FY2022 Plans of Activities
I. Plans of Major Activities
Because much of RERF’s research involves longitudinal or large scale long-term studies thattake a significant time to plan and conduct, so a number of ongoing plans for such studies
have already been presented under research achievements. Here we provide highlights of new
research plans or selected plans of note.
1. Research Projects Examining A-bomb Survivors Health1) Radiation and Cancer:
 AHS liver Cancer mechanistic study (RP1-09, Ohishi W): We will continue current
collaborative studies with Statistics and Epidemiology Departments to investigate: 1) thecontribution of the latent factors (chronic inflammation, insulin resistance, and liver
fibrosis), indexed by CRP, TNF-α, IL-6, adiponectin, leptin, and type 4 collagen, etc. to
HCC risk; 2) mediation of radiation risk for HCC by the latent factors; and, 3) determine towhat extent viral hepatitis is involved in that risk by separating HCC with chronic viral
infection from non-B/non-C HCC.
 Pathogenesis of MDS (RP1-17, Miyazaki Y and Imaizumi M): We will conduct wholegenome sequencing of blood samples collected before and after MDS diagnosis foranalyses of mutational signature and structural variation and assess specific alterations inhigh-dose exposed patients compared with low-dose exposed patients.
 CML study (RP-P2-19, Yoshida N): We will assess whether DNA and RNA from FFPE
samples can be analyzed by high-throughput sequencing. We are also going to prepare afull-scale research project proposal to evaluate the effects of radiation exposure onmolecular and pathological findings among leukemia cases that developed shortly after Abombing. We will continue current collaboration with Epidemiology Department andexternal leading specialists to conduct the study.
 Updated LSS mortality report (RP 1-75) on cancer and noncancer diseases: Analyses andpublication of the LSS Report 15 will be the highest prioritized project in the next several
years and will be continued in collaboration with the Dept. of Statistics (Sakata R and all
members).
 Pathology studies (RPs 5-89, 1-12): The indexing of specimens of formalin-fixed paraffinembedded tissues within a new database will be continued in collaboration with the
Biosample Research Center of RERF. Efforts to preserve and utilize pathological materials
from A-bomb survivors will be continued in collaboration with local hospitals in
Hiroshima and Nagasaki (Sugiyama H, Sakata R).
 As part of our goal to examine genetic susceptibility and gene-environment interaction, weare planning a genome analysis study as part of a potential large-scale multidisciplinary
GWAS program for all AHS subjects, consisting of approximately 21,000 A-bomb
survivors, using old samples preserved since 1958. We will analyze genetic polymorphismsthat may be involved in radiation-related cancer development in A-bomb survivors using
the SNP Array developed for analyzing genetic polymorphisms that may be involved incancer development in a Japanese population. DNA samples extracted from either old
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Wright-stained smears, blood-infiltrated paper discs, or Giemsa-stained chromosome slides
must be used to conduct a genome study for all AHS subjects. For this reason, it isnecessary to determine whether an SNP analysis using the SNP array is possible byamplifying a whole genome, using a very small amount of DNA obtained from a blood
specimens stored for many years. In FY2022, DNA extraction from preserved, old blood
specimens of AHS subjects will be carried out to examine a suitable preparation method
for REPLI-g amplified DNA. Then, we will evaluate DNA availability by analyzing those
DNA samples with the SNP array. (Hayashi, RP-P1-19, and a new RP in preparation).
 Most solid cancer tissue samples of the A-bomb survivors have been preserved asformalin-fixed paraffin-embedded (FFPE) tissues in the pathology laboratory. We will aim
to establish techniques enabling the molecular characterization of FFPE tissue samples. In
particular, we will create a pipeline consisting of protein elution-liquid
chromatography/mass spectrometry (LC/MS)-algorithm for biomarker identification. This
study will include multi-processes, such as chemical pretreatment of FFPE, optimization ofprotein extraction efficiency, the establishment of the pipeline of LC/MS, artificial
intelligence algorithm, and MALDI-TOF/ICP mass spectrometry imaging. Future research
will analyze the survivors’ FFPE samples to identify radiation injury-related biomarkers
using the protocols established in these studies. Tsuruyama (new RP)2) Radiation and Non-Cancer Effects:
 Atherosclerosis study [RP2-11 (Part 2 of RP7-09), Nakamizo T]: We will finish assessing
the availability of the values of multi-functional cytokines, the results of which will be
hopefully published. Subsequently, we will start analyzing the data on cytokines
representing disturbed tissue repair and differentiation potentially involved in thepathogenesis of radiation-induced atherosclerosis. We will also examine associations
among these cytokines, radiation, and clinical physiological indicators related toatherosclerosis using integrated omics and image analysis. These analyses will be
conducted jointly with the clonal hematopoiesis program project because thosepathological process are interrelated to inflammation.
