Staff
Hidenori Ojima
Position
Deputy Director of the Research Institute and Head of the Molecular Pathology Division (also affiliated with the Department of Pathology, Integrated Clinical Services).
Hidenori Ojima's Biography
Education
1990: Entered Asahikawa Medical University, Faculty of Medicine.
1996: Graduated from Asahikawa Medical University, Faculty of Medicine.
2006: Entered Keio University Graduate School of Medicine.
2008: Graduated from Keio University Graduate School of Medicine.
Professional Experience
1996: Resident, Asahikawa Medical University Hospital.
1998: Medical Staff, Department of Pathology, Asahikawa Medical University Hospital.
1999: Assistant, Second Department of Pathology, Asahikawa Medical University.
2000: Chief Resident, National Cancer Center Hospital.
2001: Researcher, Department of Pathology, National Cancer Center Research Institute.
2012: Senior Researcher, Molecular Pathology Division, National Cancer Center Research Institute.
2014: Associate Professor, Department of Pathology, Keio University School of Medicine.
2024: Tochigi Cancer Center
Deputy Director of the Research Institute.
Head of the Molecular Pathology Division.
Deputy Director of Integrated Clinical Services.
Head of the Department of Pathology.
Head of the Clinical Laboratory Center.
Head of the Biobank Center.
Visiting Researcher, Cancer Genomics Division, National Cancer Center Research Institute.
Major Academic and Research Activities
The Japanese Society of Pathology: Certified Pathologist, Supervising Pathologist, Academic Councillor.
The Japanese Cancer Association: Councillor.
Japan Liver Cancer Association:
Councillor.
Member of the Cholangiocarcinoma Treatment Guideline Committee.
Reviewer for Research Papers on Liver Cancer.
Member of the Pathology Subcommittee for the General Rules for the Study of Primary Liver Cancer.
Japanese Society of Hepato-Biliary-Pancreatic Surgery: Member of the Guidelines Committee for Biliary Cancer.
The Japan Society of Hepatology:
Member of the Liver Cancer Treatment Guideline Revision Committee.
Pathologist Liaison for the NASH Diagnosis Working Group.
The Japanese Society of Biliary Surgery: Councillor, Certified Physician.
Japanese Society of Clinical Cytology
Japanese Society of Imaging Medicine
Study Group on Hepatic Hemodynamics and Function: Secretary.
Hepatocellular Carcinoma Case Study Group: Secretary.
Japan Primary Care Association: Specialist Physician.
The United States and Canadian Academy of Pathology (USCAP)
United European Gastroenterology (UEG)
Awards
2010: Case Study Award, The Japanese Society of Pathology.
2019: Academic Research Award, The Japanese Society of Pathology.
2020: Academic Encouragement Award, Alumni Association of Asahikawa Medical University.
Social Contributions
Member of the Regional Team for Liver and Pancreatobiliary Pathology in the Consultation System, Medical Services Committee, The Japanese Society of Pathology.
Consultant, Department of Pathology Diagnostics, Cancer Medical Support Division, Cancer Control Research Institute, National Cancer Center.
Ken Yamazaki
Position
Senior Researcher
Career Background
1997: Completed Doctoral Program in Science, Graduate School of Science and Engineering, Waseda University
1997: Assistant, Department of Biology, Faculty of Education, Waseda University
2000: Research Fellow, National Cancer Center (on secondment from the Organization for Pharmaceutical Safety and Research)
2005: Special Research Assistant, Department of Pathology, Keio University School of Medicine
2020: Research Fellow, Japan Bioindustry Association (on secondment to Keio University)
2022: Assistant Professor (Special Appointment), Department of Pathology, Keio University School of Medicine
2024: Senior Researcher, Tochigi Cancer Center Research Institute
Affiliations
Japanese Cancer Association
Molecular Biology Society of Japan
Naoto Kubota
Position
Researcher
(Dual Appointment: Department of Pathology, Diagnostic Division & Biobank Center)
Career Background
2012: Graduated from Keio University School of Medicine
2012: Resident, National Hospital Organization Tokyo Medical Center
2014: Pathology Resident, Keio University Hospital; Doctoral Program in Pathology, Graduate School of Medicine, Keio University
2018: Assistant Professor, Department of Pathology, Keio University School of Medicine
2019: Chief Physician, Department of Pathology, Nippon Kokan Hospital
2020: Assistant Professor, Department of Pathology, Keio University School of Medicine
2020: Postdoctoral Fellow, University of Texas Southwestern Medical Center
