荻野周史

荻野周史（，），主要从事病理学，流行病学和分子病理流行病学研究。目前在哈佛医学院，布莱根妇女医院和丹娜法伯癌症研究院及哈佛陈曾熙公共卫生学院担任教授。荻野首次提出（MPE）这一学科概念，该学科是分子病理学和流行病学的交叉学科。

生平
于1993年获得东京大学医学院学士学位，于1994-1995年在冲绳美国海军医院实习，随后赴美，并分别在卓克索大學阿勒格尼总医院（1995-1997）及凯斯西储大学/克利夫兰大学医院（1997-1999）完成病理解剖和临床病理住院医师培训，1999-2000年在宾夕法尼亚大学医学中心进行分子病理学研究。2001年获得东京大学研究院医学系博士学位后继续在该中心从事博士后研究，2001-2004在丹娜法伯癌症研究院，布莱根妇女医院和哈佛医学院担任病理学讲师，2004年晋升为助理教授，2008年晋升为副教授，2015年晋升为丹娜法伯癌症研究院教授。继2011年在哈佛陈曾熙公共卫生学院获得流行病学硕士学位后，被任命为该学院的流行病学副教授，并2015年晋升为教授。

 研究领域和成果 
荻野于2010年首次提出 “分子病理流行病学（MPE）”Ogino S, Stampfer M.  Lifestyle factors and microsatellite instability in colorectal cancer: the evolving field of molecular pathological epidemiology. J Natl Cancer Inst 2010;102:365-367.这一概念。他认为将分子病理学研究带入流行病学研究的框架是一个独特的研究领域。此后，MPE这一概念被广泛采纳Curtin K, Slattery ML, Samowitz WS (2011). "CpG island methylation in colorectal cancer: past, present and future". Pathology Research International 2011: 902674. doi:10.4061/2011/902674. PMC 3090226. PMID 21559209.Galon J, Pagès F, Marincola FM, Angell HK, Thurin M, Lugli A, Zlobec I, Berger A, Bifulco C, Botti G, Tatangelo F, Britten CM, Kreiter S, Chouchane L, Delrio P, Arndt H, Asslaber M, Maio M, Masucci GV, Mihm M, Vidal-Vanaclocha F, Allison JP, Gnjatic S, Hakansson L, Huber C, Singh-Jasuja H, Ottensmeier C, Zwierzina H, Laghi L, Grizzi F, Ohashi PS, Shaw PA, Clarke BA, Wouters BG, Kawakami Y, Hazama S, Okuno K, Wang E, O'Donnell-Tormey J, Lagorce C, Pawelec G, Nishimura MI, Hawkins R, Lapointe R, Lundqvist A, Khleif SN, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Palmqvist R, Nagtegaal ID, Wang Y, D'Arrigo C, Kopetz S, Sinicrope FA, Trinchieri G, Gajewski TF, Ascierto PA, Fox BA (2012). "Cancer classification using the Immunoscore: a worldwide task force". Journal of Translational Medicine 10: 205. doi:10.1186/1479-5876-10-205. PMC 3554496. PMID 23034130.Ku CS, Cooper DN, Wu M, Roukos DH, Pawitan Y, Soong R, Iacopetta B (August 2012). "Gene discovery in familial cancer syndromes by exome sequencing: prospects for the elucidation of familial colorectal cancer type X". Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc 25 (8): 1055–68. doi:10.1038/modpathol.2012.62. PMID 22522846.Koshiol J, Lin SW (July 2012). "Can tissue-based immune markers be used for studying the natural history of cancer?". Annals of Epidemiology 22 (7): 520–30. doi:10.1016/j.annepidem.2012.03.001. PMC 3596808. PMID 22481034.Fini L, Grizzi F, Laghi L (2012). Ettarh R, ed. Adaptive and Innate Immunity, Non Clonal Players in Colorectal Cancer Progression. InTech. pp. 323–40. ISBN 9789535100621.Dogan S, Shen R, Ang DC, Johnson ML, D'Angelo SP, Paik PK, Brzostowski EB, Riely GJ, Kris MG, Zakowski MF, Ladanyi M (November 2012). "Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers". Clinical Cancer Research 18 (22): 6169–77. doi:10.1158/1078-0432.CCR-11-3265. PMC 3500422. PMID 23014527.Spitz MR, Caporaso NE, Sellers TA (December 2012). "Integrative cancer epidemiology--the next generation". Cancer Discovery 2 (12): 1087–90. doi:10.1158/2159-8290.CD-12-0424. PMC 3531829. PMID 23230187.Shanmuganathan R, Basheer NB, Amirthalingam L, Muthukumar H, Kaliaperumal R, Shanmugam K (January 2013). "Conventional and nanotechniques for DNA methylation profiling". The Journal of Molecular Diagnostics : JMD 15 (1): 17–26. doi:10.1016/j.jmoldx.2012.06.007. PMID 23127612.Hughes LA, Melotte V, de Schrijver J, de Maat M, Smit VT, Bovée JV, French PJ, van den Brandt PA, Schouten LJ, de Meyer T, van Criekinge W, Ahuja N, Herman JG, Weijenberg MP, van Engeland M (October 2013). "The CpG island methylator phenotype: what's in a name?". Cancer Research 73 (19): 5858–68. doi:10.1158/0008-5472.CAN-12-4306. PMID 23801749.Hagland HR, Søreide K (March 2014). "Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut microbiome and metabolic pathways". Cancer Letters. doi:10.1016/j.canlet.2014.02.026. PMID 24614287.Bishehsari F, Mahdavinia M, Vacca M, Malekzadeh R, Mariani-Costantini R (May 2014). "Epidemiological transition of colorectal cancer in developing countries: environmental factors, molecular pathways, and opportunities for prevention". World Journal of Gastroenterology : WJG 20 (20): 6055–72. doi:10.3748/wjg.v20.i20.6055. PMC 4033445. PMID 24876728. ，并且成为美国癌症研究协会（AACR）Ogino S. Molecular pathological epidemiology (MPE): Overview of its paradigm and wide applicability even without tumor tissue. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Cancer Prev Res (Phila). 2013;6(11 suppl):CN06-1.  ，流行病学研究协会（SER）Kuller LH, Bracken MB, Ogino S, Prentice RL, Tracy RP. The role of epidemiology in the era of molecular epidemiology and genomics: Summary of the 2013 AJE-sponsored Society of Epidemiologic Research Symposium. Am J Epidemiol. 2013;178(9):1350-4.