The Universityof Tokyo
Graduate School of
Pharmaceutical Sciences
Faculty of Pharmaceutical Sciences

2024

INDEX
Message from the Dean

3

History4

Facts & Figures

5

Organization Chart

6

Pharmaceutical Sciences Education Program

7

Syllabus

8

Laboratories

14

One-Stop Sharing Facility Center for Future Drug Discoveries

48

Drug Discovery Initiative

49

Education Center for Medical Pharmaceutics

50

After Graduating from Graduate School of Pharmaceutical Sciences 51

2Life on Campus

52

Message from Student and Graduate

53

International Student Advising Room

55

Facilities

56

Access Map

57

Hongo Campus

58Message from the DeanThe University of Tokyo’s Faculty of Pharmaceutical
Sciences celebrated its 150th anniversary last year in
2023, having its origins in 1873 with the five-year
pharmaceutical program in the First University District
Medical School, the precursor of the University of TokyoF a c u l t y o f M e d i c i n e . I n 19 5 8 , t h e F a c u l t y o f
Pharmaceutical Sciences of the University of Tokyo
became independent from the Faculty of Medicine andtook a new step forward. In 2006, the Faculty took its
current form with Department of Pharmaceutical Sciences(4-year program) and Department of Pharmacy (6-year
program).
The Graduate School of Pharmaceutical Sciences conducts
state-of-the-art research and education, and has been
operating as an organization consisting of the Doctor of
Pharmacy program for graduates of 6-year universities
such as the Department of Pharmacy, and the Master’s andDoctoral programs for graduates of 4-year universities suchas the Department of Pharmaceutical Sciences, with many
students from other universities and other departments.

in clinical and social pharmacy to ensure that thedeveloped drugs can be used safely by patients and tocreate a highly sustainable system for the nation. In recent
years, many “drugs” based on new principles haveemerged; small organic molecules which has a history ofover 100 years, biologics based on antibodies, nucleic aciddrugs such as mRNA vaccines, and very recent cell-based
medicine using genome editing technology. There is anincreasing need to seamlessly advance research acrossmultiple fields. Since its opening, our department has had
a wide variety of laboratories conducting cutting-edge
research in biological, chemical, physical, and clinicalsciences, and our greatest strength is the ability to conduct
cross-disciplinar y research closely within a single
department. As an important department that enhances
the value of the university “serving the health of thenation,” we will continue to strongly promote our uniqueresearch and education.

The Faculty and Graduate School of Pharmaceutical
Sciences is one of the smallest departments in the
University of Tokyo, consisting of about 800 members. I
am one of the graduates of this department, and I
remember particularly fondly the words I heard in many of
my undergraduate classes: “Now that you have entered theFaculty of Pharmaceutical Sciences, you should always
think about serving the health of the people”. I heard thisphrase from so many professors that it rubbed this idea
into my core. As a result, it has become a compass-liketeaching that appears many times when I am unsure of thedirection to take in my research as a researcher.
In order to overcome diseases, it is necessary to combine
research in a wide range of fields, including not only basic
research to clarify the causes of the disease, and to designand develop corresponding drugs, but also applied research

URANO Yasuteru
Dean
Graduate School of
Pharmaceutical Sciences
Faculty of Pharmaceutical Sciences3

History

1958▶ The Department of Pharmacy separated from theFaculty of Medicine and became an independentfaculty as the Department of Pharmaceutical
Sciences, the Faculty of Pharmaceutical Sciences.
1960▶ The Department of Pharmaceutical Technochemistry
was established.

1873▶ Department of Pharmaceutical Manufacturing wasestablished in Daiichi-Daigaku-Ku Igakko(The First University District Medical School) in Kanda
Izumicho,Tokyo.

1965▶ The Graduate School of Pharmaceutical Sciences,
The University of Tokyo was established.
(Department of Pharmaceutical Sciences andDepartment of Pharmaceutical Technochemistry)

1874▶ D a i i c h i - D a i g a k u - K u I g a k k o w a s r e n a m e d a s
Tokyo-Igakko (Tokyo Medical School).

1966▶ The Research Institute for Chemical Hazards wasestablished.

1876▶ Tokyo-Igakko was moved to Hongo, Tokyo.

1973▶ The Experimental Station for Medicinal Plant Studies
was established.

1877▶ Tokyo Daigaku,
The University of Tokyo was established.
Tokyo-Igakko was renamed as the University of Tokyo
Faculty of Medicine.
The organization of pharmaceutical education beganwith the establishment of Pharmaceutical Institute(later Department of Pharmaceutical Manufacturing in
the Faculty of Medicine). For the first 10 years,
instruction was given by foreigners and in particular a
Dutch chemist Dr. J. E. Eijkman. He left a large
amount of fine work in the study of components ofvarious domestic medicinal plants.
1886▶ The University of Tokyo was renamed as Imperial
University and the name of the Department ofPharmaceutical Manufacturing in the Faculty of
Medicine was changed to the Department ofPharmacy in the Imperial University Medical College.
Japanese who had returned from studies in Germany
took over the education of students, carried out
valuable investigations of their own, and alsoestablished the ground for pharmaceutical organic
chemistry in Japan.
1897▶ The Imperial University was renamed as Tokyo
Imperial University.
1919▶ A faculty system was introduced and renaming the
Department of Pharmacy in the Medical College as
the Department of Pharmacy in the Faculty of
Medicine, Tokyo Imperial University.
1947▶ Tokyo Imperial University was renamed as The
University of Tokyo.
1949▶ The University of Tokyo was established under the
new system (Junior division for the first two years andSenior Division for the 3rd and the 4th years).
1953▶ The Graduate School of Chemistry-related wase s t a b l i s h e d ( M a s t e r ’s P r o g r a m i n t h e f i e l d o f
Pharmaceutical Sciences).
1955▶ Doctoral Program in the field of Pharmaceutical
Sciences was added.

41976▶ The Research Institute for Chemical Hazards wasabolished, and instead the Department ofPharmaceutical Life-Science was established.
1991▶ Two departments were unified into the Department ofPharmaceutical Sciences.
1997▶ The graduate school was reorganized along with the
new system, "Graduate School Priority System" andreformed into three Departments, that is
Pharmaceutical Chemistry, Pharmaceutical Biology,
and Pharmaceutical Technology.
Although the Faculty's emphasis of education isshifted from the Undergraduate Program to the
Graduate Program, most of the faculty members also
continue undergraduate education.
2000▶ Clinical Pharmacy Course was established in the
Master’s Program.
2004▶ Pharmaceutical Sciences Research Building wasconstructed.
2006▶ Following the revision of the School Education Act, theFaculty of Pharmaceutical Sciences started a newprogram with Department of Pharmaceutical Sciences(4-year program) and Department of Pharmacy(6-year program).
2008▶ Department of Integrated Pharmaceutical Sciences
was added to the Graduate School, which consists of
total 4 departments.
2010▶ The former 4 departments in the Master’s Program
were abolished and the Department ofPharmaceutical Sciences was established.
Clinical Pharmacy Course was abolished.
2012▶ The former 4 departments in the Doctoral Program
were abolished.
Department of Pharmaceutical Sciences and Departmentof Pharmacy were established in the Doctoral Program.
Dual Speciality Course on Pharmacist Education wasestablished.