2023: Assistant Professor, Department of Pathology, Keio University Hospital
2024: Chief Physician, Department of Pathology, Tochigi Cancer Center; Researcher, Research Institute
Affiliations
Japanese Society of Pathology
Japanese Society of Clinical Cytology
Japanese Society of Hepatology
Japanese Cancer Association
Japan Liver Cancer Study Group
Makoto Abe
Position
Researcher
(Dual Appointment: Department of Pathology, Diagnostic Division & Biobank Center)
Career Background
March 2008: Graduated, Department of Earth and Environmental Science, Faculty of Science and Technology, Hirosaki University
October 2008: Transferred to Medical School, Faculty of Medicine, Fukui University
March 2013: Graduated, Fukui University Faculty of Medicine
March 2015: Completed Clinical Training, Hachinohe City Hospital
April 2015: Enrolled in Molecular Pathology, Graduate School of Hirosaki University
April 2019: Physician, Department of Pathology, Tochigi Cancer Center
2024: Chief Physician, Department of Pathology, Tochigi Cancer Center; Researcher, Research Institute
Affiliations
Japanese Society of Pathology
Japanese Society of Clinical Cytology
Japanese Cancer Association
Eisuke Miura
Position
Researcher
(Dual Appointment: Department of Pathology, Diagnostic Division & Biobank Center)
Career Background
2018: Pathology Resident, Keio University Hospital
2022: Assistant Professor, Department of Pathology, Keio University School of Medicine
2024: Physician, Department of Pathology, Tochigi Cancer Center; Researcher, Research Institute
Affiliations
Japanese Society of Pathology
Japanese Society of Clinical Cytology
Japanese Cancer Association
Japanese Lung Cancer Society
Japan Liver Cancer Study Group
International Association for the Study of Lung Cancer
Hirofumi Shirakawa
Position
Researcher
(Dual Appointment: Department of Hepatobiliary and Pancreatic Surgery)
Career Background
2000: Graduated from Ehime University School of Medicine; Surgical Resident, Department of Surgery I
2001: Resident, Department of Surgery, Matsuyama Red Cross Hospital
2004: Surgical Resident, National Cancer Center Hospital
2007: Specialized Fellow, Hepatobiliary, Pancreatic, and Gastric Surgery, National Cancer Center East Hospital; Ph.D. in Medicine, National Cancer Center Research Institute
2010: Surgeon, Gastroenterology, Tochigi Cancer Center
2017: Hepatobiliary Surgery, Tochigi Cancer Center
2020: Clinical Professor, Dokkyo Medical University
Affiliations
Japanese Society of Surgery
Japanese Society of Hepatobiliary and Pancreatic Surgery
Japanese Society of Gastroenterological Surgery
Japanese Society of Gastroenterology
Japanese Society of Endoscopic Surgery
Japanese Biliary Association
Japanese Pancreatic Society
Masatsugu Ishii
Position
Researcher
(Dual Appointment: Department of Hepatobiliary and Pancreatic Surgery)
Career Background
2008: Graduated from Tokyo Medical University
2008: Clinical Resident, Kawasaki Municipal Ida Hospital
2011: Surgeon, Saitama Social Insurance Hospital
2012: Enrolled in Graduate School, Keio University Hospital
2016: Surgeon, Isehara Cooperative Hospital
2018: Chief Surgeon, Public Fussa Hospital
2020: Pediatric and Transplant Surgery, Kumamoto University Hospital
2021: Chief Surgeon, Hepatobiliary Surgery, Tochigi Cancer Center
Affiliations
Japanese Society of Surgery
Japanese Society of Gastroenterological Surgery
Japanese Cancer Association
Japanese Society of Hepatobiliary and Pancreatic Surgery
Japanese Society of Hepatology
Reiko Ogura
Position
Researcher
Research Project Overview
The Molecular Pathology Division of the Research Institute welcomes not only pathologists from the Department of Pathology but also clinical physicians from other departments who are interested in research. Each member conducts research aligned with the common theme, “Approaching the improvement of cancer patient treatment outcomes and prognoses through pathology-based studies.” Regular research meetings are held to discuss ongoing studies, fostering a collaborative environment. Below is an overview of the research being conducted in the Molecular Pathology Division.
1. Proposal of Tumor Progression Patterns Reflecting Biological Characteristics of Biliary Tract Cancer (Intraductal Carcinoma Component; IDCC) and Elucidation of Its Molecular Mechanisms
Through detailed observations of macroscopic and histological findings in numerous biliary tract cancer surgical specimens, correlated with clinical outcomes, we identified two major patterns of tumor progression:
IDCC-associated type, characterized by the presence of intraductal carcinoma components around the tumor.
