Researcher Profile and Settings

Affiliation

• Faculty of Health Sciences　Health Sciences　Biomedical Science and Engineering

Job Title

• Associate Professor

Degree

• PhD Medicine（Queen's University Belfast）

URL

https://hisanorifukunaga.wixsite.com/laboratory

ORCID ID

•  https://orcid.org/0000-0002-6264-187X

Profile

• Dr. Hisanori Fukunaga is a Japanese physician-scientist in Radiation Biology, Genetics, Health Physics and Occupational & Environmental Health. He serves a task group member of the International Commission on Radiological Protection (ICRP).

  
  

  After receiving his medical degree from the Yokohama City University School of Medicine in Japan, Dr. Fukunaga's clinical residency was at the Soma General Hospital in Fukushima, following the 2011 Fukushima nuclear disaster. The clinical experience in Fukushima has been his driving force to pursue advanced study in the field of radiation research. Later he moved to the Queen's University Belfast in the UK, where he investigated radiation-induced male infertility and was awarded his PhD Medicine in 2019 under the supervision of Prof. Kevin M. Prise.

  
  

  As of today, Dr. Fukunaga has consistently investigated radiation-induced impacts on human health, as well as the effects of environmental stress on mitochondrial DNA.

Educational Organization

•  Bachelor's degree program　Departments of Health Sciences, School of Medicine
•  Master's degree program　Graduate School of Health Sciences
•  Doctoral (PhD) degree program　Graduate School of Health Sciences

Academic & Professional Experience

• 2024/04 - Today Hokkaido University Institute for the Advancement of Higher Education Faculty Member
• 2023/10 - Today Hokkaido University One Health Research Center Faculty Member
• 2022/07 - Today Hokkaido University Center for Environmental and Health Sciences Faculty Member
• 2022/04 - Today Hokkaido University Faculty of Health Sciences Associate Professor

Research Activities

Published Papers

• Evaluation of cell cycle–dependent migration activity following X-ray exposure: A radiobiological approach for optimization of radiotherapy with cell cycle–targeting agents.

  Ryosuke Seino, Hisanori Fukunaga

  Radiation Research in press 1938-5404 2024/04/23 [Refereed][Not invited]
   

  Radiotherapy with cell cycle-specific anticancer agents has become an important option in the control of both primary tumors and metastases. Here, we used image analysis algorithms that enable quick segmentation and tracking to describe a radiobiological approach for the optimized selection of cell cycle-targeting anticancer drugs for radiotherapy. We confirmed cell cycle-synchronization using human cervical cancer HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI) as a cell cycle-monitoring probe. Cells synchronized in the G1 and G2 phases were irradiated with X rays at 0.5–2 Gy. Each cell was identified using Cellpose, a deep learning-based algorithm for cellular segmentation, and the velocity and direction of migration were analyzed using the TrackMate plugin in Fiji ImageJ. G1 phase synchronized cells showed a dose-dependent decrease in velocity after irradiation, while G2 cells tended to increase their velocity. The migration pattern of all cells appeared to be a random walk model, regardless of the exposure dose. In addition, we used cisplatin to arrest the cell cycle. HeLa-FUCCI cells arrested at the G2 phase via cisplatin treatment showed enhanced cell migration after X-ray exposure. These results indicated that anticancer agents that arrest the cell cycle of cancer cells in a specific phase may enhance cell migration after radiotherapy. Our approach, using cellular segmentation and tracking algorithms, could enhance the radiobiological assessment of cell cycle-specific migration after irradiation to aid in optimizing radiotherapy using cell cycle-targeting agents.
• Reply to Comment on 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation'.

  Yuta Shiraishi, Yusuke Matsuya, Hisanori Fukunaga

  Physics in Medicine & Biology IOP Publishing 69 108002  0031-9155 2024/04/15 [Refereed][Invited]
   

  Liew and Mairani commented on our paper 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation' (Shiraishi et al 2024a Phys. Med. Biol.69 015017), which proposed a biophysical model to predict the dose–response curve of surviving cell fractions after ultra-high dose rate irradiation following conventional dose rate irradiation by considering DNA damage yields. They suggested the need to consider oxygen concentration in our prediction model and possible issues related to the data selection process used for the benchmarking test in our paper. In this reply, we discuss the limitations of both the present model and the available experimental data for determining the model's parameters. We also demonstrate that our proposed model can reproduce the experimental survival data even when using only the experimental DNA damage data measured reliably under normoxic conditions.
• Radiation-induced impacts on cell adhesion and its cell cycle dependence

  Ryosuke Seino, Hisanori Fukunaga

  RADIOISOTOPES 日本アイソトープ協会 73 (1) 61 - 67 0033-8303 2024/03/15 [Refereed][Not invited]
   

  In recent years, the use of artificial intelligence in imaging analysis has become increasingly popular. In particular, algorithms based on deep learning, a type of machine learning, are considered promising tools. In this study, we used Cellpose 2.0, a cell segmenta-tion algorithm based on deep learning, to analyze changes in cell adhesion following exposure to X-rays in synchronous HeLa cells. We found that the cell adhesion area of G1-phase cells increased after irradia-tion, while that of G2-phase cells decreased.
• Cell cycle dependence of cell survival following exposure to X-rays in synchronous HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators.

  Ryosuke Seino, Hiroto Uno, Kevin M Prise, Hisanori Fukunaga

  Biomedical Research Biomedical Research Press 45 (1) 25 - 31 0388-6107 2024/02/02 [Refereed][Not invited]
   

  The cell cycle dependence of radiosensitivity has yet to be fully determined, as it is technically difficult to achieve a high degree of cell cycle synchronization in cultured cell systems and accurately detect the cell cycle phase of individual cells simultaneously. We used human cervical carcinoma HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators (FUCCI), and employed the mitotic harvesting method that is one of the cell cycle synchronization methods. The imaging analysis confirmed that the cell cycle is highly synchronized after mitotic cell harvesting until 18-20 h of the doubling time has elapsed. Also, flow cytometry analysis revealed that the S and G2 phases peak at approximately 12 and 14-16 h, respectively, after mitotic harvesting. In addition, the clonogenic assay showed the changes in surviving fractions following exposure to X-rays according to the progress through the cell cycle. These results indicate that HeLa-FUCCI cells become radioresistant in the G1 phase, become radiosensitive in the early S phase, rapidly become radioresistant in the late S phase, and become radiosensitive again in the G2 phase. Our findings may contribute to the further development of combinations of radiation and cell cycle-specific anticancer agents.
• Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation.

  Yuta Shiraishi, Yusuke Matsuya, Tamon Kusumoto, Hisanori Fukunaga

  Physics in Medicine & Biology IOP Publishing 69 015017  0031-9155 2024/01/07 [Refereed][Not invited]
   

  Objective. FLASH radiotherapy (FLASH-RT) with ultra-high dose rate (UHDR) irradiation (i.e. > 40 Gy s⁻¹) spares the function of normal tissues while preserving antitumor efficacy, known as the FLASH effect. The biological effects after conventional dose rate-radiotherapy (CONV-RT) with ≤0.1 Gy s⁻¹ have been well modeled by considering microdosimetry and DNA repair processes, meanwhile modeling of radiosensitivities under UHDR irradiation is insufficient. Here, we developed an integrated microdosimetric-kinetic (IMK) model for UHDR-irradiation enabling the prediction of surviving fraction after UHDR irradiation. Approach. The IMK model for UHDR-irradiation considers the initial DNA damage yields by the modification of indirect effects under UHDR compared to CONV dose rate. The developed model is based on the linear-quadratic (LQ) nature with the dose and dose square coefficients, considering the reduction of DNA damage yields as a function of dose rate. Main results. The estimate by the developed model could successfully reproduce the in vitro experimental dose–response curve for various cell line types and dose rates. Significance. The developed model would be useful for predicting the biological effects under the UHDR irradiation.
• Possible mechanisms and simulation modeling of FLASH radiotherapy.

  Yuta Shiraishi, Yusuke Matsuya, Hisanori Fukunaga

  Radiological Physics and Technology 17 11 - 23 1865-0333 2024/01/06 [Refereed][Not invited]
   

  FLASH radiotherapy (FLASH-RT) has great potential to improve patient outcomes. It delivers radiation doses at an ultra-high dose rate (UHDR: ≥ 40 Gy/s) in a single instant or a few pulses. Much higher irradiation doses can be administered to tumors with FLASH-RT than with conventional dose rate (0.01-0.40 Gy/s) radiotherapy. UHDR irradiation can suppress toxicity in normal tissues while sustaining antitumor efficiency, which is referred to as the FLASH effect. However, the mechanisms underlying the effects of the FLASH remain unclear. To clarify these mechanisms, the development of simulation models that can contribute to treatment planning for FLASH-RT is still underway. Previous studies indicated that transient oxygen depletion or augmented reactions between secondary reactive species produced by irradiation may be involved in this process. To discuss the possible mechanisms of the FLASH effect and its clinical potential, we summarized the physicochemical, chemical, and biological perspectives as well as the development of simulation modeling for FLASH-RT.
• Mitochondrial DNA copy number variation across three generations: a possible biomarker for assessing perinatal outcomes.

  Hisanori Fukunaga, Atsuko Ikeda

  Human Genomics 17 113  2023/12/15 [Refereed][Not invited]
   

  Background: Mitochondria have their own circular multi-copy genome (mtDNA), and abnormalities in the copy number are implicated in mitochondrial dysfunction, which contributes to a variety of aging-related pathologies. However, not much is known about the genetic correlation of mtDNA copy number across multiple generations and its physiological significance. Methods: We measured the mtDNA copy number in cord blood or peripheral blood from 149 three-generation families, specifically the newborns, parents, and grandparents, of 149 families, totaling 1041 individuals. All of the biological specimens and information were provided by the Tohoku Medical Megabank Project in Japan. We also analyzed their maternal factors during pregnancy and neonatal outcomes. Results: While the maternal peripheral blood mtDNA copy number was lower than that of other adult family members, it was negatively correlated with cord blood mtDNA copy number in male infants. Also, cord blood mtDNA copy numbers were negatively correlated with perinatal outcomes, such as gestation age, birth weight, and umbilical cord length, for both male and female neonates. Furthermore, the mtDNA copy number in the infants born to mothers who took folic acid supplements during pregnancy would be lower than in the infants born to mothers who did not take them. Conclusions: This data-driven study offers the most comprehensive view to date on the genetic and physiological significance of mtDNA copy number in cord blood or peripheral blood taken from three generations, totaling more than 1000 individuals. Our findings indicate that mtDNA copy number would be one of the transgenerational biomarkers for assessing perinatal outcomes, as well as that appropriate medical interventions could improve the outcomes via quantitative changes in mtDNA.
• Validation of mitotic harvesting method with human cervical carcinoma HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators for radiation research.

  Ryosuke Seino, Hiroto Uno, Hisanori Fukunaga

  Biomedical Research Biomedical Research Press 44 (5) 181 - 186 0388-6107 2023/09/27 [Refereed][Not invited]
   

  The cell cycle is a series of events in the process of one cell giving rise to two daughter cells. The mitotic harvesting method, established by Terasima and Tolmach in the 1960s, causes minimal physiological stress on the cells and achieves a high degree of cell cycle synchrony by collecting only mitotic cells from a cultured cell system. The purpose of the present study is to validate the versatility of the mitotic harvesting method using human cervical cell line HeLa cells expressing Fluorescent Ubiquitination-based Cell Cycle Indicators (FUCCI) and to estimate the cell cycle-dependent changes in radiosensitivity in HeLa–FUCCI cells. The image analysis showed that cell cycle synchrony was maintained for at least 24 hours after mitotic cell collection. Also, the clonogenic assay demonstrated changes in radiosensitivity that were cell cycle dependent. These results indicate that the mitotic harvesting method using FUCCI-expressing cells has high versatility in the field of radiation cell biology.
• How does formal and informal industry contribute to lead exposure? A narrative review from Vietnam, Uruguay, and Malaysia.

  Kritika Poudel, Atsuko Ikeda, Hisanori Fukunaga, Marie-Noel Brune Drisse, Lesley Jayne Onyon, Julia Gorman, Amalia Laborde, Reiko Kishi

  Reviews on Environmental Health Walter de Gruyter GmbH in press 0048-7554 2023/02/06 [Refereed][Not invited]
   

  Introduction: Lead industries are one of the major sources of environmental pollution and can affect human through different activities, including industrial processes, metal plating, mining, battery recycling, etc. Although different studies have documented the various sources of lead exposure, studies highlighting different types of industries as sources of environmental contamination are limited. Therefore, this narrative review aims to focus mainly on lead industries as significant sources of environmental and human contamination. Content: Based on the keywords searched in bibliographic databases we found 44 relevant articles that provided information on lead present in soil, water, and blood or all components among participants living near high-risk areas. We presented three case scenarios to highlight how lead industries have affected the health of citizens in Vietnam, Uruguay, and Malaysia. Summary and outlook: Factories conducting mining, e-waste processing, used lead-acid battery recycling, electronic repair, and toxic waste sites were the primary industries for lead exposure. Our study has shown lead exposure due to industrial activities in Vietnam, Uruguay, Malaysia and calls for attention to the gaps in strategic and epidemiologic efforts to understand sources of environmental exposure to lead fully. Developing strategies and guidelines to regulate industrial activities, finding alternatives to reduce lead toxicity and exposure, and empowering the public through various community awareness programs can play a crucial role in controlling exposure to lead.
• An Analytical Method for Quantifying the Yields of DNA Double-Strand Breaks Coupled with Strand Breaks by γ-H2AX Focus Formation Assay Based on Track-Structure Simulation.

  Yoshie Yachi, Yusuke Matsuya, Yuji Yoshii, Hisanori Fukunaga, Hiroyuki Date, Takeshi Kai

  International Journal of Molecular Sciences 24 (2) 1386  2023/01/10 [Refereed][Not invited]
   

  Complex DNA double-strand break (DSB), which is defined as a DSB coupled with additional strand breaks within 10 bp in this study, induced after ionizing radiation or X-rays, is recognized as fatal damage which can induce cell death with a certain probability. In general, a DSB site inside the nucleus of live cells can be experimentally detected using the γ-H2AX focus formation assay. DSB complexity is believed to be detected by analyzing the focus size using such an assay. However, the relationship between focus size and DSB complexity remains uncertain. In this study, using Monte Carlo (MC) track-structure simulation codes, i.e., an in-house WLTrack code and a Particle and Heavy Ion Transport code System (PHITS), we developed an analytical method for qualifying the DSB complexity induced by photon irradiation from the microscopic image of γ-H2AX foci. First, assuming that events (i.e., ionization and excitation) potentially induce DNA strand breaks, we scored the number of events in a water cube (5.03 × 5.03 × 5.03 nm3) along electron tracks. Second, we obtained the relationship between the number of events and the foci size experimentally measured by the γ-H2AX focus formation assay. Third, using this relationship, we evaluated the degree of DSB complexity induced after photon irradiation for various X-ray spectra using the foci size, and the experimental DSB complexity was compared to the results estimated by the well-verified DNA damage estimation model in the PHITS code. The number of events in a water cube was found to be proportional to foci size, suggesting that the number of events intrinsically related to DSB complexity at the DNA scale. The developed method was applicable to focus data measured for various X-ray spectral situations (i.e., diagnostic kV X-rays and therapeutic MV X-rays). This method would contribute to a precise understanding of the early biological impacts of photon irradiation by means of the γ-H2AX focus formation assay.
• A brief overview of the registration system of radiation exposure doses for decontamination workers and their occupational health management.