Facts & Figures
Number of Academic and Administrative Staff

As of July 1, 2023

Academic Staff

Researcher

Associate
Assistant Spec. appt. Spec. appt. Spec. appt. Spec. appt.
Professors
Lecturers
professors
professors professors assoc. prof. lecturers assist.prof.
19

15

6

29

4

7

5

Administrative Staff

Subtotal

6

91

OfficeTechnical

Subtotal

21

1

22

30

Number of Students

Numbers

4th
year

143

As of May 1, 2023

Undergraduates
3rd
year

Total

5th
year

Graduates

6th
year

85
88
9
（30） （26） （4）Master’s Program

Total

Doctoral Program (Pharmaceutical Sciences)

3rd
year

4th
year

10
192
81
98
179
35
40
69
144
7
（9） （69） （18） （39） （57） （10） （11） （25） （46） （1）

8
（5）

6
（4）

10
31
354
（3） （13） （116）

Subtotal

2nd
year

3rd
year

Total

2nd
year

2nd
year

1st
year

Doctoral Program（Pharmacy）
1st
year

1st
year

Subtotal

Subtotal( ) Female students

Number of Research Students, etc.
Year

2019

2020

2021

Undergraduatelevel

2022

Number of International Students
2023

1

1

Graduate-level

9

14

6

4

6

Undergraduate
auditor

3

2

1

1

Subtotal

12

16

7

Commissioned
researcher

2

4

Total

14

20

Undergraduate

Countries
and Regions

As of May 1, 2023

Graduate School
Master’s

Doctoral

Syria

Total

Research
Student

1
（1）

1
（1）

China

5

2

Taiwan1

69Canada3

10

United States

1

1

10

7

9

Nepal

1

1

21
（3）

4

47
（3）

1

2

1
（1）

Total

As of May 1

17

6

1

18
（1）

25
（4）

2
（1）

5

54
（5）

( ) Numbers indicate MEXT Scholarship Students

Number of Doctoral Degree Holders
Year

Program
Doctorate
ThesisDoctorate

2018 2019 2020 2021 2022

Cumulative
Total

45

52

45

41

48

2,058

11

16

13

8

3

1,575

Thesis Doctorate（Old System）：571

Current Status of Graduates
Graduate School Graduates

Undergraduate-level Graduates
Academic Year

2018

2020

2021

2022

◎ △ ◎ △ ◎ △ ◎ △ ◎ △Pharmaceutical Company
Chemical industry companies
Financial, insurance, & trading companies
Education, government, research institutes, etc.
4
Others4
Subtotal（Number employed）
Seeking for further education（Graduate school） 67
Research student, other undergraduate course, etc. 2
1
Study abroad
JSPS special researcher, etc.
Others70
Subtotal
Total（Number graduating/completing program） 74
◎
△

2019

Master’s program

1

1

4

3

3

1
2

2
1

1

12

16

17

17

21

22

19

10

5

2

3

6

1

3

1

1

3

3

3

5

4

1

2

6

3

6

6

1

29

8

15

14

11

2

6

13

16

12

16

2

3

2

4

5

4

5

43

42

42

41

41

34

40

41

35

46

70 2 71 3 72 1

43

44

36

40

36

1

2

3

2
2

4

1

1

3

3

2

6

2

8

5

7

3

1

13

9

1

1

2

4

2

2018 2019 2020 2021 2022 2018 2019 2020 2021 2022
19

1

5

1 66

3

Doctoral program

6
1

12

1

2

7

8

2

4

2

3

2

3

4

4

1 67 1 75 2 75 4 73 3

48

49

41

45

42

11

12

2

4

2

7 69 9 80 9 78 10 77 8

91

91

83

86

83

45

52

43

39

48

1

3

1

1
1

Pharmaceutical Sciences
Pharmacy5Organization Chart
Organic and Medicinal Chemistry
Institute of Molecular and Cellular Bioscience

Synthetic Natural Products Chemistry
Synthetic Organic Chemistry
Natural Products Chemistry
Medicinal Plant Chemistry
Experimental Station for Medicinal Plant Studies

Advanced Elements Chemistry
Chemistry and Biology
Bioanalytical Chemistry
Physical ChemistryProtein Structural Biology
Health Chemistry
Physiological Chemistry
RNP Synthetic Biology and Biotechnology
Molecular Biology
Pathology and Development
Genetics

Department of Pharmacy

Cell Signaling

6

Protein Metabolism
Protein Dynamics
Nucleic Acids Research
Immunology and Microbiology
Applied Immunology
Molecular Neurobiology
Molecular Pharmacokinetics
Clinical Pharmacokinetics
The University of Tokyo Hospital

Chemical Pharmacology
Stem Cell Regulation and Drug Discovery
Neuropathology and Neuroscience
Drug Lifetime Management
Pharmaceutical Regulatory Science
Health Economics and Outcomes Research
Health Policy and Public Health
Targeted Protein Degradation
Molecular Pharmacology of Malignant Diseases

Department of Pharmaceutical Sciences

Laboratory

Pharmaceutical Sciences Education Program
Pharmaceutical sciences is an academic field that covers
development of pharmaceuticals and their applications. The fieldencompasses fundamental, life-related substances and theirinteractions with life; using organic chemistry, physical chemistry,and biochemistry as a base, upon which is built a wide range of
research fields, including interdisciplinary areas. With thesep a r a l l e l 6 - y e a r a n d 4 - y e a r p r o g r a m s , t h e Fa c u l t y o f
Pharmaceutical Sciences not only provides traditional training inbasic research for drug discovery but also offers some courses inadvanced training for pharmacists. (Graduates of the Departmentof Pharmacy are qualified for the national examination forpharmacists.) No differentiation is made between the

Departments of Pharmacy and Pharmaceutical Sciences from theCollege of Arts and Sciences until entering higher education,
allowing students to gain an ample understanding of researchcontent before deciding between the two departments in theirfourth year.
Our doctoral program in the Department of Pharmaceutical
Sciences, established in 2012, also provides a Dual Specialty
Course on Pharmacist Education allowing students to be qualified
for the national examination for pharmacists. (This is provided forstudents who enter the University of Tokyo by the 2017 school
year and graduate from the Department of Pharmaceutical
Sciences, Faculty of Pharmaceutical Scineces.)

10

year

Doctoral
Program

Doctoral Program

Dept. ofPharmaceutical Sciences

Dept. ofPharmacy

Graduate School of
Pharmaceutical Sciences

Dual Speciality
Course on
Pharmacist
Education

8

year

Graduate School of
Pharmaceutical Sciences

9

year

7

year

Pharmacist

6

year

Master's Program

Dept. ofPharmaceutical Sciences

5

year

Faculty of
Pharmaceutical
Sciences

Dept. ofPharmaceutical Sciences

Faculty of
Pharmaceutical Sciences

4

year

Faculty of
Pharmaceutical
Sciences

Dept.
of Pharmacy

3

year

2

year

1

year

College ofArts and Sciences

College ofArts and Sciences

College of Arts andSciences7

Syllabus

Faculty of Pharmaceutical Sciences

Department of Pharmaceutical Sciences
Taking on the goal of the previous Department of Pharmacy
curriculum, the Department aims to educate high-qualit yresearchers, focusing on developing personnel in the fields of drug
discovery and basic life-science research.
With a capacity of 90 percent of all students, the Department offers

Four-year program

graduates a two-year master’s program, then to a three-year doctoral
program. The curriculum is nearly identical to the Department ofPharmacy until the third year, allowing students to experience onthe-ground medical treatment even if they intend to pursue
research.

Department of Pharmacy

Six-year program

In response to the advancement of medical care, the purpose of
the establishment of this department is to train and develop highquality pharmacists.
One large difference from the Department of Pharmaceutical
Sciences is that the program includes six-month practical hospital/
pharmacy training. The Department’s capacity is 10 percent of all
students, providing high-quality pharmacy education to a small

number of students, aiming to create personnel who will be able
to lead this field. Six-year pharmacy departments are well overcapacity across all of Japan; to avoid disruption, the University ofTokyo’s Faculty of Pharmacy will collaborate with the Universityof Tokyo Hospital and local pharmacies in order to provide
smooth, uninterrupted practical training.

Faculty Curriculum
Lectures and practicums lie in the center of the education at theFaculty of Pharmaceutical Sciences. They are provided to students
in order for them to acquire the broad knowledge and theperspectives of pharmacists, as well as to have a clear view when
they decide which field of pharmacy they should enter as
specialists. One can say that lectures provided to faculty students
are the essence of pharmaceutical sciences. Furthermore, reflecting
the diversity in research areas in the Faculty of Pharmaceutical
Department of Pharmaceutical Sciences 80 credits(Compulsory: 62 credits, Elective: 18 credits or more)

8

Department of Pharmacy 120 credits(Compulsory: 109 credits, Elective: 11 credits or more)④ = Compulsory 4 = Elective for Department of Pharmaceutical Sciences⑥ = Compulsory 6 =Elective for Department of Pharmacy

2nd year: Autumn 1
Course Title

Sciences, the pharmacy practicums encompass a wide range oftraining areas. It is efficiently designed in a way that students will
be able to put organic chemistry, physical chemistry, biochemistry
and clinical pharmacy into practice. When students enter into
their fourth year, each student will be allocated to a class of his/her own choice and will have opportunities to get hands-on
e x per ienc e i n t he c ut t i n g- e d ge ph a r m ac y t h rou g h t heparticipation in research projects.