 In the Project 1) Detection of clonal hematopoiesis in AHS samples, we have developed
strategies for assessments of clonal expansion of HSCs (i.e., clonal hematopoiesis) andinflammatory changes in the hematopoietic system potentially contributing to theradiation-associated noncancer diseases, specifically atherosclerosis. Project 1 of thisprogram aims to test the hypothesis that, in AHS subjects who were exposed to high-dose(> 1Gy) radiation several decades ago, clonal hematopoiesis is promoted with recurrent
somatic mutations in epigenetic modifier genes (TET2, DNMT3A, ASXL1, etc) and/or
DNA damage response genes (TP53, PPM1D, etc). Clonal hematopoiesis with somatic
mutations will be evaluated by performing NGS using cryopreserved blood cells fromabout 100 subjects, in collaboration with Nagasaki University and Kyoto University.
Plasma levels of endogenous danger signals (alarmins), which may promote clonal
expansion of HSCs, will also be assessed in relation to the development of clonal
hematopoiesis following radiation exposure. This project has been approved by the Noncancer Research Cluster, outside scientific experts, and the RERF Committee on Biological
Samples, and applied for the IRB review. This study as yet to be fully approved even nextyear, until RERF develops institutional policy concerning the use of cryopreserved samples
for obtaining NGS data in A-bomb survivors. With application of an established policy tothis study, we will start the study as soon as possible. (K. Yoshida and Kusunoki, Clonal
Hematopoiesis Program, Project 1).
2 In the project 2) Evaluation of inflammation markers, clonal hematopoiesis andinflammatory phenotypes potentially related to atherosclerosis risk in atomic-bomb
survivors, project 2 (Nakamizo T): We will finish examining the availability of thecytokine measurements. Subsequently, we will start analyzing the data on inflammatory
cytokines, T cell subsets representing T cell aging, and hematological profiles potentiallyrepresenting clonal hematopoiesis.
 In the project 3) Mouse model of clonal hematopoiesis, in another mouse model using B6
mice, we will first validate our current findings of a high prevalence of radiation-induced
CH (a manuscript in preparation) and then investigate longitudinal trajectories of clonal
mutations, using blood cell phenotypes already analyzed and blood samples alreadycompleted for cell collections at various time points before and after irradiation. In
addition, we will preliminarily analyze CH-related atherosclerosis development in LDLRKO mice fed a high fat diet following whole-body irradiation, to design a full-scale study
investigating characteristics of radiation-induced CH and the involvement of CH in
atherosclerosis formation. (Kusunoki, K. Yoshida, Taga, Hamasaki, Satoh, Uchimura,
Misumi and Noda, Clonal Hematopoiesis Program, Project 3).
 Clonal hematopoiesis and inflammatory phenotypes in radiation-associated CVD: To fully
test the hypothesis that radiation promotes arteriosclerosis through clonal hematopoiesis
and pro-inflammatory phenotypes, we will examine somatic mutations that cause clonal
growth of hematopoietic cells, immune cell phenotypes and inflammatory markers. We
expect that assessments of these molecular and cellular endpoints are feasible in both alarge-scale (N=3,000) and a longitudinal (N=30-50, 30 years) studies, by using blood
samples collected from AHS participants, and by analyzing these endpoints in relation to
inflammation and arteriosclerosis indices evaluated in the AHS. The effects of radiation
exposure on clonal hematopoiesis and chronic inflammatory phenotypes including
atherosclerosis development will also be evaluated in mouse and mathematical simulation
models. Investigators to be involved will include Drs. K. Yoshida, N. Yoshida, Nakamizo,
Taga, Satoh, Hamasaki, Uchimura, Hayashi, Noda, Misumi, Cordova, Ohishi, Kusunoki,
Cologne, Imaizumi, and Hida.
3) Genetic Effects of Radiation:
 For WGS studies of the human trios comprised of atomic bomb survivors and theiroffspring, we will respond to the suggestions from the Genetics Research Cluster andexternal reviewers and proceed to approve the research protocol. A key element in theinitiation of these studies are ELSI and obtaining informed consent since many of theparents in the trio sets are deceased. After getting informed consent, we will startexperiment using WGS (Uchimura, new RP in CR162 F1 umbrella program project).
 GWAS on radiation-associated cancers in all AHS subjects: One of the important future
research goals of RERF is to study the association between the inherited genomes andradiation-associated risks of disease. Much remains to be learned about genetic
susceptibility to radiation-associated cancers and other diseases. A future study that aims todetect genetic factors that confer higher sensitivity to radiation exposure should, therefore,
provide useful information for informing radiation protection. Blood specimens from the
RERF Adult Health Study (AHS), which have been preserved since 1958 and cover
approximately 21,000 A-bomb survivors, will be used in a genome-wide analysis by SNP
array using these unique resources. The results obtained by the GWAS will be further
analyzed by large-scale phenotype-genotype association analysis by combining the3

