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Hiroyuki Seimiya

Affiliation

Education & Professional Career

1990: B.Sc., Faculty of Pharmaceutical Sciences, The University of Tokyo
1995: Ph.D. (Doctor of Pharmaceutical Sciences), The University of Tokyo
1993-1995: Predoctoral Fellow in Cancer Research, Japan Society for the Promotion of Science
1995-2004: Research Associate, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research
2000-2001: Postdoctoral Fellow, New York University School of Medicine
2004: Associate Member, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research
2005-Present: Member and Chief (Principal Investigator), Cancer Chemotherapy Center, Japanese Foundation for Cancer Research
2008-Present: Visiting Professor, Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University (concurrent)
2009-Present: Visiting Professor, Institute of Health Biosciences, The University of Tokushima Graduate School (concurrent)
2010-2020: Visiting Associate Professor, Graduate School of Frontier Sciences, The University of Tokyo (concurrent)
2014-Present: Visiting Professor, Graduate School of Medicine, Yokohama City University (concurrent)
2018-Present: Project Leader, RIKEN Program for Drug Discovery and Medical Technology Platforms (concurrent)
2020-Present: Visiting Professor, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo (concurrent)

Area of Research

• Molecular cancer therapeutics
• Telomere dynamics
• G-quadruplex
• Poly(ADP-ribosyl)ation
• Cancer stem cells

Membership

•Japanese Cancer Association: Auditor (2020-); Councilor (2006-); Member (2014-) and Chairman (2016-2019) of Conflict of Interest Committee; Member of International Sessions Organizing Committee (2008-2017); Member of International Committee (2015-); Organizing Committee Member of the 11th AACR-JCA Joint Conference (2019); Member of Program Committee of the 66th, 73rd, 75th-80th Annual Meetings
•The Japanese Association for Molecular Target Therapy of Cancer: Director (2014-2016); Councilor; Member of Ethics and Conflict of Interest Committee; Member of Program Committee of the 15th, 16th, and 18th-24th Annual Meetings; Member of Executive Committee of the 9th-11th, 13th-16th Translational Research Workshops and the 1st Seeds Needs Workshop
•Japanese Society of Medical Oncology: Member of Education Planning Subcommittee (2014-2019); Member of Terminology Subcommittee (2015-2018); Member of Program Committee of the 14th Annual Meeting (2016)
•Platform of Advanced Animal Model Support (AdAMS), Grant-in-Aid for Scientific Research on Innovative Areas, Ministry of Education, Culture, Sports, Science and Technology, Japan: Group Leader, Molecular Profiling Committee (2016-); Member of Executive Committee of the Technical Training Course for Young Scientists (2016-)
•Pharmaceuticals and Medical Devices Agency (PMDA): External Expert (2013-); Member of Working Group for Non-clinical Pharmacology Studies on Anticancer Drugs (2013, 2015-2016)
•Science Council of Japan: Member (2017-); Secretary of Subcommittee of Cancer, Committee of Clinical Medicine (2017-)
•Japan Society for the Promotion of Science: External Expert (2011 etc.); Commended External Expert (2017)
•Scientific Support Programs for Cancer Research, Grant-in-Aid for Scientific Research on Innovative Areas, Ministry of Education, Culture, Sports, Science and Technology, Japan: Member (2005-2014), Group Leader (2015), Screening Committee of Anticancer Drugs; Executive Member of Young Scientist Workshop (2011-2015)
•The JFCR International Symposium on Cancer Chemotherapy: Executive Member, Committee Member (2007-); Chairman of Program Committee of the 16th Symposium
•Nagoya International Cancer Treatment Symposium: Advisor (2013-)
•Japanese Association for RNA Interference: Councilor (2009-); Chairman of Program Committee of the 4th Annual Meeting
•Anti-Tumor Drug Development Forum: Councilor, Executive Member (2006-)
•Molecular Biology Society of Japan
•The Pharmaceutical Society of Japan
•American Association for Cancer Research (1996-)
•Cancer Science: Secretary for Editor-in-Chief (2002-2008); Associate Editor (2007-)
•Journal of Biological Chemistry: Editorial Board Member (2017-)
•Frontiers in Cancer Molecular Targets and Therapeutics: Review Editor (2011-)
•Journal of Cancer Research and Clinical Oncology: Editorial Board
•Gene Expression: Editorial Board

Awards

2000: NCI-JFCR Scientist Exchange Program Fellow
2004: Incitement Award of the Japanese Cancer Association
2016: JCA-Mauvernay Award
2017: Takashi Tsuruo Award (JAMTTC)
2019: JFCR Academic Award