＊not included as the number of credits for graduation requirements
Credits

Course Outline

Analytical Chemistry Ⅰ

1This course covers chemical equilibrium, qualitative and quantitative chemical analysis, andinstrumental analysis.

④⑥

Organic Chemistry Ⅱ

1Fundamental organic chemistry which contains Acid and Base, Nucleophilic Substitution andElimination Reactions.

④⑥

Molecular Biology

1Students will lean the fundamentals of molecular biology to understand the life sciences.

④⑥

Cell Biology

1Students will learn the fundamentals of cell biology to understand the life sciences.

④⑥

Radiation Chemistry1

Lectures pertaining to the fundamentals, applications and biological effects of isotopes andradiation (which are indispensable for the fields of medicine and pharmaceutical sciences) will begiven.

④⑥

Organic Chemistry Ⅰ

1Students will learn the fundamentals such as stereochemistry, structural chemistry, reduction andoxidation.

④⑥

Physical Chemistry Ⅱ

1Lectures are aimed to allow students to understand important concept of thermodynamics,
acquire the physicochemical perspectives and learn methods that are important in pharmaceuticalsciences.

④⑥

Physiological Anatomy of Human Body

1

Students will learn the structures and functions of each organ (i.e., anatomy and physiology) as
the basic knowledge for them to understand pharmacotherapy and pathophysiology.

④⑥

Physical Chemistry Ⅰ

1Students will aim to acquire the physiochemical concept by understanding quantum chemistry
and spectroscopy.

④⑥

Introduction to Pharmaceutical
Sciences1

The outline, history and the future vision of pharmaceutical sciences will be explained in an easy
to understand manner, allowing students to think about the relationship between pharmaceuticalsciences and society in terms of industry and medical care. Moreover, students will learn some of
the latest studies in the field of pharmaceutical sciences.

④⑥

Biostatistics

1

Students will receive lectures and practicums regarding statistical methods and experimental
methods used for drug evaluations.

４６

2nd year: Autumn 2
Course Title

Credits

Course Outline

Organic Chemistry Ⅳ

1Students will learn the typical reaction of carbonyl compounds.

④⑥

Analytical Chemistry Ⅱ

1This course covers qualitative chemical analysis, instrumental analysis, separation sciences, andanalytical methods in clinical chemistry.

④⑥

Physical Chemistry Ⅲ

1Students will learn the hierarchy of protein structure, various intermolecular interactions, enzyme
structures and the theory of enzyme reaction.

④⑥

Microbiology and Chemotherapy

1

The basic biochemical and genetic methods will be outlined using microorganisms such as E-coli
as materials. Students will also learn the mechanisms of action of antibiotics.

4 ⑥

Molecular Embryology

1

Developmental genetics will be outlined, and their application to drug discovery science will be
explained.

４６

Pharmacology Ⅰ

1Students will learn the fundamentals of pharmacology in order to understand actions of drugs
that affect the autonomic nervous system and the circulatory system.

④⑥

Functional Biology

1Students will learn the fundamental of higher-order function cell to understand life sciences.

④⑥

Pathology

1

Pathological changes of cells and tissues, classification and treatment of diseases will be explained.

④⑥

Pharmacokinetics

1

To achieve proper use of the pharmaceutical products, and contribute to the drug development,
the lecture explains the pharmacokinetics, a theoretical scheme for quantitatively understanding
the disposition of drugs in the body, and describes the factors that cause inter-individual variationin drug disposition and response.

④⑥

Organic Chemistry Ⅲ

1Students will learn chemical reaction theories such as substitution reaction, radical reaction,
reduction/oxidation reaction and addition reaction, as well as the organic electron theory which isimportant for understanding chemical reaction.

④⑥

Drug Discovery and Development

1

Researchers who have succeeded in pharmaceutical companies will be invited to the class to talkabout the current situation and future perspectives of drug discovery.

④＊

9

Syllabus

Faculty of Pharmaceutical Sciences

3rd year: Spring 1
Course Title

Credits

Course Outline

Interactive Organic Chemistry1

The fundamentals of organic chemistry by practicum and group discussion will be outlined andreviewed.

４６

Molecular Structural Bio-Sciences

1

The fundamentals and actual examples of structural analysis of biomaterials will be explainedusing the nuclear magnetic resonance method or the X-ray crystal structure analysis method.

４＊

Pharmacology Ⅱ

1Students will understand drug actions that affect the central nervous system, endocrine system
and immune system by learning the physical function and mental function.

④⑥

Immunology

1Students will understand the immune system and the immune response to infections and allergies
in the level of dynamic behaviors of tissues, cells and molecules.

４６

Laboratory Works of Pharmaceutical
Sciences Ⅰ

5

To aquire fundamental experimental operations, and experience basic organic reactions and some
practical synthesis of organic compounds.

④⑥

Laboratory Works of Pharmaceutical
Sciences Ⅱ

3

Basic experiments in bio-organic chemistry (extraction, isolation, identification and biosynthesisof natural organic compounds; the fundamentals and applications of the extinction method andthe fluorescence method; learning high-speed liquid chromatography; drug metabolism reaction
experiments; enzyme kinetics; visits to the Experimental Station for Medicinal Plant Studies)④⑥

3rd year: Spring 2
Course Title

Credits

Course Outline

1

Students will learn the chemistry of natural organic compounds having biological activity, as wellas the fundamentals of biosynthesis.

④⑥

Organic Chemistry Ⅵ

1This is a class for learning metabolism of medical drugs, fundamentals of drug development,chemistry of carbohydrates and synthetic polymers. Enzyme induction, polymorphism, metabolic
reactions, enzymes, reaction mechanisms of P-450 will be explained in molecular level. The
fundamentals of drug development such as molecular design, chemical libraries and leadcompounds, and polymers such as carbohydrates and synthetic polymers will be also explained.

④⑥

Health Chemistry1

The impact of environmental materials toward organisms will be explained.

４⑥

Cancer Biology
and Biopharmaceutical1

L ectures per ta ining to biolog y of c a ncer, clinic a nd treatment of c a ncer especia lly
pharmacotherapy will be given.

４６

Drug Informatics

1

Methods for constructing novel drug information effective in real-life medical care situations will
be explained. These methods include methodology to standardize drug information and quantify
drug reactions.

４⑥

Laboratory Works of Pharmaceutical
Sciences Ⅲ

3

Basic experiments in physico-chemistry (acquisition and analysis of drug disposition kinetic data,physicochemical analyses of proteins and structural biological analyses of protein interactions,analyses of molecular structures and understanding of the 3D structure using the X-ray diffration)④⑥

Organic Chemistry Ⅴ

3rd year: Autumn 1
Course Title

Course Outline

1

The latest knowledge regarding acceptance and transduction of extracellular signaling molecules
such as hormones will be explained.

４６

Clinical Pharmacy

1

Aiming for understanding pharmaceutical sciences in medical care, the following subjects will beoutlined: the medical system; drug development, and its efficacy and safety; diseases and their
therapeutic agents; medical care and pharmacists; fundamentals of drug compounding/formulation; drug administration guidance and drug history management; and clinicalpharmacokinetics.

④⑥

Medicinal Chemistry Ⅱ

1Students will learn organic chemistry of biologically active substances and pharmaceuticalmolecules, as well as that of molecular design.

④６

Metabolism and Disease1

Metabolism and various diseases caused by metabolic failure will be explained.

４⑥

Medicinal Chemistry Ⅰ

1Lectures pertaining to advanced level of organic synthetic chemistry, transition metal chemistry,heterocyclic ring and natural product synthetic chemistry will be given.

④６

Molecular Physiological Chemistry10

Credits

Special Lectures on Pharmaceutical
Sciences Ⅰ

1Students will learn the ethics, communication skills, etc. necessary for life-related professionals.

４⑥

Special Laboratory Works ofPharmaceutical Sciences Ⅰ

1Through the determination of genetic polymorphism of drug metabolizing enzymes, students willlearn the significance and interpretation method of genetic polymorphism in consideration of
future medical care. Furthermore, they will learn the appropriate process of research on humangenome and genes, as well as the importance of compliance of ethical guidelines.