  Hisanori Fukunaga, Tomohiro Asano

  Journal of Occupational Health Japan Society for Occupational Health 64 (1) e12357  1341-9145 2022/09/08 [Refereed][Not invited]
   

  Following the Fukushima nuclear accident in March 2011, decontamination and related works have been carried out over a wide area, mainly in Fukushima Prefecture. In November 2013, the Radiation Dose Registration and Management System for Decontamination Workers was established to manage the occupational exposure doses of workers engaged in such work. The Radiation Effects Association mainly operates the registration system. This paper summarizes existing reports on this system and occupational health issues among decontamination workers. We collected previous reports and related regulatory laws on occupational health management for decontamination workers working in Fukushima Prefecture, summarized the outline of the radiation dose registration and management system for these decontamination workers, and discussed future issues related to their health management. Approximately 100 000 decontamination workers were registered in the system as of 2020, but none showed radiation doses that exceeded the dose limit. To our knowledge, there have been no reports of decontamination workers presenting physical symptoms suspected to be related to radiation exposure. On the other hand, heatstroke countermeasures and anxiety about radiation exposure have been reported as possible issues in the occupational health management of decontamination workers. Although decontamination workers are unlikely to experience biological effects from radiation exposure, epidemiological studies are needed to examine this evidence. Further analysis is also needed on non-radiation effects, which pose occupational health concerns for decontamination workers. The registration system would allow for tracking decontamination workers, providing data for analyzing radiological and non-radiological effects.
• Narrative review of lead poisoning in humans caused by industrial activities and measures compatible with sustainable industrial activities in Republic of Zambia.

  Hokuto Nakata, Shouta M.M. Nakayama, John Yabe, Kaampwe Muzandu, Andrew Kataba, Atsuko Ikeda-Araki, Marie-Noel Brune Drisse, Lesley Jayne Onyon, Julia Gorman, Poudel Kritika, Hisanori Fukunaga, Yoshinori Ikenaka, Reiko Kishi, Mayumi Ishizuka

  Science of The Total Environment 850 157833  0048-9697 2022/08 [Refereed][Not invited]
   

  Lead (Pb) pollution and human exposure to Pb, is an important issue for the international community to address being associated with 0.90 million deaths from long-term effects. The Republic of Zambia is a typical mineral resource-rich country, with long-standing mining and smelting activities of metals including Pb in several parts of the country. This narrative review provides a comprehensive overview of previous papers that have assessed human exposure to Pb and related health effects in Zambia. Environmental remediation methods that should be applied locally, ways to reduce Pb exposure of the population, and issues that need to be addressed by various sectors are discussed. Environmental remediation methods using locally available and affordable materials are needed to ensure both sustainable industrial activities and pollution prevention. In the Zambian mining towns, including Kabwe, various research activities have been conducted, including environmental monitoring, human biomonitoring and health impact assessments. The town of Kabwe, which was one of Zambia's largest Pb mining area in the 20th century, continues to have formal and informal Pb-related industries and is known as one of the most polluted areas in the world. For example, despite the World Health Organization asserting that “For an individual with a blood Pb concentration ≥ 5 μg/dL, appropriate action should be taken to terminate exposure”, there are reports of blood Pb levels in Kabwe children exceeding 100 μg/dL. While Pb pollution is a global issue, not many places have such continuous and comprehensive research has been conducted, and there is much to be learned from the knowledge accumulated in these areas. Because the high levels of Pb accumulation in humans and the adverse health effects were clarified, we consider that it is important to combine mining activities, which are a key industry, with measures to prevent environmental pollution.
• Molecular Interactions of Normal and Irradiated Tubulins During Polymerization.

  Hisanori Fukunaga, Yuka Kimura, Ami Suzuki, Yuki Kawabata, Akinari Yokoya

  Radiation Research Radiation Research Society 198 (2) 200 - 203 0033-7587 2022/08 [Refereed][Not invited]
   

  Microtubules, one of the cytoskeletons, are highly dynamic structures that play a variety of roles in maintaining cell morphology, cell division and intracellular transport. Microtubules are composed of heterodimers of α- and β-tubulins, which are repeatedly polymerized and depolymerized. To investigate the radiation-induced impacts on the polymerization reaction of tubulins, we evaluated the molecular interactions between normal and irradiated tubulins. First, the polymerization reaction of the tubulins was measured after stepwise irradiation from 0 Gy to 1,000 Gy of X rays. The polymerization was inhibited in a dose-dependent manner. Next, the tubulins' polymerization reaction was then measured after the tubulin that was damaged from the exposure to 1,000 Gy of X rays was mixed with the normal tubulins. Our findings reveal that the radiation dose-dependent change in the degree of overall microtubule polymerization progression depends on the ratio of damaged tubulin. This result is biochemical evidence that non-DNA damage (in this case, cytoskeletal damage) from cytoplasmic radiation exposure may inhibit cell division, suggesting that some cytoskeletal damage may also affect the fate of the entire cell.
• Application of a mouse ex vivo spermatogenesis model to elucidate the mechanism of radiotherapy-related male infertility.

  Kiichi Kaminaga, Akinari Yokoya, Hisanori Fukunaga

  RADIOISOTOPES 日本アイソトープ協会 71 (1) 35 - 40 1884-4111 2022/03/15 [Refereed][Not invited]
   

  Fertility preservation in radiotherapy is of significance for the quality of life among post-treatment cancer survivors. In this study, using a mouse testicular tissue culture and a common X-ray irradiator, we analyzed the recovery process of spermatogenesis in spatially fractionated radiation fields, suggesting that spermatogonial stem cell migration may be involved in the recovery process. These tissue culture ap-proaches are expected to provide a novel insight into the mechanisms of radiotherapy-related male infertility.
• Features of accelerator-based neutron source for boron neutron capture therapy calculated by particle and heavy ion transport code system (PHITS).

  Yusuke Matsuya, Tamon Kusumoto, Yoshie Yachi, Yuho Hirata, Misako Miwa, Masayori Ishikawa, Hiroyuki Date, Yosuke Iwamoto, Shigeo Matsuyama, Hisanori Fukunaga

  AIP Advances 12 (2) 025013  2022/02/10 [Refereed][Not invited]
   

  Accelerator-based neutron sources have been developed and installed in recent decades for boron neutron capture therapy (BNCT) in several clinical facilities. Lithium is one of the targets that can produce epithermal neutrons from the 7Li(p,n)7Be near-threshold reaction, and accelerator-based BNCT systems employing a Li target are promising for cancer treatment. The accurate evaluation of the characteristics of an accelerator-based neutron source is a key to estimating the therapeutic effects of the accelerator-based BNCT. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo code, which can simulate a variety of diverse particle types and nuclear reactions. The latest PHITS code enables simulating the generation of neutrons from the 7Li(p,n)7Be reactions by using the Japanese Evaluated Nuclear Data Library 4.0 high-energy file. Thus, the PHITS code can be adopted for dose estimation during treatment planning for the accelerator-based BNCT. In this study, we evaluated the neutron fluence using the PHITS code by comparing it to reference data. The subsequent neutron transport simulations were performed to evaluate the boron trifluoride detector responses and the recoiled proton fluence detected by a CR-39 plastic detector. These comparative studies confirmed that the PHITS code can accurately simulate neutrons generated from an accelerator using a Li target. The PHITS code has a significant potential for a detailed evaluation of neutron fields and for predicting the therapeutic effects of the accelerator-based BNCT.
• A Brief Overview of Radiation-Induced Effects on Spermatogenesis and Oncofertility.

  Hisanori Fukunaga, Akinari Yokoya, Kevin M. Prise

  Cancers 14 (3) 805  2022/02/04 [Refereed][Invited]
   

  The genotoxicity of radiation on germ cells may be passed on to the next generation, thus its elucidation is not only a scientific issue but also an ethical, legal, and social issue in modern society. In this article, we briefly overview the effects of radiation on spermatogenesis and its associated genotoxicity, including the latest findings in the field of radiobiology. The potential role of transgenerational effects is still poorly understood, and further research in this area is desirable. Furthermore, from the perspective of oncofertility, we discuss the historical background and clinical importance of preserving male fertility during radiation treatment and the potential of microbeam radiotherapy. We hope that this review will contribute to stimulating further discussions and investigations for therapies for pediatric and adolescent/young adult patients.
• Stem Cell Migration: A Possible Mechanism for the Tissue-Sparing Effect of Spatially Fractionated Radiation.

  Hisanori Fukunaga

  Radiation Research Radiation Research Society 196 (6) 680 - 685 0033-7587 2021/12 [Refereed][Invited]
   

  Stem cell responses in tissues after exposure to radiation are of significance for maintaining tissue functions. From the point of view of stem cell characteristics, this article seeks to illustrate some contributions of microbeam research to spatially fractionated radiotherapy (SFRT), such as grid radiotherapy and microbeam radiotherapy. Although the tissue-sparing response after SFRT was first reported more than a century ago, current radiation dose-volume metrics are still unable to accurately predict such tissue-level changes in response to spatially fractionated radiation fields. However, microbeam approaches could contribute to uncovering the mechanisms of tissue response, significantly improving the outcomes of SFRT and reducing its adverse effects. Studies with microbeams have shown that the testicular tissue-sparing effect for maintaining spermatogenesis after exposure to spatially fractionated radiation depends on biological parameters, such as the radiation dose distribution at the microscale level for tissue-specific stem cells and the microenvironment, or niche. This indicates that stem cell survival, migration, and repopulation are involved in the tissue-level changes during or after SFRT. The illustration of microbeam applications in this article focuses on the stem cell migration as a possible mechanism of the tissue-sparing effect for preserving functionality.
• No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields.

  Hisanori Fukunaga, Kiichi Kaminaga, Eri Hirose, Ritsuko Watanabe, Noriko Usami, Kevin M. Prise, Akinari Yokoya

  International Journal of Molecular Sciences 22 (23) 12785  2021/11/26 [Refereed][Not invited]
   

  The non-targeted effects of radiation have been known to induce significant alternations in cell survival. Although the effects might govern the progression of tumor sites following advanced radiotherapy, the impacts on the intercellular control of the cell cycle following radiation exposure with a modified field, remain to be determined. Recently, a fluorescent ubiquitination-based cell-cycle indicator (FUCCI), which can visualize the cell-cycle phases with fluorescence microscopy in real time, was developed for biological cell research. In this study, we investigated the non-targeted effects on the regulation of the cell cycle of human cervical carcinoma (HeLa) cells with imperfect p53 function that express the FUCCI (HeLa–FUCCI cells). The possible effects on the cell-cycle phases via soluble factors were analyzed following exposure to different field configurations, which were delivered using a 150 kVp X-ray irradiator. In addition, using synchrotron-generated, 5.35 keV monochromatic X-ray microbeams, high-precision 200 µm-slit microbeam irradiation was performed to investigate the possible impacts on the cell-cycle phases via cell–cell contacts. Collectively, we could not detect the intercellular regulation of the cell cycle in HeLa–FUCCI cells, which suggested that the unregulated cell growth was a malignant tumor. Our findings indicated that there was no significant intercellular control system of the cell cycle in malignant tumors during or after radiotherapy, highlighting the differences between normal tissue and tumor characteristics.
• A Brief Overview of the Preclinical and Clinical Radiobiology of Microbeam Radiotherapy.

  Hisanori Fukunaga, Karl T. Butterworth, Stephen J. McMahon, Kevin M. Prise

  Clinical Oncology 33 (11) 705 - 712 0936-6555 2021/08/26 [Refereed][Invited]
   

  Microbeam radiotherapy (MRT) is the delivery of spatially fractionated beams that have the potential to offer significant improvements in the therapeutic ratio due to the delivery of micron-sized high dose and dose rate beams. They build on longstanding clinical experience of GRID radiotherapy and more recently lattice-based approaches. Here we briefly overview the preclinical evidence for MRT efficacy and highlight the challenges for bringing this to clinical utility. The biological mechanisms underpinning MRT efficacy are still unclear, but involve vascular, bystander, stem cell and potentially immune responses. There is probably significant overlap in the mechanisms underpinning MRT responses and FLASH radiotherapy that needs to be further defined.
• Mitochondrial DNA Copy Number and Developmental Origins of Health and Disease (DOHaD).

  Hisanori Fukunaga

  International Journal of Molecular Sciences MDPI AG 22 (12) 6634  2021/06/21 [Refereed][Not invited]
   

  Mitochondrial dysfunction is known to contribute to mitochondrial diseases, as well as to a variety of aging-based pathologies. Mitochondria have their own genomes (mitochondrial DNA (mtDNA)) and the abnormalities, such as point mutations, deletions, and copy number variations, are involved in mitochondrial dysfunction. In recent years, several epidemiological studies and animal experiments have supported the Developmental Origin of Health and Disease (DOHaD) theory, which states that the environment during fetal life influences the predisposition to disease and the risk of morbidity in adulthood. Mitochondria play a central role in energy production, as well as in various cellular functions, such as apoptosis, lipid metabolism, and calcium metabolism. In terms of the DOHaD theory, mtDNA copy number may be a mediator of health and disease. This paper summarizes the results of recent epidemiological studies on the relationship between environmental factors and mtDNA copy number during pregnancy from the perspective of DOHaD theory. The results of these studies suggest a hypothesis that mtDNA copy number may reflect environmental influences during fetal life and possibly serve as a surrogate marker of health risks in adulthood.
• Model development for estimating effects of boron neutron capture therapy

  Hisanori Fukunaga, Yusuke Matsuya

  Radiation Biology Research Communications 放射線生物研究会 56 (2) 208 - 223 2021/06 [Refereed][Invited]
   

  Boron neutron capture therapy (BNCT) is a radiation therapy that enables selective eradication of tumors by short-range α-particles and Li ions generated through the nuclear reaction between thermal neutron and 10B within tumor cells. With the development of the accelerator-based neutron source in recent decades, it is expected that BNCT will be available in many medical facilities worldwide in the future. BNCT irradiation requires a relatively long dose-delivery time after applying boron drugs to tumor cells via intravenous injection. During this period, it is suspected that the boron drug is heterogeneously accepted by cells and its concentration changes continuously, leading to the modification of curative effects from pharmacological and biological viewpoints. However, the model development for precisely predicting curative effects after BNCT irradiation is still ongoing. Here, we introduce the forefront of model development for accurately estimating effects during BNCT irradiation. *Japanese Article
• Hokkaido birth cohort study on environment and children's health: cohort profile 2021.

  Reiko Kishi, Atsuko Ikeda-Araki, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Naomi Tamura, Machiko Minatoya, Rahel Mesfin Ketema, Kritika Poudel, Ryu Miura, Hideyuki Masuda, Mariko Itoh, Takeshi Yamaguchi, Hisanori Fukunaga, Kumiko Ito, Houman Goudarzi

  Environmental Health and Preventive Medicine 26 (1) 59 - 59 1342-078X 2021/05/22 [Refereed][Not invited]
   

  BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.
• Disaster-related Deaths in Fukushima.

  Hisanori Fukunaga

  Japanese Journal of Health Physics 56 (1) 26 - 27 0367-6110 2021/03/31 [Refereed][Not invited]
  
• Radiation Exposure Dose Distribution of Workers Engaged in Decontamination and Related Work Following the Fukushima Nuclear Disaster.

