Shuji Ogino
Associate Professor in the Department of Epidemiology
Department of Epidemiology
The Molecular Pathological Epidemiology Laboratory (The MPE Laboratory)
The relationship between exposures and molecular changes in tumors has been examined for decades (eg, smoking -> KRAS mutation), usually under the umbrella of “molecular epidemiology”. However, this type of analysis needs a consideration of disease heterogeneity (eg, KRAS mutation present vs. absent), which necessitates a paradigm shift from conventional epidemiology. Conventional epidemiology is based on the premise that individuals with a given disease (by name) are homogeneous and can be lumped together to analyze exposure associations.
Considering this paradigm shift, “Molecular Pathological Epidemiology (MPE)” (or Molecular Pathologic Epidemiology) has been coined for integrative science which can consider inherent disease heterogeneity in epidemiology research (Ogino et al. J Natl Cancer Inst 2010; Ogino et al. Gut 2011; Ogino et al. Nat Rev Clin Oncol 2011; Ogino et al. Int J Epidemiol 2012; Ogino et al. Am J Epidemiol 2012). MPE is an interdisciplinary and transdisciplinary field of science, conceptually defined as “epidemiology of molecular heterogeneity of disease” (Ogino et al. Oncogene in press). MPE encompasses ALL HUMAN DISEASES (just as pathology and epidemiology encompass the entire spectrum of human illnesses) (Ogino et al. Mod Pathol 2013). I have been advancing the MPE field as the first “Molecular Pathological Epidemiologist (MPEist, MPE’ist, MPE-ist)” (Ogino et al. Am J Epidemiol 2012). The power and promise of MPE has been well attested by our recent study (Liao et al. N Engl J Med 2012) which discovered an interactive effect of aspirin use and colorectal cancer PIK3CA mutation on tumor behavior. As I am a unique faculty in pathology (Harvard Medical School) and epidemiology (Harvard School of Public Health), my long-term goal is to transform pathology and epidemiology into an integrative science for both education and research.
In MPE, we try to dissect complex interrelationship between; (1) environmental, dietary, lifestyle and genetic factors; (2) alterations in the tumor microenvironment and cellular molecules; and (3) disease pathways and evolution. MPE encompasses all human diseases (most of which are complex multifactorial diseases), and takes into account genome, epigenome, methylome, transcriptome, proteome, metabolome, microbiome, metagenome, reactome, and interactome. MPE is based on the “Unique Tumor Principle” (Ogino et al. Expert Rev Mol Diagn 2012) and more broadly, the “Unique Disease Principle” (Ogino et al. Mod Pathol 2013). MPE design can be used as the next step of genome-wide association study (GWAS) (“GWAS-MPE Approach”; Ogino et al. Gut 2011; Garcia-Albeniz et al. Carcinogenesis 2013). Other new concepts related to MPE include “Colorectal Continuum Paradigm / Theory / Hypothesis” (Yamauchi, Morikawa, et al. Gut 2012; Yamauchi, Lochhead, et al. Gut 2012), which underscores the importance of interplay of gut microbiota, host factors (diet, immunity, inflammation, etc.), and carcinogenesis. This novel “Colorectal Continuum Paradigm” has a considerable impact on gastrointestinal research and clinical practice. The MPE paradigm has been accepted worldwide (e.g., Hughes et al. PLoS ONE 2011; Hughes et al. Int J Epidemiol 2012; Curtin et al. Pathol Res Int 2011; Kelley et al. JNCCN 2011; Ku et al. Mod Pathol 2012; Kanthan et al. Pathol Res Int 2012; Rex et al. Am J Gastroenterol 2012; Koshiol et al. Ann Epidemiol 2012; Greystoke et al. Gastroenterol Res Practice 2012; Chia et al. Nat Rev Clin Oncol 2012; Spitz et al. Cancer Discovery 2012; Beggs et al. J Pathol 2013; Rosty et al. Mod Pathol 2013; Lam et al. Cancer Epidemiol Biomarkers Prev 2013; Campbell
et al. J Clin Oncol 2013; Weijenberg et al. Curr Nutr Rep 2013; Buchanan et al. Cancer Epidemiol Biomarkers Prev 2013; Burnett-Hartman et al. Cancer Res 2013).
A similar concept “etiologic heterogeneity” has been developed by Dr. Colin Begg (Int J Cancer 2011; Am J Epidemiol 2012). Drs. Margaret Spitz, Neil Caporaso, and Thomas Sellers have named “integrative epidemiology” to describe integration of molecular and genomic analyses (exposures and tumors) into epidemiology (Cancer Discovery 2012). This “integrative epidemiology” encompasses MPE and conventional molecular epidemiology.