biomarker data of the AHS subjects. Thus it is expected that this study will help to clarify
the susceptibility and mechanisms of radiation diseases, including radiation-related
cancers. This study will become a typical case of DSU-collaboration where
epidemiologists, clinical scientists and data scientists get together to make a large-scaleassociation study. Investigators to be involved include Drs. Hayashi, Ohishi, K. Yoshida,
Cologne, Brenner, Kato, Noda, newly hired data scientists, and a young scientist to be
newly recruited.
2. Research Projects on the Health of A-bomb Survivors Children (F1) F1 offspring clinical study (FOCS) [RP4-10, Ohishi W, Tatsukawa Y, and Hida A]: We
continue further discussion to establish methods of analysis based on multi-state models
and the datasets will be prepared in collaboration with Departments of Statistics andEpidemiology. We will start analyses to investigate the effects of parental radiation
exposure on hypertension, dyslipidemia, and diabetes in offspring of A-bomb survivors.
 Mortality surveillance in LSS, in utero, and F1 cohorts (RPs 1-75, 2-61, 4-75): Mortality
follow-up for all cohorts will continue and the data will be completed through 2018.
Archiving of early-period materials will continue in collaboration with the Research
Resource Center of RERF (Sakata R).
3. Research to Elucidate Individual Radiation Doses and the Effects of A-bombs
 With respect to dosimetry error specifically, there are a number of potential issues with thecurrent dose error corrections used at RERF that we plan to address. First, the current dose
error adjustments are based only on a classical dose error model – e.g., errors due tomisspecification of the location of the subject – but do not consider additional so-called
Berkson type error – e.g., that due to the fact that individuals at far distances, and therefore
with lower doses, do not have shielding histories, so that average transmission factors forthe corresponding shielding scenarios (inside, outside, etc.) are assigned. Second, thecurrent classical regression calibration dose error corrections are only applied at higher
doses ( > ~500 mGy in Hiroshima, > ~ 700 mGy in Nagasaki, shielded kerma). In light ofthese issues and also of the likely adoption of new organ dose estimates, Dr. Sposto and Dr.
Misumi have initiated a working group within the Department to explore improvements inthe method for correcting for dosimetry error, inspired in part by the success of theworking group led by Drs. Cologne and Yamamura on multistate modelling. The dosimetryerror working group will include discussion of the implications on dosimetry error
adjustments of primary vs secondary responses to the shielding survey, timing of theshielding interview/multiple interviews, different shielding details dependent on distancefrom hypocenter and its implications for dose error corrections at low dose, and othercharacteristics of dose error estimation that have heretofore not formally been considered.
We hope to identify specific areas of methodologic research to clarify these issues.
Related to this, Ms. Cordova will continue her work utilizing a structural equation
modeling approach to assess the magnitude of dose error in DS02 doses using various
sources of data about physiological exposure (biodosimetry), with the aim to draft amanuscript describing the results in 2022.
 The primary focus of our work on dosimetry during FY2022 is continued preparation for
the implementation of the revised organ dosimetry using updated computational phantoms,
as described above. While the Department will become prepared to implement the neworgan dosimetry, the ultimate decision of if and when to implement this new dosimetry will4

