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The Journal of Gastroenterology and Hepatology (JGH), an official journal of the Asian Pacific Association of Gastroenterology (APAGE) and an affiliated journal of several national gastroenterology and liver associations, will soon have a new Editor-in-Chief. From January 2013 Professor Mamoru Watanabe takes on this important leadership role, after completion of Professor Geoff Farrell's 6-year term.

Dr Watanabe is a Professor and Chairman in the Department of Gastroenterology and Hepatology, Department of Endoscopy, Tokyo Medical and Dental University. He is also the Director in the Advanced Clinical Center for Inflammatory Bowel Disease in this major teaching and academic Hospital.

I have known Dr Watanabe both personally and professionally during the past 30 years. He is a best friend of mine. We both graduated from the same School of Medicine, Keio University in Tokyo and worked in the same Department of Internal Medicine in Keio for 20 years. He was a 3-year junior to me, and I was his first supervisor for his clinical training in the Department of Gastroenterology in Keio. On the basis of this longstanding interaction, I hold him in the highest esteem, both as a physician and scientist, and know he will continue to make major leadership contributions to both clinical and basic investigations in gastroenterology.

It has been more than 25 years since JGH was born from the Asia-Pacific Region. Since then this journal has showed steady growth and obtained high recognition because of its high scientific quality and ability to provide timely insights into topics that match well with the current needs of the Asia-Pacific region. Moreover, JGH has contributed importantly to the increased quality of clinical practice and scientific research in the field of gastroenterology and hepatology in the Asia-Pacific area. Overall, it has become one of the most prestigious scientific journals in the gastroenterology field. I am glad to acknowledge that many Japanese scientists and clinician scientists have been engaged in the editorial board of JGH ever since its inauguration. Especially, we have to remember the late Professor Kunio Okuda, late Professor Hiromasa Ishii, and Professor Nobihiro Sato, for their outstanding contributions and efforts as Editors and Editors-in-Chief of JGH for years. I believe Professor Mamoru Watanabe will continue the tradition of the sincere contribution of Japanese scientists to the further remarkable development of JGH. As a long-time friend and as a JGH Editor, it is my privilege to introduce Dr Watanabe's career and his scientific achievements to the readers of the Journal.

After graduation from Keio University in 1979, Dr Mamoru Watanabe engaged in clinical practice in gastroenterology, and together we experienced care of a variety of intractable GI disorders. At that time, I was really impressed by his superior talent as a resident, one who not only showed a warm-hearted devotion to the care of his patients with his excellent medical knowledge, but also had a keen interest about future medical progress and a great ability to predict a medical trend. It seems he already had in mind that he should be involved in medical achievements for intractable digestive diseases in the future. Mamoru also recognized the necessity of training himself for basic research to conduct future epoch-making discoveries and innovations in medical treatment. He entered the graduate school of Keio and began research in the area of gastroenterology.

Mamoru Watanabe has been working on inflammatory bowel disease (IBD), mucosal immunology and intestinal epithelial biology for years, initially under the mentorship of late Professor Masaharu Tsuchiya (Emeritus Professor of Keio University), Professor Hitoshi Asakura (Emeritus Professor of Niigata University) and Professor Toshifumi Hibi (Current Professor of Department of Internal Medicine, School of Medicine, Keio University). It was an exciting and stimulating time at Keio University, given the vision and charisma of Dr Tsuchiya, a great chief, intent on building a world-class Division of Gastroenterology. Since then Mamoru's prodigious body of work has been disseminated in the most respected journals. He has published over 200 original articles in prominent journals including Nature, Nature Medicine, PNAS, JCI, Journal of Experimental Medicine, Cancer Research and Gastroenterology.

From 1987 to 1991, Dr Watanabe had been a postdoctoral research fellow in Norman Letvin's lab at the New England Primate Research Center in Harvard Medical School, Boston. He conducted AIDS-related research, resulting in six first author papers including one Nature, three PNASI and two J Virol papers. His achievements, along with his relationship with many famous gastroenterologists, opened the door at Harvard Medical School and American Gastroenterological Association (AGA) for Japanese researchers. Professor Daniel Podolsky was then Chief of the GI unit of Massachusetts' General Hospital in the Harvard Medical School at that time, later becoming President of the AGA, and is now President of the University of Texas, Southwestern Medical Center. Podolsky helped Mamoru personally, as well as, through him, becoming a good friend of the Japanese Society of the Gastroenterology (JSGE).