We have been utilizing comprehensive databases of two large U.S. nationwide prospective cohort studies, the Nurses’ Health Study (N=121,000 followed since 1976) and the Health Professionals Follow-up Study (N=51,500 followed since 1986), as well as CALGB trials (Alliance for Clinical Trials in Oncology). Our discoveries by the MPE approach include (to mention just several); influence of the tumor microenvironment on tumor phenotype (Straussman et al. Nature 2012); YAP1 (yes-associated protein 1; or YAP) in colorectal cancer (Barry et al. Nature 2013); interactions between aspirin use and PTGS2 (cyclooxygenase-2, COX-2) expression in colorectal cancer (Chan et al. New Engl J Med 2007; Chan et al. JAMA 2009); interactions between obesity (host energetics) and FASN (fatty acid synthase) expression in colorectal cancer (Ogino et al. J Clin Oncol 2008; Kuchiba et al. J Natl Cancer Inst 2012); interactions between host energetics and CTNNB1 (b-catenin) activation in colorectal cancer (Morikawa et al. JAMA 2011; Morikawa et al. Cancer Res 2013); LINE-1 (long interspersed nucleotide element-1) hypomethylation and colon cancer aggression (Ogino et al. J Natl Cancer Inst 2008) and colorectal cancer family history (Ogino et al. J Natl Cancer Inst 2013); one-carbon nutrients, alcohol and colon cancer risk according to TP53 (p53) status and LINE-1 methylation level (Schernhammer et al. Gastroenterology 2008; Schernhammer et al. Gut 2010); fusobacterium (microbiota) in colorectal cancer (Kostic et al. Genome Res 2012); CDK8 in colorectal cancer (Firestein et al. Nature 2008; Firestein et al. Int J Cancer 2010); VTI1A-TCF7L2 fusion (translocation) in colorectal cancer (Bass et al. Nat Genet 2011). In summary, a better understanding of heterogeneity of carcinogenic processes and influences of exogenous and endogenous factors will further contribute to personalized prevention as well as personalized treatment strategy.
To transform pathology and epidemiology by the integrative MPE field and concept, I recently launched three programs. (1) The MPE Working Group (MPE WG) aims to establish standardized methodologies in MPE research. The MPE WG currently consists of researchers in the MPE areas, including biostatistics experts such as Drs. Donna Spiegelman, Molin Wang, and Bernard Rosner. (2) International Molecular Pathological Epidemiology (MPE) Meeting aims to gather selected experts and discuss ways to advance this transdisciplinary science. The first meeting in Boston on April 24, 2013 (my birthday) went very successfully. My plan is to apply for R13/U13 for the second meeting to have a larger group of both epidemiologists and pathologists. (3) The “STROBE-MPE” initiative (Ogino et al. Am J Epidemiol 2012) is an extension of STROBE, which stands for “STrengthening of the Reporting of OBservational Epidemiology” (von Elm et al. PLoS Med 2007), and is an international guideline for epidemiology research. I always call for collaboration in this STROBE-MPE international initiative. In addition, (4) I am a member of Education and Professional Development Committee (chaired by Dr. Jay Kaufman) of Society for Epidemiologic Research (SER) to address paucity of interdisciplinary education opportunities.
The second focus of my research (which is very much related to MPE) is epigenetics and epigenomics of colorectal cancer. We have found that LINE-1 hypomethylation is highly correlated with mortality in colorectal cancer (Ogino et al. J Natl Cancer Inst 2008); that LINE-1 hypomethylated colorectal cancer is associated with family history of colorectal cancer (Ogino et al. J Natl Cancer Inst 2013); and that it is preventable by folate (leafy vegetables) and avoidance of excessive alcohol consumption (Schernhammer et al. Gut 2010). I have been characterizing the CpG island methylator phenotype (CIMP), a unique molecular phenotype in colorectal cancer. Especially, my investigation led to the discovery of “CIMP-low (CIMP-L)”, a unique phenotype in colorectal cancer which is associated with KRAS mutation (Ogino et al. J Mol Diagn 2006), which was confirmed by other investigators including Peter Laird’s group (Hinoue et al. Genome Res 2012). We were the first to apply “structural equation modeling (SEM)” to correlation structure analysis of CpG island methylation and genetic changes in colorectal cancer (Tanaka et al. Am J Pathol 2010). We have been deciphering prognostic roles of CIMP, MSI, KRAS, BRAF and PIK3CA mutations, and immune reactions in colorectal cancer (Ogino et al. J Clin Oncol 2009; Ogino et al. Gut 2009; Ogino et al. Clin Cancer Res 2009; Nosho et al. J Pathol 2010; Ogino et al. Clin Cancer Res 2012; Liao et al. Clin Cancer Res 2012; Imamura et al. Clin Cancer Res 2012).
