Welcome to CHIBA RESEARCH 2021, a publication that showcases the diverse and innovative work being

based medicine, three-dimensional holography, as well as studies on how to achieve a fair and just society.

This issue introduces the twenty-two innovative projects current-

(see page 10); and Shigeru Yoshida’s use of ghost-like

We hope you enjoy this issue of CHIBA RESEARCH and we look forward to sharing with you our latest research findings.

© iStock.com/BlackJack3D

2 1 TABLE Guided by its motto “Always aim higher,” CHIBA UNIVERSITY strives to nurture globally minded students who have broad outlooks. The university values academic diversity OF and actively conducts leading-edge fundamental and applied research. CONTENTS Top Research Program Chiba University was founded as a national university in Japan in 1949, when Chiba Normal School, established in 1874, merged with Chiba Medical College and several other educational institutions.

Currently composed of 10 faculties and 13 graduate schools, Chiba University is one of Japan’s largest 06 08 10 national universities, having about 11,000 undergraduate students, 3,500 graduate students and 3,500 MUCOSAL IMMUNOLOGY AND INTERNATIONAL CENTER FOR CHIRAL faculty members on 4 campuses located near Tokyo. The main campus at Nishi-Chiba occupies an area of THERAPEUTICS HADRON ASTROPHYSICS MATERIALS SCIENCE almost 400,000 square meters (100 acres) and is conveniently located between Tokyo Station (about Fighting Pathogens at Their Revealing Hidden Messages from Using Light to Establish a New Point of Entry the Cosmos Field of Chiral Materials 40 minutes by train) and Narita International Airport. The 850-bed University Hospital, a core hospital for the region, is adjacent to the School of Medicine on the lnohana campus. 25 SOFT MOLECULAR ACTIVATION Research Incubator Program FOR INTELLIGENT MATERIALS Humanities and Social Sciences Catalyzing the Future of Smart Materials 14 CHIBA STUDIES ON GLOBAL FAIR SOCIETY 26 ADVANCED BONE-CONDUCTION Forging a Fairer World COMMUNICATION Bone-conductionTechnology beyond Hearing Aid 15 SMALL AREA ESTIMATION AND ITS APPLICATION 27 LYMPHEDEMA MONITOR Improving Datasets Using Small Area Estimation Making Invisible Lymphedema Visible

16 TRANSLATIONAL RESEARCH PROGRAM OF PSYCHIATRY AND PSYCHOLOGY Cognitive Behavioural Theraphy Medical and Pharmaceutical Sciences Comes of Age in Japan 30 PHYTOCHEMICAL PLANT MOLECULAR SCIENCES 17 MIGRATION AND REFUGEE STUDIES Unlocking the Potential of Phytochemicals Living with People with Foreign Backgrounds 31 CANCER EPIGENOME CENTER A Different Approach to Fighting Cancer Science and Engineering 32 MEDICAL MYCOLOGY RESEARCH CENTER 20 NEXT-GENERATION THREE-DIMENSIONAL Manipulating Microbes for Human Health DISPLAY AND MEASUREMENT Future Images —More than Meets the Eye 33 MEDICINE FOR RARE DISEASES Innovative Approach Offers Hope 21 MULTIMODAL MEDICAL ENGINEERING for Intractable Problems Toward Image-Based Disease Diagnostics

34 GLYCOMEDICINE RESEARCH CENTER 22 CENTER FOR INNOVATIVE MICROWAVE Sugar Science’s Immunotheraphy Play REMOTE SENSING The Next Wave in Remote Sensing 35 LABORATORY OF DDS DESIGN AND DRUG DISPOSITION 23 IMAGING SCIENCE AND TECHNOLOGY Big Hopes for Nanotechnology Based FOR MATERIAL APPEARANCE AND AFFECT Drug Delivery Systems Affect and Realness in Digital Images 36 INTERNATIONAL HUB FOR METALLOMICS 24 INSECTS-INSPIRED BIG INNOVATION RESEARCH Looking to Nature to Revolutionize Flight Understanding the function of biometals for human and environmental health

2 3 Top Research Program

MUCOSAL IMMUNOLOGY AND THERAPEUTICS Fighting Pathogens at Their Point of Entry

INTERNATIONAL CENTER FOR HADRON ASTROPHYSICS Revealing Hidden Messages From the Cosmos

CHIRAL MATERIALS SCIENCE Using Light to Establish a New Field of Chiral Materials

© iStock.com/gremlin 4 5 MUCOSAL IMMUNOLOGY AND THERAPEUTICS FIGHTING PATHOGENS -Vaccines that induce immune responses at mucosal AT THEIR POINT OF ENTRY membranes of the intestines, lungs and other organs could help prevent deadly infections. Research Keywords: Immunology, Mucosal Immunity, Allergy

MUCOUS MEMBRANE The mucous membranes that line many FROM BASIC RESEARCH TO IN THE AIRWAY of the tracts and structures in the body are CLINICAL APPLICATIONS the first lines of defense against foreign Before new treatments can be developed, invaders. Equipped with a powerful and however, much more needs to be learned highly specialized immune system, these about the molecular architecture of the Mucous coat layered mucosal sentinels protect the surfaces and, mucosal immune system. That is why the with tiny hairlike cila. by extension, the body interior, against the International Center of Excellence is fo- threat of gastrointestinal, respiratory and cusing on basic research while simultane- sexually transmitted infections, as well as ously advancing clinical applications. It is cancer, allergies and more. also strengthening ties between research- Immune cells in the If these immune cells let their guard ers and industry in the hope of translating mucous membrane down, pathogens such as bacteria and its discoveries into therapies for patients. protect the body viruses can invade. On the other hand, To this end, Nakayama is building a robust against invasion by if they are overly vigilant, hyper-reactive pipeline of talented scientists who can pathogens such as bacteria and viruses. conditions like asthma or autoimmune move research findings seamlessly from However, if they are inflammatory bowel disease can take hold. the lab bench to the hospital bedside. too vigilant, they can Getting the balance right is the goal of “The research system we are creating is cause diseases. the International Center of Excellence unprecedented,” says Nakayama, who is in Mucosal Immunology and Innovative also vice president of Chiba University Allergy Therapeutics. and dean of the Graduate School of Med- Vaccines that directly Launched as a joint initiative between icine and the Faculty of Medicine. target the mucosal surface Chiba University and the University of Projects at the International Center of could provide more protection California, San Diego, in 2016, the center Excellence fall into three categories: than a typical injection. aims to harness the power of the muco- Hiroshi Kiyono is studying the basic sal immune system to develop the next mechanisms of mucosal immunology in generation of preventive vaccines against response to microbial infections and as- infectious, allergic and inflammatory sorted diseases; Nakayama and colleagues, diseases. including Atsushi Onodera, Motoko Most vaccines in use today are adminis- Kimura and Osamu Ohara, are focusing tered by injection. But since most infec- on allergic reactions and novel treatments tious agents enter the body at mucosal that target the mucosa; and Hiroshi surfaces, vaccinating through the nose, Nakajima and colleagues belong to the mouth, or some other mucosal route clinical research team that is developing could provide more protection. Since new vaccines and adjuvants for pathogens transmission often occurs at these sites, endemic to Japan and around the world. Members boosting the body’s ability to block that Chiba has initially committed US$2 transmission could stop an infection or million over five years to this alliance. Toshinori NAKAYAMA autoimmune reaction at its source. Together with a matching contribution Professor, Graduate School of Medicine “While existing injectable vaccines are from UC San Diego, the project will facil- able to prevent serious conditions from itate joint research and exchanges between Hiroshi NAKAJIMA Hiroshi KIYONO developing, they are not effective enough investigators and students on both sides Osamu OHARA Motoko KIMURA to defend against infection,” notes pro- of the Pacific. Atsushi ONODERA Akira SUTO gram director, Toshinori Nakayama. Yosuke KURASHIMA © Science Photo Library / Alamy Stock Photo

6 7 INTERNATIONAL CENTER FOR HADRON ASTROPHYSICS REVEALING Two towers receive information from 5,160 light-detecting HIDDEN MESSAGES sensors buried 2,500 meters beneath the South Pole.

FROM THE COSMOS The IceCube Neutrino Observatory, at the South Pole's Amundsen-Scott station. The International Center for Hadron Astrophysics is part of the Research Keywords: global collaboration constructing IceCube. Neutrino Astronomy, Cosmic Rays, South Pole, Elementary Particle Experiment

-From a remarkable observatory buried deep in the south polar ice, Chiba University astrophysicists are helping to explore the origins of the Universe.

Humans have been observing the stars of cosmic plasma, have great potential to or hydrogen nucleus. Of the trillion, trillion for tens of thousands of years, first with finally resolve this mystery.” neutrinos that pass through IceCube every our eyes, then with optical telescopes, day, the facility records just a few hundred THE ICECUBE COLLABORATION and more recently using devices that can collisions from high-energy neutrinos detect light at the extremes of the electro- Neutrinos are the most abundant particles — a minute fraction of the neutrino flux magnetic spectrum far beyond the visible in the Universe after photons (light parti- but more than enough to stimulate some range. Yet despite phenomenal progress cles). They originate in some of the most very exciting research. “We are proud of in astronomy over the past half century, violent and least understood cosmological having been key players in the discovery much of the Universe remains complete- phenomena like supernovas, galactic cores of high-energy cosmic neutrinos, which ly hidden from view, obscured by other and black holes. After their birth, they astrophysicists have been dreaming matter, other radiation sources, and light’s travel in straight lines from their source about for more than 30 years,” says interaction with the interstellar medium. with almost no deflection or absorption, Yoshida talking about his team mem- Now, scientists are on the verge of being making them ideal messengers from the bers in ICEHAP. able to peer into some of the most myste- heart of these mysterious astronomical Another important contribution of ICE- rious corners of the cosmos using not light objects. But these same properties also HAP to understanding the high-energy but neutrinos — near-massless subatomic make them exceedingly difficult to detect. Universe is its supercomputer-based mas- particles that travel close to the speed of The IceCube collaboration, involving 300 sive numerical simulation program for deep light across the Universe without being physicists from 53 institutions in 12 coun- investigation of the physical mechanisms deflected by magnetic fields or absorbed tries, has gone to extreme lengths to detect behind high neutrino production. “Through by matter. these ghost-like, high-energy particles. our simulations we are helping to uncover The International Center for Hadron The IceCube observatory is a cubic the hidden messages carried by these neu- Astrophysics (ICEHAP) led by Shigeru kilometer of crystal-clear ice, deep below trinos and to reveal the physical mechanism Yoshida is part of the global collaboration South Pole Station — the only place on by which high-energy cosmic rays are Neutrinos are subatomic Members responsible for managing the IceCube Earth where such large volumes of clear, accelerated at their source,” says Yoshida. In particles that typically Neutrino Observatory deep in the ice at pure and stable ice can be found along 2018, the IceCube collaboration has finally pass freely through matter. Shigeru YOSHIDA Other particles cannot Professor, Graduate School of Science the South Pole’s Amundsen–Scott station. with the infrastructure needed to support discovered that a special type of galaxy, penetrate the Earth, so “One of the longest standing puzzles in scientific research. By suspending thou- TXS 0506+056, is a birthplace of cosmic below the 'Dark Sector' astrophysics is the origin of high-energy sands of delicate photodetectors on strings neutrinos. This achievement was selected near the South Pole, Aya ISHIHARA Ryo NAGAI cosmic rays and neutrinos,” says Yoshi- in a network of vertical holes drilled as one of the top breakthroughs by Science. free from every other Lu LU Kenichi KIN interference, it is quiet Colton HILL Maximilian MEIER da. “The new windows to our Universe through the ice, physicists can capture In 2022, the team’s new detectors called enough for the neutrinos Ryoji MATSUMOTO Yosuke MATSUMOTO opened by neutrino observations, com- the rare explosion of energy that occurs “D-Egg” will be used at the South Pole. It to be detected. bined with powerful computer simulations when a neutrino collides with an oxygen clearly shows the steps being taken forward. Tomoyuki HANAWA Tomoaki ISHIYAMA Hideyuki HOTTA