Non-associated type, lacking such components.
Approximately 37% of resected cases fell into the IDCC-associated type, which exhibited less invasive growth and better prognosis compared to the non-associated type. This finding suggests that IDCC-associated type serves as a powerful prognostic factor and a new guideline for therapeutic decision-making, particularly in assessing the clinical and pathological significance of bile duct resection margins.
Gene expression profiling and Gene Set Enrichment Analysis (GSEA) linked to a clinicopathological database revealed that the non-associated type showed significantly higher expression of genes related to invasion, proliferation, and metastasis, especially epithelial-mesenchymal transition (EMT)-related genes, regardless of tumor site. These results not only provide molecular pathological validation of IDCC’s clinicopathological features but also highlight EMT’s critical involvement in biliary tract cancer progression. Efforts are ongoing to identify additional molecular contributors.
2. Establishment of Extensive Biliary Tract Cancer Biorepositories and Databases
To identify functional molecules reflective of biological characteristics and to verify their clinical applications, we established extensive biorepositories of biliary tract cancer specimens, linked to clinical, pathological, and genetic information.
At the National Cancer Center, we collected frozen resection specimens and established xenograft models and cell lines using immunodeficient mice. This effort resulted in:
Approximately 250 frozen specimens
26 xenograft models, one of the largest collections in Japan
13 cell lines, including subtypes
These resources, combined with a clinicopathological database of nearly 600 cases and genetic expression/abnormality data, provide a comprehensive platform for systematic biliary tract cancer research. Collaborative studies using these resources are ongoing with the National Cancer Center, and some cell lines are distributed via the Tohoku University Cell Resource Center (https://www2.idac.tohoku.ac.jp/dep/ccr/index.html).
3. Preclinical Trials of Novel Anticancer Drugs
Given the lack of effective chemotherapy for biliary tract cancer, we conducted preclinical trials of multiple novel anticancer drugs in collaboration with pharmaceutical companies. These trials utilized our biorepository and database and included drugs targeting tyrosine kinase molecules, such as Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR), which play significant roles in tumor invasion and growth.
The trials demonstrated effective drug responses, confirming the involvement of these molecules in tumor progression. Some drugs were further advanced to clinical trials through collaboration with clinicians and pharmaceutical companies. This system will continue to facilitate the discovery of new candidate molecules and their inhibitors for preclinical evaluation.
4. Molecular Pathological Studies on the Diversity of Intrahepatic Cholangiocarcinoma
We are conducting morphological classification of intrahepatic cholangiocarcinoma based on histological findings and linking these classifications to gene expression analysis. Comprehensive gene expression profiling has identified subtypes with unique clinicopathological features, and we are working to elucidate molecular biological mechanisms associated with these subtypes, potentially leading to therapeutic advancements.
5. Integrated Analysis of Sarcoma Using Histological and Genetic Profiles
Sarcomas are classified based on distinctive histological features and genetic alterations, such as gene fusions or mutations. However, due to their rarity and the limited availability of specific diagnostic antibodies, diagnosing sarcomas remains challenging.
Leveraging a large repository of sarcoma cases, we employ FISH and NGS-based integrative analysis to improve diagnosis, classification, and understanding of disease mechanisms. Additionally, we are developing diagnostic support tools and classification systems using deep learning.
6. Correlation Between Preoperative Tumor Marker Elevation and Postoperative Prognosis in Pancreatic Cancer
Despite the introduction of preoperative chemotherapy as the standard treatment in Japan since 2020, recurrence rates after pancreatic cancer resection remain high. Predicting prognosis before surgery is crucial. We are analyzing the correlation between preoperative tumor marker levels and prognosis, focusing on tumor markers measurable prior to surgery.
7. Omics-Based Classification of Hepatocellular Carcinoma (HCC)
Omics-based subtype classifications have been conducted for many cancers to improve treatment selection, prognosis prediction, and personalized therapies. While gene expression profiles have primarily been used for HCC classification, we aim to integrate other omics data to establish new subtypes that may contribute to HCC treatment.
8. Deep Learning for Lung Adenocarcinoma Diagnosis and Clinicopathological Significance
Lung cancer remains one of the leading causes of cancer-related mortality worldwide. Among its subtypes, lung adenocarcinoma is the most prevalent. We are developing a deep learning model to classify lung adenocarcinoma into finer subtypes.Although the relationships between subtype classification, malignancy, and pathological factors such as vascular invasion are gradually being understood, many questions remain. By leveraging deep learning, we aim to uncover further insights into the prognostic impact of these classifications.