④⑥

5(1) Experiments in physiological chemistry: Regulation of blood sugar levels (physiological/
metabolic experiments); proliferative response of culture cells (isotope experiments)(2) Experiments in molecular biology: Basic experiments in molecular biology using culture cells(3) Experiments in genetics: Basic experiments in molecular genetics using animal models(4) Experiments with microorganisms: Basic experiments with microorganisms and antibiotics;
basic experiments on gene manipulation④⑥

Laboratory Works of Pharmaceutical
Sciences Ⅳ

3rd year: Autumn 2
Course Title

Credits

Course Outline

Medicinal Chemistry Ⅲ

1

In lectures on organic chemistry (which is essential for drug development), the fundamentals oforganic reaction chemistry, and chemistry of bio-related reaction and physiologically active
substances will be explained. The fundamentals of chemical biology especially about photofunctional molecules will be explained.

Natural Product Chemistry1

Students will learn the origins, ingredients, evaluations and applications of natural drugs(primarily those described in the Pharmacopoeia of Japan) as well as plant biotechnology.

４⑥Pharmaceutics

1

In addition to drug delivery system, students will learn dosage forms, design/manufacturingmethods and usability evaluation methods.

4 ⑥Biophysics

1

Students will learn about the hierarchic structure of an organism (from molecules to an individual)
as well as each level of the hierarchy.

４６

Toxicological Pharmacology

1

Scientific proof of drug safety will be explained from the molecular biological, cell biological,
pathophysiological and sociological perspectives, mainly focusing on the stress response oforganisms.

４⑥

Laboratory Works of Pharmaceutical
Sciences Ⅴ

3

Basic experiments in pharmacology using whole animals and organs, observation of pathology
specimens, histochemistry, analysis of the mechanism of cell signaling, genetic experiments using
budding yeast④⑥

Special Lectures on Pharmaceutical
Sciences Ⅱ

1Students will learn the ethics, communication skills, etc. necessary for life-related professionals.

４⑥④＊

4th year: Spring 1
Course Title

Credits

Course Outline

1

St udent s w i l l le a rn t he f u nd a ment a ls of t he genera l ide a of he a lt h, epidem iolog y,pharmacoepidemiology and pharmacoeconomics.

４⑥

Clinical Pharmacology

1Students will learn the fundamentals of pharmacotherapy and clinical development with theclinical perspectives from pathophysiology through pharmacokinetics, clinical pharmacology toclinical testing. Students will also learn diagnoses, treatment and clinical trials in real-lifesituations from experts in the departments of clinicopathology, internal medicine, surgery andradiology to understand the disease “cancer.”＊⑥

Pharmaceutical Affairs Law and Patent
Law

1Students will learn the basics of the Patent Act and pharmacy-related laws and regulations.

4 ⑥Pharmaceutical Regulatory Science

1

Drug development and efficacy evaluation methods, domestic and overseas drug development
environment and guidelines will be explained using specific examples.

4 ⑥

Public Health

4th year (Department of Pharmaceutical Sciences)
Course Title

Special Laboratory Works ofPharmaceutical Sciences

Credits
20

Course Outline

Students will be allocated to a laboratory in the Faculty of Pharmaceutical Sciences (including theDept. of Pharmacy, the Univ. of Tokyo Hospital), and participate in frontline pharmaceuticalresearch.

④

11

Syllabus

Graduate School of Pharmaceutical Sciences

4th〜6th year (Department of Pharmacy)
Course Title

Credits

Course Outline

20

Students will be assigned to a laboratory in the Faculty of Pharmaceutical Sciences and participate
in frontline pharmaceutical research. They will also independently conduct research and study forpractical hospital/pharmacy training.

⑥

Practice for Clinical Pharmacy Ⅱ

4

To work as a pharmacist in the clinical practice of hospital and pharmacy, students will acquirebasic requirements for drug treatment and team approach medical care/regional medical care fromperspective of patients and living people. For Practice for Clinical Pharmacy Ⅲ・Ⅳ, students will
acquire basic knowledge, skills and attitude required for fulfilling pharmacists’ duties within the
University, such as preparation and formulation of drugs and drug administration guidance.

⑥

Practice for Clinical Pharmacy Ⅲ

10

In order to understand duties and responsibilities of hospital pharmacists and be able to participate
in team approach to medical care, students will acquire basic knowledge, skills and attitude
required for fulfilling pharmacists’ duties, such as preparation and formulation of drugs and drug
administration guidance.

⑥

Practice for Clinical Pharmacy Ⅳ

10

In order to understand social roles and responsibilities of pharmacies and be able to participate in
medical care in their local communities, students will acquire basic knowledge and skills
regarding, and attitude toward, pharmacy services under health insurance, drug supply andmanagement, information provision, health examinations and relationship with medical institutes
and local communities.

⑥

Special Laboratory Works ofPharmaceutical Sciences

20

Students will be allocated to a laboratory in the Faculty of Pharmaceutical Sciences (incl. Dept. of
Pharmacy, the Univ. of Tokyo Hospital) and participate in frontline pharmaceutical research.

⑥

Laboratory Works of Pharmaceutical
Sciences Ⅵ

Syllabus

Graduate School of Pharmaceutical Sciences

Graduate School of Pharmaceutical Sciences
Pharmaceutical education experienced major changes beginning with students entering in the 2006 school year. As a result, the Universityof Tokyo’s Faculty of Pharmaceutical Sciences established two new departments: The Department of Pharmaceutical Sciences, a four-year
program designed to train researchers in basic drug discovery, and the Department of Pharmacy, a six-year program that qualifies graduates
for the national examination for pharmacists. New graduate schools were also established based on student progression through theirprograms.
In April of 2010, we established a master’s program in pharmaceutical sciences for graduates of the four-year Department of Pharmaceutical
Sciences program. This research program unites the four departments that previously existed, creating a single department instead.
In April of 2012, we established a doctoral program in pharmaceutical sciences for graduates of the master’s program (duration of program:
three years), along with a doctoral program in pharmacy for graduates of the six-year Department of Pharmacy program (duration ofprogram: four years). The doctoral program in pharmaceutical sciences also offers a Dual Specialty Course on Pharmacist Education toqualify four-year doctoral graduates for the national examination for pharmacists (Only applied to those students enrolled at the Universityof Tokyo in April, 2017 and graduated from the Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences).

Graduate School Curriculum
The main part of graduate school curriculum is “special research” through participations in research conducted in each laboratory. At theGraduate School lectures are targeted at students in master’s program/doctoral program(Department of Pharmacy). Those lectures arehighly specialized, covering the latest information in the field, thus allowing them to be the world’s top class.
Master’s Program (two-year program)

Department of Pharmaceutical Sciences

30 credits or more including 20 credits of special research inpharmaceutical sciences must be completed.

Doctoral program

Department of Pharmaceutical Sciences (three-year program)

20 credits or more including 20 credits of special research inpharmaceutical sciences must be completed.
Department of Pharmacy (four-year program)

30 credits or more including 20 credits of special research inpharmaceutical sciences must be completed.

12

＊Courses are open every other year
Course Title

Credits

Special Lecture Basic Pharmaceutical
Science Ⅰ

2

To understand basic and advanced chemical principles and concepts that is important forpharmaceutical sciences

Special Lecture Basic Pharmaceutical
Science Ⅱ

2

To understand X-ray crystallography, structural analysis by NMR, sensitive analysis by fluorometricand mass spectrometric method, biosynthesis of natural products, and chemical biology for drug
development

Special Lecture Basic Pharmaceutical
Science Ⅲ

2

To learn the fundamentals of biopharmaceutical sciences, including biochemistry, molecular biology,
cell biology, molecular genetics, and pathology

Special Lecture Basic Pharmaceutical
Science Ⅳ

2

To learn the fundamental knowledge in the fields of pharmacokinetics, pharmacology, pathology, drug
informatics, regulatory science, pharmacobusiness, and pharmacoeconomy among clinicalpharmaceutical sciences

Special Lecture Chemical Biology

2

To learn the chemistry that are essential for carrying out cutting-edge pharmaceutical research related
to the life sciences

Special Lecture Biomolecular Analysis

2

Explains the principles of X-ray crystallography, nuclear magnetic resonance imaging, single-molecule
f luorescence imaging, and methods for high sensitivity analysis of biomolecules, and introduces ＊methods for analyzing the structure and function of biomolecules and applications of those methods

Special Lecture Cell Biology

2

Introduces the latest research trends in biopharmaceutical sciences from the perspective of cell biology

Special Lecture Molecular Biology

2

To understand living organisms according to the functions of genes and proteins and to learn thecurrent molecular biology, including disease pathophysiology, while also learning the latest methods in ＊genetics and biochemistry