8 9 CHIRAL MATERIALS SCIENCE USING LIGHT TO ESTABLISH A NEW FIELD OF CHIRAL MATERIALS

Research Keywords: Applied Optics, Optical Vortex, Chirality

-Understanding the Of the many mysteries still to be unrav- inscribed on the material’s surface. The eled in the natural sciences, one of the modified surface can then react differently universal property of chirality most compelling is the origin and power to left- and right-handed chiral molecules could lead to new materials of chirality — the property of a molecule or helical light, giving rise to a range of or object that has two mirror-image forms interesting possibilities for chemical sens- and technologies for photonics — like our left and right hands. ing, synthesis and imaging. and other applications. Chirality is universal in biology, chemistry “We can use helical light to create nano- and physics. It critically affects the bio- structures such as twisted needles, twisted chemical processes underpinning life, is a reliefs and twisted fibers,” says Omatsu. vital aspect of drug discovery, and crops up “We have also found that the same process in particle physics. Light can have chiral can polymerize fullerene — a well-known properties that affect how it interacts with functional organic molecule that is nor- matter. But how can the power of chirality mally not conductive. This causes fullerene be harnessed and controlled? And what to form a novel conductive metallic phase, new discoveries and technologies might which could be used as the basis for fab- this give rise to? These are some of the ricating electronic devices without metals questions Takashige Omatsu and his team and semiconductors.” are asking. Omatsu believes ‘nanovortices’ will one Light beams can be chiral when they are day be used for nanoscale precision imparted with so-called helical wave- control of light polarization, electron fronts, that is, polarity that rotates either orbital motion and the aggregation of left or right. “We can use ‘optical vortices’ chiral molecules. “Our research will lead to twist the physical properties of metals, to materials for next-generation photonics semiconductors and organic materials on and electronics, and new applications in the nanoscale to create chiral nanostruc- chemical synthesis, pharmacy, biology and Members tures with unique features,” says Omatsu. medicine,” he says. “It might also allow us Takashige OMATSU “Our goal is to establish chiral photonic one day to answer the scientific mystery: Professor, Graduate School of Engineering materials as an original research field and ‘Why does handedness exist in nature?’” to pioneer new technologies such as chiral Omatsu has collaborated with many Hisao ISHII Masami SAKAMOTO plasmonics and metasurfaces for nanoscale Japanese and international researchers, Takeshi MURATA Peter KRÜGER chiral chemical reactors, chiral-selective and is always looking for students and Kazuyuki SAKAMOTO Hiroyuki YOSHIDA imagers and chiral sensors,” he explains. early career researchers. “Our research Kenichi OTO Toyokazu YAMADA center brings together physicists, chemists, LIGHT CORKSCREWS Nobuyuki AOKI Kazuki NAKAMURA biologists and even medical doctors, and Takayoshi ARAI Atsushi NISHIDA Omatsu’s team focuses on the interaction we frequently have brainstorming meet- Akira YANAGISAWA Midori ARAI between helical light and materials, and ings to think up ideas for new projects,” Shiki YAGAI Kazuhiro YOSHIDA the physical properties and potential uses he says. “Several international researchers Tetsuhiro NEMOTO Motohiro AKAZOME of such modified materials. The electro- work here. There is a wonderful diversity Akira MATSUURA Yoshihiro NISHIDA magnetic field of helical light rotates as of backgrounds and expertise.” Kohji ITO Hiroki TAKAHASHI the light moves through space. When this Daisuke UMENO Naohiko ANZAI field interacts with conductive materials Keisuke IIDA Satoshi OGASAWARA like metals, nanoscale corkscrew-like variations in physical properties can be © iStock.com/loops7

10 11 Humanities and Social Sciences

CHIBA STUDIES ON GLOBAL FAIR SOCIETY Forging a Fairer World

SMALL AREA ESTIMATION AND ITS APPLICATION Improving Datasets Using Small Area Estimation

TRANSLATIONAL RESEARCH PROGRAM OF PSYCHIATRY AND PSYCHOLOGY Cognitive Behavioural Theraphy Comes of Age in Japan

MIGRATION AND REFUGEE STUDIES Living with People with Foreign Backgrounds

© piick/Shutterstock.com 12 13 CHIBA STUDIES ON GLOBAL FAIR SOCIETY SMALL AREA ESTIMATION AND ITS APPLICATION FORGING A IMPROVING DATASETS FAIRER WORLD USING SMALL AREA Members Research Keywords: Global Welfare Society, Multidisciplinary Social Science, Fairness ESTIMATION Genya KOBAYASHI Associate Professor, Graduate School of Social Science Research Keywords: Economic Statistics, Baysian Statistics, Small Area Estimation

Yuki KAWAKUBO Eisaku SATO -A multidisciplinary team of researchers looks at Shouto YONEKURA Hiromi SAITO how to create a fair society — on a global scale. -Statistical techniques can improve the accuracy and Tsubasa ITO Yuta YAMAUCHI Ryota YUASA Syonosuke SUGASAWA scope of limited information, saving time and money. Yukiko OMATA

With globalization comes the need to HOW DO WE ACHIEVE Collecting comprehensive data on popula- Survey of Family Income and Expenditure dataset of taps. The group found that access ensure that people from all cultures, A FAIR SOCIETY? tions is not always possible, or even the best (NSFIE). The sample sizes in the NSFIE to clean water accounted for 41.3 percent of countries and backgrounds are treated use of resources. Surveys can be expensive are much larger than in the FIES and thus the improvement in Tokyo’s crude death rate fairly and equally. The drive to create a just The project consists of four interrelated symposiums. “Many of our members are and time-consuming, so improving the more reliable, but because the survey is time between 1921 and 1937. This paper adds global society requires solid foundations in research groups and a further six teams involved in local and national policymaking accuracy of data with “small area problems” consuming and costly, it’s only carried out to discussions on the relative importance all countries, backed by informed govern- working to publicize the findings to a wide committees, and they are key to informing can stretch data resources further. every five years. of nutrition and clean water on mortality. ment policies and strong support networks audience. Their focus is on challenging and policy makers of our work,” says Mizushima. “Small area problems happen when an The FIES and the NSFIE collect area-level Kobayashi hopes that everyone from policy at local, regional and national levels. overcoming unfair practices on all scales, in- The project has published books and papers estimator, such as sample mean for a small aggregated data, so Kobayashi’s group used makers to businesses will soon come to Much previous research into justice and vestigating issues such as gender inequality, both in Japanese and English based on their area, becomes very unstable because of small the Fay-Herriot, a mixed regression model the group to add a finer resolution to their social change has been dominated by widening income gaps, migration, and the research outcomes, and welcomes those in- sample sizes,” explains Associate Professor routinely used in SAE. datasets. studies of Western societies, but the rapid collapse of regional and marginal communi- terested in all aspects of social science, from Genya Kobayashi, who is part of a new Chi- However, when data is in other formats changes experienced by Asian countries in ties, both in Japan and around the world. law and politics to sociology and economics. ba project called Small Area Estimation and more appropriate SAE models must be de- recent decades have spawned a growing In particular, the researchers believe that Its Application to the Analyses of Poverty, veloped. Recently, for example, Kobayashi’s field of research focused on building fair proposals and practices aimed at closing the Public Health and Disaster. group has been working to improve an societies in Asia. gap between large cities and local cities and His group is focused on overcoming such income map of Japan based on the Statistic Researchers in law, politics, economics and resolving gender gaps are essential to over- issues by developing small area estimation Bureau’s Housing and Land Survey (HLS). social sciences have recently established coming the divides. (SAE) techniques that borrow statistical Using a new statistical model that accounts the Chiba Studies on Global Fair Society The key aims of the project are to investigate strength from supplementary data. for the grouped data format of the HLS and project, with the aim of creating an inter- the development, transformation and lim- additional data from the Population Census, disciplinary research base to inform future itations of existing welfare state models and OVERCOMING INEQUITY AND they measurably reduced the uncertainty of local, national and international policies. to provide empirical evidence for how a fair PUBLIC HEALTH INSIGHTS the HLS’s income estimates. Lead researcher on the project, Jiro society can be achieved in the 21st century. SAE’s scope isn’t limited to stabilizing data, Mizushima, says the key concept is fairness. Mizushima has spent considerable time While the applications of SAE are broad, adds Kobayashi. SAE techniques can add “We define fairness as the basic element of researching aspects of the welfare state in the “small area problems arise particularly within information. For example, the HLS mod- justice,” he explains. “In fact, we argue that Netherlands, including how it has responded official statistics on which governments make el could also infer income in areas where it exceeds justice in most cases. At the same to social challenges such as global economic important political decisions. Hence, small data is missing. Using a mixture modeling time, we embrace values such as equality fluctuations and an aging population. Members area estimation techniques could lead to more approach, the team recently estimated the and liberty.” “Fairness has been the core of legal and effective policy making,” notes Kobayashi. distribution of land prices around train Jiro MIZUSHIMA Mizushima, whose research interests lie political philosophy since ancient times, and An example crops up in the monthly Family stations in and around Tokyo by making Professor, Graduate School of Social Science in welfare state reform in Europe, says the so one of our teams is examining equality Income and Expenditure Survey (FIES) inferences across areas. project aims to go beyond the traditional and fairness from a historical perspective, conducted by Japan’s Statistics Bureau. Contributing to public health discussions, in Masaya KOBAYASHI Akiko OISHI discussion of equality — it seeks to con- comparing political, economic and legal Although FIES provides the latest informa- 2018 Kobayashi collaborated on a paper that Hikari ISHIDO Masahiro OGIYAMA struct new principles that value diversity standpoints over time,” he says. “Another tion on household income and expenditure, used a spatial Poisson regression model to Hiroyuki MINAGAWA Seiichi IGARASHI among people in a global society. group will analyze the meaning of fairness at a small area level, such as a city level, the look the links between access to clean water in the 21st century, providing us with funda- Iwao FUJISAWA Kentaro SATO sample size of FIES becomes so small that and dropping mortality rates in the early mental guidelines to underpin our program.” Takayuki KAWASE Chiyo YONEMURA direct estimators are unstable and can’t grasp 1900s. Kobayashi and collaborators at the The team plans to form networks of academ- Reiko OGAWA Li XIANG detailed trends. Tokyo Institute of Technology and Duke ics across the globe. To this end, they have But FIES, says Kobayashi, can borrow University in the United States looked hosted five highly successful international statistical strength from data in the National at death rates in Tokyo in 1930 against a

14 15 TRANSLATIONAL RESEARCH PROGRAM OF PSYCHIATRY AND PSYCHOLOGY MIGRATION AND REFUGEE STUDIES COGNITIVE LIVING WITH PEOPLE WITH

BEHAVIOURAL THERAPHY Members FOREIGN BACKGROUNDS COMES OF AGE IN JAPAN Eiji SHIMIZU Director and Professor, Research Center for Research Keywords: Psychiatry, Psychology, Cognitive Behavioral Therapy Child Mental Development Research Keywords: Globalization, Migration and Refugee Studies, Multicultural Coexistence

