Shuji Ogino, MD, PhD, MS(Epidemiology) is Associate Professor of Pathology at Harvard Medical School, and a practicing molecular pathologist at Brigham and Women's Hospital, and Dana-Farber Cancer Institute. As a recognized leader in molecular pathology of colorectal cancer, Dr. Ogino has been a pioneer of the emerging interdisciplinary field of science, termed "Molecular Pathological Epidemiology (MPE)". Dr. Ogino has recently established this new concept (J Natl Cancer Inst 2010;102:365-7. Gut 2011), by virtue of his very unique expertise, combining knowledge and experience in epidemiology, biostatistics and molecular pathology. MPE merges molecular pathology and epidemiology, to gain insights into the mechanisms of carcinogenesis and tumor progression. Through better understanding of the carcinogenic process, MPE contributes to personalized medicine and personalized prevention. MPE has become an important strategy in cancer epidemiology, and Dr. Ogino has been playing a major role in this new scientific endeavor as the first "Molecular Pathologic Epidemiologist".
Dr. Ogino received MD (1993) and PhD (2001) degrees from University of Tokyo, and Master of Science (MS) from Harvard School of Public Health, where he studied epidemiology and biostatistics. Dr. Ogino completed AP/CP residency at Allegheny General Hospital (1995-1997) and Case Western Reserve University (1997-1999). In 1998, Dr. Ogino attended lectures by Drs. Frederic Barr and Marc Ladanyi, and decided to pursue a career in molecular pathology. Then, Dr. Ogino spent 1 year in the laboratory of Dr. Sanford Markowitz, where he first learned colon cancer molecular biology. Dr. Ogino completed Molecular Pathology Fellowship and postdoctoral research at University of Pennsylvania, under enthusiastic supervisions of Drs. Debra Leonard and Robert Wilson. Dr. Ogino was appointed to the faculty of the Department of Pathology at Brigham and Women's Hospital and Harvard Medical School as Instructor in 2001, being promoted to Assistant Professor (2004) and then to Associate Professor (2008).
Since 2001, Dr. Ogino has created and expanded a colorectal cancer database, with indispensable support from Drs. Charles Fuchs and Massimo Loda. Dr. Ogino has been utilizing two nationwide prospective cohort studies, the Nurses' Health Study (N=121,701 women followed since 1976, founded by Dr. Frank Speizer) and the Health Professionals Follow-up Study (N=51,529 men followed since 1986, founded by Dr. Walter Willett). In these cohort studies, dietary, lifestyle and family history data, as well as biospecimens (blood, cheek cells, tissue, etc.) have been prospectively collected over decades. Dr. Ogino can link molecular changes in colorectal cancer to specific dietary and lifestyle data as well as clinical outcome. Thus, Dr. Ogino's tumor database has become an unprecedented resource, and is regarded as "the world largest colorectal cancer database" (by Dr. Todd Golub at The Broad Institute). Utilizing this high-dimensional tumor database, Dr. Ogino has been able to generate remarkable amounts of high quality data, which can broadly serve for the scientific community, not only pathology but also oncology, gastroenterology, and epidemiology. As a prolific researcher, Dr. Ogino has authored over 100 original publications, for 80% of which he is the first or last author.
Dr. Ogino's pioneering and unique contributions in MPE led to a landmark study, which found that aspirin prevents colorectal cancer through inhibition of PTGS2 (cyclooxygenase-2) (N Engl J Med 2007;356:2131-42). This groundbreaking research not only proved the preventive effect of aspirin, but also provided profound insights on mechanisms of cancer preventive effect of aspirin. Dr. Ogino has shown that deficiency of one-carbon nutrients (i.e., folate and B vitamins) causes colon cancer with global DNA (LINE-1) hypomethylation (Gut 2010;59:794-9), and TP53-mutated colon cancer (Gastroenterology 2008;135:770-80), but does not influence MSI or KRAS mutational status (Cancer Epidemiol Biomarkers Prev 2008;17:2895-8). Dr. Ogino has shown that MGMT germline polymorphism is strongly associated with promoter methylation and gene silencing (Carcinogenesis 2007;28:1985-90). Dr. Ogino's contribution also led to the discovery that regular aspirin use significantly prolongs survival of colon cancer patients, particularly if tumors express PTGS2 (COX-2) (JAMA 2009;302:649-58), which generated substantial national publicity. Dr. Ogino has discovered a number of other host-tumor interactions (which influence tumor behavior) including BMI-FASN (J Clin Oncol 2008;26:5713-20), age/BMI-CDKN1A (p21) (Cancer Epidemiol Biomarkers Prev 2009;18:2513-21), BMI/physical activity-CDKN1B (p27) (Cancer Epidemiol Biomarkers Prev 2009;18:1849-58. Clin Cancer Res 2009;15:5931-6), BMI-STMN1 (Am J Gastroenterol 2009;104:2047-56), cancer family history-CDX2 (Clin Cancer Res 2009;15:4665-73), and T cell subsets-MSI (J Pathol 2010;222:350-66). Examining tumor-host interactions is a novel paradigm of MPE study design which Dr. Ogino invented (J Clin Oncol 2008;26:5713-20) to elucidate mechanisms of interactive effects of host and tumor factors on tumor progression.