  Hisanori Fukunaga, Tsubasa Ogawa, Tomohiro Asano, Atsuo Ito

  Health Physics 120 (3) 251 - 257 0017-9078 2021/03 [Refereed][Not invited]
   

  Since the Fukushima nuclear disaster in March 2011, decontamination operations have been conducted across a wide area of Japan. The Japanese System of Registration and Management of Radiation Exposure Doses for Decontamination and Related Work, which was launched in November 2013, is administered by the Radiation Effects Association with the participation of prime contractors who perform decontamination and related work. This study aims to investigate the radiation exposure dose distribution of workers engaged in decontamination and related work, using data obtained from the above registration system. We analyzed the radiation exposure dose distributions among workers in 11 Fukushima prefectural municipalities (Futaba, Iitate, Katsurao, Kawamata, Kawauchi, Namie, Naraha, Minamisōma, Okuma, Tamura, and Tomioka) from 2013 to 2018. The mean radiation exposure doses of workers in each municipality were generally low, although a Kruskal-Wallis test showed a significant regional difference in the figures. The highest mean dose was 0.5 mSv in Okuma in 2018, and the second highest was that of Futaba. The workers engaged in the land development and construction of the interim facilities may have been exposed to more radiation than other workers across 11 Fukushima prefectural municipalities. Following large-scale nuclear accidents or radiation emergencies, radiation dose monitoring and health management for each worker need to be optimized according to their work assignments.
• Spatially Fractionated Microbeam Analysis of Tissue-sparing Effect for Spermatogenesis.

  Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Karl T. Butterworth, Ritsuko Watanabe, Noriko Usami, Takehiko Ogawa, Akinari Yokoya, Kevin M. Prise

  Radiation Research Radiation Research Society 194 (6) 698 - 706 0033-7587 2020/12 [Refereed][Not invited]
   

  Spatially fractionated radiation therapy (SFRT) has been based on the delivery of a single high-dose fraction to a large treatment area that has been divided into several smaller fields, reducing the overall toxicity and adverse effects. Complementary microbeam studies have also shown an effective tissue-sparing effect (TSE) in various tissue types and species after spatially fractionated irradiation at the microscale level; however, the underlying biological mechanism remains elusive. In the current study, using the combination of an ex vivo mouse spermatogenesis model and high-precision X-ray microbeams, we revealed the significant TSE for maintaining spermatogenesis after spatially fractionated microbeam irradiation. We used the following ratios of the irradiated to nonirradiated areas: 50:50, 150:50 and 350:50 µm-slit, where approximately 50, 75 and 87.5% of the sample was irradiated (using center-to-center distances of 100, 200 and 400 µm, respectively). We found that the 50 and 75% micro-slit irradiated testicular tissues showed an almost unadulterated TSE for spermatogenesis, whereas the 87.5% micro-slit irradiated tissues showed an incomplete TSE. This suggests that the TSE efficiency for spermatogenesis is dependent on the size of the nonirradiated spermatogonial stem cell pool in the irradiated testicular tissues. In addition, there would be a spatiotemporal limitation of stem cell migration/competition, resulting in the insufficient TSE for 87.5% micro-slit irradiated tissues. These stem cell characteristics are essential for the accurate prediction of tissue-level responses during or after SFRT, indicating the clinical potential for achieving better outcomes while preventing adverse effects.
• The Effect of Low Temperatures on Environmental Radiation Damage in Living Systems: Does Hypothermia Show Promise for Space Travel?

  Hisanori Fukunaga

  International Journal of Molecular Sciences 21 (17) 6349  2020/09/01 [Refereed][Not invited]
   

  Low-temperature treatments (i.e., hypothermia) may be one way of regulating environmental radiation damage in living systems. With this in mind, hibernation under hypothermic conditions has been proposed as a useful approach for long-term human space flight. However, the underlying mechanisms of hypothermia-induced radioresistance are as yet undetermined, and the conventional risk assessment of radiation exposure during hibernation remains insufficient for estimating the effects of chronic exposure to galactic cosmic rays (GCRs). To promote scientific discussions on the application of hibernation in space travel, this literature review provides an overview of the progress to date in the interdisciplinary research field of radiation biology and hypothermia and addresses possible issues related to hypothermic treatments as countermeasures against GCRs. At present, there are concerns about the potential effects of chronic radiation exposure on neurological disorders, carcinogenesis, ischemia heat failures, and infertility in astronauts; these require further study. These concerns may be resolved by comparing and integrating data gleaned from experimental and epidemiological studies.
• Alzheimer’s Disease and Specialized Pro-Resolving Lipid Mediators: Do MaR1, RvD1, and NPD1 Show Promise for Prevention and Treatment?

  Keishi Miyazawa, Hisanori Fukunaga, Yasuko Tatewaki, Yumi Takano, Shuzo Yamamoto, Tatsushi Mutoh, Yasuyuki Taki

  International Journal of Molecular Sciences 21 (16) 5783  2020/08/12 [Refereed][Not invited]
   

  Alzheimer’s disease (AD) is a common neurodegenerative disease and a major contributor to progressive cognitive impairment in an aging society. As the pathophysiology of AD involves chronic neuroinflammation, the resolution of inflammation and the group of lipid mediators that actively regulate it—i.e., specialized pro-resolving lipid mediators (SPMs)—attracted attention in recent years as therapeutic targets. This review focuses on the following three specific SPMs and summarizes their relationships to AD, as they were shown to effectively address and reduce the risk of AD-related neuroinflammation: maresin 1 (MaR1), resolvin D1 (RvD1), and neuroprotectin D1 (NPD1). These three SPMs are metabolites of docosahexaenoic acid (DHA), which is contained in fish oils and is thus easily available to the public. They are expected to become incorporated into promising avenues for preventing and treating AD in the future.
• Radiation Tissue Biology with Microbeams and Tissue Cultures as an Interface of Health Physics and Radiobiology

  Hisanori Fukunaga, Akinari Yokoya

  Japanese Journal of Health Physics 日本保健物理学会 55 (2) 92 - 96 0367-6110 2020/07/20 [Refereed][Not invited]
   

  Tissue is a complex system with a highly dynamic structure to maintain a stable internal environment. The homeostatic mechanisms could be involved in radiation-induced effects at the tissue level. Also, tissue-weighting factors have been regarded as an essential index for the guideline released from the International Committee on Radiological Protection. Thus, for both radiobiology and health physics, it is important to understand radiation-induced tissue-level responses. The applications of microbeams and tissue cultures illustrated in this article focus on their relevance to radiation tissue biology that provides a novel approach for greater accuracy in risk assessment of radiation exposure. We review on recent progress in both microbeams and tissue cultures, which is promising for providing novel insights into radiation tissue biology. In addition, we present the use of ex vivo mouse testicular tissue culture as an experimental model of spermatogenesis to investigate radiobiological effects with microbeams. Our model represents a unique application in the field, with significant potential for deeper mechanistic insight into radiation-induced tissue-level effects and appropriate radiological protection. *Japanese Article
• Implications of radiation microdosimetry for accelerator-based boron neutron capture therapy: A radiobiological perspective.

  Hisanori Fukunaga, Yusuke Matsuya, Koichi Tokuuye, Motoko Omura

  British Journal of Radiology 93 20200311  2020/05/06 [Refereed][Not invited]
   

  Boron neutron capture therapy (BNCT) has great potential to selectively destroy cancer cells while sparing surrounding normal cells. The basic concept of BNCT was developed in the 1930s, but it has not yet been commonly used in clinical practice, even although there is now a large number of experimental and translational studies demonstrating its marked therapeutic potential. With the development of neutron accelerators that can be installed in medical institutions, accelerator-based BNCT is expected to become available at several medical institutes around the world in the near future. In this commentary, from the point of view of radiation microdosimetry, we discuss the biological effects of BNCT, especially the underlying mechanisms of compound biological effectiveness. Radiobiological perspectives provide insight into the effectiveness of BNCT in creating a synergy effect in the field of clinical oncology.
• A Model for Estimating Dose-Rate Effects on Cell-Killing of Human Melanoma after Boron Neutron Capture Therapy.

  Yusuke Matsuya, Hisanori Fukunaga, Motoko Omura, Hiroyuki Date

  Cells 9 (5) 1117  2020/04/30 [Refereed][Not invited]
   

  Boron neutron capture therapy (BNCT) is a type of radiation therapy for eradicating tumor cells through a 10B(n,α)7Li reaction in the presence of 10B in cancer cells. When delivering a high absorbed dose to cancer cells using BNCT, both the timeline of 10B concentrations and the relative long dose-delivery time compared to photon therapy must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such changes have not yet been evaluated. Here, we propose an improved integrated microdosimetric-kinetic model that accounts for changes in microdosimetric quantities and dose rates depending on the 10B concentration and investigate the cell recovery (dose-rate effects) of melanoma during BNCT irradiation. The integrated microdosimetric-kinetic model used in this study considers both sub-lethal damage repair and changes in microdosimetric quantities during irradiation. The model, coupled with the Monte Carlo track structure simulation code of the Particle and Heavy Ion Transport code System, shows good agreement with in vitro experimental data for acute exposure to 60Co γ-rays, thermal neutrons, and BNCT with 10B concentrations of 10 ppm. This indicates that microdosimetric quantities are important parameters for predicting dose-response curves for cell survival under BNCT irradiations. Furthermore, the model estimation at the endpoint of the mean activation dose exhibits a reduced impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) compared to 60Co γ-rays irradiation with low LET. Throughout this study, we discuss the advantages of BNCT for enhancing the killing of cancer cells with a reduced dose-rate dependency. If the neutron spectrum and the timelines for drug and dose delivery are provided, the present model will make it possible to predict radiosensitivity for more realistic dose-delivery schemes in BNCT irradiations.
• The Tissue-Sparing Effect of Spatially Fractionated X-rays for Maintaining Spermatogenesis: A Radiobiological Approach for the Preservation of Male Fertility after Radiotherapy.

  Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Ritsuko Watanabe, Takehiko Ogawa, Akinari Yokoya, Kevin M Prise

  Journal of Clinical Medicine 9 (4) 1089  2020/04/11 [Refereed][Not invited]
   

  Radiotherapy can result in temporary or permanent gonadal toxicity in male cancer patients despite the high precision and accuracy of modern radiation treatment techniques. Previous radiobiological studies have shown an effective tissue-sparing response in various tissue types and species following exposure to spatially fractionated radiation. In the present study, we used an ex vivo mouse testicular tissue culture model and a conventional X-ray irradiation device to evaluate the tissue-sparing effect (TSE) of spatially fractionated X-rays for the protection of male fertility from radiotherapy-related adverse effects. We revealed a significant TSE for maintaining spermatogenesis in the ex vivo testes model following spatially fractionated X-ray irradiation. Moreover, we experimentally propose a possible mechanism by which the migration of spermatogonial cells, from the non-irradiated areas to the irradiated ones, in irradiated testicular tissue, is essential for the TSE and maintaining spermatogenesis. Therefore, our findings demonstrate that the control of TSE following spatially fractionated X-rays in the testes has a considerable potential for clinical application. Interdisciplinary research will be essential for further expanding the applicability of this method as an approach for the preservation of male fertility during or after radiotherapy.
• High-precision microbeam radiotherapy reveals testicular tissue-sparing effects for male fertility preservation.

  Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Karl T. Butterworth, Ritsuko Watanabe, Noriko Usami, Takehiko Ogawa, Akinari Yokoya, Kevin M. Prise

  Scientific Reports 9 (1) 12618  2019/10 [Refereed]
   

  Microbeam radiotherapy (MRT) is based on a spatial fractionation of synchrotron X-ray microbeams at the microscale level. Although the tissue-sparing effect (TSE) in response to non-uniform radiation fields was recognized more than one century ago, the TSE of MRT in the testes and its clinical importance for preventing male fertility remain to be determined. In this study, using the combination of MRT techniques and a unique ex vivo testes organ culture, we show, for the first time, the MRT-mediated TSE for the preservation of spermatogenesis. Furthermore, our high-precision microbeam analysis revealed that the survival and potential migration steps of the non-irradiated germ stem cells in the irradiated testes tissue would be needed for the effective TSE for spermatogenesis. Our findings indicated the distribution of dose irradiated in the testes at the microscale level is of clinical importance for delivering high doses of radiation to the tumor, while still preserving male fertility.
• Updated understanding of WRN variants using the Japanese whole‐genome reference panel 3.5KJPNv2.

  Hisanori Fukunaga, Kevin M Prise, Yasuyuki Taki

  Geriatrics & Gerontology International 19 (9) 961 - 962 1444-1586 2019/09 [Refereed][Not invited]
  
• Diversity of ATM gene variants: a population-based genome data analysis for precision medicine.

  Hisanori Fukunaga, Yasuyuki Taki, Kevin M. Prise

  Human Genomics 13 (1) 38  1473-9542 2019/08 [Refereed][Not invited]
   

  Background Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder that causes deficiency or dysfunction of the ataxia-telangiectasia mutated (ATM) protein. Not only AT patients, but also certain ATM heterozygous mutation carriers show a significantly reduced life expectancy due to cancer and ischemic heart disease; in particular, female carriers having particular alleles have an increased risk of breast cancer. The frequency of such risk heterozygotes at a population level remains to be fully determined, and evidence-based preventive medical guidelines have not yet been established. Methods Using the 3.5KJPNv2 allele frequency panel of Japanese Multi Omics Reference Panel v201902, which shows single-nucleotide variant (SNV) and insertion/deletion (INDEL) allele frequencies from 3552 Japanese healthy individuals, we investigated the diversity of ATM gene variants. Results We detected 2845 (2370 SNV and 475 INDEL) variants in the ATM gene, including 1338 (1160 SNV and 178 INDEL) novel variants. Also, we found a stop-gained SNV (NC_000008.11:g.108115650G > A (p.Trp266*)) and a disruptive-inframe-deletion (NC_000008.11:g. 108181014AAGAAAAGTATGGATGATCAAG/A (p.Ala1945_Phe1952delinsVal) and two frameshift INDELs (NC_000008.11:g.108119714CAA/C (p.Glu376fs) and NC_000008.11:g.108203577CTTATA/C (p.Ile2629fs)), which would be novel variants predicted to lead to loss of ATM functionality. Conclusion The combination of population-based biobanking and human genomics provided a novel insight of diversity of ATM gene variants at a population level. For the advancement of precision medicine, such approach will be useful to predict novel pathogenic/likely pathogenic variants in the ATM gene and to establish preventive medical guidelines for certain ATM heterozygotes pertaining to their risk of particular diseases.
• Precision Radiotherapy and Radiation Risk Assessment: How Do We Overcome Radiogenomic Diversity?

  Hisanori Fukunaga, Akinari Yokoya, Yasuyuki Taki, Karl T. Butterworth, Kevin M. Prise

  The Tohoku Journal of Experimental Medicine 247 (4) 223 - 235 0040-8727 2019/04 [Refereed][Not invited]
   

  Precision medicine is a rapidly developing area that aims to deliver targeted therapies based on individual patient characteristics. However, current radiation treatment is not yet personalized; consequently, there is a critical need for specific patient characteristics of both tumor and normal tissues to be fully incorporated into dose prescription. Furthermore, current risk assessment following environmental, occupational, or accidental exposures to radiation is based on population effects, and does not account for individual diversity underpinning radiosensitivity. The lack of personalized approaches in both radiotherapy and radiation risk assessment resulted in the current situation where a population-based model, effective dose, is being used. In this review article, to stimulate scientific discussion for precision medicine in both radiotherapy and radiation risk assessment, we propose a novel radiological concept and metric – the personalized dose and the personalized risk index – that incorporate individual physiological, lifestyle-related and genomic variations and radiosensitivity, outlining the potential clinical application for precision medicine. We also review on recent progress in both genomics and biobanking research, which is promising for providing novel insights into individual radiosensitivity, and for creating a novel conceptual framework of precision radiotherapy and radiation risk assessment.
• Non-uniform radiation-induced biological responses at the tissue level involved in the health risk of environmental radiation: a radiobiological hypothesis.