Eiji KIMURA Makoto ICHIKAWA Chikae ISOBE Miho IWATA -Better access to mental health care in schools, at work Fumiko SUNAGAMI Keito NAKAMICHI -The Global-Local Nexus and online could help people of all age groups suffering Tomihisa NIITSU Aika TOMOTO from anxiety, depression and other related conditions. Yoshiyuki HIRANO Toshiyuki OTANI Kenichiro SHIMAI Kensuke YOSHIMURA THE INCREASED TRANSNATIONAL of people with practical initiatives in the local impact and results in severe losses for society. MOVEMENT OF PEOPLE area. It comprehensively studies the back- Instead of marginalizing and excluding THOUGHTS ground for this global mobility, networks that children with international backgrounds, we hat we think affects contributed to the first study that visu- Until countries started closing their borders enable it, policies and institutions, education must provide an environment in which they how we feel an act alised changes in brain activity during due to COVID-19, the cross-border mobility and employment of migrants in Japan to can apply their latent skills. “As the Japanese psychotherapy in 2015. Using functional of people was part and parcel of everyday life identifying the challenges affecting multicul- population shrinks at an accelerating rate, it magnetic resonance imaging (fMRI), the in a globalized world. Some crossed borders tural coexistence in Chiba. has become urgent to create a positive cycle results indicated that the left posterior for study or work, while others had no choice First, we study the migration trajecto- that integrates the education and employment parietal cortex plays a vital role in cog- but to flee across boundaries to escape conflict ries through multidisciplinary approach. of migrants. This is a significant undertak- CBT nitive restructuring — a process used in and persecution. Globalization has increased Backgrounds, global norms and networks ing, both academically and policy wise,” says EMOTIONS BEHAVIOURS CHANGING PERCEPTIONS CBT that enables people to challenge hat we feel affects hat we do affects the number of migrants and refugees, creating provide the context in which mobility has Ogawa. how we think an act how we think an feel existing beliefs. numerous impacts worldwide that lead to the been shaped, facilitated or hindered. Second, A society that recognizes diversity and where In 2016, Shimizu and his colleagues showed burgeoning of research in the field of hu- we focus on education and employment of different cultures coexist would be a better that CBT can help reduce social anxiety for pa- manities and social sciences on migration and migrants and children with foreign roots in one not only for migrants, but also for the © www.betterhelp.com tients ineffectively treated with antidepressants. transnational mobility of people. Chiba. Japanese, who are themselves diverse in terms In recognition of the growing need for As witnessed in the 2015 Syrian refugee crisis Taking a multidisciplinary approach en- of class, gender, ethnicity, social position, and professional CBT care, at the end of 2018 in Europe, Britain’s withdrawal from the compassing international relations, history, so- physical and mental challenges. Major efforts are underway to help treat and Shimizu of Chiba University’s Research the Japanese government began to certify EU, the massive flow of Rohingya refugees ciology, economics, management, educational prevent anxiety-related disorders in Japan Center for Child Mental Development licensed psychologists. The national health from Myanmar to neighboring countries, the studies, law and area studies, we present the —where as many as one in four people and Chiba University Hospital’s Cognitive insurance system has been updated to cover movement of people has significantly influ- research findings, facilitate networking and experience mental health problems during Behavioral Therapy Center. “However, CBT doctor-administered CBT for patients with enced and altered the society. policy advocacy. their lifetime. resources in Japan are still relatively scarce.” depressive disorders, anxiety disorders and As of late 2019, approximately three million Social Anxiety Disorder (social phobia), one Chiba University and its affiliated hospital bulimia nervosa. registered foreign residents are living in Japan, INTERGRATING EDUCATION AND of the most prevalent, is characterised by are spearheading efforts to address this. There are also moves to introduce CBT- led by several policy initiatives including the EMPLOYMENT an intense fear of social situations. In some The Chiba Improving Access to Psycho- based anxiety prevention programs in amended Immigration Control and Refugee cases, social phobia can lead to addiction, logical Therapies (Chiba-IAPT) program, Japanese elementary schools. Recognition Act and the “300,000 Interna- The keyword of this research is multicultural depression or suicidal behaviour. adapted from a UK model, became the first A 2018 study, designed by Yuko Urao and tional Students Plan”, which aimed to increase coexistence. “The term ‘multicultural coexis- Many doctors, legislators and patients now post-qualification training course of its supervised by Shimizu, examined the effec- the number of international students. tence’ is often used to mean the integration recognise cognitive behavioural therapy kind in 2010. tiveness of an anxiety prevention program Migrants are engaged in different types of of migrants into society. In contemporary Members (CBT) as an effective treatment for social “It’s important to tailor treatments to named Journey of the Brave, targeted at work that sustain our daily lives and contrib- Japan, the critical issue is to ensure the rights phobia. By changing negative patterns reflect not only cultural differences, but also Reiko OGAWA children aged 10–12 years. Consisting of ute to the economy. However, their contribu- of migrants and integrate education and of thinking and behavior, CBT can help personal differences,” Shimizu adds. His Professor, Graduate School of Social Sciences ten 45-minute sessions held during school tion is not always visible. Migrants include employment,” says Ogawa. Japan has ratified children overcome anxiety and the fear of team are developing new tailored interven- hours, the program involved deepening un- people of various backgrounds and Japanese many international treaties, but the failure of uncertainty, adolescents better manage de- tions, such as internet-based CBT (iCBT), Ayako SASAKI Tomoko FUKUDA derstandings of anxiety, monitoring feelings, society is in fact quite diverse; however, sharp international norms to penetrate domestic pression and irritability, and adults deal with which are low-cost, easy to use, and provide Chihiro NAKAMURA Kaoru SHIMIZU and developing assertiveness skills to reduce boundaries are often drawn between “Japan/ affairs has caused many challenges. One of a host of stressful life experiences. optional anonymity. Harumichi YOKOO Yuichi TSUCHIDA social stress. Japanese” and “foreign countries/ foreigners”. these challenges is education for children with In 2017, his group released a study protocol Satoko KOBAYASHI Naoki SAKIYAMA While further follow-up studies are planned, There is also a tendency to perceive people in foreign roots. Thus far, education policies in A LEADING CENTRE FOR CBT for iCBT on patients with persistent insom- Yoshie TAKAMITSU Ai SAITO preliminary results indicate that the program terms of prejudice and stereotypes based on Japan have not given a clear place to these RESEARCH AND EDUCATION nia. They have also produced a simplified, Keiko SAKAI Hiroko GOTO can help children manage their anxiety levels. the intersections of race, class, and gendered children. Therefore, low education levels, drop five-minute program that can be used to Ken ISHIDA “Our hope is that in ten years’ time, all hierarchies that exists in Japan. out and unemployment have become pressing We are now actively trying to increase the help reduce depressive symptoms. children in Japan will have access to this Led by Reiko Ogawa, this research group issues. Many studies have shown that a lack number of CBT experts in Japan,” says Eiji As part of his wider research, Shimizu program,” Shimizu says. aims to integrate the transnational mobility of educational opportunities causes a lifelong

16 17 Science and Engineering

NEXT-GENERATION THREE-DIMENSIONAL DISPLAY AND MEASUREMENT

Future Images —More than Meets the Eye

MULTIMODAL MEDICAL ENGINEERING Toward Image-Based Disease Diagnostics

CENTER FOR INNOVATIVE MICROWAVE REMOTE SENSING The Next Wave in Remote Sensing

IMAGING SCIENCE AND TECHNOLOGY FOR MATERIAL APPEARANCE AND AFFECT Affect and Realness in Digital Images

INSECTS-INSPIRED BIG INNOVATION Looking to Nature to Revolutionize Flight

SOFT MOLECULAR ACTIVATION FOR INTELLIGENT MATERIALS Catalyzing the Future of Smart Materials

ADVANCED BONE-CONDUCTION COMMUNICATION Bone-conductionTechnology beyond Hearing Aid

LYMPHEDEMA MONITOR Making Invisible Lymphedema Visible

© iStock.com/Nongkran_ch 18 19 NEXT-GENERATION THREE-DIMENSIONAL DISPLAY AND MEASUREMENT MULTIMODAL MEDICAL ENGINEERING FUTURE IMAGES Members TOWARD IMAGE-BASED Hideaki HANEISHI Professor, Center for Frontier Medical Engineer MORE THAN MEETS THE EYE DISEASE DIAGNOSTICS Tadashi YAMAGUCHI Hideki HAYASHI Kenji YOSHIDA Kazuyuki SAITO Research Keywords: Computer Holography, Volumetric Display, High Performance Computing Research Keywords: Medical Engineering, Physical Measurement, Multimodality Kazuya KAWAMURA Takashi UNO Toshiya NAKAGUCHI Mikio SUGA Takashi ONISHI Yuzuru IKEHARA Yasuo IWADATE Koichi HAYANO -Advances in three-dimensional image display and -Novel, high-precision imaging techniques are being Hao LIU Ken-ichi TSUBOTA measurement techniques have applications in multiple fields, used to provide non-invasive disease diagnosis and guide WenWei YU Hiroki SUYARI from medicine to communication and entertainment. future treatments.

digital holographic microscopy and ultrarapid piece of information, while another standing Non-invasive, precise diagnosis of diseases registration method that transforms two data standing of different diseases,” says Haneishi. Members holographic imaging techniques.” somewhere else will see completely different using advanced medical imaging tech- sets into one coordinated system using MRI The Multimodal Medical Engineering Tomoyoshi SHIMOBABA Among the team’s recent successes is a small, information. nologies could one day replace traditional and pathological images of brain tumors. program has access to highly specialized Professor, Graduate School of Engineering inexpensive, zoomable holographic projec- “Our volumetric display simultaneously techniques based on biopsy and dissection. “If we can establish the technology for equipment and technologies that can help tion system, suitable for use in classrooms, provides several observers with different With this prospect in mind, researchers at registering two kinds of images, then MRI realize researchers’ ideas.