In April 2000, Dr Watanabe accepted the position of Professor and Chairman, Department of Gastroenterology and Hepatology at Tokyo Medical and Dental University, where he currently serves. He also leads two other clinical gastroenterology divisions, the Department of Endoscopy and the Advanced Clinical Center for Inflammatory Bowel Disease. At Tokyo Medical and Dental University, his work continues to have a tremendous impact and he and his team have met numerous challenges both in the research field and in clinical care.

Dr Watanabe has used his expertise to mentor many co-investigators in clinical sciences and trials, to advance basic research and the principles of evidence-based medicine. His extraordinary professional standards always provide inspiration to all those with whom he works. This has built up the Division of Gastroenterology at Tokyo Medical and Dental University with talented faculty members and gastroenterologists, comprising an unprecedented intellectual environment. It is no surprise that his currently leading department has become an extremely popular GI center for training and research among Japanese schools and institutes.

Mamoru Watanabe's research interests are in immune-modulating therapy for IBD, cellular and molecular biological aspects of IBD, mucosal immunology, molecular biological aspects of inflammation-related carcinogenesis, and regeneration and differentiation of intestinal epithelial cells. Most recently, he has turned his attention to intestinal epithelial stem cell biology.

An early discovery was the recognition that interleukin (IL)-7 is an essential factor for the pathogenesis of IBD, being responsible for the persistence of chronic T cell-mediated colitis. Mamoru has shown that IL-7 is constitutively produced by intestinal goblet cells. He is the first scientist who found the critical role of IL-7 in mucosal immunology and this ground-breaking paper was published in the Journal of Clinical Investigation in 1995.[1] IL-7 transgenic mice develop colitis that mimics the histopathological characteristics of human IBD (J Exp Med 1998).[2] CD4+ T cells that express high levels of IL-7Rα reside in inflamed lamina propria (LP) (Journal of Immunology [JI] 2003, JI 2011) and IL-7–/– mice do not develop colitis (JI 2007). Further, IL-7 levels of colitic intestine are lower than in normal gut as a result of the disappearance of goblet cells (JI 2008).

On the basis of the latter observation, Watanabe hypothesized that CD4+ T cells are maintained outside the intestine as memory stem cells. Since spleen and lymph nodes were dispensable for the development of chronic colitis (JI 2007), he demonstrated that, CD4+ cells preferentially reside in bone marrow (BM) of colitic mice (Gastroenterology 2007, JI 2009).[3] Importantly, these resident BM CD4+ memory T cells are closely associated with IL-7-producing stromal cells (Gastroenterology 2007). He also demonstrated using intrarectal administration of CD4+ T cells that CD4+ T cells constantly recirculate from LP to BM (Gastroenterology 2011).[4] All of these findings indicate that the IL-7/IL-7R signal is an important target for therapy of IBD, which is a novel strategy to deplete pathogenic memory T cells. In addition, Dr Watanabe also clarified the role of co-stimulatory molecules such as CD86 (Gastroenterology 1999), B7-H1 (JI 2003), and ICOS (Gastroenterology 2003), cytokines such as IL-18 (Gastroenterology 2000), γδ T cells (PNAS 1999, Immunity 2000), B cells (Gastroenterology 2001, JI 2004) and regulatory T cells (JI 2003, JI 2004, JI 2007, JI 2009) for the pathogenesis of IBD.

Dr Watanabe next turned his attention to colitis-associated carcinogenesis, because he recognized that colon colitic cancer incidence in Asia is likely to increase in line with the increase of ulcerative colitis. First, Dr Watanabe has identified the specific gene expression (Cancer Res. 1999) and gene mutations (Cancer Res. 2003) only in colitis-associated colon cancer, suggesting the mechanism of colitis-associated carcinogenesis is different from sporadic colon carcinogenesis.

In further functional studies of carcinogenesis relevant to sporadic colorectal cancer, Dr Watanabe showed that aberrant Wnt signal directly suppressed the differentiation state of cancer to degrade the Atoh1 protein, which is the master gene for the differentiation of intestinal epithelial cells (Gastroenterology 2007).[5] More importantly, Dr Watanabe discovered that Atoh1 protein is co-expressed with beta-catenin and that inflammatory cytokines modulate Atoh1 protein stabilization in crosstalk between cytokine signaling and Wnt signaling (J Biol Chem. 2008). Finally, Dr Watanabe has obtained evidence that co-localization with Atoh1 and beta-catenin induces not only the mucinous phenotype but also the ‘cancer stemness’ and chemo-resistance in colitis-associated carcinogenesis. These studies prove that Atoh1 is involved in the malignant potential of carcinogenesis, a finding that has therapeutic implications for colitis-associated cancer.