Special Lecture Disease Biology

2

From a biological perspective, outlines the academic disciplines and the mechanisms leading to disease＊
onset while focusing primarily on infection and immunity

Special Lecture ClinicalPharmaceutical Science2

To learn cutting-edge medical and pharmaceutical research in an omnibus format

Special Lecture Social Pharmaceutical
Science2

To gain a deeper understanding of the relationship between pharmaceutics and society from a variety
of different angles, including information, statistics, government policy, business management, the ＊pharmaceutical industry, etc

Special Lecture English for Science2

To train in both listening and speaking by learning topics related to pharmaceutical sciences in English

Special Lecture Pharmaceutical
Regulatory Science2

To learn regulatory frameworks and practical methodology for evaluating the effectiveness, safety,
risks, and benefits of new pharmaceuticals

2This course aims on the systematic comprehension of pharmacotherapy and clinical development ofdrugs on the basis of pathophysiology of diseases; students will learn pharmacokinetics, clinicalpharmacology and regulatory and ethical issues of clinical trials. This course also aims on thecomprehension of the cancer as a disease; students will learn practical aspects of diagnosis, treatment
and clinical trial from medical professionals in clinical pathology, internal medicines, surgical therapy,
radiation therapy and others.

Special Lecture Clinical Science

Course Outline＊＊

Department of Pharmaceutical Sciences
Course Title

Credits

Course Outline

Special Studies for Pharmaceutical
Science Ⅰ

20(Master’s course) To gain a foothold toward specialization; learn pharmaceutical modes of thought andlogical, cutting-edge methodology; and develop advanced analytical skills through practice, seminars, andindividualized laboratory research activities

Special Studies for Pharmaceutical
Science Ⅱ

20(Doctoral course) To establish deep roots in a specialization; learn pharmaceutical modes of thought andlogical, cutting-edge methodology; and develop advanced analytical skills through individualizedlaboratory research activities

Course Title

Credits

Course Outline

Practical Studies for Clinical Pharmacy

4

To acquire the practical methodology, awareness of the issues, and independence to respond to the needs ofsociety in sophisticated medical environments

Practical Studies for Social Pharmacy

4

To acquire the practical methodology, awareness of the issues, and independence to respond to the needs ofsociety in medical administration environments

Practical Studies for Drug Discovery

4

To acquire the practical methodology, awareness of the issues, and independence to respond to the needs ofsociety in drug discovery environments

Special Studies for Pharmacy

20

To learn—through practice, seminars, and individualized laboratory research activities—comprehensive
methodology pertaining to the interaction of molecules and organisms for the purpose of discovering andappropriately using pharmaceuticals

Department of Pharmacy

13

Laboratory ofOrganic and Medicinal ChemistryProf. T. Ohwada
Assoc. Prof. Y. Otani

Synthesis of novel intelligent molecules which linkchemical structures to biological functions in organic andmedicinal chemistry

http://www.f.u-tokyo.ac.
jp/~yakka/english.html

Research Topics
1. S
 ynthesis of new compounds exhibiting characteristic structural features andproperties, finally relevant to biological functions
2. N
 ew reactions to functionalize aromatic compounds based on designed
superelectrophiles
3. D esign and synthesis of intelligent molecules, which will have impacts on
functions of membrane proteins
4. C omputational modeling and simulations of organic and macromolecular systems
Our

aims

of

researchesemphasize on design andsynthesis of structurally novel

14

Luying Chen, Akiharu
Uwamizu, Misa Sayama,
Kuniyuki Kanob, Yuko Otan,
Sho Kondo, Asuka Inoue,
Junken Aoki , Tomohiko
OhwadaExploration of LPS 2 agonist
binding modes using the
combination of a newhydrophobic scaffold andhomology modeling
European Journal of
Medicinal Chemistry, 252,
115271 (2023)

organic molecules, which are

Yuko Otani, Xin Liu, Hisashi
Ohno, Siyuan Wang, Luhan
Zhai, Aoze Su, Masatoshi
Kawahata, Kentaro
Yamaguchi, Tomohiko
OhwadaAmide nitrogenpyramidalization changes
lactam amide spinning
Nature Communications
volume 10, Article number:
461 (2019).

nitrosamines, and structures of multiply positively charged molecules. We study nitrogen-pyramidal

Ohwada, T., Tani, N.,
Sakamaki, Y., Kabasawa, Y.,
Otani, Y., Kawahata, M.,
Yamaguchi, K.
Stereochemical evidence forstabilization of a nitrogencation by neighboring
chlorine or bromine.
Proc. Natl. Acad. Sci. U.S.A.
110: 4206-4211 (2013)

membrane proteins such as ion channels,

characteristic

in

terms

of

structural (bonding) featuresand intrinsic functions such as
chemical

reactivities

andbiological functions. Designsof such novel molecules are
based on our finding new
chemistry including groundstate
amide

stablenon-planar

peptidesHelical structure of artificial amino acid peptide stable in waterandamides and related nitrosamines, i.e., molecules that take nonplanar structures, different from thecommon planar amides. We apply this chemistry to construction of molecules of highly ordered structures
such as helix peptide mimetics stable in water. We also develop new chemistry involving dication ortrication molecules and apply them as superelectrophiles to synthesize a variety of novel multifunctionalized aromatic compounds, which
are pharmaceutically relevant. We are also
creating chemical molecules, which will be
useful to controlling biological events ofneurotransporters and G-protein-coupled
receptors. These molecules also contributeto understanding the phyisiological functionsof these membrane proteins. We combine all
the experimental projects with computational
chemistry,
Chemical modulation of functions of membrane proteins

which

will

lead

to

deep

understanding of the underling chemistry.

Laboratory

Laboratory ofSynthetic Natural Products ChemistryProf. M. Inoue
Assoc. Prof.
H. ItohAssist. Prof.
K. Hagiwara
Project Assist. Prof.
H. Fujino
https://inoue.f.u-tokyo.ac.
jp/e_index.html

Total synthesis and functional analysis of biologically
active natural products

Research Topics
1. D evelopment of new synthetic methodologies for total synthesis
2. T otal synthesis of highly oxygenated polycyclic natural products
3. T otal synthesis and functional analysis of ion channel-forming molecules
4. T otal synthesis and functional analysis of antimicrobial molecules
5. S
 ynthesis of new artificial molecules by modification of natural products templates
Natural products have been tremendously important in biology and human medicine because of their

Watanabe, T., Oga, K., Matoba, H.,
Nagatomo, M., Inoue, M. Total
Synthesis of Taxol Enabled byIntermolecular Radical Coupling
and Pd-Catalyzed Cyclization. J.
Am. Chem. Soc. 145: 25894-25902(2023)

power to modulate signal transductions of biological system. Since the removal of sub-structures of the

Watanabe, Y., Morozumi, H.,
Mutoh, H., Hagiwara, K., Inoue, M.
Total Synthesis of (−)-Batrachotoxin
Enabled by a Pd/Ag-Promoted
Suzuki–Miyaura Coupling Reaction.
Angew. Chem. Int. Ed. 62:e202309688 (2023)

proteins. Therefore, they are powerful

Shimakawa, T., Nakamura, S., Asai,
H., Hagiwara, K., Inoue, M. Total
Synthesis of Puberuline C. J. Am.
Chem. Soc. 145: 600-609 (2023)

natural products often leads to significant losses of their activity, total chemical syntheses of their entire
structures with a precision at an atomic level are necessary to provide sufficient amounts of material
required for biological and medical applications. Architecturally complex natural products with molecularweight over 1000 are capable of highly
specific interactions with their target
agentsforselectively

controlling

intricate biological systems. The goalof our research program is efficient,practical and flexible syntheses ofgigantic

naturalmolecules,

which

include highly oxygenated polycyclic
natural products as well as ion channelforming peptides. At the core of thisWang, Y., Nagai, T., Watanabe,I., Hagiwara, K., Inoue, M. Total
Synthesis of Euonymine andEuonyminol Octaacetate. J. Am.
Chem. Soc. 143: 21037-21047(2021)

research program is the development

Hirose, A., Watanabe, A., Ogino, K.,
Nagatomo, M., Inoue, M. Unified
Total Syntheses of Rhamnofolane,
Tigliane, and Daphnane
Diterpenoids. J. Am. Chem. Soc.
143: 12387-12396 (2021)

synthesis of new artificial analogs by

Itoh, H., Tokumoto, K., Kaji, T.,
Paudel, A., Panthee, S.,
Hamamoto, H., Sekimizu, K.,
Inoue, M. Development of ahigh-throughput strategy fordiscovery of potent analogues ofantibiotic lysocin E. Nat. Commun.
10: 2992 (2019)of new strategies for assemblingarchitecturally complex natural products
in a concise fashion. These synthetic
developments would enable unified
modificationofnaturalproducts

templates. The new synthetic methods
for the natural products and thesynthetic analogs will allow us to tailor
and enhance their drug like properties,
to gain control over diverse signaltransductions thereby offering new
research methods for the study of life
science.