Takashi KAKUE Takashi OKAMOTO medical applications and entertainment information,” explains Shimobaba. “This the Multimodal Medical Engineering pro- features that are strongly related to the patho- “We welcome engineers and medical Atsushi SHIRAKI Tomoyoshi ITO products. Shimobaba’s team refined math- very exciting feature is quite new, and we gram are combining medical and engineer- logical features of tumors can be highlighted. researchers who wish to work at the cut- Seiichi KOAKUTSU Michiko TAKAGAKI ematical image manipulation techniques to are considering new applications for using ing expertise to create novel, noninvasive This may eventually allow us to diagnose us- ting-edge of research and development with Shigeo SHIODA Yota YAMAMOTO ensure a high-resolution, non-grainy holo- it, such as developing multi-language imaging-based methods for diagnosing and ing only MRI,” says Haneishi. “Determining direct clinical applications,” says Haneishi. graphic image even when zooming in and signage for the Tokyo Olympics in 2020,” treating disease. the relationships between different data sets out. The researchers are further developing he says. Such 3D displays may benefit from The program uses various scanning tech- helps us build up detailed pictures of what is Technologies based on three-dimensional algorithms that can reduce ‘speckle noise’ in advanced aerial projection techniques, also niques, or ‘modalities’, including comput- going on inside the body, not only for diag- (3D) image displays and holography may reconstructed images to avoid degradation under development by Shimobaba’s team. erized tomography, magnetic resonance nosis but also to improve our understanding conjure up visions of science fiction, but the in image quality. “Networking is the key to our success,” imaging (MRI) and ultrasound, to analyze of disease development,” he adds. Next-generation Three-dimensional Display says Shimobaba. “Many students who have cellular and organ variations caused by and Measurement program aims to make ONE IMAGE, MULTIPLE VIEWS graduated from our laboratory move on to different diseases. NOVEL OPTICAL PROBES these advanced tools part of everyday life. conduct research in academia or in private The program’s goal is to develop highly Holograms create true three-dimensional Another aim is to reconstruct large 3D companies, and we continue to work with precise, non-invasive imaging methods, Alongside conventional imaging techniques, images, which allow the viewer to see an images with a large viewing angle — them. In this way, we expand our project and while boosting existing imaging techniques the researchers are also exploring novel opti- object from all angles. They are created using something that is difficult to realize using build fruitful working relationships across to improve resolution and enable more-de- cal probes. One example involves a method coherent light sources such as lasers, which current technologies. academia and industry.” tailed tissue analysis, says program leader for monitoring microcirculation — the flow can store the complex light interference pat- “We are also developing accurate holographic Hideaki Haneishi. of red blood cells — in the body. The probe terns required to accurately recreate an entire measurement systems, which will be invalu- “Many current disease diagnostics, partic- comprises multicolored light-emitting di- 3D object in full color. However, the main able in medical science because they allow ularly for cancer, involve highly invasive, odes (LEDs). As the LED light is scattered drawback of holography is the immense com- researchers to image and measure samples in unpleasant procedures to clarify the type and through the tissue, it is partly absorbed by putational burden of producing high-quality 3D alongside visualizing moving phenomena stage of the disease,” explains Haneishi. “We molecules in the red blood cells, generating holograms, not to mention creating moving in real time,” explains Shimobaba. are investigating, for example, the develop- a clear, detailed picture of the cells and their 3D video images in real time. In another exciting field of research, the ment of a system to diagnose breast cancer microcirculatory network. Leader of the 3D program, Tomoyoshi Shi- team is exploring a form of 3D image using very-high-frequency ultrasound.” Building on previous work, the team hopes mobaba says his team is developing ultrafast creation called volumetric displays — the Rather than physically sampling and dissect- to use this probe to estimate features such as algorithms and dedicated computers for ho- difference being that, while holograms can ing lymph nodes from potentially cancerous the oxygen saturation of each blood vessel lography to create the world’s first real-time only be seen clearly by a few people at a tissue, his team has shown that it is possible in areas around suspected tumors in real holographic 3D display system. time, volumetric displays can be viewed by to analyse cell characteristics of lymph nodes time. This could aid diagnosis and further our “These dedicated computers will have a com- multiple people from different viewpoints. using ultrasound. Their technique highlights understanding of vascular behavior in and putational speed three or four orders of mag- And, in an even more challenging concept, metastasis positive and negative cells in lymph around tumors. “Ultimately, we would like to nitude higher than the household computers they are trying to create multi-viewpoint nodes, enabling rapid, painless diagnosis. build on these imaging techniques and use of today,” adds Tomoyoshi Ito, advisor on the images with plural information appearing Haneishi and his team are also devising ways machine learning and artificial intelligence project. “Based on this dedicated technology, in specific directions. In other words, one to combine data from two or more modalities. technologies to relate measured signals and we will investigate holographic projection, person standing at one place will see one For example, in 2016 they developed an image diagnoses, to develop a comprehensive under-

20 21 CENTER FOR INNOVATIVE MICROWAVE REMOTE SENSING IMAGING SCIENCE AND TECHNOLOGY FOR MATERIAL APPEARANCE AND AFFECT THE NEXT WAVE AFFECT AND REALNESS IN REMOTE SENSING IN DIGITAL IMAGES

Research Keywords: Microwave Remote Sensing, Synthetic Aperture Radar, Research Keywords: Engineering for Material Appearance, Image Sensing, Visual Psychology Environment and Disaster Monitoring Members

Jasaphat Tetuko SRI SUMANTYO -Microsatellites and remote imaging technology are Professor, Center for Environmental Remote Sensing -Understanding how the human brain interprets images revolutionizing the way we predict earthquakes and Kazuteru NAMBA Wen LIU could underpin the future of internet shopping, virtual monitor disaster zones. Katsumi HATTORI Hiroyuki NAKATA communication, digital fabrication and even non-invasive Chiharu HONGO Akira KATO medicine.

© iStock.com/wacomka When internet purchases arrive and seem UNDERSTANDING THE MECHANISM ployed on both large and small aircraft, as well nothing like their picture, it can be a disap- OF MATERIAL APPEARANCE AND as on the JX UAV. The CP-SAR sensor is the pointing experience for shoppers. So, while AFFECT first of its kind, utilizing interference between big e-commerce players are increasingly left- and right-handed circularly polarized investing in technologies to help personalize Among the work done by the diverse group virtual reality headsets coming from technolo- light to obtain precise information about the products or shop via phone or virtual reality is a study analyzing affects and emotions. A gy giants such as Sony, Panasonic, Canon and Earth’s surface in a compact, lightweight and headset, a significant stumbling block is ren- research team led by Norimichi Tsumura, who Nikon. While he also mentions cosmetics and inexpensive sensor. dering realistic, digitally produced images. is also the leader of this research project, has automotive painting, one team have already We have developed several techniques based “To achieve a realistic rendering of some- developed a technology to visualize the amount had some remarkable success in one crucial, on SAR imaging to monitor infrastructure and thing, we also need to deeply consider of hemoglobin, which carries oxygen in the but quite unique area — medical diagnostics. areas affected by disasters such as forest fires, human perception,” explains Keita Hirai, blood, on the images taken with a smartphone The pulse measurement technology devel- landslides, subsidence and volcanic eruptions,” a member of the “Creation of Material camera. If you take a video of your face using oped by the research team of Tsumura has says Sri Sumantyo. Appearance and Affective Imaging” group this technology, you can also measure your already produced remarkable results in medical © iStock.com/Sirintra_Pumsopa Engineers in this team are developing two nov- at Chiba University’s Graduate School of heart rate based on the increase or decrease diagnosis via the internet communication. It el microsatellites. One is equipped with radio Engineering. How we perceive a material, in the amount of hemoglobin. Furthermore, is expected to be applied to a wide range of The Microwave Remote Sensing Labora- a change such as an earthquake or a landslide, occultation and electron density temperature he says, can also be linked to cognition, not by capturing a slight change in the interval use, from non-invasive medical diagnosis to tory is far more than a laboratory. It is an researchers can determine how much the land probe sensors for measuring the atmospheric just physical phenomena. between heartbeats, it is possible to grasp the improving understanding of physical exercise experimental aerospace workshop where has moved. signatures thought to precede earthquakes, To examine the complex effect of the mind’s respiratory rate and the balance between the using a simple smartphone app. Furthermore, world experts in remote sensing collaborate The research team has a well-developed while the other is a CP-SAR satellite with eye, Chiba University have drawn from sympathetic nerve and the parasympathetic this research project connects the expertise of with mechanical and aerospace engineers research-and-development program with lightweight gold-coated mesh antenna. These a diverse range of researchers, including nerve. It is expected as a technology for mea- various researchers in order to establish new to construct state-of-the-art microsatellites, 15 researchers, 25 students and facilities for satellites are poised to take the lab’s research engineers, psychologists, and medical and suring human affects and emotions. imaging technologies that integrate material unnammed aerial vehicle (UAV), and air- designing, manufacturing, calibrating and beyond the stratosphere. cognitive scientists. Another group found that our perception of appearance and affective engineering, which borne sensors. The research team specializes operating SAR for UAV, aircraft, and micro- “Our microsatellite program is very exciting for Recently, Hirai’s team developed a new colour is affected by our understanding of its monitors human emotional states and provides in microwave-radar technology for detecting satellite applications. future SAR sensor applications and planetary system for texture evaluation, and through dimensionality. The same viewer looking at the images with high quality material appearance. ground movements and earthquake predic- exploration,” says Sri Sumantyo. “We eventu- participant feedback have devised a set of same image saw colours differently depending tors as part of a new generation of remote ADVANCED AEROSPACE FACILITIES ally aim to have five microsatellites in orbit, algorithms that can produce more realistic on whether they interpreted the image as two sensing technologies. which will provide real-time monitoring for digital representations of patinas and colours dimensional or three dimensional. Viewing “Microwave radiation is particularly useful for “Our facilities include an anechoic chamber for global disaster mitigation and research.” overlaid onto textured fabrics in digital images with one eye or both, and whether the Members remote sensing because it penetrates cloud, calibrating sensors, a satellite–ground commu- The team has strong collaborations with Jap- images. The aim, he says, is to one day digital- image or the viewer’s head was moving, also haze and fog, allowing us to observe the Earth’s nication system, and microsatellite calibration anese and overseas research institutions and in- ly simulate photo-real fabric appearance via affected how natural the image seemed. This Norimichi TSUMURA surface from space,” explains Josaphat Tetuko and measurement systems. We also have a dustry — it has more than 50 agreements with a smart device. Hirai points out that this will work, says Hirai, is important for better smart Associate Professor, Graduate School of Engineering Sri Sumantyo who leads this research project. simulator for designing microwave circuits and research and industry partners throughout the not only be helpful to internet shoppers, but device production. “A more informed colour The core area in this research project is the de- antennas, along with a suite of manufacturing world. The group also encourages short- and that these algorithms could also find applica- management system, for example, may help Takahiko HORIUCHI Keita HIRAI velopment of synthetic aperture radars (SARs) equipment,” says Sri Sumantyo. “We even have long-stay programs, and Double Degree Pro- tions in rapidly advancing digital fabrication realize more accurate colour reproduction Yoko MIZOKAMI Shoko IMAIZUMI for microwave remote sensing to monitor land our own 6-meter experimental UAV, the JX, gram for Master and Doctoral Courses under techniques, such as printing digital patinas between different devices: displays, cameras Michinari KOHRI Noriko YATA deformation. SAR emits a microwave signal which we developed in this laboratory.” various government programs, through which onto fabrics or objects, and manufacturing and printers,” he explains. Toshihiko MATSUKA Kensuke YOSHIMURA in the direction of the target and then detects They have already developed SAR sensors for more than 500 students and researchers representative digitally-designed 3D products. Hirai says the group’s work will influence the Rumi TOKUNARA Ayumi AMEMIYA microwaves scattered from the target. By com- circularly polarized (CP) microwave radiation from many different countries have worked In fact, the group aims to contribute to indus- most cutting-edge imaging technology, such as Eriko KOBAYASHI Kazuki NAKAMURA paring SAR images obtained before and after in the L, C and X bands, which have been de- at the lab. tries as diverse as cosmetics and medicine. the omni-directional 3D camera systems and Shunji KOTSUKI Shinichi INOUE

22 23 INSECTS-INSPIRED BIG INNOVATION SOFT MOLECULAR ACTIVATION FOR INTELLIGENT MATERIALS Members

Takayoshi ARAI LOOKING TO NATURE TO CATALYZING THE FUTURE OF Professor, Graduate School of Science

Members Hirofumi KANOH Shoji MATSUMOTO Katsuhiko MORIYAMA Yasushi YOSHIDA REVOLUTIONIZE FLIGHT Hao LIU SMART MATERIALS Nobuyuki ICHIKUNI Tomonori OHBA Professor, Graduate School of Engineering Research Keywords: Bioinspired Engineering, Biological flight, Drone Yasuhiro YAMADA Shoichi KATSUTA Research Keywords: Synthetic Chemistry, Catalytic Reaction, Iodine Bond Takeshi MORITA Hyuma MASU Akio NAMIKI Kazuya OKAWA Fumio SAKANE Takeshi MURATA Toshiyuki NAKATA Michinari KOHRI Takuya HASHIMOTO Shigeru ARAI Toshihiko MATSUKA Tomokazu USHITANI Kazuhiro YOSHIDA Takashi MINO -The beating wings of insects hold the secrets Arii WATANABE Yuma TAKAHASHI -Catalysts developed from soft iodine, graphene Hideaki SHIROTA Masaya NAKAJIMA Hiroyuki ISHIKAWA Akira KATO to controlled low-speed flight and Micro Aerial Vehicles. and metal complexes could transform smart material Shinji HARADA Shingo HARADA technologies. Tomoya UEHARA Mamoru TAKADA Keisuke IIDA Yasuhiro YAMADA Manabu TSUKADA