be made by the RERF leadership in conjunction with US Department of Energy (DOE) andthe Japanese Ministry of Health Labor and Welfare (MHLW). The planning is under way
for a joint meeting in early 2022 between representatives of DOE, MHLW, the ODWG,
and RERF, to present the work that has been done thus far and to discuss any issues that
may exist regarding the adoption of this new dosimetry system at RERF. If there isagreement to proceed to utilize the new organ dosimetry, Ms. Funamoto and Mr. Shimizu
will continue the work of integrating this new dosimetry into the current RERF dosimetry
software and database.
4. Project to Release of Research Results and to Collaborate with Other Scientific
Organizations
Continuing collaborations: Long term collaborations are listed below and these are
expected to continue in 2022:
a.
b.
c.
d.
e.

Partnership with the University of Washington
Partnership with Kurume University
Collaborations with the US National Cancer InstituteCollaborations with the University of Florida
Collaborations with Outside Investigators:
39 Japanese Institutions
12 North American Institutions
4 European Institutions
1 Asian, Oceanian Institution

5. Training Programs for Domestic and Overseas Specialists
RERF will hold a training course for non-epidemiologist radiation researchers to learn thebasics of epidemiological research and increase understanding of radiation health risks. In
addition, RERF will train persons capable of working in the fields of radiation protection,
radiation emergency medical care, and radiobiological research. Furthermore, decisions onwhether these activities could be held and how they would be held will be madeconsidering the status of COVID-19 pandemic.
Activity plans for FY2022:
i) RERF will hold an online or in-person epidemiological training course for radiation
biologists in Japan to enhance understanding of results from epidemiology research on
A-bomb survivors.
ii) RERF will accept overseas research trainees to support the activities of suchorganizations like the International Council for Health Care of the Radiation-exposed(HICARE), the Nagasaki Association for Hibakusha’s Medical Care (NASHIM), andthe Japan International Cooperation Agency (JICA).
iii) If there are any invitations for the MHLW-sponsored FY2022 International Exchange
and Research Program, RERF will consider accepting trainees from overseas.
iv) The Department of Statistics will apply to the International Fellowships for Researchin Japan program, sponsored by the Japan Society for the Promotion of Science (JSPS),
upon application from candidate trainees, and provide research opportunities to young
post-doctoral researchers from various countries.

56. Public Information Programs
From the days of its establishment until the present, RERF has investigated the medical
effects of radiation, in atomic bomb survivors and their children (the second-generation).
In terms of RERF’s public information programs of utmost importance are our efforts tocommunicate in simple fashion our research results to atomic bomb survivors and thechildren of A-bomb survivors, both of whom have long understood and cooperated in
RERF’s research, as well as members of the public. To succeed at communicating withsuch audiences, good relations with national and international media, starting withmembers of the media in Hiroshima and Nagasaki, are crucial to reaching a wide audience
with our messaging. In FY2022, RERF will work on the public information programs,
outlined below, to ensure that such target audiences can gain further understanding about
RERF.
i)

RERF public lecture series
RERF’s new public lecture series, initiated in 2019, targets peace volunteer guides
among other such individuals, in partnership with external organizations such as theHiroshima Peace Memorial Museum. This series was temporarily shelved due to thecoronavirus pandemic but will be reinitiated once the coronavirus is contained. Basedon such efforts, RERF will be able to provide an opportunity to enhance understandingof the foundation’s research and learn more about radiation’s health effects to evengreater numbers of atomic bomb survivors, second-generation survivors, and the
public.

ii) RERF Open House event
RERF will hold its 27th and 25th Open House events at the Hiroshima and Nagasaki
RERF Laboratories, respectively. In continuation from last year, in FY2022, RERF
will once again consider holding the Open House events in a virtual format, out ofconsideration of the effects of the continued spread of the coronavirus.
iii) Strengthening of social media-related activities
Given limited contact with the public due to the COVID-19 pandemic, social media
such as Facebook and Twitter have become the most effective method ofcommunicating with the outside community. In FY2022, social media platforms will
be used effectively to achieve the goal of obtaining understanding from atomic bomb
survivors, the second-generation, local communities, and the media. Through aparticular focus on visual information on Facebook and Twitter, a series of videos,
including those related to the Open House, will be created to give outside people
access to our facilities, research, explanations of research policies, and so on, througha virtual format. RERF will also continue refining our messaging on the platforms,
with the aim of both increasing our follower numbers and expanding our reach andengagement through increased sharing of our posts by our followers.
iv) Promotion of public relations activities targeting media
RERF will respond to the extent possible to media requests for coverage of RERF
related to various issues surrounding our research and policies this year, with the aimof allowing the media to accurately understand ABCC–RERF’s research achievements
and to report based on that clear understanding. In FY2022, RERF’s PR staff plans tohold lectures and study sessions for the media, in continuation from similar efforts
made last year.