Dr. Ogino has been the first to extensively characterize colorectal cancers with global DNA hypomethylation. Dr. Ogino discovered that global DNA (LINE-1) hypomethylation was associated strongly with poor prognosis (J Natl Cancer Inst 2008;100:1734-8), chromosomal instability (Int J Cancer 2008;122:2767-73) and IGF2 DMR (differentially methylated region) hypomethylation (Gastroenterology 2010;139:1855-64). Dr. Ogino has shown LINE-1 methylation status of synchronous colorectal cancers is concordant, implying the presence of a common pathogenic mechanism or a field effect (Gastroenterology 2009;137:1609-20). Dr. Ogino has identified LINE-1 extreme hypomethylators as a previously unrecognized, distinct subset of colorectal cancers, affecting younger patients (Mol Cancer 2010;9:125).
Dr. Ogino has been the leading investigator in characterizing colorectal cancers with the CpG island methylator phenotype (CIMP-high). Utilizing the large tumor database and real-time quantitative DNA methylation analysis (MethyLight), Dr. Ogino has elucidated the characteristics of CIMP-high cancer, including its associations with BRAF mutation (Gut 2006;55:1000-6), cancer synchronicity (Gastroenterology 2009;137:1609-20), DNMT3B expression (Clin Cancer Res 2009;15:3663-71), CDKN1A expression (J Pathol 2006;210:147-54), CDKN1B loss (Mod Pathol 2007;20:15-22), inactive PTGS2 (Neoplasia 2006;8:458-64), inactive CTNNB1 (Neoplasia 2007;9:569-77), TGFBR2 mutation (Hum Pathol 2007;38:614-20), SIRT1 expression (Mod Pathol 2009;22:922-32), and distinctive pathologic features (Am J Surg Pathol 2006;30:1175-83). Dr. Ogino was the first to validate standard CIMP markers for routine clinical use (J Mol Diagn 2007;9:305-14. PLoS ONE 2008;3:e3698). Importantly, Dr. Ogino has shown that CIMP-high is associated with good prognosis independent of BRAF mutation and MSI status (Gut 2009;58:90-6).
Dr. Ogino discovered a distinct subset of tumors with low degree of CIMP (CIMP-low), associated with KRAS mutation, MGMT methylation and other molecular changes (J Mol Diagn 2006;8:582-8. Gut 2007;56:1564-71. BMC Cancer 2007;7:72. Mod Pathol 2008;21:245-55). The existence of CIMP-low has subsequently been supported by multiple other groups, leading to acceptance of the concept of CIMP-low. Most recently, utilizing a novel biostatistical strategy, Dr. Ogino has shown that KRAS and BRAF mutations lead to differential propensity of locus-specific CpG island methylation, which provides insights into multiple carcinogenic pathways (Am J Pathol 2010;177:2731-40).
Utilizing his high-dimensional tumor database, Dr. Ogino has been evaluating various other colorectal cancer biomarkers (e.g., PIK3CA mutation, 18q LOH) for potential clinical use, and publishing high quality data (e.g., J Clin Oncol 2009;27:1477-84. J Clin Oncol 2009;27:4591-8. Gastroenterology 2009;136:1242-50. Am J Pathol 2010;176:2292-301. Nature 2008;455:547-51. several Clin Cancer Res papers, several J Mol Diagn papers, etc.).
Dr. Ogino's laboratory is currently funded by NCI R01 (as Principal Investigator); four other R01's (as Co-Investigator); two P01 Program Project Grants (as Co-Investigator); P50 Grant for Harvard GI Cancer SPORE and its Developmental Project Award (as PI); the Bennett Family Fund for Targeted Therapies Research; and the National Colorectal Cancer Research Alliance.
Because of his unique combination of expertise in molecular pathology, epigenetics, epidemiology, biostatistics and bioinformatics, Dr. Ogino has been much sought after as a peer-reviewer. Dr. Ogino has served in NCI Study Section, as a reviewer for Association for International Cancer Research and NIH National Library of Medicine, and as Editorial Board Member for 11 journals (J Pathol, Clin Cancer Res, Mod Pathol, J Mol Diagn, Expert Rev Mol Diagn, Int J Clin Exp Pathol, Anal Quant Cytol Histol, etc.). Dr. Ogino has served as a reviewer for over 60 journals including many high profile journals in diverse fields (e.g., NEJM, Nat Med, Nat Rev Cancer, PNAS, Lancet, Lancet Oncol, J Natl Cancer Inst, Am J Hum Genet, Gastroenterology, Gut, Cancer Res, Nucleic Acids Res, Oncogene, Am J Pathol, Hum Mut, Am J Gastroenterol, Environ Health Perspect, J Med Genet, Cancer Prev Res, Clin Chem, etc.).
Dr. Ogino has been frequently invited to give lectures at institutions in the U.S. and abroad, and at various meetings such as USCAP, AACR, Digestive Disease Week (DDW), Association for Molecular Pathology (AMP), etc. Dr. Ogino has served in numerous national and international committees (e.g., USCAP, CAP, AMP and CLSI committees). Dr. Ogino received AMP Executive Officer's Award and was designated for CAP Foundation Scholar's Award. Most importantly, Dr. Ogino has mentored students, residents, fellows and junior faculty members, some of whom are becoming next generation leaders in pathology and the emerging field of "Molecular Pathological Epidemiology (MPE)".