Inspired by the fascinating flying ability of ultra-low-speed wind tunnel capable of air- more reliable and agile than anything based The very idea of materials that change their catalysts, predominantly using iodine, can and ring-shaped molecules. “We are lucky insects and humming birds, Chiba Universi- flow as slow as half a metre a second. They on today’s rotor-based technology. In 2019, shape or function as required sparks the be used to develop highly targeted medi- that Chiba prefecture in Japan is one of the ty’s Biomechanical Engineering Laboratory use it to observe and analyse the flight of we established the Center for Aerial Intelli- imagination. Smart materials are impres- cations,” he explains. “A second type is ‘soft world’s leading producers of iodine,” says has been conducting pioneering research on live birds and insects such as moths, beetles gent Vehicles, aiming at creating innovation sive artificial molecules, often inspired by Π-electron’ using carbon nanotubes and Arai. “In fact, the Chiba Iodine Resource beating-wing flight for more than 20 years. and dragonflies, as well as micro air vehicles from a new mechanism of flight. In the naturally occurring chemicals, which have the graphene, which would provide a unique Innovation Center (CIRIC) has opened at Headed by Professor Hao Liu, the lab is on (MAVs), very small drones with potential meantime, we continue to collaborate on the potential to revolutionize design. They under- reaction sphere for catalysis. The third type, Chiba University in July, 2018. A key goal of the verge of revolutionizing the very concept uses in disaster relief and covert operations. development of advanced, flapping MAVs, go changes that are reversible and repeatable, ‘soft metal’ catalysts allow us to introduce our program is to perfect iodine-based soft of flight itself. “Using high-speed imaging and particle as well as help improve the reliability of meaning they can function as molecular soft elements such as gold and copper into molecular activation.” “Insects have this amazing ability to hover image velocimetry data, we were able to rotor-based drones by introducing flexible switches, valves and sensors. Other smart target molecules.” Recent success for Arai’s team includes and execute highly controlled flight in both create a computer model of an insect and wing technology.” materials include shape-memory alloys that the development of an aminoiminophe- still air and turbulent wind gusts,” says Liu. its flight mechanism, and from there we return to their original shape after bending, NEW CATALYST DESIGN noxy-copper carboxylate catalyst that can “Scientists once knew very little about how made an experimental robot insect that metal-bearing polymers that can switch from trigger high yields of O-cyclized molecules. insects generate aerodynamic force in tur- actually flew. That was another pioneering insulator to conductor and drug-delivery Arai says one of the main goals of the pro- These can, in turn, be used to generate a bulent environments, and even less about breakthrough,” says Liu. systems that slowly release pharmaceuticals gram is to create new asymmetric catalysts, particular chiral compound that is invaluable how they are able to maintain such agile “Our research brings together biology, engi- where and when they are needed. which are used to generate large numbers for use in antimicrobial and antiosteoporotic control in flight.” neering, computational physics, biorobotics Researchers at the Soft Molecular Activa- of very specific molecules. Most biological compounds. and neuroscience, and we collaborate with tion for Intelligent Materials program are molecules are chiral, meaning they exist in “A crucial part of our research is designing BIOLOGY INSPIRES MICRO the likes of Cambridge and the Universi- leading investigations into catalysts made one of two mirror-image forms called enan- catalysts that can be reused multiple times, AIR VEHICLES ty of London on some really interesting from soft molecules that could one day tiomers. Many drugs and smart materials use thereby creating cost-effective, sustainable international, cooperative projects. Chiba transform smart material design. just one specific enantiomer, and so catalysts methods for generating useful compounds,” Conventional flight is based on the unin- is definitely a world leader in this area with Lead researcher Takayoshi Arai says the are needed to direct the chemical reactions says Arai. His team recently designed a terrupted flow of air over the curved upper a strong interdisciplinary team and world- program is focused on developing powerful toward forming the correct enantiomer. recyclable catalyst made from a zinc-poly- and lower surfaces of a wing, which causes a class facilities.” catalysts to create novel smart materials us- For example, iodine has been used to help meric ligand complex. The polymeric ligand ‘suction’ effect that lifts the wing upward. The lab’s research now focuses on develop- ing three catalyst types. “Firstly, soft halogen synthesize specific enantiomers of cyclic allows the catalyst to be separated from the “Fixed wings need smooth airflow to gener- ing insect-inspired flight systems, which he final product by a simple filtration process, ate lift,” explains Liu. “Turbulence over the expects to lead to big developments in the meaning it can be reused — indeed, poly-Zn wing can lead to disaster. Our first major design of insect- and bird-size MAVs. remained a stable and active catalyst for breakthrough in unravelling the mystery “For example, we think it’s wing flexibility creating iodine-based ring-shaped molecules of insect flight was that most flying insects that gives insects much of their resilience more than five times. in fact generate most of their lift force by to wind gusts, but we are also seeing that “By introducing soft elements to target mol- creating a vortex on the leading edge of the insects use their body much more than we ecules, our research will facilitate the devel- flapping wing. It’s a completely different thought to control direction and movement, opment of smart materials with smooth and principle of flight to conventional flight.” both actively and passively. This is com- rapid responses,” says Arai. “We welcome It all started in 1996 with Liu’s development pletely different to the conventional wing- anyone interested in research at the forefront of the first computational fluid dynamics based control used by planes today and has of iodine-related soft molecular activation simulation for insect flight, which led to the potential to revolutionize flight control chemistry to come and work in this diverse the discovery of the universal leading-edge strategies in general,” says Liu. and challenging field at Chiba.” vortex mechanism in insect and bird flight. “Ultimately we want to develop an in- © Akiko Sato To delve deeper, the laboratory installed an sect-inspired autonomous drone that is far

24 25 ADVANCED BONE-CONDUCTION COMMUNICATION LYMPHEDEMA MONITOR

BONE-CONDUCTION Members MAKING INVISIBLE Members Seiji NAKAGAWA Masahiro TAKEI TECHNOLOGY BEYOND Professor, Center for Frontier Medical Engineering LYMPHEDEMA VISIBLE Professor, Graduate School of Engineering

Shingo KUROIWA Yoshihiro SHIMOMURA Shinsuke AKITA Ryoji YAGI HEARING AID Yasuo HORIUCHI Keita ISHIBASHI Yoshihiro SHIMOMURA Michiko SUGAWARA Sho OTSUKA Satoki ZENBUTSU Nobuyuki MITSUKAWA Akira MITSUHASHI Research Keywords: Bone Conduction, Hearing Aid, Biomedical Engineering Research Keywords: Electrical Impedance Tomography (EIT), lymphedema, Cloud Computing Masashi SEKINE Takafumi SANGAI Takuro HORIKOSHI Tadashi YAMAGUCHI Ichiro MANABE Mikio SUGA Kenji YOSHIDA -Elucidating the perceptual mechanisms of ultrasonic bone conduction -A low-cost and easy-to-use tomography device can ensure early and cartilage conduction with a view to new device development. detection and proper understanding of lymphedema.

Against the background of the aging society cartilage conduction, and try to apply them to standards and hearing-related safety stan- “Lymphedema,” or stagnant lymph flow and construction of a new electric tomography using machine learning and big data analysis and diversifying lifestyles, there is a grow- hearing aids and smartphones. dards. Fundamental understanding of the abnormal swelling of the arms and legs that began at the University of Manchester, UK. of the lymphedema images. With this de- ing need for a broader range of options in perceptual mechanisms is essential to solving may occur following the removal of lymph Takei had also participated in this project vice, patients can check their edema stage by hearing aids and audio devices. Among the PERCEPTUAL MECHANISMS AND these challenges. nodes by surgery or radiotherapy, occurs in called “European Action.” Several challenges themselves at home. various technologies used for hearing aids, DEVICE DEVELOPMENT “Research on ultrasonic bone conduction about 30% of patients who had surgery for occurred during this project, and the mem- To elucidate the mechanism of development bone conduction has mainly been used for and cartilage conduction have just begun, gynecological cancers such as breast cancer ber researchers tried to solve these problems and progression of lymphedema, not only compensating conductive hearing loss caused Bone-conducted ultrasonic waves can and most of their perceptual mechanisms and uterine cancer. “It has been considered one by one. They developed the sensors, the engineering and medical knowledge but also by middle or outer ear disorders. In recent be perceived as a sound even by severely are still unknown. For example, the mecha- as an abandoned sequela for a long time and electrical circuits to reduce noise and speed- pharmaceutical and scientific considerations years, the incidental benefits of bone conduc- hearing-impaired people who cannot hear nisms of how the bone-conducted ultrasonic has only recently garnered the attention of ing up, the image reconstruction software are crucial. By implementing the knowledge tion technology, such as benefits in speech even with the use of a conventional hearing waves are propagated and easily perceived are researchers,” says Masahiro Takei. “The risk with mathematical inverse problem-solving gained from such integrated research to the perception under noisy conditions, less sound aid. Prototype testing of an ultrasonic bone unclear when the vibrator is attached to the of lymphedema onset lasts for a lifetime, capability, and proceeded with developing prototype, Takei’s team aim to improve the leakage, and usability in water, have come to conduction hearing device showed that, with neck, chest, or even the upper arm. Most of and the condition cannot be fully cured if the appropriate procedures for industrial accuracy and convenience of the machine. attract attention. However, the perceptual the use of this device, about half of severe- the technical challenges of bone conduction detected late, so the patients are forced to and biological use. However, the prototype “Ultimately, we want to visualize the medi- mechanism of bone conduction is complicat- ly hearing-impaired persons were able to cannot be solved without understanding the have a significant psychological burden. For equipment had cost millions of yen, and the cal condition in real-time on a mobile device ed and has yet to be fully understood. perceive verbal sounds, and around 30% were perceptual characteristics and propagation a good prognosis, early detection of stages accuracy was not sufficient for practical use. and to reduce the pain of patients.” “The sound we usually hear through our able to identify the words being spoken. The process of bone conduction.” 0 and 1 of lymphedema is critical, but there “At that time, I thought it would be inno- earholes is called air conduction. While there cartilage conduction is technology in which Nakagawa believes that if he advances bone is still no effective detection device for this vative if we could easily see our inside of is only one pathway for air conduction, the vibrator is attached to the pinna cartilage, conduction technology based on a deep purpose.” the body with a machine that costs around there are at least four pathways available for and now it is applied to hearing aids for understanding of such mechanisms, it opens Takei is now forming a research team of tens of thousands of yen,” says Takei. Thus bone conduction,” says Seiji Nakagawa. “The patients with atresia of the ear canal and also up possibilities for new applications. engineering, medical, pharmaceutical, and emerged the breakthrough technology—a perceptions of bone-conducted sound largely to speakerless smartphones. “For example, we are now going to develop scientific experts from Chiba University, small electric tomography with diagnostic changes according to frequency and location, The cartilage conduction and the ultrasonic bone conduction headphones and micro- aiming to improve the accuracy of detection function. The new system works as follows: and at times differ largely from the sound bone conduction are both ground-breaking phones that can be used even under severely by developing IoT lymphedema tomograph- several electrodes are placed on the body, and perceptions by air conduction.” Nakagawa approaches. There are still some challenges noisy conditions, and an earphone for infants ic monitor with artificial intelligence (AI) a weak electric current is passed through the and his team are working to elucidate audi- before applying them to practical products who often resist the use of conventional system that can be used at home. body. The system produces images showing tory perceptual mechanisms with a focus on for widespread use: improvement of sound earphones or headphones. Furthermore, bone the distribution of conductivity and dielec- ground-breaking bone conduction phenome- transmission performance, wearability and conduction is also suitable as an interface for A SMALL ELECTRIC TOMOGRAPHY tric constant in the body at each frequency na, including ultrasonic bone conduction and comfort of use, and development of industry smart glasses, which people think to be the using a wearable sensor to measure the next-generation information terminal.” As a mechanical engineer, Takei’s belief is potential, small hardware, and mathematical “Chiba University has many faculty members “to make invisible things visible by using a algorithms. with expertise and knowledge in human machine.” So far, he has been working on Currently, Takei’s research team is working interface technology and acoustic signal developing hardware and software related on developing an easy-to-use IoT lymph- processing. We can develop new devices by to electrical tomography. Tomography refers edema tomographic monitor. First, with bringing those strengths together for projects to cross-section visualization measurement, the monitor, impedance data measured by a centered on bone conduction technology. as in computed tomography (CT). Medical small unit from the multi-electrode winded We also have collaborative partnerships with CT is a large machine that costs hundreds sensors are sent to the cloud computing businesses in Japan and abroad and hope to of millions of yen, and it is impossible for unit. Next, 4D images of limb cross-sections achieve innovation by pursuing fundamental patients themselves to use it easily at home. are reconstructed at high speed on the cloud research for mechanism elucidation as well This challenge has been recognized around using specialized software. Finally, edema as the development of practical applications,” the world. In the 1990s, the theoretical (including early-stage edema) is diagnosed says Nakagawa.