和美国预防肿瘤学会（ASPO）Epplein M, Bostick RM, Mu L, Ogino S, Braithwaite D, Kanetsky PA. Challenges and Opportunities in International Molecular Cancer Prevention Research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report. Cancer Epidemiol Biomarkers Prev. 2014;23(11):2613-7. doi: 10.1158/1055-9965.EPI-14-0848. Epub 2014 Oct 2.等国际会议的专题。MPE是采用分子病理学流行病学的方法从分子、个体和群体的水平进行病因学的研究。通过对现有的流行病学研究中组织样本和数据的研究分析，荻野发表了大量的文章论述危险因素（如环境、饮食、生活方式和遗传因素等）的暴露和疾病的分子病理学特征之间的相互关系（例如，携带PIK3CA突变基因的结直肠癌），其中很多发现 Chan AT, Ogino S, Fuchs CS. Aspirin use and risk of colorectal cancer according to cyclooxygenase-2 expression. N Engl J Med 2007;356:2131-42.Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. JAMA 2009;302:649-658.Morikawa T, Kuchiba A, Yamauchi M, Meyerhardt JA, Shima K, Nosho K, Chan AT, Giovannucci E, Fuchs CS, Ogino S. Association of CTNNB1 (β-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer. JAMA 2011;305:1685-1694. PMCID:PMC3087286109Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, Davis A, Mongare MM, Gould J, Frederick DT, Cooper ZA, Chapman PB, Solit DB, Ribas A, Lo RS, Flaherty KT, Ogino S, Wargo JA, Golub TR. Tumor microenvironment contributes to innate RAF-inhibitor resistance through HGF secretion.  Nature 2012;487:500-504. PMCID:PMC3711467Nishihara R, Lochhead P, Kuchiba A, Jung S, Yamauchi M, Liao X, Imamura Y, Qian ZR, Morikawa T, Wang M, Spiegelman D, Cho E, Giovannucci E, Fuchs CS, Chan AT, Ogino S. Aspirin use and colorectal cancer incidence risk according to BRAF mutation status. JAMA 2013;309:2563-2571.Ogino S, Liao X, Imamura Y, Yamauchi M, McCleary NJ, Ng K, Niedzwiecki D, Saltz LB, Mayer RJ, Whittom R, Hantel A, Benson III AB, Mowat RB, Spiegelman D, Goldberg RM, Bertagnolli MM, Meyerhardt JA, Fuchs CS, for the Alliance for Clinical Trials in Oncology. Predictive and prognostic analysis of PIK3CA mutation in stage III colon cancer intergroup trial. J Natl Cancer Inst 2013;105:1789-1798.Barry ER, Morikawa T, Butler BL, Shrestha K, de la Rosa R, Yan KS, Fuchs CS, Magness ST, Smits R, Ogino S, Kuo CJ, Camargo FD.  Restriction of intestinal stem cell expansion and the regenerative response by YAP. Nature 2013;493:106-110. PMCID:PMC3536889Fink SP, Yamauchi M, Nishihara R, Jung S, Kuchiba A, Wu K, Cho E, Giovannucci E, Fuchs CS, Ogino S, Markowitz SD, Chan AT. Aspirin and the risk of colorectal cancer in relation to the expression of 15-hydroxyprostaglandin dehydrogenase (HPGD). Sci Transl Med 2014;6:233re2.以及阐述 MPE的概念Ogino S, Galon J, Fuchs CS, Dranoff G. Cancer immunology – integrated analysis of host and tumor factors for personalized medicine. Nat Rev Clin Oncol 2011:8:711-719.Ogino S, King EE, Beck AH, Sherman ME, Milner DA, Giovannucci E. Interdisciplinary education to integrate pathology and epidemiology: Towards molecular and population-level health science. Am J Epidemiol 2012;176:659-667.Ogino S, Giovannucci E. Lifestyle factors and colorectal cancer microsatellite instability – Molecular pathological epidemiology science, based on unique tumour principle. Int J Epidemiol 2012;41:1072-1074.Ogino S, Fuchs CS, Giovannucci E. How many molecular subtypes? Implications of the unique tumor principle in personalized medicine. Expert Rev Mol Diagn  2012;12:621-628.Ogino S, Lochhead P, Chan AT, Nishihara R, Cho E, Wolpin BM, Meyerhardt JA, Meissner A, Schernhammer ES, Fuchs CS, Giovannucci E (April 2013). "Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease". Modern Pathology 26(4): 465–84.Field AE, Camargo Jr CA, Ogino S. The merits of subtyping obesity: one size does not fit all. JAMA 2013;310:2147-2148.Ogino S, Lochhead P, Giovannucci E, Meyerhardt JA, Fuchs CS, Chan AT. Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology. Oncogene 2014;33:2949-2955.Lochhead P, Chan AT, Giovannucci E, Fuchs CS, Wu K, Nishihara R, O’Brien M, Ogino S. Progress and opportunities in molecular pathological epidemiology of colorectal premalignant lesions. Am J Gastroenterol 2014;109(8):1205-1214. 的文章都发表在该领域具有影响力的杂志上。通过MPE的研究方法荻野发现了阿司匹林可以增加携带PIK3CA基因突变的结直肠癌患者的生存期 Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, Meyerhardt JA, Giovannucci E, Fuchs CS, Chan AT, Ogino S. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med 2012;367:1596-1606. ，内镜筛查有助于降低结肠癌的发病率和死亡率，以及结肠镜检5年内发生的大肠癌与其CIMP（CpG 岛甲基化表型）和MSI （微卫星不稳定性）有关Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, Inamura K, Kim SA, Kuchiba A, Yamauchi M, Imamura Y, Willett WC, Rosner BA, Fuchs CS, Giovannucci E, Ogino S, Chan AT.  Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013;369:1095-1105.。Ogino 于2013年举办首届分子病理流行病学（MPE）会议，并于2014年12月4-5号在波士顿召开第二次会议The Ogino MPE lab ( http://ogino-mpe-lab.dana-farber.org  )Ogino S, Campbell PT, Nishihara R, Phipps AI, Beck AH, Sherman ME, Chan AT, Troester MA, Bass AJ, Fitzgerald KC, Irizarry RA, Kelsey KT, Nan H, Peters U, Poole EM, Qian ZR, Tamimi RM, Tchetgen Tchetgen EJ, Tworoger SS, Zhang X, Giovannucci EL, van den Brandt PA, Rosner BA, Wang M, Chatterjee N, Begg CB.，
 。