Upcoming Events of MPE
(September 11, 2013)
MPE Working Group Meeting, at Kresge 907, Harvard School of Public Health, Boston, MA
(September 26, 2013)
Keynote Lecture (Shuji Ogino) “Molecular Pathological Epidemiology (MPE): A Paradigm Shift to Address Heterogeneity of Disease Etiologies and Pathogenesis” at German Society of Epidemiology (DGEpi) Annual Meeting in Leipzig, Germany.
(October 29, 2013)
MPE Session [“Molecular Pathological Epidemiology (MPE): Integrative Interdisciplinary Science”] chaired by Shuji Ogino at 12th Annual AACR Frontiers in Cancer Prevention Research Meeting in National Harbor, MD.
1st lecture (Shuji Ogino): “Molecular Pathological Epidemiology (MPE): Overview of Its Paradigm and Wide Applicability Even without Tumor Tissue”
2nd lecture (Peter Campbell, American Cancer Society): “Insight into the role of lifestyle in colorectal cancer etiology though molecular pathological epidemiology: Unmasking the links with obesity and smoking”
3rd lecture (Celeste Leigh Pearce, University of Southern California): “Integrating epidemiological, pathological, clinical and omic data in ovarian cancer”
http://www.aacr.org/home/scientists/meetings–workshops/frontiers-in-cancer-prevention-research.aspx
(October 30, 2013)
Lecture (Shuji Ogino) “Tumor Biomarker Discovery for Aspirin Chemoprevention by Molecular Pathological Epidemiology (MPE) Approach” in Plenary Session (“Inflammation”) chaired by Raymond DuBois at 12th Annual AACR Frontiers in Cancer Prevention Research Meeting in National Harbor, MD.
http://www.aacr.org/home/scientists/meetings–workshops/frontiers-in-cancer-prevention-research.aspx
(November 6, 2013)
MPE Working Group Meeting, at Kresge 907, Harvard School of Public Health, Boston, MA
(November 14, 2013)
Lecture (Shuji Ogino) on biostatistics for molecular pathologists / diagnosticians at Association for Molecular Pathology (AMP) Annual Meeting in Phoenix, AZ.
http://www.2013amp.org/preliminary_program.cfm
(Fall 2013)
Lecture (Reiko Nishihara, HarvardSchool of Public Health, Dana-Farber Cancer Institute) “Molecular Pathological Epidemiology (MPE) of Cancer: Findings on Aspirin, Colonoscopy, Smoking and More!” (tentative title), in Work-in-Progress Lecture Series, Dept. of Epidemiology, HarvardSchool of Public Health, Boston, MA
(January 8, 2014)
MPE Working Group Meeting, at Kresge 907, Harvard School of Public Health, Boston, MA
(March 12, 2014)
Lecture (Shuji Ogino) “Molecular Pathological Epidemiology (MPE): Integrative Science to Analyze Environment, Host and Cancer” hosted by Curtis Harris, at National Cancer Institute (NCI), National Institute of Health (NIH), Bethesda, MD.