26 27 Medical and Pharmaceutical Sciences

PHYTOCHEMICAL PLANT MOLECULAR SCIENCES Unlocking the Potential of Phytochemicals

CANCER EPIGENOME CENTER A Different Approach to Fighting Cancer

MEDICAL MYCOLOGY RESEARCH CENTER Manipulating Microbes for Human Health

MEDICINE FOR RARE DISEASES Innovative Approach Offers Hope for Intractable Problems

GLYCOMEDICINE RESEARCH CENTER Sugar Science’s Immunotheraphy Play

LABORATORY OF DDS DESIGN AND DRUG DISPOSITION Big Hopes for Nanotechnology Based Drug Delivery Systems

INTERNATIONAL HUB FOR METALLOMICS RESEARCH Understanding the function of biometals for human and environmental health

© iStock.com/BlackJack3D PHYTOCHEMICAL PLANT MOLECULAR SCIENCES CANCER EPIGENOME CENTER UNLOCKING THE POTENTIAL A DIFFERENT APPROACH OF PHYTOCHEMICALS TO FIGHTING CANCER Members Atsushi KANEDA Professor, Graduate School of Medicine Research Keywords: Plant Molecular Science, Phytochemical, Gene Research Keywords: Cancer, Epigenome, Inhibitor Ichiro MANABE Tomoaki TANAKA Tetsuhiro NEMOTO Kiyoe URA Hisahiro MATSUBARA Ichiro YOSHINO -Advanced genetic and genomic techniques -A new center aims to combat cancer by rewriting Hideki HANAOKA Tomohiko ICHIKAWA are transforming our understanding of how the epigenetic modifications harbored by tumor cells. Hiroyuki MATSUE Emiko SAKAIDA Toyoyuki HANAZAWA Yoko SHINAGAWA phytochemicals can improve human health.

© iStock.com/mashuk

ENLISTING PHYTOCHEMICALS UNRAVELING MOLECULAR Members Cancer is thought of as a genetic disease, TO FIGHT DISEASE with mutations to a cell’s DNA causing MECHANISMS Kazuki SAITO a normal cell to give birth to a malignant Director, Plant Molecular Science Center Kazuki Saito, who leads the Phytochemical group conducts animal trials to assess the tumor. Yet epigenetic alterations, which Kaneda points to ongoing investigations of The Cancer Epigenome Center includes Plant Molecular Sciences program, says that pharmaceutical potential of molecules. In leave the DNA sequence intact, can be just gastric cancer as an example of this strategy researchers from a wide range of backgrounds Mami YAMAZAKI Naoko YOSHIMOTO because phytochemicals display considerable particular, they have extensively investigated as important in a cell’s transformation to in action. Patients with this cancer exhibit and specialties. This multidisciplinary team Amit RAI Hiroki TAKAHASHI natural diversity, they have huge potential Lycopodium alkaloids (LAs), molecules cancer. Even though epigenetic regulation different levels of DNA methylation in their approach, says Kaneda, is essential for turning Daisuke UMENO Takashi TSUCHIMATSU to fight disease. “Although phytochemicals found in the vascular plant Lycopodiaceae, through mechanisms such as methyl tags tumor cells, depending on the pathogen the center’s discoveries into clinically mean- Hajime SATO Kohji ITO have been used in pharmaceuticals and which may help to treat Alzheimer’s disease and histone modifications does not alter the responsible for the disease. The cancer-causing ingful treatments and diagnostic tools. “We Masami ISHIBASHI Mariko KITAJIMA ancient remedies for many years, it is only and schizophrenia. DNA sequence, it can chemically modify bacterium Helicobacter pylori is one source will help determine the mechanisms of Akiko TAKAYA Noriyuki KOGURE now, with the advent of next-generation The third group is investigating how the genome to signal which genes should be of irregular methylation. Epstein-Barr virus cancers and develop new cancer drugs through Tomoko IGAWA Mitsumasa HANAOKA DNA sequencing, that we can really begin plants respond to different environmental turned on and off. When tumor-suppressor is another pathogen of gastric cancer, which collaborating with experts in medicine, physics Eiji GOTO Natsuko KAGAWA to understand how they work and unlock stresses by growing plants in different arti- genes are silenced or oncogenes are activated not only inactivates tumor suppressor genes by and pharmacy,” he says. Takashi SHIMADA Hidenori SASSA their full potential,” says Saito. ficial environments and monitoring their in this way, many different forms of cancer inducing extreme DNA hypermethylation, but Yasumasa HARA Shinji KIKUCHI The program consists of three collabora- responses to change. can result. also activates proto-oncogenes via an epigen- Taira MIYAHARA Takanori SAITO tive research groups, each working on a “Our aim is to optimize plants so that they Fortunately for medicine, epigenetic etic mechanism the research group has named specific theme. produce high-quality phytochemicals that we alterations are not permanent. They can be “enhancer infestation” (Nat Genet 2020). One group is focusing on the genomics of can harvest for use in medicines and func- undone to prevent or reverse cancer, leaving Kaneda and his colleagues are using clinical Since ancient times, people have used the medicinal plants and food crops with the tional foods,” explains Saito. “Our insights a cell with its entire complement of normal samples and cell experiments to unravel the natural compounds in plants, known as phy- key aim of revealing the genomic principles will enable us to grow rare plants more DNA intact. molecular mechanisms that induce hyperactive tochemicals, for medicinal and nutritional use. of phytochemical production. Employing successfully and will also inform agricultural This is exactly what researchers at the methylation patterns following infection with Now, scientists at Chiba University are using state-of-the-art technologies, the researchers practices for commercial crops in the future.” Cancer Epigenome Center are striving to these pathogenic agents. They ultimately hope advanced genetic and genomic techniques identify and clarify the roles of unknown While the group is focusing on phytochem- do. Led by Atsushi Kaneda, the center is to stop the process in its tracks. Similar proj- to verify how phytochemicals are generated genes, as well as investigate plant metabolism. icals, it also conducts wide-ranging inter- seeking to understand the various epigenetic ects are ongoing to combat colorectal cancers in plants, how they can be manipulated to In 2016, Saito’s team assembled a draft disciplinary studies and hence welcomes drivers that contribute to different types — which Chiba researchers have shown can optimize certain plant groups, and how they genome for licorice (Glycyrrhiza uralensis), researchers and students with backgrounds of cancer and then develop new drugs that be categorized into three types, depending on may help tackle lifestyle- and aging-related which is used worldwide as a natural sweet- in chemistry, horticulture, genetics and overturn these effects. methylation levels — as well as blood cancers diseases. ener and a medicinal component. pharmacy who are interested in this exciting “We will explain key epigenomic aberrations and other types of tumor. Plants naturally generate chemicals for various They identified several components known and rapidly developing area of research. and their molecular causes,” says Kaneda. With an eye to developing novel therapeutics, purposes, including for attracting pollinators to play a positive role in human health “And then, taking advantage of small mole- chemists at the Cancer Epigenome Center and defending themselves. These specialized within the plant, while pinpointing key cules that bind to DNA in a sequence-spe- are working on new methods to efficiently metabolites allow plants to colonize spe- genes, the manipulation of which could lead cific manner, we will develop drugs that synthesize molecules that can act on epigene- cific niches in the food chain, adapt to new to crop improvements. can rewrite the accumulated epigenomic tic aberrations. One such group of molecules is environments and evolve to survive potential The second team is identifying novel phy- aberrations or prevent them accumulating in the pyrroleimidazole polyamides. These mole- stressors. Crucially, phytochemicals also exhibit tochemicals and active products in a wide targeted genomic regions.” cules can bind to DNA at specific sites in the properties that can help treat human diseases. variety of plants, searching for drug com- genome, and when coupled to an epigenetic Examples in modern medicine include mor- ponents to tackle diseases such as cancer, inhibitor they can prevent methylation-based phine, the antimalarial drug artemisinin and dementia and diabetes. As well as isolating gene silencing. Kaneda hopes to deploy the © iStock.com/vitanovski chemotherapy agents derived from taxanes. and analyzing promising molecules, the molecules to edit the epigenome at targeted regions to regulate tumor formation.

30 31 MEDICAL MYCOLOGY RESEARCH CENTER MEDICINE FOR RARE DISEASES INNOVATIVE APPROACH MANIPULATING MICROBES OFFERS HOPE FOR FOR HUMAN HEALTH Members Research Keywords: Infection and Immunity, Microbiota, Superorganism INTRACTABLE PROBLEMS Mitsutoshi YONEYAMA Professor, Medical Mycology Research Center Research Keywords: Rare Disease, Intractable Cancer, iPS Cell

Shinobu SAIJO Koichi HIROSE -Detailed investigations of host–microbe interactions Tomohiro TAMACHI Akiko TAKAYA could yield new therapies against infectious agentsand Yoshiyuki GOTO Hiroshi ASHIDA -The ReDenim network is developing therapies to autoimmune diseases. Kinnosuke YAHIRO Arifumi IWATA treat rare and intractable diseases. Koji ONOMOTO