  Hisanori Fukunaga, Kevin M. Prise

  Environmental Health 17 (1) 93  1476-069X 2018/12 [Refereed][Not invited]
   

  Background: The conventional concept of radiation protection is based on epidemiological studies of radiation that support a positive correlation between dose and response. However, there is a remarkable difference in biological responses at the tissue level, depending on whether radiation is delivered as a uniform or non-uniform spatiotemporal distribution due to tissue sparing effects (TSE). From the point of view of radiation micro-dosimetry, environmental radiation is delivered as a non-uniform distribution, and radiation-induced biological responses at the tissue level, such as TSE, would be implicated in individual risk following exposure to environmental radiation. Hypothesis: We hypothesize that the health risks of non-uniform radiation exposure are lower than the same dose at a uniform exposure, due to TSE following irradiation. Testing the hypothesis requires both radiobiological studies using high-precision microbeams and the epidemiological data of environmental radiation-induced effects. The implications of the hypothesis will lead to more personalized approaches in the field of environmental radiation protection. Conclusion: The detection of spatiotemporal dose distribution could be of scientific importance for more accurate individual risk assessment of exposure to environmental radiation. Further radiobiological studies on non-uniform radiation-induced biological responses at the tissue level are expected.
• Microbeam evolution: from single cell irradiation to pre-clinical studies

  Mihaela Ghita, Cristian Fernandez-Palomo, Hisanori Fukunaga, Pil M. Fredericia, Giuseppe Schettino, Elke Bräuer-Krisch, Karl T. Butterworth, Stephen J. McMahon, Kevin M. Prise

  International Journal of Radiation Biology 94 (8) 708 - 718 0955-3002 2018/07/28 [Refereed][Invited]
  
• Application of an Ex Vivo Tissue Model to Investigate Radiobiological Effects on Spermatogenesis

  Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Noriko Usami, Ritsuko Watanabe, Karl T. Butterworth, Takehiko Ogawa, Akinari Yokoya, Kevin M. Prise

  Radiation Research 189 (6) 661 - 667 1938-5404 2018/06/01 [Refereed][Not invited]
   

  The formation of sperm by the testes through the process of spermatogenesis is highly radiosensitive and can be affected by environmental, occupational and therapeutic radiation exposures. In this study, we applied an ex vivo mouse testis organ culture as an experimental model of spermatogenesis to investigate the radiobiological effects and to demonstrate its feasibility as a tool to determine response to complex, modulated radiation fields. This model uses Acr-GFP transgenic mice, which express the marker green fluorescent proteins specific for meiosis to allow observation of functional changes in real-time that can be used to analyze radiation-induced changes in the process of spermatogenesis. Our results showed that the model can accurately reproduce radiation-induced male germ cell toxicity, such as temporary infertility and permanent sterility. Furthermore, using a monochromatic X-ray microbeam, we applied this model to investigate the effects of heterogeneous radiation fields on testis tissue ex vivo. Our model represents a unique application in the field, which offers significant potential for gaining further mechanistic insight into radiation effects on the process of spermatogenesis.
• A case of low-grade primary cardiac lymphoma with pericardial effusion diagnosed by combined18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) imaging and effusion cytology

  Hisanori Fukunaga, Yasuko Tatewaki, Tatsushi Mutoh, Hideo Shimomura, Shuzo Yamamoto, Chiaki Terao, Tomoko Totsune, Manabu Nakagawa, Yasuyuki Taki

  American Journal of Case Reports 19 292 - 295 1941-5923 2018/03/14 [Refereed][Not invited]
   

  Objective: Rare disease Background: Primary cardiac lymphoma is rare and can be an aggressive disease, depending on the grade. A case is reported of low-grade primary cardiac lymphoma associated with a pericardial effusion. 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) imaging was useful in the diagnosis and in evaluating the disease activity in this case. Case Report: A 72-year-old Japanese woman visited a general practitioner, complaining of dyspnea associated with cardiac tamponade. Pericardiocentesis was performed, and Group V malignant cells were identified by cytology, suspicious for malignant lymphoma. Whole-body FDG-PET/CT scans showed no pleural effusion or lymph node metastasis supporting the diagnosis of primary cardiac lymphoma diagnosed on pericardial effusion. The laboratory investigations showed that levels of serum soluble interleukin-2 (IL-2) receptor (sIL-2R), a diagnostic and prognostic marker for malignant lymphoma, were not elevated (258 U/ml). A six-month follow-up FDG-PET/CT scan showed an increased volume of the pericardial effusion and mild but abnormal uptake diffusely in the pericardial space, and the sIL-2R was slightly elevated (860 U/ml). No abnormal FDG accumulation outside the retained pericardial effusion was noted, which was compatible with a clinical picture of low-grade primary cardiac lymphoma, and in a period of watchful waiting during the first two years later, the sIL-2R had reduced to 195 U/ml. Conclusions: This is a rare case of low-grade primary cardiac lymphoma detected in a pericardial effusion, and highlights the utility of the FDG-PET/CT scan as a valuable diagnostic and follow-up modality.
• Low-dose radiation-induced risk in spermatogenesis

  Hisanori Fukunaga, Karl T. Butterworth, Akinari Yokoya, Takehiko Ogawa, Kevin M. Prise

  International Journal of Radiation Biology 93 (12) 1291 - 1298 0955-3002 2017/12/02 [Refereed][Not invited]
  
• Neuro-myelomatosis of the brachial plexus – An unusual site of disease visualized by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT): A case report

  Hisanori Fukunaga, Tatsushi Mutoh, Yasuko Tatewaki, Hideo Shimomura, Tomoko Totsune, Chiaki Terao, Hidemitsu Miyazawa, Yasuyuki Taki

  American Journal of Case Reports 18 478 - 481 1941-5923 2017/05/01 [Refereed][Not invited]
   

  Objective: Rare disease Background: Peripheral or cranial nerve root dysfunction secondary to invasion of the CNS in multiple myeloma is a rare clinical event that is frequently mistaken for other diagnoses. We describe the clinical utility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scanning for diagnosing neuro-myelomatosis. Case Report: A 63-year-old woman whose chief complaints were right shoulder and upper extremity pain underwent MRI and 18F-FDG PET/CT scan. MRI revealed a non-specific brachial plexus tumor. 18F-FDG PET/CT demonstrated intense FDG uptake in multiple intramedullary lesions and in the adjacent right brachial plexus, indicating extramedullary neural involvement associated with multiple myeloma, which was confirmed later by a bone marrow biopsy. Conclusions: This is the first reported case of neuro-myelomatosis of the brachial plexus. It highlights the utility of the 18F-FDG PET/CT scan as a valuable diagnostic modality.
• An autopsy of intravascular large B-cell lymphoma with hemophagocytic syndrome

  Hisanori Fukunaga, Kazumasa Kawashima, Hiromi Kumakawa, Yuko Hashimoto, Yuta Takahashi

  JRSM Open 8 (5) 205427041769505 - 205427041769505 2054-2704 2017/05 [Refereed][Not invited]
   

  Intravascular large B-cell lymphoma presents with highly variable symptoms caused by the occlusion of small vessels by neoplastic cells in a variety of organs.
• Radiobiological Implications of Fukushima Nuclear Accident for Personalized Medical Approach

  Hisanori Fukunaga, Akinari Yokoya, Yasuyuki Taki, Kevin M. Prise

  The Tohoku Journal of Experimental Medicine 東北ジャーナル刊行会 242 (1) 77 - 81 0040-8727 2017/05 [Refereed][Not invited]
   

  On March 11, 2011, a devastating earthquake and subsequent tsunami caused serious damage to areas of the Pacific coast in Fukushima prefecture and prompted fears among the residents about a possible meltdown of the Fukushima Daiichi Nuclear Power Plant reactors. As of 2017, over six years have passed since the Fukushima nuclear crisis and yet the full ramifications of the biological exposures to this accidental release of radioactive substances remain unclear. Furthermore, although several genetic studies have determined that the variation in radiation sensitivity among different individuals is wider than expected, personalized medical approaches for Fukushima victims have seemed to be insufficient. In this commentary, we discuss radiobiological issues arising from low-dose radiation exposure, from the cell-based to the population level. We also introduce the scientific utility of the Integrative Japanese Genome Variation Database (iJGVD), an online database released by the Tohoku Medical Megabank Organization, Tohoku University that covered the whole genome sequences of 2,049 healthy individuals in the northeastern part of Japan in 2016. Here we propose a personalized radiation risk assessment and medical approach, which considers the genetic variation of radiation sensitivity among individuals, for next-step developments in radiological protection.

• Collision tumor with diffuse large B cell lymphoma and gastric cancer.

  Fukunaga H, Asama H, Kaneda H, Takahashi Y

  Japanese Journal of Clinical Oncology 46 (10) 968 - 969 0368-2811 2016/10 [Refereed][Not invited]
  
• Now Is the Time to Consider Personalized Effective Dose.

  Fukunaga H, Yokoya A, Taki Y

  International Journal of Radiation Oncology, Biology, Physics 96 (2) 479 - 480 0360-3016 2016/10 [Refereed][Not invited]
  
• Unsung Heroes Throughout the 2011 Fukushima Catastrophe.

  Fukunaga H, Sato M

  Family Medicine 48 (6) 482 - 483 0742-3225 2016/06 [Refereed][Not invited]
  
• Clinical examinations after the Fukushima disaster: a case report of Soma General Hospital.

  Fukunaga H, Hoshi Y, Takahashi Y

  Clinical Chemistry and Laboratory Medicine 54 (4) e133 - e134 1434-6621 2016/04 [Refereed][Not invited]
  
• Asymptomatic Primary Malignant Melanoma of the Gastroesophageal Junction.

  Fukunaga H, Kaneda H, Kumakawa H, Takahashi Y

  Internal Medicine 日本内科学会 55 (6) 709 - 710 0918-2918 2016/03 [Refereed][Not invited]
  
• Hemodialysis after the Fukushima disaster: a case report of Soma General Hospital.

  Fukunaga H, Manome M

  Clinical and Experimental Nephrology 日本腎臓学会 20 (1) 151 - 152 1342-1751 2016/02 [Refereed][Not invited]
  
• Low-dose radiation risk and individual variation in radiation sensitivity in Fukushima.

  Fukunaga H, Yokoya A

  Journal of Radiation Research 日本放射線影響学会 57 (1) 98 - 100 0449-3060 2016/01 [Refereed][Not invited]
   

  *Special Article Collection - Fukushima（福島論文コレクション）に選出
• Pharmaceutical Service after the Fukushima Disaster: A Case Report of Soma General Hospital.

  Hisanori Fukunaga, Toshiyuki Momonoi, HIromi Kumakawa

  Yakugaku Zasshi 日本薬学会 136 (1) 139 - 142 0031-6903 2016/01 [Refereed][Not invited]
   

  Despite being damaged by the 2011 Tohoku earthquake, tsunami, and nuclear disaster, Soma General Hospital, located approximately 40 km north of Fukushima Daiichi nuclear power plant, was able to fulfill its role as a key regional hospital in northeast Fukushima. To elucidate the pharmaceutical service in response to the disaster, we investigated the hospital's operations in 2011 according to the medical records and prescriptions. One of the difficulties that the department of pharmaceutical service faced at that time was the increase in emergency healthcare requests by evacuated patients from other hospitals and clinics. Herein, we propose the following countermeasures to be considered in future disaster preparations: (1) establishing a medical and pharmaceutical service coordinator for disaster relief; (2) sharing all local patients' medical information in emergencies (at least contraindicated drugs or allergy history); and (3) reviewing disaster stockpiles, especially pharmaceuticals (both at the hospital and in nearby locations). *Japanese Article
• Mental Health Crisis in Northeast Fukushima after the 2011 Earthquake, Tsunami and Nuclear Disaster

  Hisanori Fukunaga, Hiromi Kumakawa

  The Tohoku Journal of Experimental Medicine 237 (1) 41 - 43 0040-8727 2015/09 [Refereed][Not invited]
   

  The great earthquake of 11 March 2011 and resulting tsunami caused serious damage to various areas of the Pacific coast in northeast Fukushima, and all the residents faced fears of meltdown of the reactors at the Fukushima Daiichi Nuclear Power Plant. One of the most seriously affected areas was the district of Soso, located in the northeast part of Fukushima prefecture, with 12 municipalities (Soma City, Minamisoma City, Shinchi Town, Namie Town, Futaba Town, Okuma Town, Tomioka Town, Naraha Town, Hirono Town, litate Village, Katsurao Village and Kawauchi Village). The district of Soso is home to approximately 200,000 residents, many of whom were seriously affected by the threefold disaster. During the subsequent four years, the population of Soso decreased by nearly 10%. In March 2011 before the disaster, five hospitals and two clinics for psychiatric patients, along with 712 inpatients, were operating in the district of Soso. However, as of March 2015, there were only one hospital and three clinics, along with approximately 50 inpatients, although a new mental health clinic in Soma City was opened in 2012 for supporting victims suffering from the disaster. We hereby suggest that the patients and residents of northeast Fukushima may be undergoing mental health crisis. In fact, disaster-related psychological stress could have induced several physical and mental disorders. The mid- and long-term supports are urgently needed not only for psychiatric patients but also for all residents in the district of Soso.
• Radiology After the Fukushima Disaster: A Case Report Of Soma General Hospital

  Hisanori Fukunaga, Shigeyoshi Owada

  Journal of the American College of Radiology 12 (8) 773 - 774 1546-1440 2015/08 [Refereed][Not invited]
  
• After the earthquake, tsunami and nuclear crisis

  Hisanori Fukunaga

  Journal of the Royal Society of Medicine 108 (4) 151 - 152 0141-0768 2015/04 [Refereed][Not invited]
  
• Disaster Management at Soma General Hospital in Response to the Great East Japan Earthquake.

  Fukunaga H, Kumakawa H

  Japan Medical Association Journal : JMAJ 57 (5-6) 331 - 334 1346-8650 2014/12 [Refereed][Invited]
  
• Relative age effect on Nobel laureates in the UK.

  Fukunaga H, Taguri M, Morita S

  JRSM Short Reports 4 (10) 2042533313492514 - 204253331349251 2013 [Refereed][Not invited]
  
• Label-free biomedical imaging of hydrodynamics in single human cells.

  Fukunaga H, Yoshimura H, Nishina Y, Nagashima Y, Tachibana M

  Biomedical Research 31 (3) 177 - 181 0388-6107 2010 [Refereed][Not invited]
   

  Intracellular hydrodynamics is of considerable importance to regulate cellular functions. Using Raman microspectroscopy and imaging, we visualized the time-dependent changes of water concentration in single human acute promyelocytic leukemia HL-60 cells, and also showed the label-free biomedical imaging of water molecules, lipids and proteins for analyzing molecular distribution. Taken together, our results demonstrated that we can distinguish between intracellular water and other major cell components, and that when the physiological status of cells changes with time, the Raman spectral intensities for intracellular water concentration also changes. Therefore, this biospectroscopic analysis of intracellular hydrodynamics can provide biomarkers to examine activities in dynamic living systems, and has significant potential in determining cell specificity for novel therapeutic approaches.

