francis Avery Jones British Society of Gastroenterology Research Medal. Appointed Professor of Medicine at the University of Liverpool in 1998 where he served a number of senior administrative posts including Head of the Division of Gastroenterology and Head of the Department of Medicine. He was an Associate Editor of GUT (2003 – 04) then its Deputy Editor (2005 – 2007). He currently serves on the Council of the British Society of Gastroenterology and in 2010 was appointed as its first Secretary of International Affairs. In 2010 he was appointed the University of East Anglia as its first Professor of Translational Medicine.

 

All Publications

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Fischer, A., Zundler, S., Atreya, R., Rath, T., Voskens, C., Hirschmann, S., López-Posadas, R., Watson, A., Becker, C., Schuler, G., Neufert, C., Atreya, I., Neurath, M. F.

(2016)

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo

in Gut

Full Text UEA Repository

(Article)


Lopez-Posadas, R., Becker, C., Gunther, C., Tenzer, S., Amann, K., Billmeier, U., Atreya, R., Fiorino, G., Vetrano, S., Danese, S., Ekici, A. B., Wirtz, S., Thonn, V., Watson, A., Brakebusch, C., Bergo, M., Neurath, M., Atreya, I.

(2016)

Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation

in Journal of Clinical Investigation

126.

pp. 611-626

Full Text UEA Repository

(Article)


Martini, E., Wittkopf, N., Gunther, C., Leppkes, M., Okada, H., Watson, A. J., Podstawa, E., Backert, I., Amann, K., Neurath, M., Becker, C.

(2016)

Loss of Survivin in Intestinal Epithelial Progenitor Cells Leads to Mitotic Catastrophe and Breakdown of Gut Immune Homeostasis

in Cell Reports

14.

pp. 1062-1073

Full Text UEA Repository

(Article)


Kelly, P., Besa, E., Zyambo, K., Louis-Auguste, J., Lees, J., Banda, T., Soko, R., Banda, R., Amadi, B., Watson, A.

(2016)

Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

in PLoS Neglected Tropical Diseases

10.

Full Text UEA Repository

(Article)


Miguel, J., Maxwell, A., Hsieh, J., Harnisch, L., Alam, D., Polk, B., Lien, C., Watson, A., Frey, M. R.

(2016)

Epidermal growth factor suppresses intestinal epithelial cell shedding both in vitro and in vivo via a MAPK dependent pathway

in Journal of Cell Science

Full Text UEA Repository

(Article)


Watson, A. J.

(2016)

Confocal Laser Endomicroscopy in the Management of IBD: Clearly Superior?

in Digestive Diseases and Sciences

61.

pp. 1785-1787

Full Text

(Editorial)


Watson, A. J., Biancheri, P., Patterson, A.

(2016)

The mucosal microbiome and recurrence after surgery for Crohn’s disease

in Gastroenterology

150.

pp. 1682-1684

Full Text UEA Repository

(Article)


Kelley, A., Beeching, N., Roberts, P., Watson, A., Beadsworth, M.

(2016)

Clostridium difficile: a healthcare associated infection of unknown significance in adults in sub-Saharan Africa

in Malawi Medical Journal

28.

Full Text UEA Repository

(Article)


Gunther, C., Buchen, B., He, G., Hornef, M., Torow, N., Neumann, H., Wittkopf, N., Martini, E., Basic, M., Bleich, A., Watson, A. J. M., Neurath, M. F., Becker, C.

(2015)

Caspase-8 controls the gut response to microbial challenges by Tnf-alpha-dependent and independent pathways

in Gut

64.

pp. 601-610

Full Text UEA Repository

(Article)


Williams, J. M., Duckworth, C. A., Burkitt, M. D., Watson, A. J. M., Campbell, B. J., Pritchard, D. M.

(2015)

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

in Veterinary Pathology

52.

pp. 445-455

Full Text UEA Repository

(Article)


Dammann, K., Khare, V., Lang, M., Claudel, T., Harpain, F., Granofszky, N., Evstatiev, R., Williams, J. M., Pritchard, D. M., Watson, A., Gasche, C.

(2015)

PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation

in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

1853.

pp. 2349–2360

Full Text UEA Repository

(Article)


Man, A. L., Bertelli, E., Rentini, S., Regoli, M., Briars, G., Marini, M., Watson, A. J., Nicoletti, C.