Research Projects

1. Telomere dynamics and cancer
To proliferate, cells need to replicate their DNA. However, classical replication machinery cannot completely replicate the very ends of chromosomes (telomeres). Therefore, telomeres, which are specialized structures that protect eukaryotic chromosome termini, gradually shorten after each cell cycle. When telomeres reach the limit of shortening, the cells cannot divide any further. This phenomenon, called replicative senescence (aging of a cell), is one of the systems that prevent carcinogenesis. In most cancer cells, the telomere-synthesizing enzyme, telomerase, stably maintains telomeres. Accordingly, cancer cells have the ability to divide infinitely. We have developed a series of telomerase inhibitors that block the unlimited growth of cancer cells.
Now we are pursuing basic research on the telomeric non-coding RNA (TERRA)-mediated regulation of cancer progression and the development research of new anticancer drugs that target G-quadruplex, a specialized higher-order structure of telomeric and other G-rich nucleic acids.

Selected publications: Naasani et al. Cancer Res (1999), Seimiya et al. EMBO J (2000), Seimiya et al. Mol Cancer Ther (2002), Seimiya et al. Cancer Cell (2005), Ohishi et al. Cancer Res (2010), Takahashi et al. Mol Cell Biol (2011), Miyazaki et al. Clin Cancer Res (2012), Hirashima et al. Mol Cell Biol (2013), Ohishi et al. Mol Cell Biol (2014), Hirashima & Seimiya. Nucleic Acid Res (2015), Hasegawa et al. BBRC (2016), Nakamura et al. Sci Rep (2017) , Fujiwara et al. Sci Rep (2018), Okamoto & Seimiya. Cells (2019), Okamoto & Seimiya. J Biol Chem (2019)

2. Cell regulation by poly(ADP-ribosyl)ation
Poly(ADP-ribosyl)ation (PARsylation), one of the most dramatic post-translational modifications of proteins, is catalyzed by poly(ADP-ribose) polymerases (PARP). PARsylation regulates various biological events, including genomic stability, gene transcription, and so forth. We still have many questions about this process, such as the molecular basis for functional specificity elicited from PAR chains. Recently, PARP1/2 inhibitors have been approved as synthetic lethal therapeutic drugs against BRCA1/2-deficient cancer cells, and other PARP family enzymes have also been postulated as therapeutic targets. We focus on tankyrases, the PARP members that enhance telomere elongation by telomerase and promote the oncogenic Wnt/beta-catenin signaling in human cancer cells. We are developing tankyrase inhibitors as innovative anticancer drugs and pursuing research on biomarkers that predict the efficacy oftankyrase inhibitors.

Selected publications: Seimiya & Smith. J Biol Chem (2002), Seimiya et al. Mol Cell Biol (2004), Seimiya et al. Cancer Cell (2005), Muramatsu et al. Cancer Sci (2007), Muramatsu et al. Exp Cell Res (2008), McCabe et al. Oncogene (2009), Yashiroda et al. BBRC (2010), Ohishi et al. Cancer Res (2017), Tanaka et al. Mol Cancer Ther (2017), Mashima et al. Oncotarget (2017) , Mizutani et al. Cancer Sci (2018), Okamoto et al. Oncotarget (2018), Shirai et al. J Med Chem (2019), Mizutani et al. BBRC (2020), Jang et al. Mol Cancer Ther (2020), Shirai et al. J Med Chem (2020)

3. Cancer stem cells as therapeutic targets
Cancer heterogeneity is derived from stochastic clonal evolution and cellular hierarchy, in the latter of which cancer stem cells (CSCs) reside on the top position. CSCs, which are self-renewable, multipotent, and highly tumorigenic, exhibit drug resistance and a metastatic potential. Therefore, CSCs are postulated as a queen bee that hinders cancer eradication. Molecular signaling pathways and microenvironmental niches that regulate survival, proliferation, and stemness of CSCs have been identified from various cancers. These factors would be promising targets for anticancer drug development. In our laboratory, we focus on glioma stem cells and gastric CSCs. Specifically, we utilize functional genomics and comprehensive transcriptome analyses to pursue therapeutic targets of CSCs. We are also developing chemical compounds called G-quadruplex ligands, which have a preferential anti-proliferative effect on glioma stem cells.

Selected publications: Miyazaki et al. Clin Cancer Res (2012), Mashima et al. Cancer Res (2014), Ouchi et al. (2016), Hasegawa et al. BBRC (2016), Nakamura et al. Sci Rep (2017), Mashima et al. Br J Cancer (2019) , Jang et al. Mol Cancer Ther (2020), Kawakami et al. Cancer Sci (2020)

• JFCR
• The Cancer Institute Hospital of JFCR
• Cancer Institute
• Cancer Chemotherapy Center
• Cancer Precision Medicine Center
• NEXT-Ganken Program
• School of Cytotechnology

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• Donation
• Link concerming research
• Japanese