6v) Public outreach related to RERF’s biosample-related studies
Regarding the conduct of RERF’s biosample-related research, information aboutstakeholder and other outside committee deliberations will continue to be actively
conveyed to the public through the use of media and social media.
vi) Enhancement of RERF website
In FY2022, RERF will continue aiming at enhancement of its homepage throughfurther refinement of information delivery related to our research synopsis project.
Particular focus will be placed on conveying readily understandable research-related
and other information to the public, through the utilization of more video and othermethods.
vii) Enhancement of online news-delivery system
RERF’s email magazine system, E-News, which replaced the printed Update
newsletter, will be streamlined to increase work efficiency and ease with which thelatest research results and information about RERF events and activities can be
distributed, attracting readers to RERF as ‘members’ by offering a sense of ‘buy-in’
with respect to RERF as an organization.
viii) School Visit ProgramThis program was first established in FY2016 to convey to elementary, junior-high,and high-school students the reality of radiation health effects. In FY2022, RERF willkeep this program in place in preparation for a time when interest in the activity
recovers once the pandemic is contained. In the future, in addition to in-person
teaching, RERF will focus on creation of videos with the same content as school visits
to allow schools across Japan, and perhaps even the world, to access the information
for learning about radiation health effects.
ix) Internship (work experience) project
RERF has been accepting interns, mostly those with scientific backgrounds, for sometime, but RERF plans to invite trainees such as students to learn about how to perform
RERF’s facility tours and other public relations work.
x) Other public relations activities• RERF will actively promote the foundation’s important scientific papers to thedomestic and overseas media via press releases and press conferences.
• With the aim of improving public understanding of our research, RERF initiated in
FY2018 a new series of paper synopses that explain all of our research with simpler
prose and smaller word counts than used previously in our “summary explanation”
series for specialists. Through continuation of this series in FY2022, the aim is toimprove understanding by the public and media of RERF’s research results.
• A persistent goal again in FY2022 will be the creation of a system for RERF personnel
to handle facility tours in English for overseas visitors, in preparation for when the
tours are restarted in the future after the coronavirus pandemic is contained.
• By increasing our effort at communicating RERF’s research with the aim of improved
transparency related to RERF research and establishment of good communication withthe public, in particular A-bomb survivors, their children, and the media, the PublicAwareness Campaign working group was formed in January 2019. In FY2022, thePAC working group will meet and discuss about how to provide information to the
public on important topics such as the human genome, genetics studies, and other such7

topics.
• When it is possible again after the coronavirus pandemic is contained, RERF willcontinue to target small public groups of A-bomb survivors and their children, whowill be invited to come to RERF and speak with directors and staff about
ABCC/RERF history and research results, with the aim of achieving greater
understanding about RERF.
II. Operation and Management of RERF
1. Research Resource CenterWith the introduction of the Research Resource Center Operating Committee, personnel
will be assigned to work on the RRC development as a primary work assignment for the
first time. In addition, a senior contract programmer will be hired to oversee technicaldevelopment. Major efforts on RERF’s data infrastructure are needed. The identification ofan appropriate underlying framework is required and will receive top priority.
The Content Management System (CMS) pilot will be completed and a full rollout of the
CMS should be anticipated. Integration of the CMS with RERF’s newly-started “Scanning
Center” should also occur. The CMS will store and categorize scans of paper documents
and digital publications. It will allow full search, a feature that is currently not available at
RERF.
A digital presence (web site) with rudimentary functions (data search/assembly,
manuscript/RP search, streamlined procedures to initiate data sharing, etc. will be put inplace and be developed in conjunction with the new Office of Research Support.
2. Review on the relocation of the Hiroshima Laboratory
We will continue deliberating the two candidate sites for the relocation of Hiroshima
Laboratory: The Hiroshima Comprehensive Health Center and Hiroshima University’s
Kasumi Campus. At the same time, we will also carefully examine the facilities needed toachieve RERF’s mission and implement our strategic plans.
3. Transition to a full Audit
RERF is aiming to obtain a full audit by an external auditing firm to supplement the audit
by the Auditors. Deloitte Touch Tohmatsu LLC, with whom we have a contract forinvestigation services for the audit, will conduct an investigation of the opening balancesfor FY2022 from March to May 2022 and submit the investigation report in June of thesame year. If it is determined in the investigation report that it is feasible to undertake a fullaudit, an audit contract will be signed in July 2022, and RERF will begin receiving fullaudits from FY2022.
4. Revision of the rules and regulations
RERF revises the current regulations and establishes new regulations by responding to the
Deloitte Touche Tohmatsu’s findings and results of regular reevaluation by the sections incharge. Along with continuing to respond to the Deloitte’s findings quickly and suitably in
FY2022, required revisions will be made to keep the foundation’s management operations
appropriate. Doing so will provide regulations befitting of a public interest incorporated
foundation funded by the U.S. and Japanese government subsidies.

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