(2015)

Age-associated modifications of intestinal permeability and innate immunity in human small intestine

in Clinical Science

129.

pp. 515-527

Full Text UEA Repository

(Article)


Huels, D., Ridgeway, R., Radulescu, S., Leushacke, M., Campbell, A., Biswas, S., Leedham, S., Serra, S., Chetty, R., Moreaux, G., Parry, L., Matthews, J., Song, F., Hedley, A., Kalna, G., Ceteci, F., Reed, K. R., Meniel, V. S., Maguire, A., Soderberg, O., Barker, N., Watson, A., Larue, L., Sansom, O.

(2015)

E-cadherin can limit the transforming properties of activating β-catenin mutations

in The EMBO Journal

34.

pp. 2321-2333

Full Text UEA Repository

(Article)


Sreekumar, J., France, N., Taylor, S., Matthews, T., Turner, P., Bliss, P., Brook, A. H., Watson, A. J. M.

(2015)

Diagnosis of Helicobacter pylori by carbon-13 urea breath test using a portable mass spectrometer

in Sage Open Medicine

3.

Full Text UEA Repository

(Article)


Watson, A.

(2015)

Claudins and barrier dysfunction in intestinal inflammation: cause or consequence?

in Gut

64.

pp. 1501-1502

UEA Repository

(Article)


Brooks, J., Watson, A.

(2015)

The Enteric Virome in Inflammatory Bowel Disease

in Gastroenterology

149.

pp. 1120-1121

Full Text

(Comment/debate)


Parsons, B. N., Wigley, P., Simpson, H. L., Williams, J. M., Humphrey, S., Salisbury, A., Watson, A. J. M., Fry, S. C., O'Brien, D., Roberts, C. L., O'Kennedy, N., Keita, A. V., Söderholm, J. D., Rhodes, J. M., Campbell, B. J.

(2014)

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

in PLoS ONE

9.

Full Text UEA Repository

(Article)


Lim, L. G., Neumann, J., Hansen, T., Goetz, M., Hoffman, A., Neurath, M. F., Galle, P. R., Chan, Y. H., Kiesslich, R., Watson, A.

(2014)

Confocal endomicroscopy identifies loss of local barrier function in the duodenum of patients with Crohn's disease and ulcerative colitis

in Inflammatory Bowel Diseases

20.

pp. 892-900

Full Text UEA Repository

(Article)


Hall, L. J., Walshaw, J., Watson, A. J. M.

(2014)

Gut Microbiome in New-Onset Crohn's Disease

in Gastroenterology

147.

pp. 932–934

Full Text UEA Repository

(Article)


Watson, A. J. M.

(2014)

Confocal Laser Endomicroscopy and NSAID Enteropathy: Where Next?

in Digestive Diseases and Sciences

59.

pp. 1344-1346

Full Text

(Editorial)


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Key Research Interests

I have a long-standing interest in the regulation of cell death in intestinal epithelial cells. Recently I have become interested intestinal epithelial cell shedding, a special form of cell death which arises as a consequence of the high flux of epithelial cell which arise from stem cells at the base of crypts and migrate up to the villi in the case of the small intestine or intestinal surface in the case of the colon. When a cell is shed a discontinuity is created in the epithelial monolayer that has been named a “gap”. Under normal conditions the “gap” is short lived and barrier function is maintained at sites of cell shedding. However, during inflammation cell shedding is increased and can become confluent leading to the formation of micro-ulcers. Barrier function is also sometimes lost during inflammation, creating sites for the potential entry of microorganisms and luminal antigens. This work focuses on mouse models and multiphoton microscopy and imaging of cell shedding in humans by confocal endomicroscopy.




Figure 1 A group of shedding cells from human small intestine imaged by confocal endomicroscopy



Figure 2 A cell undergoing shedding from the human small intestine. H & E staining.




Figure 3. An epithelial gap in the mouse small intestine. Nuclei are stained with Hoechst 33258 and cytosol with green fluorescent protein. The side panels show z-axis reconstructions of the x and y planes of the main image.

I am also interested in wnt signalling and the early stages of the pathogenesis of colorectal cancer and have identified in humans a number of targets of wnt signalling.

 

Selected publications
 

D Moussata, M Goetz, A Gloeckner, M Kerner, B Campbell, A Hoffman, S Biesterfeld, B Flourie, JC Saurin, PR Galle, MF Neurath, *AJM Watson, *R Kiesslich. Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in IBD in vivo. Gut 2011;60:26-33. AJMW corresponding author and joint senior author

A. Marchando, Shen L, Graham WV, Edelblum KL, Duckworth CA, Guan Y, Montrose MH, Turner JR, Watson AJM. The epithelial barrier is maintained by in vivo tight junction expansion during pathologic intestinal epithelial shedding. Gastroenterology 2011 (In press).

