Gastroenterology and Hepatology 1

Cellular Mechanisms in Basic and Clinical Gastroenterology and Hepatology

Principal investigators

Prof.Dr. D.W. Hommes, Dr. G.R. van den Brink, Dr. J.C.H. Hardwick, Dr. B. van Hoek, Dr. H.F.A. Vasen, Dr.Ir. H.W. Verspaget

Aim and focus

All research in the department of Gastroenterology and Hepatology is performed with the aim to increase the understanding of cellular mechanisms in (patho)physiological processes of the gastrointestinal tract and liver in order to translate this into innovations for the diagnosis and treatment in clinical gastroenterology and hepatology. The research focus is to evaluate the functional and clinical impact of (mesenchymal) stem cells and intra- and intercellular factors like Hedgehog signaling, the Bone Morphogenetic Protein pathway, glucocorticoid signaling, the lectin-complement pathway and matrix metalloproteinases on chronic inflammation, carcinogenesis, liver disease and liver transplantation.  

Position in international context

The department is actively participating in several international study groups (e.g. Belgian Inflammatory Bowel Disease Research Group, European Crohn's and Colitis Organisation) and trials to explore new therapies for Inflammatory Bowel Disease, i.e. Crohn's disease and ulcerative colitis. For liver transplantation the LUMC is member of several international networks [e.g. the ELTR (European Liver Transplantation Registration)]. International collaboration on matrix metalloproteinases in inflammation and cancer is established through the International Society for Fibrinolysis and Proteolysis (ISFP). Regarding familial tumour syndromes the department of Gastroenterology and Hepatology is closely linked to the Netherlands Foundation for the Detection of Hereditary Tumours (Stichting Opsporing Erfelijke Tumoren). The organisation and the research done in this field has an excellent international reputation and it is often used by other countries to develop similar programmes. The department is heavily involved in the design and the execution of large international studies, at the level of basic research/genomics as well as at the level of clinical/translational research with (family) screening and intervention studies.

Content / highlights / achievements

The department plays a crucial role in the further development and performance of Liver Transplantation in the LUMC, with favourable clinical results. New treatment modalities with biologicals for Inflammatory Bowel Disease are introduced and evaluated, participation in research on genotype-phenotype associations is established in EU FP-6 and FP-7 programmes. The research on genetics of Colorectal Cancer has led to new internationally accepted guidelines for genetic screening of family members, the so-called Revised Bethesda Guidelines. Basic research on colorectal carcinogenesis is performed with support of NWO-Veni grants.

Future themes

Research efforts will focus on the relation between genetics and inter- and intracellular mechanisms with chronic inflammation of the bowel, liver, and in liver transplantation and cancer. Close interaction between patient care and research using (national) biobank facilities provides an optimal opportunity to perform translational studies in these research areas.

Cohesion within the LUMC

The research on genetics and on features of premalignant conditions of the gastrointestinal tract and liver is part of the Oncology theme in the LUMC cancer center. The liver transplantation programme is very well embedded in the broader LUMC transplantation theme. Research on liver transplantation and on chronic inflammatory conditions of the gastrointestinal tract is included in several sub-themes of the LIFI (Leiden Institute for Immunology). The research is conducted particularly in close collaboration with the departments of  Surgery, Human Genetics, Pathology, Radiology and several departments participating in the LIFI.

Key publications

Brink GR van den, Hedgehog signaling in development and homeostasis of the gastrointestinal tract. Physiological Reviews 2007; 87: 1343-1375.
IF 31.4

Kubben FJGM, Sier CFM, Meijer MJW, Berg M van den, Reijden JJ van der, Griffioen G, Velde CJH van de, Lamers CBHW, Verspaget HW. Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. British Journal of Cancer 2006; 95: 744-751.
IF 4.5

Hendriks YMC, Jong AE de, Morreau H, Tops CJM, Vasen HFA, Wijnen JT, Breuning MH, Bröcker-Vriends AHJT. Diagnostic approach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma): a guide for clinicians. CA A Cancer Journal for Clinicians 2006; 56: 213-225.
IF 63.3

Jong AE de, Hendriks YMC, Kleibeuker JH, Boer SY de, Cats A, Griffioen G, Nagengast FM, Nelis GF, Rookus MA, Vasen HFA. Decrease in mortality in Lynch syndrome families due to surveillance. Gastroenterology 2006; 130: 665-671.
IF 12.5

D'Haens G, Baert F, Assche G van, Caenepeel Ph, Vergauwe Ph, Tuynman H, Vos M de, Deventer SJH van, Stitt L, Donner A, Vermeire S, Mierop FJ van de, Coche JCh, Woude J van der, Ochsenkuhn T, Bodegraven AA van, Hootegem PP van, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes DW. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet 2008; 371: 660-667.
IF 25.8

Hardwick, JCH, Kodach, LL, Offerhaus, GJA, Brink, GR van den. Bone morphogenetic protein signalling in colorectal cancer. Nature reviews Cancer 2008; 8: 806-812.
IF 31.6

Löwenberg M, Verhaar AP, Brink GR van den,  Hommes DW. Glucocorticoid signaling: a nongenomic mechanism for T-cell immunosuppression. Trends in Molecular Medicine 2007; 13: 158-163.
IF 5.9

Plevy S, Salzberg B, Assche G van, Regueiro M, Hommes DW, Sandborn W, Hanauer S, Targan S, Mayer L, Mahadevan U, Frankel M, Lowder J. A phase I study of visilizumab, a humanized anti-CD3 monoclonal antibody, in severe steroid-refractory ulcerative colitis. Gastroenterology 2007; 133: 1414-1422.
IF 12.5

Ringers J, Dubbeld J, Baranski AG, Coenraad MJ, Sarton E, Schaapherder AFM, Hoek B van. Reuse of auxiliary liver grafts in second recipients with chronic liver disease. American Journal of Transplantation 2007; 7: 2615-2618.
IF 6.8

Hawinkels LJAC, Verspaget HW, van Duijn W, van der Zon JM, Zuidwijk K, Kubben FJGM, Verheijen JH, Hommes DW, Lamers CBHW, Sier CFM. Tissue level, activation and cellular localisation of TGF-beta1 and association with survival in gastric cancer patients. British Journal of Cancer 2007; 97: 398-404.
IF 4.5