In his recent research, Dr Watanabe has examined fundamental functions of intestinal stem cells, and how this impacts on regeneration of the intestinal mucosa. This is exemplified first by his studies of epithelial regeneration by bone marrow-derived cells, providing a striking idea that bone marrow-derived cells can be recruited to sites where epithelial damage has occurred, and at the same time contribute to epithelial regeneration by integrating themselves into the intestinal mucosa as epithelial cells. This result has been published in Nature Medicine 2002.[6] His group has further shown that such recruitment of bone marrow-derived cells acts as a unique ‘transit-rescue system’ in graft-versus-host disease patients, which functions completely independently from the residing intestinal stem cell system (Gastroenterology 2005).[7] The most recent ground-breaking studies of Dr Watanabe have opened a way not only to long-term culture of primary intestinal epithelial cells, but also to the use of those cells as a cellular source for transplantation. Specifically, Watanabe's group have established a sophisticated and well-optimized culture system for primary colonic epithelial cells; this is highly distinct from other studies, as Lgr5+ stem cells can be preferentially maintained at an extremely high concentration in vitro. Taking advantage of such a unique culture system, Dr Watanabe has successfully showed that transplantation of those cultured cells to dextran sodium sulphate (DSS)-colitis mice significantly improves the repair process of the damaged colonic mucosa, and subsequently results in long-term integration of donor-derived epithelial stem cells within the host colonic epithelium. He has also shown that such a ‘transplantation therapy’ can be started, and also accomplished from a single LGR5+ stem cell, thereby elegantly demonstrating the ‘power-of-one’ in intestinal regeneration. These results have been published in the April 2012 Issue of Nature Medicine.[8] Moreover, these studies have received attention from many investigators in the stem cell biology area. Nature has highlighted these works twice in the section of ‘Research Highlights’ and ‘NEWS and VIEWS’, and Science Translational Medicine highlights in the section of ‘Focus’.

As to his capabilities as a leader in biomedical publishing, Dr Watanabe has already proved that he is a great Editor-in-Chief by all the improvements he brought to the Journal of Gastroenterology (JG), the official journal of the JSGE, causing its impact factor to remarkably increase from 1.209 in 2004, to 4.160 in 2011. He had become an Editor-in-Chief in April 2005 and finished his 6-year term in March 2011. He was the youngest ever Editor-in-Chief of JG. This remarkable success depended on his team of associate editors. He had asked the president of the JSGE to increase the number of associate editors and change all members into young and promising investigators. With his continuous enthusiasm for JG and encouragement to associate editors, they applied tremendous hard efforts to establish JG as an international journal. Most of the associate editors were either associate or assistant professors at that time, but now more than half of them became full professors of departments of gastroenterology and hepatology in the many major universities in all over Japan.

Professor Mamoru Watanabe has made strenuous efforts to improve the peer review system. He introduced an on-line submission system to JG soon after he became Editor-in-Chief. He pushed associate editors to make a quick decision process, and subsequently the average time from submission to first decision in 2011 became 14 days. In his Editor-In-Chief term of JG, Dr Watanabe established strict initial evaluation processes by the editor, and leading by example, he himself made such an initial decision for 15–20 papers each week. More than 70% of the submitted papers were subjected to immediate rejection on the basis of unsuitability for publication. This category included most retrospective clinical studies that failed to establish new concepts, and some prospective clinical studies with only small numbers of subjects. With these efforts, the acceptance rate of JG decreased from 26% in 2004 to 16% in 2011. Watanabe also promoted JG to many leaders of gastroenterology and hepatology in other countries, especially at the time of international meetings. This resulted in a substantial increase in the number of submissions, from 361 in 2004 to 985 in 2011. In particular, the submission rate from abroad increased from 25% in 2004 to 63% in 2011. With his great efforts, we are sure that the impact factor of JGH will increase and reach 5.0 in 2–3 years.

Dr Watanabe is now a Councilor of the JSGE, responsible for establishing and revising clinical guidelines for all areas of gastroenterology and hepatology. He will be the Secretary-General of the 100th commemorative meeting for the JSGE in 2014. Mamoru Watanabe is one of the top leaders in the IBD area and has been serving as a chairman of The Research Committee of Inflammatory Bowel Disease, Research on Measures of Intractable Disease organized by the Japanese Ministry of Health, Labor and Welfare. He is also a committee member of the Science Council of Japan and councilors for many major medical societies, such as the Japanese Society of Internal Medicine, the Japan Gastroenterological Endoscopy Society, and the Japanese Society for Mucosal Immunology.