15

Laboratory ofSynthetic Organic ChemistryProf. M. Kanai
Assoc. Prof.
S. Kawashima
Assist. Prof.
H. Mitsunuma
Assist. Prof.
Y. Yamanashi
https://gousei.f.u-tokyo.ac.
jp

Catalysis for clean, robust, and concise complex
molecule synthesis and new modal medicine

Research Topics
1. D evelopment of new catalysis to facilitate complex molecule synthesis
2. C lean, robust, and concise synthesis of pharmaceuticals and their leads
3. Catalytic H2 and O2 activation
4. C onceptually new approach to promote human health
The main theme of our research is the development of revolutionary catalyses facilitating new drug designand synthesis. In this direction, we would like to promote human health based on the catalysis
development. Chemical synthesis in 21st century should be clean, robust, and concise, no matter how
complex the target molecules are. The “ideal synthesis” will be only possible by new catalytic
methodologies. Moreover, new catalyses will expand the diversity of readily available building blocks,
leading to structurally novel artificial drug design. Sustainability based on new catalysis is another directionof our research. Specifically, we are interested in catalytic activations of small molecules such as H2 andO2.

Fujiwara, Y., Yamanashi, Y.,
Fujimura, A., Sato, Y., Kujirai,
T., Kurumizaka, H., Kimura,
H., Yamatsugu, K.,
Kawashima, S. A., Kanai, M.
Live-cell epigenome
manipulation by synthetic
histone acetylation catalyst
system. Proc. Natl. Acad. Sci.
U.S.A., 118: e2019554118(2021)
Nagashima, N., Ozawa, S.,
Furuta, M., Oi, M., Hori, Y.,
Tomita, T., Sohma, Y., Kanai, M.
Catalytic photooxygenation
degrades brain A β in vivo.
Sci. Adv. 7: eabc9750 (2021)
Maruyama, K., Ishiyama, T.,
Seki, Y., Sakai, K., Togo, T.,
Oisaki, K., Kanai, M.
Protein Modification at
Tyrosine with Iminoxyl
Radicals. J. Am. Chem. Soc.
143: 19844-19855 (2021)

16

Artificial Catalysis in Cells for Synthetic Epigenetics

Catalytic Oxygenation of Aβ as a Potential Therapeutic Chemical Reaction

Biomacromolecules as Substrates for Chemical Catalysis

Laboratory

Laboratory of

Natural Products ChemistryProf. I. Abe
Assoc. Prof. T. Mori
Assist. Prof. R.Ushimaru
http://www.f.u-tokyo.ac.
jp/~tennen/index-e.html

We establish the mechanisms of natural productbiosynthesis as a science in their own right, to construct
a rational system for the production of new and useful
substances
Research Topics
1. T he biosynthesis and bioengineering of medicinal natural products(genome mining, engineered biosynthesis)
2. T he enzyme biocatalysts(structure-function analysis, enzyme engineering, mechanistic studies)
3. T he search for bioactive substances and isolation/structure determination

Tao, H., Lauterbach, L., Bian,
G., Chen, R., Hou, A., Mori,
T., Cheng, S., Hu, B., Lu, L.,
Mu, X., Li, M., Adachi, N.,
Kawasaki, M., Moriya, T.,
Senda, T., Wang, X., Deng,
Z., Abe, I., Dickschat, J. S.,
Liu, T. Discovery of nonsqualene triterpenes. Nature
606: 414-419 (2022)
Tao, H., Ushimaru, R.,
Awakawa, T., Mori, T.,
Uchiyama, M., Abe, I.
Stereoselectivity andsubstrate specificity of the
Fe(II)/α-ketoglutaratedependent oxygenase TqaL.
J. Am. Chem. Soc. 144:
21512-21520 (2022)

Natural organic compounds, prominent among which are antibiotics such as penicillin, are gifts fromnature, and the benefits they have bestowed upon humankind as sources for the pharmaceuticals, etc.,that maintain health is inestimable. In our laboratory, we study the process of biosynthesis of naturalorganic compounds produced by plants and microorganisms, using not only the foundation discipline oforganic chemistry, but also incorporating
the methods of biochemistry andmolecular biology in an effort tounderstand the enzymes that catalyzeeach biosynthesis reaction and thefunctions and control mechanisms ofthe genes that govern their expression
at the molecular level. In addition, weareexpandingourresearch

into“biosynthesis engineering,” by whichrational systems for the biologicalTao, H., Mori, T., Chen, H.,
Lyu, S., Nonoyama, A., Lee,
S., Abe, I. Molecular insights
into the unusuallypromiscuous and catalyticallyversatile Fe(II)/αketoglutarate-dependentoxygenase SptF. Nat.
Commun. 13: 95 (2022)

production

Barra, L., Awakawa, T., Shirai,
K., Hu, Z., Bashiri, G., Abe, I.
β-NAD as a building block innatural product biosynthesis.
Nature 600: 754-758 (2021)

expressed, while at the same timeMori, T., Zhai, R., Ushimaru,R., Matsuda, Y., Abe, I.
Molecular insights into theendoperoxide formation by
Fe(II)/α-KG-dependentoxygenase NvfI. Nat.
Commun. 12: 4417 (2021)

of

new

and

usefulsubstances can be designed andconstructed, based on the mechanisms

Concept of “biosynthesis engineering,” by which non-naturalcompounds are generatedof biosynthesis that have been brought
to light.

We also are carrying out

research on the mechanisms by which
the bioactivity of natural products is
searching for natural products that are
active in intracellular signaling.

Synthetic biology of complex natural products

17

Laboratory of

Advanced Elements ChemistryProf.
M. Uchiyama
Project Assoc. Prof.
M. Nakajima
Lecturer N. Toriumi
http://www.f.u-tokyo.ac.
jp/~kisoyuki/

Understanding of chemical phenomena at the atomic andelectron levels and creation of a new science of materials
through flexible construction of molecules
Research Topics
1. R
 esearch on structure, bonding, aromaticity, and movement of molecules
2. D evelopment of new reactions to freely manipulate chemical bonds
3. T heoretical and synthetic chemistry for manipulating light
4. R esearch on the origin of life and the evolution of matter

Matsuyama, T., Togashi, K.,
Nakano, M., Sato, H.,
Uchiyama, M.
Revision of Peniroquesine
Biosynthetic Pathway by
Retro-biosynthetic Theoretical
Analysis: Ring Strain Controls
the Unique Carbocation
Rearrangement Cascade
JACS Au, 2023, 3: 1596–1603.
Yanagi, S., Matsumoto, A.,
Toriumi, N., Tanaka, Y.,
Miyamoto, K., Muranaka, A.,
Uchiyama, M.
A Switchable Near-InfraredAbsorbing Dye Based on
Redox-Bistable
Benzitetraazaporphyrin
Angew. Chem. Int. Ed., 2023,
62: e202218358.

Our laboratory focuses on understanding the properties and phenomena of substances by “language ofchemistry” such as molecules, atoms, and electrons (Seeing /Knowing); on developing reactions thatmanipulate the bonds between atoms completely in control (Designing); and on producing functional
materials (Producing).
In our laboratory, we strive to develop technologies for the precise chemical conversion of tiny, tinymolecules less than 1 billionth of a meter in size (nanometer scale; nm). Thanks to recent advances inspectroscopy and theoretical calculation, it is getting possible to accurately predict and reproduce
snapshots of the state of the electrons that form materials, as well as of reactions between molecules.
With the 3 methods, namely, synthetic chemistry, spectroscopy, and theoretical calculation as the pillarsof our science, we expand upon elements chemistry in an interdisciplinary manner as we meet thechallenges of elucidating life phenomena and creating a new materials science.