Watson AJM, Duckworth CA. Gut microbiota control gut permeability through GLP2. Gastroenterology 2010;138(2):779-81.

Watson A.J.M. The new “connexin” to the pathogenesis of E.coli diarrhoea. Gut 2010;59:154-155.

Watson A.J.M., Collins PD. Treatment of Inflammatory Bowel Disease with genetically engineered bacteria. Gastroenterology 2010;139:685-687.

Watson A.J.M., Collins PD. Colon cancer: A civilization disorder. Falk Symposium 176 Digestive Diseases 2011 (In press).

Watson A.J.M. Tremelling M. Mucosal gene expression signatures that predict response of Ulcerative Colitis to Infliximab. Gastroenterology 2011 Feb;140(2):729-31

Marchiando AM, Shen L, Graham WV, Weber CR, Schwarz BT, Austin JR, Guan Y, Watson AJM, Montrose MH, and Turner JR. Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo. Journal of Cell Biology 2010;189(1):111-26.

Heidi K Baumgartner, Julia V Gerasimenko, Christopher Thorne, Pawel Ferdek, Tullio Pozzan, Alexei V Tepikin, Ole H Petersen, Robert Sutton, Alastair J. M. Watson, Oleg V. Gerasimenko.Calcium elevation in mitochondria is the main Ca2+ requirement for mPTP opening. Journal of Biological Chemistry 2009;284(31):20796-803.

Ralf Kiesslich, Martin Goetz, Elizabeth M. Angus, Qiuping Hu, Yanfang Guan, Chris Potten, Terry Allen, Markus F. Neurath, Noah F. Shroyer, Marshall H. Montrose, Alastair J.M. Watson. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. Gastroenterology 2007;133:1769-78.

Alice.J Walmesley, Jehad Zweiri, Stephen E. Christmas, Alastair.J.M Watson. Rofecoxib has different effects on chemokine production in colorectal cancer cells and tumour immune splenocytes. Journal of Immunotherapy 2007;6:614-623.

Alice.J Walmesley, Jehad Zweiri, Stephen E. Christmas, Alastair.J.M Watson. Rofecoxib has different effects on chemokine production in colorectal cancer cells and tumour immune splenocytes. Journal of Immunotherapy 2007;6:614-623.

Bach SP, Williamson SE, O'Dwyer ST, Potten CS, Watson AJM. Regional localisation of p53-independent apoptosis determines toxicity to 5-fluorouracil and pyrrolidinedithiocarbamate in the murine gut. British Journal of Cancer 2006; 95: 35-41.

Bullen TF, Forrest S, Campbell F, Dodson AR, Hershman MJ, Pritchard DM, Turner JR, Montrose MH, Watson AJM. Characterization of epithelial cell shedding from human small intestine. Lab Invest. 2006 Oct;86(10):1052-63.

Dekker B, Keen H, Lyons S, Disley L, Hastings D, Reader A, Ottewell P, Watson AJM and Zweit J. MBP-Annexin V Radiolabelled Directly with Iodine-124 can be used to Image Apoptosis In Vivo using PET. Nuclear Medicine and Biology 2005; 32:241-252.

Alastair J.M. Watson, Shaoyou Chu, Leah Sieck, Oleg Gerasimenko, Tim Bullen, Fiona Campbell, Michael McKenna, Tracy Rose, and Marshall H. Montrose. Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. Gastroenterology 2005;129:902-912.

Gerasimenko JV, Gerasimenko OV, Palejwala A, Tepikin AV, Petersen OH, Watson AJM. Menadione-induced apoptosis: roles of cytosolic Ca2+ elevations and the mitochondrial permeability transition pore. J Cell Science 2002:115;485-497.

Marshman E, Ottewell P.D. Potten C.S. and Watson A.J.M. Caspase activation during spontaneous and radiation-induced apoptosis in the murine intestine. J Pathol 2001;195:285-292

 


External Activities and Indicators of Esteem

  • Member of the Governing Council of the British Society of Gastroenterology (BSG)
  • BSG Secretary for International Affairs
  • Trustee of the British Society of Gastroenterology

Key Responsibilities

My main administrative role is building clinical research on the Norwich Research Park.