Books etc

• Never Let the Light Fade: Memories of Soma General Hospital in Fukushima

  Hisanori Fukunaga (Single work)
  Amazon Kindle 2018/08 

  Digital Book (ASIN: B07G7XXJ1T)
• Never Let the Light Fade: Memories of Soma General Hospital in Fukushima (Japanese edition)

  Hisanori Fukunaga (Single work)
  Kahoku Shimpo 2017/06 (ISBN: 487341363X) 176

  

Conference Activities & Talks

• Offspring & Next Generation: Introduction of related video and poster presentation.  [Invited]

  Hisanori Fukunaga

  The 7th International Symposium on the System of Radiological Protection (ICRP 2023)  2023/11  Tokyo
• [Cousins Award Finalists] Rethinking tissue reactions to radiation: The tissue-sparing effect as a threshold for radiation-induced male infertility.  [Invited]

  Hisanori Fukunaga, Kevin M. Prise

  The 7th International Symposium on the System of Radiological Protection (ICRP 2023)  2023/11  Tokyo
• Radiation-induced impacts on spermatogenesis.  [Invited]

  Hisanori Fukunaga

  The 53th Annual Meeting of the Japanese Society of Spermatology  2023/10  Sendai
• Lessons Learned from the 2011 Fukushima Nuclear Accident.  [Invited]

  Hisanori Fukunaga

  The 6th FHS International Conference (FHS 2023)  2023/10  Sapporo
• Random Threshold Model: A Low-dose Radiation-induced Risk Assessment Approach Considering Individual Susceptibility to Cancer.  [Not invited]

  Hisanori Fukunaga, Takashi Yanagawa

  The 7th European Radiation Protection Week (ERPW 2023)  2023/10  Dublin
• 環境放射線被ばく後の精子形成と次世代影響  [Invited]

  福永 久典

  JST創発的研究支援事業 「融合の場」第２回  2023/07  東京
• Toward novel radiation technology development and innovation from my ”FOREST" research program  [Invited]

  Hisanori Fukunaga

  The 39th Annual Meeting of the Japan Society of Drug Delivery System  2023/07  Tokyo 

  *若手ワークショップ【創発研究者が語るDDS研究の未来予想図】に登壇 科学技術振興機構による創発的研究支援事業は「多様性と融合による破壊的イノベーションの創出」を目的としている。本事業は、当初2020年度から2022年度まで、学位取得後15年以内の若手研究者を対象に採択し、7年間（最長10年以内）で5000万円の研究助成を行う予定で開始された。この事業への応募から採択に至るまでの経緯など個人的な経験も交えながら、創発研究者として遂行している放射線研究の内容と将来展望について概説する。放射線事故・原子力災害後の環境放射線被ばく、とくに精巣の被ばくから次世代影響がどのように生じるかは依然として明らかになっていない。我々は、時空間的に「不均一なエネルギー付与」という環境放射線被ばくの特徴に着目し、遺伝子改変マウスや生体内イメージングを用いて、精巣被ばくと遺伝的影響を結ぶメカニズムの解明に挑戦している。このような試みは、放射線科学、細胞生物学、生殖医学などの従来の学問領域の垣根を越えて、「遺伝情報の継承」という生命の本質に独自の観点から迫るものであり、とくに次世代へと遺伝情報を精確に伝える巧緻な機構の一端が明らかになる可能性が期待されている。また、本研究から予想される別の成果として、放射線被ばく後の雄性妊孕性温存の開発があり、将来、がん治療における放射線不妊の低減化への応用が期待される。さらに、本研究によって環境放射線被ばく後の生殖能障害の低減化が明らかになれば、新しい放射線生物学・防護学体系の創造につながる可能性もある。例えば国際放射線防護委員会（ICRP）や、原子放射線の影響に関する国連科学委員会（UNSCEAR）のレポート・提言作成に反映されるなど、グローバルな放射線・原子力政策にも影響を与える成果が期待される。本演題を通じて、新しい創発研究の誕生や、ドラッグデリバリーシステム研究分野と放射線研究分野との新しい共同研究の発展にすこしでも貢献することができれば幸いである。
• [AARR Young Scientist Award Lecture] The tissue-sparing effect of microbeam radiotherapy for preserving male fertility  [Invited]

  Hisanori Fukunaga

  The 5th Asian Congress of Radiation Research (ACRR 2022)  2022/11  Mumbai
• Elucidation of physiological significance of mitochondrial DNA copy number  [Not invited]

  Hisanori Fukunaga, Yuma Yamada

  The 8th Hokkaido University Cross-Departmental Symposium  2022/10  Sapporo
• Molecular interactions of normal and X-ray irradiated tubulins during polymerization.  [Not invited]

  Hisanori Fukunaga, Akinari Yokoya

  The 68th Annual Meeting of the Radiation Research Society  2022/10  Waikoloa, Hawaii
• ホウ素中性⼦捕捉療法（BNCT）におけるホウ素線量の細胞周期依存性  [Not invited]

  福永 久典, 松谷 悠佑, 谷内 淑惠, 伊達 広行

  第59回日本放射線腫瘍学会生物部会学術大会  2022/06  札幌
• 環境放射線被ばく後の精子形成と次世代影響  [Invited]

  福永 久典

  JST創発的研究支援事業「融合の場」第１回公開シンポジウム  2022/05  北海道大学
• Environmental Radiation and Health: Implications of the 2011 Fukushima Nuclear Accident.  [Invited]

  Hisanori Fukunaga

  International Online Scientific Seminar CEHS-UA  2021/11  Sapporo (Online) 

  *Joint seminar with the Toxicological Center, University of Antwerp.
• Post-Disaster Health Care: Implications of the 2011 Fukushima Nuclear Accident.  [Invited]

  Hisanori Fukunaga

  Joint KARP-JHPS-CSRP Workshop on "Perspectives of Young Radiation Protection Professionals through Some Issues related to the Fukushima Accident"  2021/08  Deoksan, Chungnam (Web)
  Download
• Stem Cells vs. Radiation: Does radiation exposure induce non-specific acceleration of biological aging?  [Invited]

  Hisanori Fukunaga

  The 9th Symposium of the Smart-Aging Research Center, Tohoku University  2021/02  Sendai 

  Epidemiological and experimental studies have shown that radiation exposure shortens lifespan. Recently, radiation has become associated with a much wider spectrum of age-related diseases, including not only tumor induction but also cardiovascular disease. Radiation-mediated aging appears to be associated with oxidative stress, DNA damage, inflammation, senescence, and carcinogenesis, although there are several molecular and cellular quality controls, such as DNA damage repair and apoptosis. However, tissue-based quality controls, including stem cell competition, remain to be fully determined. Using a combination of high-precision X-ray microbeam techniques and the unique ex vivo spermatogenesis model (1), we demonstrated, for the first time, the tissue-sparing effect (TSE) of spatially fractionated X-rays for the preservation of spermatogenesis (2). TSE is the phenomenon by which normal tissues tolerate single exposures to narrow planes of synchrotron X-rays (micro-planar beams; microbeams) of up to several hundred Gy (3). Our analysis revealed the survival and potential migration steps of non-irradiated germ stem cells in the radiation-exposed testicular tissue that would be needed for effective TSE for spermatogenesis (2). Also, our findings showed that the TSE in irradiated testicular tissue was more effective when more spermatogonial stem cells survived after irradiation (4). These results indicate that non-irradiated stem cell competition for residence in the stem cell niche in the irradiated tissue is important for TSE. This tissue microenvironment–based selection is likely to function as a tissue-based quality control measure after irradiation that is independent of the molecular and cellular quality controls. In addition, we recently demonstrated that the TSE of spatially fractionated X-rays has considerable potential for future clinical applications, as it responds to a wide range of X-ray energy (5). Further investigation into stem cell migration and competition in various tissues and species is expected soon, and the findings of this investigation will provide a special cue to enhancing the benefits of radiotherapy while preventing its adverse effects, as well as to further understanding the tissue-based quality controls, including the role of stem cells, in radiation-mediated aging. [References] (1) Fukunaga, H. et al. Radiat. Res. 189, 661–7 (2018). (2) Fukunaga, H. et al. Sci. Rep. 9, 12618 (2019). (3) Fukunaga, H. & Prise, K. M. Environ. Health 17, 93 (2018). (4) Fukunaga, H. et al. Radiat. Res. 194, 698–706 (2020). (5) Fukunaga, H. et al. J. Clin. Med. 9, 1089 (2020).
  Download
• 福島第一原子力発電所事故後の被災地医療支援から東北メディカル・メガバンク機構でのバイオバンク研究へ  [Invited]

  福永 久典

  2020年度第2回CEHS公開セミナー  2021/02  札幌（Web開催）  北海道大学
  
• A radiogenomic approach for understanding individual differences in radiosensitivity  [Not invited]

  Hisanori Fukunaga

  The 63rd annual meeting of the Japanese Radiation Research Society  2020/10  Fukushima 

  As a means of increasing the effectiveness of radiation treatment while also minimizing its risks, we need a more thorough understanding of individuals’ differences in radiosensitivity. This is challenging, since the underlying mechanisms of this sensitivity remain undetermined. Radiogenomics aims to identify the link between clinical variabilities in responses to radiotherapy and individuals’ genomic biomarkers, with a view to predicting an individual’s response to and the toxicity of radiation therapy. To date, several genes have been proven to be involved in individual radiosensitivity; these include DNA damage response genes (e.g., ATM, ATR, BRCA1/2, LIG4, PTEN, RAD51, WRN, and XRCC1), However, the levels of diversity of these gene variants among the general population are unclear. To address this issue, we conducted a population-based genetic analysis using based on Japanese Multi Omics Reference Panels (jMorp) released by the Tohoku Medical Megabank Organization. In the present study, we investigated the diversity of ATM gene variants and identified 2845 (2370 SNV and 475 INDEL) variants in the gene, including 1338 (1160 SNV and 178INDEL) novel variants. We also found a stop-gained SNV (p.Trp266*), a disruptive-inframe-deletion (p.Ala1945_Phe1952delinsVal), and two frameshift INDELs (p.Glu376fs and p.Ile2629fs), which were variants predicted to lead to a loss of ATM functionality. The combination of population-based biobanking and radiogenomics is capable of providing novel insights into the diversity of ATM gene variants at the population level. In the coming era of precision medicine, such an approach will be useful for increasing the efficacy of radiotherapies while minimizing their risks.
• Radiation-induced bystander effect on the cell cycle of HeLa-FUCCI cells  [Not invited]

  Hisanori Fukunaga, Kiichi Kaminaga, Akinari Yokoya

  The 33rd Annual Meeting of the Japanese Society for Radiation Oncology  2020/10  Sapporo 

  【目的】細胞は細胞間コミュニケーションを介して細胞集団の恒常性を維持している。その集団の一部に放射線照射を受けると、細胞間コミュニケーションを介して、損傷シグナルが集団全体に伝達される。この放射線誘導バイスタンダー効果（RIBE）により放射線非照射を受けていない細胞にもゲノム不安定性、染色体異常、細胞死などが誘発されることが知られているが、細胞周期への影響は未だ十分に明らかになってはいない。そこで本研究では、細胞周期の進行をリアルタイムに観察できる蛍光プローブFUCCIを導入したHeLa細胞を用いて、RIBEによる細胞周期への影響を解析することを目的とする。 【方法】FUCCIを導入したHeLa細胞に放射線を照射すると、G2/M期の遷延が認められる。そこで、HeLa-FUCCI細胞集団の半分に8 Gyを照射し、照射細胞と非照射細胞を同一フラスコで共培養して、両群の細胞周期の変化を解析した。さらに、放射光X線マイクロビームを用いて200 μmスリット照射し、照射細胞と非照射細胞を同一フラスコで共培養して、両群の細胞周期の変化を解析した。 【結果】放射線照射後のHeLa-FUUCI細胞にはG2/M期の遷延が認められたものの、半分照射、マイクロスリット照射ともに、照射群と非照射群の共培養による細胞周期の変化は認められなかった。 【結語】本研究ではRIBEによる細胞周期への影響は明らかではなかった。RIBEは細胞の種類によって程度が異なることでも知られており、今後、他の細胞株を用いるなどの実験系の見直しと、更なる解析が求められる。
• [Umegaki Award Lecture] Tissue-sparing effect of microbeam radiotherapy for preserving male fertility  [Invited]

  Hisanori Fukunaga

  The 33rd Annual Meeting of the Japanese Society for Radiation Oncology  2020/10  Sapporo 

  放射線は、生殖機能に影響し、妊孕性を喪失させる。しかし、その放射線不妊メカニズムは、現在でも十分に明らかになっていない。放射線被ばくによる生物影響は、たとえ同じ被ばく線量であっても、その空間的な線量分布が均一か不均一かによって大きく異なることが先行研究から判っている。そこで、我々は「空間分割照射をうまく活用することで妊孕性を維持できるのではないか」と仮説をたてた。 本研究では、まず精子幹細胞から生殖能のある精子まで分化誘導を可能とするex vivo精巣器官培養法と、減数分裂期特異的にAcr-GFPが精子形成細胞に発現するトランスジェニックマウスを組み合わせた。次に放射光X線マイクロビーム照射装置や、300 μmスリット状照射を可能とする鉛遮蔽材を用いて、精子形成に対する不均一放射線場における生物影響を蛍光顕微鏡下で詳細に解析した。 マイクロビーム照射範囲をストライプ状に設定したところ、精巣体積約50%に当たるように５ Gy照射した場合（すなわち2.5 Gy換算相当）と、2.5 Gyを全体に均一に照射した場合ではAcr-GFP発現の程度に有意な違いが認められた。すなわち、精巣における組織代償効果によって、空間的に不均一な放射線被ばく後で精子形成が維持されることが示された。さらに、この組織代償効果は、様々なエネルギーのX線で生じることも示された。 精巣における組織代償効果の解明と制御は放射線不妊の克服につながる可能性がある。今後、マイクロビーム放射線治療法の臨床応用に向けて、さらなる研究が期待される。
• Radiation exposure dose distribution of workers engaged in decontamination work following the 2011 Fukushima nuclear accident.  [Not invited]

  Hisanori Fukunaga, Tsubasa Ogawa, Tomohiro Asano, Atsuo Ito

  The 93rd annual meeting of the Japan Society for Occupational Health  2020/05  Asahikawa 

  【目的】2011年3月に発生した東日本大震災、福島第一原子力発電所事故後、除染特別地域中心に福島県の広域にわたって除染作業が行われている。2013年11月に「除染等業務従事者等被ばく線量登録管理制度」が発足し、除染等業務を実施する元請事業者の参加を得ながら、公益財団法人放射線影響協会が主体となって運営している。このような除染等業務従事者の被ばく線量モニタリングは他に類を見ない試みであり、今後の除染等業務従事者の健康管理法の策定にも影響しうることから、放射線防護学のみならず産業衛生学の観点からもきわめて重要であると考えられる。本研究では、この除染等業務従事者等被ばく線量登録管理制度を活用し、2013年から2018年にかけて登録された除染等業務従事者の地域別被ばく線量分布の実態について検討することを目的とする。 【方法】2019年5月28日時点の制度参加事業者によって登録された除染特別地域等（飯舘村、大熊町、川内村、川俣町、葛尾村、伊達市、田村市、富岡町、浪江町、楢葉町、双葉町、南相馬市、三春町）における2018年定期線量データを解析し、市町村別の除染等業務従事者の被ばく線量分布を導出した。 【結果】2018年は除染等業務従事者のべ28,417名（複数の市町村で作業した場合はそれぞれに登録）分の被ばく線量データが登録され、うち26,370名（92.7%）の被ばく線量が年間1 mSv以下であった。合計で8,390.7人・mSvであり、平均線量は0.3 mSv（2017年度と同水準）、最大線量は9.6 mSvであった。市町村別は下図の通りであり、平均線量が最も高かったのは大熊町で0.5 mSvであった。 【考察】除染等業務従事者等被ばく線量登録管理制度に2018年に登録された除染等業務従事者等の中で、職業人の被ばく線量限度である年間50 mSvを超える被ばくをした者はおらず、総じて低値であった。大熊町で平均線量が最も高かった背景として、同町の中間貯蔵施設関連業務中の被ばく線量が、他の業務中のものと比較して、相対的に高かった可能性が考えられる。今後、除染等業務の内容に応じた線量モニタリング方法および健康管理方法の最適化が求められるかもしれない。更なるモニタリングデータの蓄積と解析が必要である。
• High-precision X-ray microbeam analysis reveals testes tissue-sparing effects for male fertility preservation.  [Not invited]

  Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Ritsuko Watanabe, Karl T. Butterworth, Takehiko Ogawa, Akinari Yokoya, Kevin M. Prise

  The 16th International Congress of Radiation Research (ICRR 2019)  2019/08  Manchester, UK 

  Background: Infertility is still an unfortunate adverse effect of most cancer therapies, including radiotherapy, as it impacts the quality of life of survivors during their pre-reproductive and reproductive years. Advances in radiation treatment techniques have evolved to a high level of precision and accuracy. However, radiotherapy can still result in gonadal toxicity in male patients. Damage to spermatogenesis can result from either direct radiation of the testes or the scattered dose received during the radiation treatment of cancers, such as prostate, bladder, rectal, and bone cancers. Aim: In this study, we addressed the issue by using microbeam radiotherapy to test for tissue-sparing effects (TSE) to preserve male fertility following radiotherapy. Methods: We used a novel ex vivo mouse testes organ culture as an experimental model of spermatogenesis (Fukunaga et al. Radiat Res 2018). To investigate the TSE of microbeam radiotherapy for spermatogenesis, we performed high-precision 200, 50 and 12.5 μm-slit irradiation, where approximately 50% of the sample was irradiated via a four-dimensional slit system of the X-ray microbeam irradiator. The 5.35 keV monochromatic X-ray microbeam irradiation was performed using the synchrotron beamline BL-27 at the Photon Factory, High Energy Accelerator Research Organization (KEK), Tsukuba, Japan. Results/Conclusions: We report a breakthrough in the field of male fertility, showing, for the first time, a microbeam radiotherapy mediated TSE for spermatogenesis. Also, our high-precision X-ray microbeam analysis showed that the effective TSE require the survival and migration of the non-irradiated germ stem cells in the irradiated testes tissue, indicating its clinical application to preserve male fertility following radiotherapy. Furthermore, our findings resulted in the proposal of a novel fundamental concept, where the dynamics of components in the irradiated tissue, such as specific stem cells and the microenvironment, or niche, regulate the tissue homeostasis for maintaining specific functions in response to non-uniform radiation fields.
• Non-uniform radiation-induced effects on spermatogenesis.  [Invited]

  Fukunaga H

  The 12th Quantum Medicine Annual Meeting  2019/02  Mito  Ibaraki University
   

  背景：低線量あるいは低線量率の放射線による被ばく影響の特徴はその「不均一な線量分布」にある。高線量域においては照射範囲内の全細胞を放射線トラックが複数回通過する（ヒットする）と確率的にみなされるが、低線量域では放射線がヒットする細胞は全体の一部に留まることになる。すなわち、照射範囲内において「放射線がヒットする細胞とヒットしない細胞が混在する」という状況が生じうる。このような不均一な線量分布が生じる低線量域では、高線量域のように線量依存的に生物学的影響を推定することが出来ず、放射線による被ばく影響の評価を困難にしてきた。 目的：本研究では、マウス精巣器官培養法と放射光X線マイクロビームを組み合わせ、「放射線がヒットする細胞とヒットしない細胞が混在する」状況を人為的に作り出し、不均一放射線照射場が精子形成に与える生物学的影響について検討した。 方法：2011年に我々の共同研究グループによって精子幹細胞から生殖能のある精子まで分化誘導を可能とする器官培養法が開発された(Sato et al. Nature 2011)。この系を応用した器官培養上の精巣組織（ex vivo）に対して、放射光X線マイクロビームを用いた精密なマイクロスリット照射を行うことによって、これまで実現不可能だった精子形成に対する不均一放射線照射場影響をリアルタイムで顕微鏡下に観察した。 結果：まず、精巣組織全体に均一にX線を照射して精子形成を検討し、線量依存的に精子形成が一次的あるいは永久的に阻害されるのが確認された（Fukunaga et al. Radiat Res 2018）。これらは臨床的に一時的不姙、永久不妊に相当するものと考えられた。さらに、マイクロビーム照射範囲を操作し、精巣体積約50%に当たるように5Gyを照射した場合（すなわち2.5Gy換算相当）と、2.5Gyを全体に照射した場合で、精子形成阻害の程度に明らかな違い（Tissue-sparing effects）が認められた。 考察：「放射線がヒットする細胞とヒットしない細胞が混在する」という不均一放射線照射場条件では、組織当たり同じ被ばく線量であっても精巣組織内の空間的な照射分布条件の差異によって精子形成に対する放射線影響が変わることが示された。このような組織レベルでの放射線被ばく応答を鑑みると、組織感受性が線量率（時間）、線量分布（空間）などの放射線被ばく条件によって変化する可能性が示唆された。
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• Personalized effective dosimetry for radiation risk assessment and precision medical applications.  [Not invited]

  Hisanori Fukunaga, Akinari Yokoya, Karl T. Butterworth, Kevin M. Prise

  The 3rd European Radiation Protection Week (ERPW 2018)  2018/10  Rovinj, Croatia 

  *Selected for CONCERT Travel Award
• Application of an ex vivo organ culture method to investigate impacts on spermatogenesis following exposure to intensity- and distribution-modulated radiation fields.  [Not invited]

  Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Karl T. Butterworth, Ritsuko Watanabe, Noriko Usami, Takehiko Ogawa, Akinari Yokoya, Kevin M. Prise

  Joint Annual Meeting of the Association for Radiation Research and the Irish Radiation Research Society  2018/06  Belfast, UK
• 精巣器官培養法を用いた精子形成に対する不均一放射線照射場影響に関する検討  [Not invited]

  福永 久典, 神長 輝一, 宇佐美 徳子, 小川 毅彦, Kevin M. Prise, 横谷 明徳

  2017年度量子ビームサイエンスフェスタ（第9回MLFシンポジウム・第35回PFシンポジウム）  2018/03
• Radiobiological Implications of Fukushima nuclear accident and radiation-induced effects on spermatogenesis.  [Invited]

  Hisanori Fukunaga

  Monday Talk (Department of Medical Physics, Northern Ireland Cancer Centre)  2017/12  Belfast, UK 

  *Invited Talk
• Development of an ex vivo spermatogenesis technique for advanced radiotherapeutic science.  [Not invited]

  Hisanori Fukunaga, Kiichi Kaminaga, Takuya Sato, Karl T. Butterworth, Akinari Yokoya, Takehiko Ogawa, Kevin M. Prise

  The 26th Conference of the Federation of National Societies of Biochemistry and Molecular Biology in the Asian and Oceanian Region (ConBio 2017)  2017/12  Kobe, Japan 

  *Selected for QUB Graduate School Travel Support
• Development of personalized effective dosimetry for radiation risk assessment and precision medical applications.  [Not invited]

  Hisanori Fukunaga, Karl T. Butterworth, Kevin M. Prise

  The 1st European Alliance for Personalized Medicine Congress (EAPM 2017)  2017/11  Belfast, UK
• Development of personalized effective dosimetry for radiation risk assessment and clinical applications.  [Not invited]

  Hisanori Fukunaga, Akinari Yokoya, Karl T. Butterworth, Kevin M. Prise

  The 63rd Radiation Research Society Annual Meeting  2017/10  Cancun, Mexico 

  *Selected for RRS Scholar-In-Training Travel Award
• After the Earthquake, Tsunami and Nuclear Crisis - Memories of a Young Doctor.  [Invited]

  Hisanori Fukunaga

  The 12th Asia Oceania Congress of Nuclear Medicine and Biology (AOCNMB 2017)  2017/10  Yokohama, Japan 

  *Invited Talk
• Individual variation in radiosensitivity and personalized radiation risk assessment.  [Not invited]

  Fukunaga H, Yokoya A, Taki Y

  The 54th annual symposium of the Japan Radioisotope Association  2017/07  Tokyo
• Development of personalized effective dosimetry for radiation risk assessment and clinical applications.  [Not invited]

  Hisanori Fukunaga

  The 148th IDAC Bi-Annual Meeting  2017/07  Sendai  Tohoku University
   

  *Selected for the Presentation Award
• A Case of Low-Grade Primary Cardiac Lymphoma with Pericardial Effusion Diagnosed by Combined 18F-Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) Imaging and Effusion Cytology.  [Not invited]

  Fukunaga H, Shimomura H, Tatewaki Y, Terao C, Totsune T, Abe M, Mutoh T, Taki Y, Arai A, Takanami K, Takase K

  The 134th Tohoku-Hokkaido Regional Conference of the Japanese Radiological Society  2016/06  Sapporo, Japan
• Collision tumor with diffuse large B cell lymphoma and gastric cancer: a case report.  [Not invited]

  Fukunaga H

  Fukushima Regional Medical Case Report Symposium  2016/02  Fukushima, Japan 

  *Resident Case Report Grand Prix of Fukushima Medical Association
• Collision tumor with diffuse large B cell lymphoma and gastric cancer.  [Not invited]

  Fukunaga H, Takahashi Y, Asama H, Kawashima K, Kato T, Matsuoka N, Kaneda H, Kumakawa H

  The 155th Tohoku Regional Conference of the Japan Gastroenterological Endoscopy Society  2015/07  Fukushima, Japan
• Asymptomatic primary malignant melanoma of the gastroesophageal junction.  [Invited]

  Fukunaga H, Takahashi Y, Kumakawa H, Yamaki H, Sato M

  Fukushima Regional Medical Case Report Symposium  2014/12  Fukushima, Japan
• A case of bleeding ulcer after left main coronary artery (LMCA) trombosis with acute myocardial infarction.  [Not invited]

  Fukunaga H, Sato M, Ando K, Kawashima K

  The 159th Tohoku Regional Conference of the Japanese Circulation Society  2014/12  Sendai, Japan
• Asymptomatic Primary Malignant Melanoma of the Gastroesophageal Junction in Soma after the 2011 Fukushima Nuclear Accident.  [Not invited]

  Fukunaga H, Takahashi Y, Asama H, Kawashima K, Kumakawa H, Kaneda H

  The 154th Tohoku Regional Conference of the Japan Gastroenterological Endoscopy Society  2014/12  Sendai, Japan
• Blood pressure difference of more than 100 mmHg between arms caused by stenosis of the brachiocephalic trunk.  [Not invited]

  Fukunaga H, Ando K, Sato M

  The 34th Fukushima cardiovascular disease therapy symposium  2014/08  Fukushima, Japan
• Radiation effects on microtubule polymerization.  [Not invited]

  Fukunaga H

  The 49th Japan Radioisotope Association Annual Symposium  2012/04  Tokyo, Japan 

  *Selected for Young Scientist Presentation Award
• Label-free biomedical imaging of hydrodynamics in single human cells.  [Not invited]

  Fukunaga H, Tachibana M, Nagahisma Y, Aoki I

  The 99th Annual Meeting of the Japanese Pathological Society  2010/04  Tokyo, Japan

MISC

• 令和 3 年度（2021） 研究奨励助成金交付研究の紹介：加速器型ホウ素中性子捕捉療法における10B - BPA細胞内濃度・分布 と細胞周期依存性に関する研究

  福永 久典  放影協ニュース  116-  4  -5  2023/10  [Not refereed][Invited]
   

  *令和 3 年度（2021） 研究奨励助成金交付研究の紹介
• The Tissue-Sparing Effect of Microbeam Radiotherapy for Preserving Male Fertility.

  Hisanori Fukunaga  Journal of Radiation and Cancer Research  13-  (4)  176  -177  2022/10  [Refereed][Invited]
  
• マイクロビーム放射線治療における組織代償効果のメカニズム(A Possible Mechanism for the Tissue-Sparing Effect of Microbeam Radiotherapy)

  福永 久典, 横谷 明徳  日本放射線影響学会大会講演要旨集  65回-  12  -12  2022/09
• Investigation of local energy deposition and dose-rate effects in boron neutron capture therapy (BNCT) using the PHITS code

  Hisanori Fukunaga, Yusuke Matsuya, Motoko Omura  JASTRO NEWSLETTER  144-  (3)  9  -10  2022/06  [Not refereed][Invited]
  
• 日中韓合同ワークショップ「福島原発事故に関する諸問題についての若手専門家の展望」の開催の報告

  福永 久典  北海道医報  1243-  30  -31  2022/04  [Not refereed][Invited]
  
• Micro-slit X-ray irradiation reveals testicular tissue-sparing effects: an attempt for high-precision radiotherapy for male fertility preservation

  Hisanori Fukunaga, Kevin M. Prise, Akinari Yokoya  Photon Factory Highlights 2019  54  -55  2020/11  [Not refereed][Invited]
   

  The preservation of male fertility during or after radiotherapy has long been expected for the quality of life for cancer survivors during reproductive years. To approach this clinical issue, we focused on the tissue-sparing effect (TSE) in the testes in response to microbeam radiotherapy (MRT). In this study, we used ex vivo testicular tissue cultures obtained from Acr-GFP transgenic mice and revealed, for the first time, the significant TSE of high-precision MRT for maintaining spermatogenesis using live-tissue fluorescent imaging. This suggests that MRT is a promising approach for preserving male fertility.
• Maintaining spermatogenesis following exposure to micro-slit X-rays for clinical application.

