Maikel Peppelenbosch (1967) studied Medicine at the University of Utrecht, the Netherlands and trained in Medical Biology between 1985 and 1989. In 1994, he completed his thesis (cum laude) on the Action and Function of Receptor Protein Tyrosine Kinases -the role of arachidonic acid metabolites and tyrosine phosphatases. He subsequently became a Postdoctoral associate from 1993-1995 with Prof. dr Johannes L. Bos, Physiological Chemistry, Utrecht University and then with Dr Anne Ridley, Ludwig Institute for Cancer Research, London and with prof dr Walter Fiers in Gent, Belgium. After his return to The Netherlands he became Research leader at the Laboratory for Experimental Intarnal Medicine, Academical Medical Center, Amsterdam. In July 2004 he became Professor of Cell Biology and chairman of the Immunology, Department of Cell Biology, University Medical Center Groningen, University of Groningen. In October 2009 he became professor of Experimental Gastroenterology and head of the Laboratory of Gastroenterology and Hepatology at the Erasmus MC, University Medical Center Rotterdam, Rotterdam The Netherlands.
Following my studies in Medical Biology & Medicine at the Utrecht University, I was for ten years a fundamental researcher in developmental biology and immunology (e.g. Peppelenbosch et al. Cell 69, 295-303; Cell 74: 565-575; Cell 81: 849-856). In the second half of the nineties, however, I became fascinated by the biology of gastrointestinal tract, trying to understand both how the tract maintains histostasis in face of the unrelenting sequence of cell proliferation, differentiation and apoptosis which takes place in the intestine, as well as by the mechanisms that enable the mucosal immune system to tolerate billions of commensal bacteria but adequately attack pathogens if they present themselves in the intestine. I have endeavoured to apply the insights gained for designing improved diagnosis and therapy, especially with respect to IBD, GE cancer and Barrett's oesophagus. The research involved ranges from highly clinical to very fundamental. An example of the former are my efforts to open up novel therapeutic options for the treatment of GE disease, e.g. by initiating a trail employing IL-10 producing L. lactis for the treatment of Crohn's disease (Braat et al. Clin Gastroenterol Hepatol. 4:754-9), which was the first trail ever in which humans were treated with a genetically modified organism and showed that mucosal delivery of biologicals using this route is possible.
Another example is my contribution to the insight that application of modulators of intracellular signal transduction is both feasible and potentially effective in GE pathology, e.g. in a study evaluating the effect of the c-Raf inhibitor CNI-1493 in Crohn's disease (Hommes et al. Gastroenter. 122:7-14). More translational are my studies exploring the molecular mechanism of action of different medications in GE pathology, e.g. establishing that Infliximab acts through apoptosis to induce remission in Crohn's disease (Van den Brande et al. Gastroenter. 126: 935-6), studies showing that statins act by inducing BMP transcription to prevent colorectal cancer (Kodach et al. Gastroenterol. 134:1332-41) or dissecting the molecular mechanisms by which NSAIDS and mesalazine exert their chemopreventive effects with respect to GE cancer (e.g. Tuynman et al. Cancer Res. 68:1213-20). Very fundamental are the studies as to the role of morphogens in the control of GE physiology (e.g. the role of Hedgehog [van den Brink et al. Nature Gen. 36:277-82]) , establishing the pivotal role of BMP signalling in inducing Barrett's oesophagus (Milano et al. Gastroenterol. 132:2412-21) but that conversely BMP signalling counteracts colorectal cancer (Hardwick et al. Gastroenterol. 126:111-21). Especially paradigm-shifting are my studies establishing the role of Notch and Asb signalling in compartment size in the GE tract (Diks et al. Nature Cell Biol. 10:1190-8), which may explain in molecular terms why the murine intestine is smaller as the human intestine, but also why the intestines of apes are larger as those of humans. As many diseases in the GE tract basically involve deregulation of compartment size (cancer, fibrosis etc.) I hope this work may turn out to be highly clinically relevant.