Dr Watanabe's activities are not limited to Japan. He has delivered numerous invited and honorary lectures on clinical and basic research at international meetings. He has been a councilor of the Immunology/Microbiology/IBD section of the AGA for years, and regularly chairs IBD sessions each year at Digestive Diseases Week (DDW) in the USA. In DDW 2012 San Diego, he had a chance to give a Meet-the-Investigator Luncheon for his excellent basic works. For his research area, he has been serving as the Councilor of the Society of Mucosal Immunology as a representative of the Asia-Pacific region for 4 years. In the IBD field, he has been one of 60 members of the International Organization for the Study of IBD (IOIBD), and was a member of European Crohn's and Colitis Organization (ECCO) Working Party for Gastro 2009, London. With these achievements, he has served as an editorial board member of Gastroenterology for 6 years, and now is on the editorial board of Current Opinion in Gastroenterology, a Section Editor for the Immunology Section of Inflammatory Bowel Diseases, and Associate Editor of Mucosal Immunology. In Asia, he has given many invited and honorary lectures on clinical and basic research in Korea and China. He is one of six key persons to establish a new society, the Asian Organization for Crohn's and Colitis (AOCC).

In relationship to JGH, Dr Watanabe first became subject editor in November 2010, and then coordinating editor in March 2012. He said that he would like to enjoy interactions with all editors from various parts of the Asian-Pacific region. Moreover, he promises to continue to promote JGH as a journal, which brings the region together. He also sincerely hopes that JGH will well meet the requirements of many enthusiastic young doctors and scientists in this region, and may become a good platform from which they can send their well-timed information about new scientific progress. Professor Mamoru Watanabe enjoys the full confidence of his peers about his efficient handling and fair judgment on scientific and publishing matters. During his tenure as Editor-in-Chief, JGH will continue to attract high quality articles that advance the science and practice of gastroenterology and hepatology. With his great efforts, we are sure that the impact factor of JGH will continue to rise and become the no. 1 journal, at least in the Asia-Pacific region in a few years.

Mamoru Watanabe indicates that he owes his great success in large part to great and generous mentors and many talented GI fellows and postdoctoral fellows. Equally important, however, has been the support of his wife Michiko Watanabe and his son Satoshi Watanabe, who constantly help him with great understanding. Mamoru's long marriage to Michiko and his son remain phenomenal. I know his son is on track to become the next medical scientist in the family.

Dr Watanabe has one of the most notable reputations in the world in the gastroenterology research field. I am sure that he will be a leader of gastroenterology in both clinical and research fields in Japan, and also in international societies. He has been an extremely diligent and enthusiastic clinician who has shown considerable interest in gastroenterology work. I have no doubt that he has the intellectual skills and desire to succeed as an Editor-in-Chief of JGH. It is difficult to imagine a more appropriate candidate to hold such an important position in Asia. I would be extremely happy if everyone in the Asian Pacific region would help him to succeed as an Editor-in-Chief of JGH.

References

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  2. References
  • 1
    Watanabe M, Ueno Y, Yajima T et al. Interleukin-7 is produced by human intestinalepithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J. Clin. Invest. 1995; 95: 29452953.
  • 2
    Watanabe M, Ueno Y, Yajima T et al. Interleukin-7 transgenic mice develop chronic colitis with decrease of interleukin-7 protein accumulation in the colonic mucosa. J. Exp. Med. 1998; 187: 389402.
  • 3
    Nemoto Y, Kanai T, Makita S et al. Bone marrow retaining colitogenic CD4+ T cells may be a pathogenic reservoir for chronic colitis. Gastroenterology 2007; 132: 176189.
  • 4
    Nemoto Y, Kanai T, Shinohara T et al. Luminal CD4+ T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation. Gastroenterology 2011; 141: 21302139.
  • 5
    Tsuchiya K, Nakamura T, Okamoto R, Kanai T, Watanabe M. Reciprocal targeting of Hath1 and β-catenin by Wnt-glycogen synthase kinase 3b in human colon cancer. Gastroenterology 2007; 132: 208220.
  • 6
    Okamoto R, Yajima T, Yamazaki M et al. Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract. Nat. Med. 2002; 8: 10111017.
  • 7
    Matsumoto T, Okamoto R, Yajima T et al. Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine. Gastroenterology 2005; 128: 18511867.
  • 8
    Yui S, Nakamura T, Sato T et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell. Nat. Med. 2012; 18: 618623.