Iida, T., Kanazawa, J.,
Matsunaga, T., Miyamoto, K.,
Hirano, K., Uchiyama, M.
Practical and Facile Access toBicyclo[3.1.1]heptanes: Potent
Bioisosteres of metaSubstituted Benzenes
J. Am. Chem. Soc., 2022, 144:
21848–21852.
Sakamoto, K., Nagashima, Y.,
Wang, C., Miyamoto, K.,
Tanaka, K, Uchiyama, M.
Illuminating Stannylation
J. Am. Chem. Soc., 2021, 143:
5629–5635.
Miyamoto, K., Narita, S.,
Masumoto, Y., Hashishin, T.,
Kimura, M., Ochiai, M.,
Uchiyama, M.
Room-temperature Chemical
Synthesis of C2
Nature Commun., 11: 2134
(2020).

18

Developing new reactions and designing/producing new materials based oncomputational chemistry and theoreticalchemistry (Adopted for the cover ofChemistry: A European Journal)Life sciences and materials science that open new frontiers in basicorganic chemistry and elemental chemistry

Laboratory

Laboratory ofChemistry and Biology

Prof. Y. Urano
Assist. Prof. T. Ueno
Assist. Prof.
T. Komatsu
Assist. Prof.
R. Tachibana
http://www.f.u-tokyo.ac.
jp/~taisha/en/"Chemical Biology" and "Chemical Medicine" in order topromote life science research and to develop novel
medical tools
Research Topics
1. F
 undamental photophysical and photochemical research to establish rational
design principle for novel chemical tools
2. T heoretical design, synthesis and biological application of novel chemical tools,
including sensor molecules and signal perturbation techniques for cellularsignaling molecules, such as Ca2+ ion, reactive oxygen species, or various
enzymes
3. D evelopment of chemical tools, e.g, MRI probe and fluorescent probe, fordiagnostic imaging and their in vivo application
4. C linical use of our newly developed fluorescence probes for rapid imaging oftumor with human clinical fresh specimens
5. R
 esearch on drug discovery: Searching for novel lead compounds that control
disease-related proteins, and development of high-quality screening systems
Our laboratory conducts research on the analysis and perturbation of dynamic living systems, using

Kuriki Y, Kamiya M, Kubo H,
Komatsu T, Ueno T,
Tachibana R, Hayashi K,
Hanaoka K, Yamashita S,
Ishizawa T, Kokudo N, Urano
Y: Establishment of Molecular
Design Strategy To Obtain
Activatable Fluorescent
Probes for
Carboxypeptidases. J. Am.
Chem. Soc., 140: 1767-1773,2018.

chemistry as a powerful tool. One of the important goals in modern life sciences is to elucidate thedynamic behaviors of biomolecules in situ in the living cells/organisms. So far, our laboratory has
succeeded in developing bioimaging probes/other chemical tools including signal perturbation
methodology and high quality screening systems by applying the probe design strategies that weestablished. Likewise, we utilize our probe design principle to establish chemical tools for clinical use,
including a tumor-specific intraoperative fluorescence imaging methodology. On top of that, we are now
conducting dozens of pilot clinical trial projects by utilizing above mentioned chemical tools with external
collaborators in domestic hospital and abroad.
The above-described areas of research have attracted enormous attention in recent years under thename of“ Chemical Biology”, and we believe that they will open up new horizons in life sciences.

Umezawa K, Yoshida M,
Kamiya M, Yamasoba T,
Urano Y: Rational design ofreversible fluorescent probes
for live-cell imaging andquantification of fast
glutathione dynamics. Nat.
Chem., 9: 279-286, 2017.
Uno SN, Kamiya M,
Yoshihara T, Sugawara K,Okabe K, Tarhan MC, Fujita
H, Funatsu T, Okada Y,
Tobita S, Urano Y: A
spontaneously blinking
fluorophore based on
intramolecularspirocyclization for live-cellsuper-resolution imaging.
Nat. Chem., 6: 681-689,
2014.

Development of bioimaging probes

19Laboratory of

Bioanalytical Chemistry

We measure the functions of biomolecules at the level ofa single molecule to elucidate vital functions
Assoc. Prof.
M. Tsunoda
Assist. Prof.
K. Okabe
http://www.f.u-tokyo.ac.
jp/~funatsu/English/index_E.
html

Research Topics
1. R
 esearch on the principles of action by which biomolecular machines such as
molecular chaperonin and ribosomes operate
2. S ingle-molecule fluorescence imaging of intracellular mRNA processing andtransport
3. D evelopment of micro nanodevices for analyzing the functions and interactions of
biomolecules
In order to understand living organisms, it isnecessary to conduct research at a variety of

T. Ohtawa, A. Hattori, M.
Isokawa, M. Harada, T.
Funatsu, T. Ito, M. Tsunoda,
Determination of intracellular2-hydroxyglutarate
enantiomers using twodimensional liquid
chromatography. J.
Chromatogr. Open 1: 100005(2021)

different levels. The lowest level is that at which

T. Fujiwara, T. Funatsu, M.
Tsunoda, Fast analysis using
pillar array columns:
Quantification of branchedchainα-keto acids in humanplasma samples. J. Pharm.
Biomed. Anal. 198: 114019(2021)

the “cell,” at which life functions are first expressed,

A. Sakamoto, S. Kunou, K.
Shimada, M. Tsunoda, T.
Aoki, C. Iriyama, A. Tomita, S.
Nakamura, F. Hayakawa, H.
Kiyoi, Pyruvate secreted frompatient-derived cancerassociated fibroblasts
supports survival of primary
lymphoma cells. Cancer Sci.
110: 269-278 (2019)
A. Hattori, M. Tsunoda, T.
Konuma, M. Kobayashi, T.
Nagy, J. Glushka, F. Tayyari,
D. McSkimming, N. Kannan,
A. Tojo, A. Edison, T. Ito,
Cancer progression by
reprogrammed BCAA
metabolism in myeloid
leukaemia. Nature 545:
500-504 (2017)20

biomolecules such as proteins and DNA work.
When

these

come

together,biologicalsupramolecules, cells, organs, and the like are
created, while at the higher end, individualorganisms,

societies,

andecosystems

areconstituted. We focus on the level of the smallest
unit, the “biomolecule,” together with the level ofFluorescence microscope system for imaging single
molecules within living cells

to find answers to questions like “By whatmechanisms do biomolecules function?” and “When they aggregate, what kinds of systems do they
construct?” Concretely speaking, we bind a fluorescent dye to a single biomolecule and observe it witha sensitive fluorescence microscope. Some biomolecules can exhibit their functions even at the level ofthe single molecule. For example, the motor protein known as kinesin moves on rail proteins calledmicrotubules. Humankind does not at this point in time possess the technology for creating this kind ofmolecular machine, but we believe that humankind will be able to make this kind of molecular machinein the near future through research on the motor protein. On the other hand, self-assembly of a variety ofdifferent biomolecules creates complex systems which differ greatly from manmade ones. By researchingsuch biological systems, we close in on the mysteries of life.

The principle of single-molecule imaging of enzyme reaction (ATPase) using evanescent illumination

Laboratory

Laboratory ofPhysical Chemistry

Prof.
K. Takeuchi

Approaching life from dynamic structural information
obtained by original NMR strategies.

Assist. Prof. Y. Kofuku
Assist. Prof.
Y. Tokunaga

Research Topics

https://biophys.f.u-tokyo.
ac.jp

1. F
 unctional mechanism of biologically and pharmacologically important proteinsbased on dynamic structural information.
2. F unctional mechanism of biomolecules that regulate signal transduction andenergy metabolism based on interaction analysis.

Takeuchi, K., Misaki, I., Tokunaga,
Y., Fujisaki, M., Kamoshida, H.,
Takizawa, T., Hanzawa, H.,
Shimada I. Conformational
Plasticity of Cyclic Ras-Inhibitor
Peptides Defines Cell
Permeabilization
Activity. Angew Chem Int
Ed. 60, 6567-6572 (2021).