荻野采用MPE的研究方法提出在大肠癌研究模型从两段式结肠模型（近段和远段结肠）Iacopetta B. Are there two sides to colorectal cancer? Int J Cancer. 2002;101:403–8.
Gervaz P, Bucher P, Morel P. Two colons-two cancers: paradigm shift and clinical implications. J Surg Oncol. 2004;88:261–6.
Carethers JM. One colon lumen but two organs. Gastroenterology. 2011;141:411–2.
Albuquerque C, Bakker ER, van Veelen W, et al. Colorectal cancers choosing sides. Biochim Biophys Acta. 2011;1816:219–31.到大肠连续模型Yamauchi M, Lochhead P, Morikawa T, Huttenhower C, Chan AT, Giovannucci E, Fuchs C, Ogino S. Colorectal cancer: a tale of two sides or a continuum? Gut. 2012 Jun;61(6):794-7.的转变。该假设是通过对 1400多例大肠癌病例分析，得出不同部位的结肠癌与其微卫星不稳定（MSI），CpG岛甲基化表型（CIMP）和BRAF突变频率呈线性关系Yamauchi M, Morikawa T, Kuchiba A, Imamura Y, Qian ZR, Nishihara R, Liao X, Waldron L, Hoshida Y, Huttenhower C, Chan AT, Giovannucci E, Fuchs CS, Ogino S. Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut 2012;61:847-854. PMCID:PMC3345105 ，这一大肠连续模型已得到支持 Jess P, Hansen IO, Gamborg M, Jess T; Danish Colorectal Cancer Group. A nationwide Danish cohort study challenging the categorisation into right-sided and left-sided colon cancer. BMJ Open. 2013 May 28;3(5).Papagiorgis P. Colorectal cancer: dichotomous or continuum model? Perhaps, a combination of both. Gut. 2013 Oct;62(10):1519-20.。
此外，荻野还提出了一些新的研究模式，包括“GWAS-MPE” Ogino S, Chan AT, Fuchs CS, Giovannucci E. Gut. 2011 Mar;60(3):397-411. doi: 10.1136/gut.2010.217182. Epub 2010 Oct 29. Review. PMID 21036793 Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field. ，“ 独特肿瘤原则”Ogino S, Fuchs CS, Giovannucci E. Expert Rev Mol Diagn. 2012 Jul;12(6):621-8. doi: 10.1586/erm.12.46. Review. PMID 22845482 How many molecular subtypes? Implications of the unique tumor principle in personalized medicine.  ，“独特疾病原则”Ogino S, Lochhead P, Chan AT, Nishihara R, Cho E, Wolpin BM, Meyerhardt JA, Meissner A, Schernhammer ES, Fuchs CS, Giovannucci E. Mod Pathol. 2013 Apr;26(4):465-84. doi: 10.1038/modpathol.2012.214. Epub 2013 Jan 11. Review. PMID 23307060 Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease. ，“病因场效应模型” Lochhead P, Chan AT, Nishihara R, Fuchs CS, Beck AH, Giovannucci E, Ogino S. Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression. Mod Pathol. 2015;28(1):14-29. doi: 10.1038/modpathol.2014.81. Epub 2014 Jun 13. PMID 24925058. （即多种治病因素包括饮食、生活方式、环境、微生物、激素和基因等及其相互作用下的形成肿瘤易感组织微环境，致使肿瘤形成、演化和进展）以及“生命历程流行病学 - MPE模型”Nishi A, Kawachi I, Koenen KC, Wu K, Nishihara R, Ogino S. Lifecourse epidemiology and molecular pathological epidemiology. Am J Prev Med 2015;48:116-119. ，所有这些模型都与MPE领域相关。

