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Dr Tim Raine

Dr Tim Raine

Tim Raine is accepting applications for PhD students.

Tim Raine is available for consultancy.


Research Interests

I am a consultant gastroenterologist, with a clinical subspecialty interest in inflammatory bowel disease (IBD). My research is focussed on understanding the regulation of the gastrointestinal immune system, in particular in the context of IBD.

In my PhD thesis with Prof. Anne Cooke (University of Cambridge), I explored the effects of Salmonella infection and gastrointestinal helminth infection on the function of tissue resident innate immune cells and modulation of autoreactivity. For my postdoctoral research, I have worked with Prof. Adrian Hayday (King’s College, London), Prof Chris Rudd (Cambridge Institute for Medical Research) and Prof Arthur Kaser and Dr Miles Parkes (University of Cambridge). I have developed new techniques for the extraction and characterisation of immunocytes from human gut endoscopic biopsies. Using these techniques, together with ex vivo analysis methods including polychromatic flow cytometry, live cell confocal microscopy and microfluidic systems, I have been able to study human gastrointestinal lymphocytes using material from a range of patient groups including healthy control volunteers (a group not amenable to study using traditional large scale methods with surgical resection material). In particular, together with Dr Carl Anderson (Wellcome Trust Sanger Institute, Hinxton), I have developed novel laboratory and computational approaches for the understanding the transcriptomic (RNA-Seq / expression microarrays) and chromatin state (ATAC-Seq) landscape of individual immune cell populations. By setting these data within the context of genetic polymorphisms and microbial signatures associated with IBD, we aim to understand the immunological basis for genetic risk in IBD. Through this work, I have been appointed as an honorary faculty member at the Wellcome Trust Sanger Institute.

In addition, I have an interest in human clinical trials in IBD, and serve on the British Society of Gastroenterology (BSG) IBD Clinical Research Group. I am lead investigator for the NIHR funded IASO trial of IL-1 blockade in acute severe ulcerative colitis. I am a named investigator on several ongoing industry-sponsored clinical trials, and work with a number of pharmaceutical companies, including GSK on their first-in-man/early phase clinical trials unit.

I am a member of the European Crohn's and Colitis Organisation (ECCO) and past chair of the Young-ECCO committee that serves the interests and needs of gastroenterologists, GI surgeons and gastroenterology scientists in training.  In 2016 I was awarded the BSG Young Gastroenterologist of the Year award. I am an author on several sets of ECCO guidelines on management of IBD and the upcoming BSG guidelines for the management of IBD (in development).

I am the senior author of the Oxford Handbook for the Foundation Programme and the Oxford Handbook of Clinical Medicine (10th edition), and a chapter author on Crohn’s disease for the Oxford Textbook of Medicine (6th edition).

Keywords

mucosal immunology

Topics

  • Ulcerative Colitis
  • Crohn's disease

Key Publications

Kopylov U, Raine T and 34 co-middle authors, Roblin X Impact of Infliximab and Cyclosporine on the Risk of Colectomy in Hospitalized Patients with Ulcerative Colitis Complicated by Cytomegalovirus-A Multicenter Retrospective Study. Inflamm Bowel Dis. 2017 doi: 10.1097/MIB.0000000000001160.

Thomas JP, Raine T, Reddy S, Belteki G Probiotics for the prevention of necrotising enterocolitis in very low-birth-weight infants: a meta-analysis and systematic review. Acta Paediatr. 2017 doi: 10.1111/apa.13902.

Magro F, [15 middle authors], Raine T, Harbord M, Rieder F 3rd European Evidence-based consensus on diagnosis and management of ulcerative colitis. part 1: Definitions, Diagnosis and Special situations J Crohn’s Colitis 2017 11:649-670.

Harbord M, Raine T and 10 co-middle authors, Dignass A & Carbonnel F, 3rd European Evidence-based consensus on diagnosis and management of ulcerative colitis. part 2: Current Management J Crohn’s Colitis 2017 doi: 10.1093/ecco-jcc/jjx009.