  Hisanori Fukunaga, Akinari Yokoya  Isotope News  771-  (771)  24  -27  2020/10  [Not refereed][Invited]
  
• Prize Winners of Academic Societies 2019

  Hisanori Fukunaga  Tohoku Igaku Zasshi  132-  (1)  72  2020/06  [Not refereed][Invited]
   

  「第33回独創性を拓く先端技術大賞 フジテレビジョン賞」の受賞対象研究『不均一な放射線被ばく後の精子形成能の検討～原子力災害後の環境放射線被ばくリスクの解明を目指して～』に関する概説
• 福島第一原子力発電所事故後の除染等業務従事者の地域別被ばく線量分布

  福永 久典, 小川 翼, 浅野 智宏, 伊藤 敦夫  産業衛生学雑誌  62-  (臨増)  386  -386  2020/05  [Refereed][Not invited]
  
• Maintaining spermatogenesis following exposure to synchrotron micro-slit X-rays

  Hisanori Fukunaga  Radiation Effects Association News  103-  14  -17  2020/04  [Not refereed][Invited]
   

  *令和元年度放射線影響研究奨励賞受賞研究の概要
• 海外留学という宝探し

  福永 久典  放射線治療研究センターたより 週報  53-  1  2019/12  [Not refereed][Invited]
  
• 放射線生物影響の階層性

  福永 久典  放射線治療研究センターたより 週報  52-  1  2019/12  [Not refereed][Invited]
  
• アイルランド代表 街に希望

  福永 久典  読売新聞  (51643)  2019/10  [Not refereed][Not invited]
   

  *英国北アイルランドのカルチャーナイトとラグビーW杯のアイルランド代表（南北合同代表）について寄稿
• 不均一な放射線被ばく後の精子形成能の検討 ～原子力災害後の環境放射線被ばくリスクの解明を目指して～

  福永 久典  独創性を拓く先端技術大賞  2019/07  [Not refereed][Not invited]
   

  *第33回（2019年度）独創性を拓く先端技術大賞・フジテレビジョン賞受賞論文
• 令和 3 年度（2021） 研究奨励助成金交付研究の紹介：精巣器官培養法を用いた不均一な放射線被ばく後の精子形成能の検討

  福永 久典  放影協ニュース  100-  9  -10  2019/07  [Not refereed][Invited]
   

  *平成29年度（2017）研究奨励助成金交付研究の紹介
• 器官培養したマウス精巣に対するすだれ状X線マイクロビーム照射と精子形成に与える影響

  福永 久典, 神長 輝一, 佐藤 卓也, 渡辺 立子, 宇佐美 徳子, 小川 毅彦, 横谷 明徳, Kevin M. Prise  Photon Factory Activity Report 2018  36-  2017G565  2019/07  [Not refereed][Invited]
  
• EU離脱 悲劇繰り返すな

  福永 久典  読売新聞  (51367)  2019/01  [Not refereed][Not invited]
   

  *英国北アイルランド留学中に体験したBrexit（英国のEU離脱）に関する情勢について寄稿
• ウィリスの古里を訪ね

  福永 久典  神奈川新聞  (27443)  2019/01  [Not refereed][Not invited]
   

  *幕末、明治期に活躍した医師ウィリアム・ウィリスの故郷について寄稿
• 日本近代医学の源流を辿って ～ウィリアム・ウィリスとエニスキレン

  福永 久典  倶進会たより  159-  23  -24  2018/04  [Not refereed][Not invited]
  
• Application of an ex vivo organ culture method to investigate impacts on spermatogenesis following exposure to intensity- and distribution-modulated radiation fields

  福永 久典, 神長 輝一, 宇佐美 徳子, 小川 毅彦, Kevin Prise, 横谷 明徳  量子ビームサイエンスフェスタ(Web)  2017-  2018
• 精巣組織器官培養法を用いた放射線照射影響の検討と治療への応用

  福永 久典, 神長 輝一, 佐藤 卓也, Butterworth Karl, 横谷 明徳, 小川 毅彦, Prise Kevin  生命科学系学会合同年次大会  2017年度-  [4AT18  -0500)]  2017/12  [Not refereed][Not invited]
  
• 放射線に挑む ～英国Queen's University Belfast大学院留学記

  福永 久典  倶進会たより  157-  26  -27  2017/10  [Not refereed][Invited]
  
• 被災地・福島での研修が教えてくれたこと

  福永 久典  週刊医学界新聞  (3215)  2017/03  [Not refereed][Invited]
   

  *福島原発事故被災地での臨床研修に関する依頼原稿
• 大規模ゲノムバンクiJGVDを用いた放射線感受性遺伝子変異の検討と個別化放射線被ばくリスク評価

  福永 久典, 横谷 明徳, 瀧 靖之  アイソトープ・放射線研究発表会要旨集  54th-  2017
• 第1回倶進会留学基金を受けるにあたって

  福永 久典  倶進会たより  154-  10  -11  2017/01  [Not refereed][Invited]
  
• 意地、薫り立つ

  福永 久典  日本経済新聞  (46928)  2016/10  [Not refereed][Not invited]
   

  *香大賞・環境大臣賞受賞エッセイ
• 心嚢液貯留に集積亢進を認めたFDG-PET/CTの1例

  福永 久典, 下村 英雄, 舘脇 康子, 寺尾 千秋, 戸恒 智子, 阿部 十也, 武藤 達士, 瀧 靖之, 荒井 晃, 高浪 健太郎, 高瀬 圭  核医学  53-  (1)  567  -567  2016/02  [Not refereed][Not invited]
  
• 研修医日記

  福永 久典  倶進会たより  146-  32  -33  2015/01  [Not refereed][Invited]
  
• Oishinbo's treatment of the Fukushima Daiichi disaster

  Hisanori Fukunaga  Isotope News  728-  28  -29  2014/12  [Not refereed][Not invited]
  
• Birthdays of Nobel Laureates

  Hisanori Fukunaga  Isotope News  708-  (708)  22  -23  2013/04  [Not refereed][Not invited]
  
• Non-invasive intracellular water molecule imaging analysis using Raman microspectroscopy

  Hisanori Fukunaga, Masaru Tachibana, Yoji Nagashima, Ichiro Aoki  Proceedings of the Japanese Society of Pathology  99-  (1)  374  -374  2010/03  [Not refereed][Not invited]
  

Awards & Honors

• 2022/11 AARR Young Scientist Award, Asian Association for Radiation Research (AARR)
   

  受賞者: Hisanori Fukunaga
• 2022/10 Hokkaido University Research Encouragement Award for Young Researchers-Silver Prize
   

  受賞者: 福永 久典
• 2022/09 Nakayama Award for Young Scientists, Nakayama Foundation for Human Science
   「マイクロビームによる精密な空間制御と精子形成能の温存―マイクロビーム放射線治療の開発」 

  受賞者: Hisanori Fukunaga
• 2022/06 Japan Radioisotope Association RADIOISOTOPES Best Paper Award
   Application of a Mouse Ex Vivo Spermatogenesis Model to Elucidate the Mechanism of Radiotherapy-Related Male Infertility 

  受賞者: Kiichi KaminagaAuthors: Kiichi Kaminaga, Akinari Yokoya, Hisanori Fukunaga
• 2021/11 FOREST (Fusion Oriented REsearch for disruptive Science and Technology) program, Japan Science and Technology Agency FOREST elected researcher
   

  受賞者: Hisanori Fukunaga
• 2021/10 Radiation Research Editors' Award, Radiation Research Society
   

  受賞者: Hisanori Fukunaga
• 2021/06 Young Researcher Award, Japan Health Physics Society
   「マイクロビームと組織培養を用いた放射線組織生物学―保健物理学と放射線生物学の接点として―」 

  受賞者: Hisanori Fukunaga
• 2020/10 Umegaki Award, Japanese Society for Radiation Oncology (JASTRO)
   「マイクロビーム放射線治療法による精巣組織代償効果と精子形成維持」 

  受賞者: Hisanori Fukunaga
• 2020/07 LEADER (Leading Initiative for Excellent Young Researchers) program, Japanese Ministry of Education, Culture, Sports, Science and Technology LEADER candidate
   

  受賞者: Hisanori Fukunaga
• 2020/04 Young Radiation Researcher Award, Radiation Effects Association
   「シンクロトロン放射光X線マイクロビームと精巣器官培養法を用いた不均一な放射線被ばく後の精子形成能の検討」 

  受賞者: Hisanori Fukunaga
• 2019/07 Advanced Technology Award (Fuji Television Network Award for Excellent Student Researchers)
   「不均一な放射線被ばく後の精子形成能の検討 ～原子力災害後の環境放射線被ばくリスクの解明を目指して～」 

  受賞者: Hisanori Fukunaga主催：フジサンケイ ビジネスアイ 後援：文部科学省、経済産業省、フジテレビジョン、産経新聞社、ニッポン放送
• 2018/10 CONCERT Travel Award, European Joint Programme for the Integration of Radiation Protection Research (CONCERT)
   

  受賞者: Hisanori Fukunaga
• 2017/10 Scholar-In-Training Travel Award, Radiation Research Society
   

  受賞者: Hisanori Fukunaga
• 2017/07 The 148th IDAC Bi-annual Meeting Research Presentation Award, Institute of Development, Aging and Cancer (IDAC), Tohoku University
   

  受賞者: Hisanori Fukunaga第31回加齢研研究員会主催発表コンテスト
• 2016/10 International Studentship, Queen's University Belfast
   

  受賞者: Hisanori Fukunaga
• 2016/05 Kaori Essay Prize (Japanese Environment Minister’s Award for Excellence in Essay Writing)
   

  受賞者: Hisanori Fukunaga主催：松栄堂 後援：日本経済新聞社大阪本社
• 2016/02 2015 Resident Case Report Grand Prix 3rd Prize, Fukushima Prefecture
   

  受賞者: Hisanori Fukunaga
• 2015/12 Doctor of Excellence, Some General Hospital
   

  受賞者: Hisanori Fukunaga
• 2013/06 GRE Summer School 2013 Vacation Studentship, Centre for Gene Regulation and Expression, University of Dundee
   

  受賞者: Hisanori Fukunaga
• 2012/09 The 49th Annual Meeting Young Scientist Presentation Award, Japan Radioisotope Association
   

  受賞者: Hisanori Fukunaga
• 2011/03 President's Encouragement Prize, Yokohama City University
   

  受賞者: Hisanori Fukunaga
• 2010/10 Dean's Prize (Gold Medal), Yokohama City University School of Medicine
   

  受賞者: Hisanori Fukunaga

Research Grants & Projects

• 時空間分割放射線治療の医数学的研究と治療計画アルゴリズムの開発研究

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2024/04 -2029/03 

  Author : 白土 博樹, 小野寺 康仁, 福永 久典, 西岡 蒼一郎, 小亀 翔揮
• Spermatogenesis and transgenerational effects after exposure to environmental radiation

  Japan Science and Technology Agency：Fusion Oriented Research for Disruptive Science and Technology Program (FOREST)

  Date (from‐to) : 2022/04 -2029/03 

  Author : Hisanori Fukunaga

   

  放射線事故・原子力災害後の環境放射線被ばく、とくに精巣の被ばくから次世代影響がどのように生じるかは明らかではありません。本研究では、環境放射線被ばくの時空間的に「不均一なエネルギー付与」という特徴に着目し、遺伝子改変マウスや生体内イメージングを用いて、精巣被ばくと遺伝的影響を結ぶメカニズムの解明に挑みます。放射線の次世代影響を制御し、より高度な安全性に基づく革新的イノベーションの創出を目指します。
• Development of Microbeam Radiotherapy for the Preservation of Male Fertility

  Takeda Science Foundation：Medical Research Grants

  Date (from‐to) : 2023/09 -2028/03 

  Author : Hisanori Fukunaga
• Investigation on the testicular tissue-sparing effect following spacially fractionated irradiation and the development of mathematical model

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2024/04 -2027/03 

  Author : Hisanori Fukunaga, Akinari Yokoya, Hiroki Shirato, Ryoya Fukasaki, Yutaro Kabata, Masahiro Mizuta, Yasuhito Onodera

   

  本研究では、雄性生殖細胞特異的に発現するAcrosin に発光タンパク質Luciferase を標識した精子形成可視化マウスを用いて、空間分割照射（マイクロスリット照射）後の精巣で予想されるTSEについてin vivoイメージングによる検証を行う。同時に、空間分割照射後TSEの原理を説明できる数理モデル開発に取り組む。期待される成果として、放射線防護学体系の堅牢化や、妊孕性温存を可能とする新規放射線治療技術の基盤的知見の創出が挙げられる。
• Development of DNA damage estimation system based on spatial pattern of radiation track structure

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2022/04 -2026/03 

  Author : Yusuke Mtatsuya, Hisanori Fukunaga, Shigeo Matsushima, Ken Akamatsu, Takeshi Kai, Tamon Kusumoto

   

  令和4年度は、DNA損傷を高速に推定可能なDNA損傷予測システムの開発に向けて、(1)化学モデルの開発、(2)イオン線照射実験の準備、(3)光子線や炭素線照射後のDNA損傷測定データの蓄積を進めた。開発や測定を進める中で得られた成果の一部は、国際的に著名なジャーナルにて3報の発表を行った。 当該年度の化学モデルの開発においては、既存の放射線輸送計算コードPHITSに実装されているイオン飛跡構造解析モードKURBUCを応用し、陽子線照射後のDNA損傷収率の計算を行うことで、高LET照射時の化学過程の重要性を確認した。同時に、当初予定していなかったが、PHITSによる計算から得られる相互作用の空間情報から、ラジカルの初期収量と時間変化を計算するコード開発に成功し、DNA損傷の発生メカニズムに関する研究を一層進めている。このコード開発に基づき、DNA損傷予測を高精度に再現する化学モデルの開発に着手した。 次に、当該年度の照射実験の準備については、東北大学高速中性子実験室の陽子ビームと中性子線の物理特性の評価を進めた。同時に、高崎量子応用研究所に設置されている低エネルギー炭素イオン源（TIARA）を使用した照射実験を行い、原子間力顕微鏡を使用することで、25 MeV/nおよび10 MeV/n炭素線（高LETイオン線）照射後に発生する様々なDNA損傷（一本鎖切断、二本鎖切断、クラスター損傷）収量の定量的測定に成功した。現在、得られた実測値に基づき、開発中の化学モデルの妥当性の確認を進めている。 以上の化学モデル開発ならびにイオン線照射実験の蓄積から、高LET放射線後の化学過程の重要性が確認され、化学モデル開発の開発ならびに検証を大いに進展させることに成功した。したがって、様々な放射線タイプにより生じるDNA損傷を高速に推定可能なDNA損傷予測システムの開発に向けて大幅に研究が進展したと思われる。
• Biochemical Analysis of Radiation Effects on Microtubule Polymerization Reactions

  Suhara Memorial Foundation：Research Grant

  Date (from‐to) : 2023/04 -2024/03 

  Author : Hisanori Fukunaga
• Changes in maternal blood mitochondrial DNA copy number due to exposure to environmental chemicals and their effects on children

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2021/04 -2024/03 

  Author : 福永 久典

   

  ミトコンドリアは、独自のゲノム（mtDNA）を有しており、ヒトの場合、16,569塩基対の環状多コピーゲノムとして一細胞当たり数十～数千コピーが存在し、母性遺伝する。しかし、このmtDNAコピーの複製・維持機構に関する分子メカニズムや、その生理的・病理的意義は依然として解明されていない。本研究は、mtDNAコピー数がどのように遺伝継承され、母の妊娠中の環境影響などにより子のmtDNAコピー数がどのように修飾され、出生時体重などに影響を及ぼすのか明らかにすることを目的とする。 2022年度は、東北大学東北メディカル・メガバンク機構（以下、ToMMo）から分譲された「ToMMo三世代コホート調査」参加者の7人家族（父方祖父母、母方祖父母、父母、新生児）149組、合計1041名分の末梢血、臍帯血由来DNA試料から、mtDNAコピー数をリアルタイムPCR法を用いて測定した。我々の知る限り、本研究は1000名以上の三世代家族からmtDNAコピー数を測定した初めての分子疫学研究であり、mtDNAコピー数に関する年齢・性別の分布の詳細を明らかにすることができた。 今後、これらの測定結果から、mtDNAコピー数の家族内の遺伝的相関を検討する。また、妊娠中の環境化学物質曝露が新生児の出生時体重などに及ぼす次世代影響について解析を行うため、mtDNAコピー数と母親の妊娠前あるいは妊娠期間中の生活習慣（喫煙歴、飲酒歴、運動習慣など）、新生児の体格（出生時体重など）との相関も検討する。その成果は、ミトコンドリア遺伝学だけでなく、環境衛生学、周産期医学などの発展にも資するものと期待される。
• Intracellular concentration and distribution of 10B-BPA and its cell cycle dependence in accelerator-based boron neutron capture therapy

  Radiation Effects Association：Research Grant

  Date (from‐to) : 2022/01 -2023/03 

  Author : Hisanori Fukunaga
• The effect of maternal exercise habits on mitochondrial DNA copy number in blood cells and offspring's birth weight

  Nakatomi Foundation：Research Grant

  Date (from‐to) : 2022/01 -2022/12 

  Author : Hisanori Fukunaga
• Environmental Effects -Fukushima-

  Ito Foundation：International Travel Support

  Date (from‐to) : 2022/10 -2022/10 

  Author : Hisanori Fukunaga
• Measurement of environmental chemicals using micro-beam PIXE

  Akiyama Life Science Foundation：Grant-in-Aid for Early-Career Scientists

  Date (from‐to) : 2021/09 -2022/03 

  Author : Hisanori Fukunaga
• Dose-rate effects and micro-dosimetry of BNCT.