Education
1993 (MD) University of Tokyo
2001 (PhD) University of Tokyo
2010 (MS in Epidemiology) Harvard School of Public Health
Hospital and academic appointments, and other roles
1995-1997 Resident in Pathology, AlleghenyGeneralHospital, DrexelUniversity, Pittsburgh, PA
1997-1999 Resident in Pathology, CaseWestern ReserveUniversity, Cleveland, OH
1999-2001 Molecular Pathology Fellow and Postdoctoral Fellow, University of Pennsylvania
2001-2004 Instructor in Pathology, HarvardMedicalSchool, and Dana-Farber Cancer Institute
2001- Pathologist, Brigham and Women’s Hospital, Boston, MA
2003- Member, Cancer Epidemiology Program, Dana-Farber / HarvardCancerCenter
2003- Member, Gastrointestinal Malignancies Program, Dana-Farber / HarvardCancerCenter
2004-2008 Assistant Professor of Pathology, HarvardMedicalSchool, and Dana-Farber Cancer Institute
2008- Associate Professor of Pathology, HarvardMedicalSchool, and Dana-Farber Cancer Institute
2012- Associate Professor, Department of Epidemiology, HarvardSchool of Public Health
2012- Head, The Molecular Pathological Epidemiology Laboratory (The MPE Lab)
2012- Leader, Molecular Pathological Epidemiology (MPE) Working Group
Awards and Honors
2004 Executive Officer’s Award, from Association for Molecular Pathology (AMP)
2011 Ramzi Cotran Young Investigator Award, from United States and CanadianAcademy of Pathology (USCAP)
2012 Meritorious Service Award, from Association for Molecular Pathology (AMP)
Office Address
Department of Medical Oncology
Dana-Farber Cancer Institute
450 Brookline Ave., Room M422
Email: shuji_ogino@dfci.harvard.edu
Administrator / Secretary:
Ms. Yumiko Fujita
Department of Medical Oncology
Dana-Farber Cancer Institute
450 Brookline Ave., Room M422A
Tel: 617-632-1972
Fax: 617-582-8558
Email: yumiko_fujita@dfci.harvard.edu
Members of The Ogino Lab
[The MPE Laboratory - Interdisciplinary multi-institutional Lab - Dana-Farber Cancer Institute (DFCI), Brigham and Women's Hospital (BWH), Harvard Medical School (HMS), and Harvard School of Public Health (HSPH)]
Research fellows and other trainees (background, expertise)
Ran Gao, MS (DFCI) (Biostatistics)
Kentaro Inamura, MD, PhD (DFCI / HMS) (Liaison from/to Curtis Harris Lab, NCI / NIH) (Pathology)
Seungyoun Jung, ScD (BWH / HMS) (Epidemiology, Nutrition)
Sun A Kim, MD, PhD (DFCI / HMS) (Pathology)
Ting-Ting Li, MD (DFCI / HMS) (Gastroenterology)
Kosuke Mima, MD, PhD (DFCI / HMS) (GI Surgery)
Akihiro Nishi, MD, DrPH (HSPH) (Liaison from Ichiro Kawachi Lab) (Social Epidemiology)
Reiko Nishihara, PhD, RN, MW, PHN (DFCI / HMS / HSPH) (Epidemiology, Nursing)
Zhi Rong Qian, MD, PhD (DFCI / HMS) (Pathology)
Sung Kwan Shin, MD (DFCI / HMS) (Gastroenterology)
Yasutaka Sukawa, MD, PhD (DFCI / HMS) (Gastroenterology)
Mai Yamauchi, PhD (DFCI / HMS) (Cancer Biology)
Students
Temitope Agabalogun (HarvardCollege)
Kathryn Fitzgerald, MS (HSPH ScD course in Epidemiology / Nutrition)
Research Assistant
Yumiko Fujita (DFCI, Administrative Assistant)
Associated members
Gregory J Kirkner, MPH (BWH, Project Manager of the Nurses’ Health Study)
Kaori Sato, MS (DFCI, Biostatistician at Gastrointestinal Cancer Center)
Kana Wu, MD, PhD (HSPH, Senior Research Scientist)
Xuehong Zhang, MB, ScD (BWH/HMS, Instructor in Medicine)
The Ogino Lab Alumni (past members, including liaisons from/to collaborating labs)
Yoshifumi Baba (2008-2010)
Mohan Brahmandam (2002-2006)
Mami Cantor (2001-2005, 2009)
Inga Dorfman (2005-2006)
Ron Firestein (William Hahn Lab) (2008-2009)
Kevin Golden (2009-2010)
Marika Hayashi (2009-2010)
Yu Imamura (2010-2013)
Natsumi Irahara (2008-2009)
Takako Kawasaki (2003-2008)
Aya Kuchiba (2010-2013)
Shoko Kure (2008-2009)
Jinbo Li (2003)
Xiaoyun Liao (2010-2013)
Paul Lochhead (2011-2012)
Teppei Morikawa (2010-2012)
Chungdak Namgyal (2004-2005)
Katsuhiko Nosho (2007-2010)
Akiyo Ogawa (2006)
Mutsuko Ohnishi (2007-2008)
Ayano O’Reily (2009)
Jeanne Shen (2011-2012)
Kaori Shima (2008-2011)
Yuko Suemoto (2007-2008)
Ruifang Sun (2011-2012)
Maiko Suzuki (2010)
Noriko Tanaka (Yamaguchi) (2009-2010)
Saori Toyoda (2008-2009)
Noboru Uchiyama (2007)
Jing Xie (2010-2011)
Chong Xu (2002)
Taiki Yamaji (2006)
Jing Zhou (2003)
Web links
http://researchfaculty.brighamandwomens.org/BRIProfile.aspx?id=5797
http://bwhpathology.partners.org/CV.aspx?pathologistName=SO26
http://www.dfhcc.harvard.edu/membership/profile/member/1099/0/