studying molecular interactions in different TWO-PRONGED APPROACH Members host-microbial systems. One, led by Shinobu Saijo, is focused on fungal and Shinichiro MOTOHASHI Motohashi belongs to the tumor immunity Motohashi. And the two teams will also bacterial infections in the skin of mice and Professor, Graduate School of Medicine team, which intends to capitalize on Chiba have access to support units at the universi- humans; another, led by Koichi Hirose, University’s expertise in developing cell- ty’s Core Clinical Research Hospital, a des- Tomohiro Tamachi, and Arifumi Iwata is Hideki HANAOKA Koji ETO based immunotherapies. Their approach ignation granted to Chiba University under investigating the microbes — both good Itsuko ISHII Masayuki KURODA uses tumor-destroying natural killer T-cells Japan’s Medical Care Act. Hideki Hanaoka and bad — that reside in the respirato- Kiyoshi HIRAHARA Kotaro SUZUKI to search for combination therapies that and Itsuko Ishii develop the support units ry tract. A third group, which includes Sonoko MISAWA Katsunori FUJII can further modulate the tumor immune to apply basic science toward therapeutic Yoshiyuki Goto, Hiroshi Ashida, and microenvironment in a favorable way. They applications. Kinnosuke Yahiro, is concentrating on the also intend to identify biomarkers that can This support includes consultation services gut microbiome and how opportunistic Scientists at Chiba University have a predict how individual patients will respond on issues such as intellectual property, intestinal infections gain a foothold; while long track record of excellence in clinical to these treatments. project management, clinical trial design the fourth, led by Akiko Takaya, is research, particularly for investigations in Led by Sonoko Misawa, the rare-disease and other steps needed to fulfill the promise The human body is made up of a staggering how hosts and commensal microbes commu- working on more basic mechanisms of patients with immune-related diseases. team, including Masayuki Kuroda and of translational medicine. “Our ultimate goal 30 trillion cells or so. But just as numerous, if nicate as a superorganism.” immunological memory in response to And Chiba University researchers have Katsunori Fujii, is using immune-modu- is to form a therapeutic cluster that can be not more so, are the several hundred trillions Creating a superorganism is an apt meta- microbial invaders. made a number of important breakthroughs lating drugs and gene therapies to address applied to a wide variety of rare and intrac- of microbial co-inhabitants that teem in and phor for what Yoneyama is trying to achieve “Results obtained from our projects will in basic immunology and disease biology. immune-related peripheral nerve disease table diseases,” Motohashi says. He can even on us. These microbiotas are essential to our because, through the melding of minds from help efforts to create innovative new However, connecting these two areas, a and hereditary disease. Kotaro Suzuki and foresee a day when the infrastructure created well-being, and a distortion in its balance can across Chiba and around the world, the therapeutics against infectious diseases and field known as translational research, has Kiyoshi Hirahara are aiming to develop new through ReDenim could be used to develop trigger a wide range of disorders. center can make a far greater impact than any will eventually lead to improvements in often been less successful. treatments based on the analysis of patho- new therapies for common diseases, such as Only recently, however, have scientists come individual scientist working independently. human health,” says Yoneyama, whose own That is a problem that Shinichiro Moto- logical conditions using animal models of diabetes or lung cancer. to appreciate just how critical this collection At Chiba University, the investigators come research focuses on the mechanisms of hashi wants to fix. Motohashi leads Chiba’s autoimmune diseases and tissue fibrosis. Koji Judging by the progress they have made so of microbiota is for determining human from the Medical Mycology Research Center, innate antiviral immunity with Koji Research and Development Network of Eto and his collaborators of orthopedics and far, Motohashi and his coworkers are well on health and disease. They are also becoming the Graduate School of Medicine, and the Onomoto. Innovative Medicine for Rare and Intrac- plastic surgery, Seiji Ohtori, Sumihisa Orita, their way to fulfilling their dream, and their excited about the prospect of how manipulat- Graduate School of Pharmaceutical Sciences, To assist all these research projects, table Diseases — ReDenim. The network is Yasuhiro Shiga, and Nobuyuki Mitsukawa, potential is widely recognized. ReDenim has ing this microbial ecosystem could form the while external collaborators are based in the investigators from each group have access aiming to provide the clinical support and are developing a new method of wound already forged collaborations with some of basis for the next generation of life-saving United States, Germany, and elsewhere in Ja- to the Japanese government’s network resources needed to take discoveries from healing using platelet-rich plasma derived the world’s leading experts in cancer immu- therapeutics. Led by Mitsutoshi Yoneyama, pan. These scholars, together with others from of core facilities — a resource known as the lab to the clinic. from iPS cells. Kuroda is also working notherapy and rare diseases, and is working researchers at the Medical Mycology Re- around the world, convene each November the Joint Usage/Research Center, which In particular, ReDenim has singled out two with the tumor immunity team to develop with Japanese drug companies to partner on search Center have launched a comprehen- at the Medical Mycology Research Center is staffed by specialized researchers and disease areas for which there are currently transgenic adipocyte technology that can additional research projects. sive research effort to dissect the intricacies for the annual Global Network Forum on technicians who can run state-of-the- no good treatment options — deadly forms be applied to cancer treatments, in addition of host-microbe interactions in the skin, lung, Infection and Immunity. art experiments, including with fungi and of cancer, such as head and neck tumors; to his research target, hereditary metabolic intestines, and bone marrow. other microbes. A bioinformatics unit at and rare diseases that each afflict fewer than diseases. “Dysregulation of host-microbe interactions EXPLORING HOST–MICROBE Chiba led by Hiroki Takahashi helps with 50,000 people in Japan, but collectively Importantly, both teams will share research can give rise to a wide variety of human INTERACTIONS computational analyses. affect about 10 percent of the population. experiences, technology platforms and man- disorders, including opportunistic infections, ufacturing facilities. “Sharing the know-how allergies, and autoimmune disease,” explains The team that Yoneyama has put together to treat each disease within the network will Yoneyama. “It is hence crucial to understand is roughly divided into four groups, each accelerate drug development,” says

32 33 GLYCOMEDICINE RESEARCH CENTER LABORATORY OF DDS DESIGN AND DRUG DISPOSITION

SUGAR SCIENCE'S BIG HOPES FOR Members Members Hidetaka AKITA IMMUNOTHERAPHY PLAY Professor, Graduate School of Pharmaceutical Sciences Hiroto KAWASHIMA NANOTECHNOLOGY BASED Research Keywords: Immunology, Biochemistry, Glycobiology Professor, Graduate School of Pharmaceutical Sciences Akihiro HISAKA Naohiko ANZAI DRUG DELIVERY SYSYEMS Kousei ITO Takeshi MURATA Motoyuki ITOH Noritaka NISHIDA Kunikazu MORIBE Satoshi OGASAWARA Hirofumi DOHI Noritaka YAMAGUCHI Research Keywords: Drug Delivery, Nanobio, Vaccine Hiroki TANAKA Kenjirou HIGASHI -By bridging the gap between glycoscience and medicine, Yasunori MATSUMOTO Keisuke UEDA Shigeki AOKI major advances in immunology and drug development Hiroto HATAKEYAMA Hiromi SATO are imminent. -Drug delivery systems that nanocarriers could enhance the Yu SAKURAI

effectiveness of therapies ranging from genetics-based cancer treatments Alzheimer's medicines. Lymphocytes are the body’s warrior cells. glycans produced by two enzymes — glycans,” Kawashima says. “Some specialize They circulate through the bloodstream N-acetylglucosamine-6-O-sulfotransferase in biological functions, while others focus on and arrive at sites in the body such as the 1 (GlcNAc6ST-1) and GlcNAc6ST-2 — synthesis or analyze glycan structures. The also showed that ssPalmE-LNP enhanced spleen and lymph nodes, where they combat are essential for the binding of lymphocytes, idea is to bring all of these researchers togeth- the therapeutic effect of an antibody used harmful bacteria, viruses and even cancer and consequently play a vital role in con- er, build new collaborations and understand to combat immune system supressing cells. Sugars, or glycans, are integral to this trolling lymphocyte homing in mice. the function of glycans across many programmed cell death protein 1 (PD-1), migratory process called lymphocyte After working on this study at California’s biological phenomena.” raising hopes for combination therapies to homing, which is of intense interest to Burnham Institute, Kawashima returned The new centre has plans to collaborate combat cancer. researchers. These scientists hope to target to Japan in 2005, bringing with him the with teams both nationally, for example, at Brain disorder treatments also stand to glycans to find new immunotherapies and ‘knockout’ mice (deficient in the two key the Glycomedicine Technology Research benefit from nanocarriers. Recent studies drugs for autoimmune diseases. enzymes) he had developed. At Chiba he Center and the National Institute of Ad- suggest that using ssPalm as an alternative “We now know that glycans — chains of has used these to continue hunting for new vanced Industrial Science and Technology to viruses that deliver genetic material sugar molecules that have diverse func- antibodies that target glycans. (AIST), and internationally. could improve treatments. tions in our bodies — play an essential Already, Kawashima has developed antibod- In experiments with Hokkaido University GLYCOMEDICINE TAKES OFF in 2018, Akita’s team used ssPalm in the role in lymphocyte homing,” says Hiroto ies that will specifically bind to the building © iStock.com/Dr_Microbe Kawashima, a professor at Chiba Univer- blocks of glycans and disable them in studies delivery of messenger RNA (mRNA) to sity’s Graduate School of Pharmaceutical Today, the expanding fields of glycoscience published in The Journal of Biological neurons and astrocytes — star-shaped cells Sciences, Laboratory of Microbiology and (the study of glycans) and glycomedicine Chemistry in 2010 and 2015. This could halt Drug delivery systems that nanocarriers could ed amines enable membrane destabilisation. found in the brain and spinal cord increas- Immunology. (combining glycoscience and medicine) are the dysfunctions involved in autoimmune enhance the effectiveness of therapies ranging The other, a disulfide bond (SS) that can be ingly implicated in neurodevelopment and “These glycans are found on the surface leading to breakthroughs in drug devel- disease, in which the immune system is from genetics-based cancer treatments to cleaved in a reducing environment such as in disease. of endothelial cells in lymph nodes,” he opment and diagnostics for autoimmune overreacting. Alzheimer’s medicines. the cytoplasmic material inside cells, triggers By surpassing the limitations of other forms explains. “Thanks to glycans, lymphocytes diseases. “Usually, it’s very difficult to generate mono- Personalised medicine — tailoring medical the release of NABDs in specific cells. of delivery (such as DNA-based artificial recognize and bind to the surface of those Chiba University’s Glycomedicine Research clonal antibodies against carbohydrates,” treatments to individual needs — may no In proof-of-concept studies in mice in 2016, gene carriers), mRNA therapeutics could cells.” Lymph nodes activate lymphocytes Center, which opened in August 2017, marks says Kawashima. This difficulty in producing longer be far-off. the researchers showed that lipid-based be used to treat many conditions, includ- to fight disease. a shift towards accelerating such break- clones of these antibodies is because carbohy- Developments in nanocarriers have progressed nanoparticles, formed using ssPalm, enabled ing Alzheimer’s, Parkinson’s, Huntington’s In a study published in Nature Immunology throughs in Japan. drate antigens are not generally very antigen- rapidly, promising targeted delivery and efficient delivery to the liver of a genetic disease and other neurological disorders. in 2005, Kawashima and his colleagues in “Many researchers here at Chiba Univer- ic. “To get around this problem, we immu- release of nucleic acid-based drugs (NABDs), treatment that uses small interfering RNA. “Our strengths at the Faculty of Pharma- Japan and the United States showed that sity have been working independently on nized knockout mice with cells expressing the an emerging class of therapeutics designed to They have since gone on to develop sec- ceutical Science include our expertise in missing sugar chains, which are highly prone target diseases at the genetic level. ond-generation ssPalm, which uses Vitamin characterizing physicochemical properties, to stimulating the production of antibodies.” E as a waterproofing scaffold (ssPalmE). and evaluation of pharmacokinetics and The next step will be to further investigate and A BREAKTHROUGH MOLECULE One of the biggest challenges for cancer pharmacodynamics, as well as safety,” Akita identify new ideas for drug development and therapeutics researchers, Akita explains, explains. These skills could potentially to collaborate with pharmaceutical companies In 2013, Akita’s group reported on SS-cleav- will be “to develop DNA- and RNA-based contribute to a wide range of fields he says, to bring them to market. able Proton-Activated Lipid-like Material vaccines that could target unique genetic including immunology and cancer research. “Right now, there are lots of antibody drugs,” (ssPalm), a molecule designed and tested changes in individual cancers.” “We need to keep our eyes open to societal says Kawashima. These immunotherapies over five years that showed promise for The hope is that the versatility of ssPalm needs,” Akita adds. “Until now, we have target issues such as rheumatoid arthritis and drug delivery. could help maximise drug efficacy while been concentrating on materials science. cancer, but, he says, new advances are limited The molecule itself consists of two main reducing side effects. For example, in mouse We have only just begun to enter the arena by a shortage of molecules to target. “Glycans components: One, tertiary amines, are acti- studies performed in 2018, Akita’s group of nucleic acid-based therapeutics. I believe have unexplored potential, so this is an excit- vated in response to an acidic environment, demonstrated that a plasmid DNA- innovations arise when you can look beyond © Akiko Sato ing time to be looking into developing new such as the endosome compartment inside encapsulating lipid nanoparticle (ssPalmE your own particular filed, and apply original candidate drugs based on glycoscience.” the cells of plants and animals. These activat- -LNP) induced anti-tumour effects. They technologies in unexpected ways.”