  Japanese Society for Radiation Oncology：Grant-in-Aid for Research on Radiation Oncology

  Date (from‐to) : 2019/10 -2021/09 

  Author : Hisanori Fukunaga, Yusuke Matsuya, Motoko Ohmura
• Non-uniform Radiation-induced Effects and Boron Neutron Capture Therapy

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2019/08 -2021/03 

  Author : 福永 久典
• Radiation-induced effects on microtubule polymerization.

  Yokohama Foundation for the Advancement of Medical Science：Research Grant for Young Scientist

  Date (from‐to) : 2019/08 -2020/03 

  Author : Hisanori Fukunaga
• Genetic diversity in radiosensitiviy in Japan.

  Japan Radiological Society：Research Grant from Bayer Yakuhin

  Date (from‐to) : 2019/04 -2020/03 

  Author : Hisanori Fukunaga
• Low-dose radiation-induced risk and bystander signaling in stem cells.

  Mitsukoshi Health and Welfare Foundation：International Research Scholarship

  Date (from‐to) : 2017/04 -2019/09 

  Author : Hisanori Fukunaga
• Low-dose radiation-induced effects on spermatogonial stem cells.

  Japan Radiation Effects Association：Research Grant

  Date (from‐to) : 2018/04 -2019/03 

  Author : Hisanori Fukunaga
• Low-dose radiation-induced effects on stem cells and bystander signaling.

  Marubun Research Promotion Foundation：International Exchange Scholarship and Research Grant

  Date (from‐to) : 2017/04 -2019/03 

  Author : Hisanori Fukunaga
• Systems biology for cellular responses to radiation stress

  Japan Society for the Promotion of Science：Grant-in-Aid for Scientific Research (B)

  Date (from‐to) : 2016/07 -2019/03 

  Author : Akinari Yokoya, Yuya Hattori, Tatsuhiko Imaoka, Hisanori Fukunaga, Kiichi Kaminaga, Masatoshi Sugimoto, Ritsuko Watanabe

   

  A novel experimental approach was established to investigate nonlinear cellular responses to radiation stresses using synchrotron X-ray microbeam which allows targeting a particular region in a cell or cell population. Combining the beam technique with fluorescent probes, cell competition induced by irradiation or tissue-sparing effect can be analized. The theoretical modeling of cellular response initiated by DNA damage and repair, as well as various network reactions including feedback loops in the radiation adaptive response, was also established.
• Low-dose radiation-induced effects on spermatogonial stem cells and bystander signaling.

  Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care：Research Grant for Medical Research

  Date (from‐to) : 2017/10 -2018/03 

  Author : Hisanori Fukunaga
• Mechanism of cluster DNA damage induction and its repair processes in vivo

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research (Grant-in-Aid for Scientific Research (B))

  Date (from‐to) : 2015/04 -2018/03 

  Author : Akinari Yokoya, Ritsuko Watanabe, Nobuyoshi Akimitsu, Toshitaka Oka, Masatoshi Ukai, Kentaro Fujii, Yuya Hattori, Miho Noguchi, Yudai IzumiI, Hervé du Penhoat Marie-Anne

   

  Repair process of clustered DNA damage induced by X-irradiation was investigated using EGFP-plasmid DNA transfected into non-irradiated mammalian cells. The repair kinetics of the irradiated plasmids in the cells visualized as the EGFP fluorescence emission indicates that the damage was hardly repaired. Hydrated deoxyribose (dR) films were irradiated with soft X-rays. Yields of desorbed ions from the films were significantly suppressed by water. Molecular dynamics calculation indicates that the fast proton transfer from dR to the hydrated water might cause the suppression. Furthermore, dynamics of low energy secondary electrons around DNA molecule was investigated using a dynamic Monte Carlo code. The results show that pre-hydrated electrons are formed over a few nm from the parent cations and result in additional base lesions, which may be finally converted into a harmful double strand break by base excision processes.
• Travel Award for ERPW 2018 "Personalized effective dosimetry for radiation risk assessment and precision medical applications."

  CONCERT - European Joint Programme for the Integration of Radiation Protection Research：Travel Award

  Date (from‐to) : 2018 

  Author : Hisanori Fukunaga
• Support for Publication "Never Let the Light Fade: Memories of Soma General Hospital in Fukushima."

  Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care：Support for Publication

  Date (from‐to) : 2018 

  Author : Hisanori Fukunaga

   

  *Support for the book publication (ASIN: B07G7XXJ1T).
• Travel Grant for the 2017 RRS Annual Meeting "Development of personalized effective dosimetry for radiation risk assessment and clinical applications."

  Kato Memorial Bioscience Foundation：Travel Grant

  Date (from‐to) : 2017 

  Author : Hisanori Fukunaga
• Travel Grant for CONBIO 2017 "Development of personalized effective dosimetry for radiation risk assessment and clinical applications."

  Queen's University Belfast：Graduate School Travel Grant

  Date (from‐to) : 2017 

  Author : Hisanori Fukunaga
• Travel Award for the 2017 RRS Annual Meeting "Development of personalized effective dosimetry for radiation risk assessment and clinical applications."

  Radiation Research Society：Scholar-In-Training (SIT) Travel Award

  Date (from‐to) : 2017 

  Author : Hisanori Fukunaga
• Travel Grant to Yokohama City University.

  Northern Ireland License Training Group：NILTG Travelling Bursary

  Date (from‐to) : 2017 

  Author : Hisanori Fukunaga
• Low-dose radiation-induced risk in spermatogonial stem cells and bystander signalling.

  Queen's University Belfast：International Studentship

  Date (from‐to) : 2016 

  Author : Hisanori Fukunaga
• Low-dose radiation-induced risk in spermatogonial stem cells and bystander signalling.

  Nakayama Foundation of Human Science：International Research Scholarship

  Date (from‐to) : 2016 

  Author : Hisanori Fukunaga
• Low-dose radiation-induced risk in spermatogonial stem cells and bystander signalling.

  Yokohama City University GUSHINKAI Alumni Association：International Research Scholarship

  Date (from‐to) : 2016 

  Author : Hisanori Fukunaga
• Mechanism of protecting Dbf4 at kinetochores from APC/C-dependent degradation.

  Lister Institute of Preventive Medicine：Summer Studentship

  Date (from‐to) : 2013/06 -2013/08 

  Author : Hisanori Fukunaga
• Travel Grant to visit Dundee University "Mechanism of protecting Dbf4 at kinetochores from APC/C-dependent degradation."

  Yokohama Foundation for the Advancement of Medical Science：Travel Grant

  Date (from‐to) : 2013 

  Author : Hisanori Fukunaga
• Scholarship for the YCU-UCSD Exchange Program.

  Japan Student Services Organization：Travel Grant

  Date (from‐to) : 2012/02 -2012/03 

  Author : Hisanori Fukunaga

   

  *YCU-UCSD Exchange Program Student
• Label-free biomedical Raman imaging of hydrodynamics in single human cells.

  ICHIJU Industrial Science and Technology Promotion Foundation：Research Grant

  Date (from‐to) : 2009/04 -2011/03 

  Author : Hisanori Fukunaga
• Raman micro-spectroscopy on single living human cells.

  Yokohama Foundation for the Advancement of Medical Science：Yokohama Medical Student Research Grant

  Date (from‐to) : 2008 -2009 

  Author : Hisanori Fukunaga

Educational Activities

Teaching Experience

Social Contribution

Social Contribution

Social Contribution

• 令和５年度「国民との科学・技術対話」推進に関する研究支援事業 （「Academic Fantasista」）

  Date (from-to) : 2023/06/22-Today

  Role : Lecturer

  Sponser, Organizer, Publisher  : 北海道大学・北海道新聞
• 出張授業：「両刃の剣」放射線の身体への影響を考える

  Date (from-to) : 2023/11/29

  Role : Lecturer

  Sponser, Organizer, Publisher  : 北海道大学・北海道新聞

  Event, Program, Title : Academic Fantasista 2023

  北海道札幌北高等学校
• WHOオフィサーと語る～地球の未来とSDGs～

  Date (from-to) : 2023/06/04

  Role : Presenter

  Sponser, Organizer, Publisher  : 北海道大学環境健康科学研究教育センター

  Event, Program, Title : 北海道大学祭

  札幌キャンパス
• Double-edged Sword: Radiation-induced Biological Effects

  Date (from-to) : 2022/11/03

  Role : Lecturer

  Sponser, Organizer, Publisher  : Hokkaido University

  Event, Program, Title : 2022 Public Lectures of the Faculty of Health Sciences

  General 札幌キャンパス
• 環境×健康×SDGs ～世界が直面する問題の解決を目指そう～

  Date (from-to) : 2021/10/26-2021/11/09

  Role : Presenter

  Event, Program, Title : 北海道大学令和3年度公開講座

  General オンライン開催 開催日時：10月26日（火）、11月5日（金）、11月9日（火）各日18:00～19:30 講座内容：私たちはだれもが健康な生活を送りたいと願っています。健康には、私たちの身の回りの環境が大きく関係しています。そこで本講座では、「環境×健康」という観点から、私たちがどうSDGsに取り組めるかを考えます。 募集人数：80名 受講対象者：どなたでも（高校生以上向け）
• 大規模接種会場における問診等業務に従事する医師派遣

  Date (from-to) : 2021/06-2021/08

  Role : Organizing member

  Sponser, Organizer, Publisher  : 札幌市保健福祉局ワクチン接種担当部・北海道大学

  General 札幌コンベンションセンター 北海道大学派遣医師として、札幌市白石区の札幌コンベンションセンターが会場となった新型コロナウイルスワクチン大規模接種業務支援に参加
• 南三陸病院（旧・公立志津川病院）・循環型医師支援システム（東日本大震災復興支援）

  Date (from-to) : 2020/08-2020/11

  Role : Organizing member

  Sponser, Organizer, Publisher  : 東北大学東北メディカル・メガバンク機構

  General 南三陸病院
• 新型コロナウィルス感染症軽傷者等宿泊療養支援事業

  Date (from-to) : 2020/05

  Role : Organizing member

  Sponser, Organizer, Publisher  : 宮城県・東北大学

  General La楽リゾートホテルグリーングリーン 東北大学派遣医師として、仙台市青葉区のLa楽リゾートホテルグリーングリーンが会場となった宮城県新型コロナウィルス感染症軽傷者等宿泊療養支援事業に参加
• 南三陸病院（旧・公立志津川病院）・循環型医師支援システム（東日本大震災復興支援）

  Date (from-to) : 2019/02-2019/03

  Role : Organizing member

  Sponser, Organizer, Publisher  : 東北大学東北メディカル・メガバンク機構

  General 南三陸病院
• 認知症・フレイルを正しく診断する -加齢画像外来が拓く未来-

  Date (from-to) : 2018/09/27

  Role : Lecturer

  Event, Program, Title : 南三陸病院研修会

  General 南三陸病院 講師として、南三陸病院で開催された公開セミナーに参加、講演
• 南三陸病院（旧・公立志津川病院）・循環型医師支援システム（東日本大震災復興支援）

  Date (from-to) : 2018/08-2018/09

  Role : Organizing member

  Sponser, Organizer, Publisher  : 東北大学東北メディカル・メガバンク機構

  General 南三陸病院 東北大学東北メディカル・メガバンク機構の連携地域医療専従医師（ToMMo クリニカル・フェロー）として、東日本大震災の被災地域にある南三陸病院（旧・公立志津川病院）で地域医療支援に従事
• 明日の公立相馬総合病院の話をしよう ～初めての研修医として伝えたいこと～

  Date (from-to) : 2016/02

  Role : Lecturer

  Sponser, Organizer, Publisher  : 公立相馬総合病院看護部

  Event, Program, Title : 内科・整形外科合同勉強会

  General 公立相馬総合病院 講師として、福島県相双地方で福島原発事故後も診療を継続した唯一の地域中核病院である公立相馬総合病院の看護部勉強会に参加、講演
• 福島県臨床研修病院ネットワークガイダンス

  Date (from-to) : 2014/11/21

  Role : Appearance

  Sponser, Organizer, Publisher  : 福島県・福島県臨床研修病院ネットワークガイダンス

  College students 福島県医師会館 公立相馬総合病院代表として、福島県立医科大学医学部医学科生を対象とした病院説明会（福島県医師会館）に参加、講演
• 福島県臨床研修病院ネットワークガイダンス in 東京2014

  Date (from-to) : 2014/06/14

  Role : Appearance

  Sponser, Organizer, Publisher  : 福島県・福島県臨床研修病院ネットワーク

  College students ステーションコンファレンス東京 招待パネリストとして、福島県出身の医学生のためにステーションコンファレンス東京で開催されたガイダンスに参加、講演
• 清水商業高校 OB によるサッカー教室（東日本大震災復興支援）

  Date (from-to) : 2011/07/17

  Role : Organizing member

  Sponser, Organizer, Publisher  : 世界こども財団

  High school students 相馬光陽サッカー場（福島県相馬市） メディカルサポートボランティアとして、復興支援イベントである相馬高校対清水商業高校の練習試合支援活動に参加
• 川内村健康相談会（東日本大震災復興支援）

  Date (from-to) : 2011/07/16

  Role : Organizing member

  Sponser, Organizer, Publisher  : 福島県川内村災害対策本部

  General 川内村小学校（福島県川内村） 医学生ボランティアとして、東日本大震災後に川内村に残った約200名の村民を対象とした健康相談、健診に参加
• 児童養護施設学習支援

  Date (from-to) : 2009/04-2011/03

  Role : Lecturer

  Sponser, Organizer, Publisher  : 横浜市三春学園

  Junior high school students 家庭教師として、児童養護施設・横浜市三春学園の中学生を対象とした学習支援活動に参加
• ひらめき☆ときめきサイエンス「身近な生理現象を理解しよう ―汗とおしっこの出る仕組み―」

  Date (from-to) : 2008/08/22

  Role : Lecturer

  Sponser, Organizer, Publisher  : 日本学術振興会・横浜市立大学

  横浜市立大学医学部 学生チューターとして、横浜市立大学医学部（福浦キャンパス）で開催された「ひらめき☆ときめきサイエンス」イベントに参加

Academic Contribution

• The 7th International Symposium on the System of Radiological Protection (ICRP 2023)

  Date (from-to) :2023/11/06-2023/11/09

  Role: Panel chair etc

  Type: Competition etc

  Organizer, responsible person: International Commission on Radiological Protection (ICRP)

  Tokyo, Japan

Others

• 2019/10 「ストライプ照射」だと放射線の影響は軽減される ～放射線の当たり方が一様でない場合、従来の単純な予測は当てはまらない～

  *量子科学技術研究開発機構、Queen's University Belfast、横浜市立大学、高エネルギー加速器研究開発機構から研究成果プレスリリース