 荣誉 
 2004年，分子病理学协会（AMP），总裁奖 
 2011年，美国加拿大病理学协会，拉姆兹•科特兰青年研究奖
 2012年，分子病理学协会（AMP），功勋奖
 2014年，汤森路透 The world’s Most Influential Minds:2014
 () Thomson Reuter. Retrieved September 5, 2014.， 最具影响力的科学家
 2014年，美国临床调查协会（ASCI），委员
 2014年，美国实验生物学会联合会杰出科学奖委员会http://www.faseb.org/About-FASEB/Who-We-Are/Governance/Board-Ordinary-Committees.aspx 
           Retrieved September 15, 2014.，委员
 外部链接 
Harvard T.H. Chan School of Public Health faculty profile (http://www.hsph.harvard.edu/shuji-ogino/ )
The Ogino MPE lab ( https://web.archive.org/web/20190515032651/http://ogino-mpe-lab.dana-farber.org/ )
Dana-Farber/ Harvard Cancer Center faculty profile( http://www.dfhcc.harvard.edu/membership/profile/member/1099/0/ )
Brigham & Women’s Hospital faculty profile (http://researchfaculty.brighamandwomens.org/BRIProfile.aspx?id=5797 )
Harvard University faculty directory(http://www.harvard.edu/faculty）

 参考文献 

Category:日本病理学家
Category:東京大學校友
Category:哈佛大学教授
Category:哈佛医学院教师
Category:日本医学家
Category:在美国的日本学者
Category:哈佛公共衛生學院校友