34 35 INTERNATIONAL HUB FOR METALLOMICS RESEARCH

UNDERSTANDING THE INSTITUTE FOR GLOBAL PROMINENT RESEARCH FUNCTION OF BIOMETALS FOR HUMAN AND Members To accelerate innovative research beyond the borders of academic disciplines, the Yasumitsu OGRA IGPR was founded at Chiba University in 2016 as a core institution for world-lead- ENVIRONMENTAL HEALTH Professor, Graduate School of Pharmaceutical Sciences ing research. IGPR has been actively supporting research projects with potential impact as a global hub for world-class research. Tomoya UEHARA Noriyuki SUZUKI Research Keywords: biometal science, metallomics, theranostics Yasunori FUKUMOTO Yuki TANAKA The institute is also focused on the capacity development of young researchers -Metallomics opens new frontiers in eco-toxicology, disease who will lead new research fields in the next generation. Currently, IGPR is support- prevention, drug discovery, and medical diagnosis and therapy. ing more than 20 research projects in diverse areas.

metal ions to elemental nanoparticles.” Inves- tigating this mechanism requires a technique that can measure metal nanoparticles in TEL : +81-43-290-2916 high-matrix biological samples. Ogra and Mail : [email protected] others are confident that they can establish URL : igpr.chiba-u.jp/global this technique and are looking ahead to apply it for bioremediation, resource recovery (bio- mining) and in the field of medicine. Previous technologies have used plants to eliminate toxic metals and recover useful metals from © Akiko Sato the environment. Recovering these metals as ACADEMIC RESEARCH & elements instead of ions will be significantly more efficient than existing techniques. RESEARCH IN METALLOMICS IS INNOVATION MANAGEMENT Biological phenomena are recognized as a col- “The technique that we are trying to estab- lection of organic chemical reactions consisting UNDERPINNED BY UNIQUE ANA- LYTICAL TECHNIQUES lish to measure metal nanoparticles can be of carbon, hydrogen, oxygen, and nitrogen. developed for the accurate measurement of ORGANIZATION (IMO) A trace amount of metals, such as iron, zinc, elements in individual cells.” If a technique copper, and selenium, play an important role The research group made discoveries based on that quantifies the metal concentrations in IMO was established in 2020 at Chiba University as a hub to enhance academic re- in controlling these reactions. These metals a unique biometal analytical technique. “Our individual cells can be established, we can have specifically required for physiological reactions method is the only analytical technique for a more detailed understanding of patholo- search and collaboration between industry, academia and government. IMO fosters are called “essential metals.” Contrary to the measuring biometals. We aim to expand appli- gies involving metals. It is anticipated that in innovation by strengthening fundamental and advanced research, cross-sectoral essential metals, some metals disturb the phys- cations by refining existing methods to enable the future, applications will prevent diseases collaboration, and venture support system. iological reactions. Since there are many indus- biometal analysis at a single cell level, whereas through AI using big data obtained from trially useful “non-essential metals” in our daily prior biometal analysis was performed at the peripheral cells on elements in individual cells. life, some non-essential metals are the risk in level of tissues or organs,” says Yasumitsu This research project also entails research on URL: imo.chiba-u.jp human and environmental health. In addition, Ogra, the leader of this project. the production of metal-containing drugs excess amounts of essential metals also disturb One of these single cell-level analyses spec- using the unique physicochemical proper- the physiological reactions. Hence, organisms ified the function of metal nanoparticles, or ties of elements in the bottom half of the have the mechanisms underlying the distinction biogenic nanoparticles, which are produced periodic table, which have been seldom used Research Promotion Division of essential and non-essential metals, and the by organisms. It has been generally under- as medication. They will conduct research Tel: +81-43-290-3833 homeostasis of essential metals. The disturbance stood that organisms take in, use, and secrete on practical application of theranostics that Mail: [email protected] of the mechanisms results in critical problems metals as ions, and they do not replace metal employs radioactive metals to develop a novel in human and environmental health. ions with metal elements. However, certain medical technology for simultaneous diagnosis Intellectual Property Strategy Division Metallomics is a study of metallome which micro-organisms, higher-order plants, and and treatment. Furthermore, the group led by Tel: +81-43-290-3831 means metal-containing biomolecules. Metals animals show an exception. Tomoya Uehara will continue their research Mail: [email protected] can induce various physiological and toxico- “Our analytical technique revealed that higher in the field of diagnostics and treatment with logical effects in a very small amount, in other plants and animals exhibit a common mech- radioactive metals, using a SPECT/CT device Venture Support Division words, the metal concentrations are very low in anism to convert metal ions into elements for small animals. This research project will Tel: +81-43-290-3519 organisms. Thus, analytical techniques for a trace which involves detoxification of the ions of serve as a comprehensive research hub that © iStock.com/farakos amount of metals are crucial to understand the non-essential metals and excess amount of unravels the relationship between organisms Mail: [email protected] biological and toxicological functions of metals. essential metals. In other words, they detoxify and metals. 36 37 RELATED RESEARCH CENTERS MESSAGE FROM THE DIRECTOR OF IGPR

· Center for Environmental Remote Sensing · Medical Mycology Research Center · Soft Molecular Activation Research Center, Chiba Iodine Resource Innovation Center · Molecular Chirality Research Center

· Center for Frontier Medical Engineering a new mechanism for detecting floors to take different measures to implement · Center for Environment, Health and Field Science and walls by sensing airflow fluctuations the projects. Associate Professor Genya · Research Center for Child Mental Development generated by mosquitoes. This study Kobayashi, who is leading the project was published in Science and widely on small area estimation and its applica- · Plant Molecular Science Center featured in national newspapers. tion, has analyzed the data of coronavi- · International Center for Hadron Astrophysics Professor Takayoshi Arai, who is leading rus infection using statistical models to · Center for Aerial Intelligent Vehicles the project on soft molecular activation, estimate the effects of behavior change · International Center of Excellence in the Mucosal Immunology has succeeded in catalytic asymmetric before and after the state of emergency and Innovative Allergy Therapeutics iodoesterification from simple alkene declared by the Japanese government · Center for Artificial Intelligence Research in Therapeutics Takeshi Tokuhisa substrates and carboxylic acids. Pub- and to predict infection outbreaks. Director, IGPR and lished in Angewandte Chemie Interna- Starting in October 2020, the bioin- · Shanghai Jiao Tong University and Chiba University President of Chiba University tional Edition, this new research was spired engineering research project led International Cooperative Research Center accomplished by precisely controlling by Prof. Hao Liu held a VR exhibition on multiple interactions in a single catalytic drones where you could learn the tech- It gives me great pleasure to inform reaction and is expected to contribute nology developed by the project as well you that the 2021 edition of CHIBA to the development and improvement as the history of aviation and the de- RESEARCH is now available. All of the of medicines. velopment of robotics technology. This research projects introduced in this Professor Hidetaka Akita and Assistant unique and interactive virtual exhibition issue have been carried out with the Professor Hiroki Tanaka have been re- has attracted many visitors. In addition, support of the Institute for Global Prom- searching nanotechnology-based drug IGPR held a symposium in November inent Research (IGPR), a university-wide delivery systems. They have successfully 2020 as part of IGPR’s initiative to foster organization of Chiba University. IGPR developed a lipid-like material that the development of next-generation was established in 2016 with the goal self-degrades after being taken into researchers. The symposium served as a to enhance prominent international re- cells. This study published in Advanced platform for young researchers engaged search projects of Chiba University and Functional Materials is expected to be in IGPR research projects to brush up foster the development of young scien- applied in systems that deliver various their skills and effectively communicate tists who will lead the next-generation drugs to target cells. The cancer epig- their findings to people outside of their research. This is an original attempt to enome research team led by Professor specialization. bring together research resources from Atsushi Kaneda has studied the mech- Through promoting world prominent all sources throughout the university, anism of how Epstein-Barr virus (EBV) research at IGPR, Chiba University and support and promote high-quality infection causes gastric cancer. Pub- continues to make vital contributions to research in a wide range of disciplines. lished in Nature Genetics, this research society. I strongly hope that this issue of The projects have produced many in- will contribute to elucidation of the CHIBA RESEARCH will help you gain a novative research outputs and findings. causes and establishment of treatment deeper appreciation of the University’s Assistant Professor Toshiyuki Nakata, methods for cancers involving the virus. cutting edge research activities. who is working on the bioinspired engi- Due to the worldwide spread of the new neering research project, has proposed coronavirus in 2020, we were required © iStock.com/farakos

38 39 HOKKAIDO

ABOUT WHERE IS THIS MAGAZINE CHIBA UNIVERSITY? TOHOKU

CHIBA Prefecture is located at the east edge of the South Copyright © 2021 Chiba University. Kanto region. It has a population of approximately 6 mil- All rights reserved. lion, the 6th largest among the 47 prefectures in Japan. Chiba is the center of Keiyo Industrial Area and has the KANTO

well-developed industry. The three sides of the prefecture CHUBU Design and layout: are surrounded by the sea, which helps Chiba's growth in KANSAI Ikjoon Chang, Takumi Sato the seafood industry as well. CHUGOKU Editing and coordination: Chiba University has 4 campuses in Chiba Prefecture. SHIKOKU Midori Ishii, Ayako Shimura KYUSHU Nishichiba Campus (Main Campus) is located between Na- rita International Airport and Tokyo Station. It takes about Narita Airport 30 to 40 minutes by train to Tokyo Station and also Narita Tokyo The information in this publication International Airport. Chiba University was correct at the time of going to press in January 2021. The views expressed by contributors in this publication are not necessarily those of Chiba University. PUBLIC TRANSPORT TO CHIBA

1. KASHIWA-NO-HA CAMPUS Fuchuhonmachi Kashiwanoha Campus 5-min walk from the Tsukuba Express Kashiwanoha-campus KASHIWA-NO-HA Station. Minami-Nagareyama Tsukuba CAMPUS Take the Tobu bus bound for National Cancer Center or Kita-SenjuA Matsudo biko Suido Kashiwanoha Park from bus stop No2 at JR Kashiwa Sta- tion or near the east exit of Tobu Kashiwa Station. Nippori MATSUDO CAMPUS 2. MATSUDO CAMPUS Ueno 10-min walk from Matsudo Station Mitaka Ichikawa Shinjuku Akihabara Shin Kamagawa (JR Joban line, Tokyo Metro Chiyoda Line, Shin-Keisei Line) Nishi-Funabashi Tokyo

Narita Airport 3. NISHI-CHIBA CAMPUS Hamamatsu Cho Funabashi Minami-Funabashi Narita 2-min walk from JR Nishi-Chiba Station to the South Gate Shinagawa Haneda Airport Tsudanuma of Nishi-Chiba Campus Kurihama 7-min walk from Keisei Midoridai Station to the Main Gate Keisei Tsudanuma Sakura Inage of Nishi-Chiba Campus Midoridai NISHI-CHIBA 10-min walk from Chiba Monorail Tendai Station to the CAMPUS 1-33 Yayoi-cho, Inage-ku, Nishi-chiba North Gate

Chiba-shi, Chiba, Keisei Chiba Chiba 4. INOHANA CAMPUS 263-8522 Japan INOHANA After arriving at JR Chiba Station or Keisei Chiba Station, CAMPUS www.chiba-u.jp/e Chiba a bus stop can be found in front of JR Chiba Station east

Chiharadai exit 7. Take the bus bound for Chiba University Hospital or Minami-Yahagi and get off at the School of Medicine En- Kimitsu Kazusa-Ichinomiya trance bus stop. To get to the university hospital, get off at the Chiba University Hospital stop.