Danese S, Fiorino G, Raine T et al. ECCO position statement on the use of biosimilars for inflammatory bowel disease – An update J Crohns Colitis. 2017 11:26-34

Mücke V, Mücke MM, Raine T* & Bettenworth D* (*joint senior authorship) Diagnosis and treatment of anemia in patients with inflammatory bowel disease Annals of Gastroenterology 2017 30:15-22

Cader MZ, Boroviak K, Zhang Q, Assadi G, Kempster SL, Sewell GW, Saveljeva S, Ashcroft JW, Clare S, Mukhopadhyay S, Brown KP, Tschurtschenthaler M, Raine T, Doe B, Chilvers ER, Griffin JL, Kaneider NC, Floto RA, D'Amato M, Bradley A, Wakelam MJ, Dougan G, Kaser A. C13orf31 (FAMIN) is a central regulator of immunometabolic function. Nat Immunol. 2016 17:1046-56.

Harbord M, Raine T and 18 co-2nd authors, Carbonnel F The First European Evidence-Based Consensus on Extra-Intestinal Manifestations in Inflammatory Bowel Disease, J Crohn’s Colitis 2016 10:239-54.

Kraiczy J, Nayak K, Ross A, Raine T, Mak TN, Gasparetto M, Cario E, Rakyan V, Heuschkel R, Zilbauer M. Assessing DNA methylation in the developing human intestinal epithelium: potential link to inflammatory bowel disease. Mucosal Immunol. 2015 doi:10.1038/mi.2015.88

Raine T, Liu J, Anderson C, Parkes M, Kaser A Generation of primary human intestinal T cell transcriptomes reveals differential expression at genetic risk loci for immune mediated disease. Gut. 2015 64:250-9

Raine T Vedolizumab for inflammatory bowel disease: Changing the game, or more of the same? UEG Journal 2014  2:333-44

Raine T Insights from immunology: new targets for new drugs? Best Practice & Research Clinical Gastroenterology: Novel Developments in Crohn's Disease 2014 28:411-20

Adolph TE, Tomczak MF, Niederreiter L, Ko HJ, Böck J, Martinez-Naves E, Glickman JN, Tschurtschenthaler M, Hartwig J, Hosomi S, Flak MB, Cusick JL, Kohno K, Iwawaki T, Billmann-Born S, Raine T, Bharti R, Lucius R, Kweon MN, Marciniak SJ, Choi A, Hagen SJ, Schreiber S, Rosenstiel P, Kaser A, Blumberg RS. Paneth cells as a site of origin for intestinal inflammation. Nature. 2013 503(7475):272-6. 

Niederreiter L, Fritz TM, Adolph TE, Krismer AM, Offner FA, Tschurtschenthaler M, Flak MB, Hosomi S, Tomczak MF, Kaneider NC, Sarcevic E, Kempster SL, Raine T, Esser D, Rosenstiel P, Kohno K, Iwawaki T, Tilg H, Blumberg RS, Kaser A. ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells. J Exp Med. 2013 Sep 23;210(10):2041-56.

Jenke AC, Postberg J, Raine T, Nayak KM, Molitor M, Wirth S, Kaser A, Parkes M, Heuschkel RB, Orth V, Zilbauer M. DNA methylation analysis in the intestinal epithelium-effect of cell separation on gene expression and methylation profile. PLoS One. 2013;8(2):e55636. 

Raine T, Kaser A. Seventeen in Crohn's disease: less prime than we thought? Gut. 2012;61(12):1653-4. 

Gibbons DL, Abeler-Dörner L, Raine T, Hwang IY, Jandke A, Wencker M, Deban L, Rudd CE, Irving PM, Kehrl JH, Hayday AC. Cutting Edge: Regulator of G protein signaling-1 selectively regulates gut T cell trafficking and colitic potential. J Immunol. 2011 Sep 1;187(5):2067-71.

Raine T, Brown D, Bowness P, Hill Gaston JS, Moffett A, Trowsdale J, Allen RL. Consistent patterns of expression of HLA class I free heavy chains in healthy individuals and raised expression in spondyloarthropathy patients point to physiological and pathological roles. Rheumatology 2006 45(11):1338-44
 
Raine T, Zaccone P, Mastroeni P, Cooke A. Salmonella typhimurium infection in nonobese diabetic mice generates immunomodulatory dendritic cells able to prevent type 1 diabetes. J Immunol. 2006 177(4):2224-33.

Other Publications

Oxford Handbook for the Foundation Programme (Oxford Handbooks Series) 4th Edition Raine T, Dawson J, Sanders S, Eccles S Oxford University Press July, 2014 ISBN 0199683816

Oxford Handbook of Clinical Medicine (Oxford Handbooks Series) 10th edition Wilkinson IB, Raine T, Wiles K, Goodhart A, Hall C, O’Neill H Oxford University Press July 2017 ISBN 0199689903