3. D
 evelopment of nuclear magnetic resonance (NMR) techniques to analyze thestructure and dynamics of high-molecular-weight proteins.
4. S ample preparation strategies to reproduce the functional environment of
biomolecules and sophisticated stable isotope labeling methods.
5. In-cell NMR and its application to intracellular drug discovery.
The structural information of proteins plays a vital role in elucidating biological functions and theirapplications to drug discovery. In addition, it has become clear that proteins do not adopt only a single

Mizukoshi, Y., Takeuchi ,K.,
Tokunaga, Y., Matsuo, H., Imai, M.,
Fujisaki, M., Kamoshida, H.,
Takizawa, T., Hanzawa, H.,
Shimada, I., Targeting the cryptic
sites: NMR-based strategy to
improve protein druggability bycontrolling the conformational
equilibrium. Sci Adv. 6, eabd0480(2020).

conformation but also an equilibrium among multiple functional conformations.

Tokunaga, Y., Takeuchi, K., Okude,
J., Ori, K., Torizawa, T., Shimada, I.,
Structural Fingerprints of an Intact
Monoclonal Antibody Acquired
under Formulated Storage
Conditions via 15N Direct
Detection Nuclear Magnetic
Resonance. J Med Chem. 63,
5360-5366 (2020).

as well as macromolecules

Takeuchi, K., Imai, M., Shimada, I.,
Conformational equilibrium
defines the variable inductionof the multidrug-bindingtranscriptional repressor QacR.
Proc Natl Acad Sci U S A. 116,
19963-19972 (2019).

original NMR methods, weBoeszoermenyi, A., Chhabra, S.,
Dubey, A., Radeva, D.L., Burdzhiev,
N.T., Chanev, C.D., Petrov, O.I.,
Gelev, V.M., Zhang, M., Anklin, C.,
Kovacs, H., Wagner, G., Kuprov, I.,
Takeuchi, K., Arthanari, H. Aromatic
19
F- 13C TROSY: a background-free
approach to probe biomolecular
structure, function, and dynamics.
Nat Methods. 16, 333-340 (2019).

These dynamic properties are directly related to the expression and regulation of protein functions. In ourlab, we analyze the structure and dynamics of proteins mainly by using NMR to understand biologicalphenomena through elucidating the functional mechanisms of biomolecules.
We focus on membraneproteins,

such

as

G-proteincoupled receptors(GPCRs) and transporters,
thatsignalregulate

intracellulartransduction

andenergy metabolism, which
are important in biologicalandpharmaceuticalsciences.

Bydeveloping

have obtained structure anddynamics information of themacromolecules of interest
that were previously difficult
to analyze. In addition, we

Fig.1: B iological phenomena elucidated by dynamic structural analysis using
NMR in our laboratory. (A) Structural equilibrium determines(B) transcriptional activity of multidrug-resistant transcription factors(Proc Natl Acad Sci (2019) 116, 19963. (C) Drug efficacy of each ligandof GPCR (β2 adrenergic receptor) (Nat Commun (2012) 3, 1045;
Angew Chem Intl Ed (2014), 53, 13376)

are developing an in-cell
NMR strategy to analyze thestructure and dynamics ofproteins in the actual cellularenvironment and extending
these strategies to establish
intracellular drug discovery.

Fig2: N ovel NMR experiments developed in our laboratory and their application
to mAb (J Med Chem (2020) 63, 5360; Nat Methods (2019) 16, 333).

21

Laboratory ofProtein Structural Biology

Prof. T. Shimizu
Assoc. Prof. U. Ohto
Assist. Prof. Y. Hirano
Assist. Prof. Z. Zhang
http://www.f.u-tokyo.ac.
jp/~kouzou/eng_index.html
Structural basis for thioredoxin-mediatedsuppression of NLRP1 inflammasome. (2023)
Zhang Z, Shibata T, Fujimura A, Kitaura J,
Miyake K, Ohto U, Shimizu T.
Nature 622(7981), 188-194
TLR3 forms a laterally aligned multimericcomplex along double-stranded RNA for
efficient signal transduction. (2023)
Sakaniwa K, Fujimura A, Shibata T,
Shigematsu H, Ekimoto T, Yamamoto M,
Ikeguchi M, Miyake K, Ohto U, Shimizu T.
Nature Commun. 14(1):164

Research Topics
1. S
 tructural analyses of proteins and nucleic acids using X-ray crystallography andsmall angle X-ray scattering
2. S tructures of immune-system proteins and their complexes
3. S tructures of proteins in signal transduction and their complexes
4. S ingle particle analysis by cryo-electron microscopy
Structural biology seeks to provide a complete and coherent picture of biological phenomena at themolecular and atomic level. The three-dimensional structure of macromolecules at an atomic level cancreate an actual picture of how they work. These days, structural biology is also called structural cellbiology and/or structural life science, and is changing into the research field toward life science. Our

Structural insight into the activation of an
Arabidopsis organellar C-to-U RNA editing
enzyme by active site complementation (2023)
Toma-Fukai S, SawadaY , Maeda A, Shimizu
H, Shikanai T, Takenaka M, Shimizu T The
Plant Cell 35, 1888-1900

laboratory aims at achieving a comprehensive understanding of structure/function relationships of key

Structure of SARS-CoV-2 membrane protein
essential for virus assembly (2022)
Zhang Z, Nomura N, Muramoto Y, Ekimoto T,
Uemura T, Liu K, Yui M, Kono N, Aoki J,
Ikeguchi M, Noda T, Iwata S, Ohto U &Shimizu T
Nature Commun. 13: 4399

we take small angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM). SAXS can provide

Structure of the bile acid transporter and HBV
receptor NTCP (2022)
Asami J, Kimura KT, Fujita-Fujiharu Y, Ishida
H, Zhang Z, Nomura Y, Liu K, Uemura T, Sato
Y, Ono M, Yamamoto M, Noda T, Shigematsu
H, Drew D, Iwata S, Shimizu T, Nomura N,
Ohto U.
Nature. 606(7916):1021-1026

three dimensional structures that are required for drug design and discovery.

Cryo-EM structures of Toll-like receptors incomplex with UNC93B1 (2021)
Ishida H, Asami J, Zhang Z, Nishizawa T,
Shigematsu H, Ohto U, Shimizu T
Nature Struc Mol Biol. 28, 173-180
Ohto U, Shibata T, Tanji H, Ishida H,
Krayukhina E, Uchiyama S, Miyake K, Shimizu
T (2015)Structural basis of CpG and inhibitory DNA
recognition by Toll-like receptor 9
Nature 520, 702-705
Tanji H, Ohto U, Shibata T, Miyake K, Shimizu
T (2013)Structural reorganization of the Toll-likereceptor 8 dimer induced by agonistic ligands
Science 339, 1426-1429

22

Determining three-dimensional structures of proteins andnucleic acids, and elucidating their functions in living
cells

cellular components and processes, and roles in living cells. In the elucidation of three-dimensional
structures, X-ray crystallography is extensively used since this method provides us with detailed structural
information on the biological functions and roles. We also take an interdisciplinary approach, combinedwith methods of biophysics, biochemistry, molecular biology, genetic and protein engineering. Moreover,a wealth of structural information on biomolecules in solution and is compatible with a wide range ofexperimental conditions. Cryo-EM has triggered a revolution in structural biology and has become anewly dominant discipline. Especially, single particle cryo-EM has become a powerful method for atomic
structure determination. With these structural biological approaches, we can obtain the information on
We are now carrying out structural biological researches into immune-system proteins, nuclear proteinsand proteins in signal transduction.

Laboratory

Laboratory of

Health ChemistryProf. J. Aoki
Assoc. Prof. N. Kono
Assist. Prof. K. Kano
https://sites.google.com/
view/eiseikagaku-en/

Exploration of new functions for biomembranes andtheir constituent lipids

Research Topics
1. R eveal the physiological and pathological functions of lysophospholipids thatwork via GPCR
2. D
 iscover new bioactive lipids and their receptors

Omi J, Kato T, Yoshihama Y,
Sawada K, Kono N, Aoki J.
Phosphatidylserine synthesis
controls oncogenic B cell
receptor signaling in B cell
lymphoma. J Cell Biol.
223:e202212074 (2024).

3. Identify novel molecules involved in phospholipid biosynthesis and homeostasis,and elucidating their functions.

Sugahara S, Ishino Y, Sawada
K, Iwata T, Shimanaka Y, Aoki
J, Arai H, Kono N. Diseaserelated PSS1 mutant impedes
the formation and function of
osteoclasts. J Lipid Res.
64:100443 (2023).
Kawana H, Ozawa M, Shibata
T, Onishi H, Sato Y, Kano K,
Shindou H, Shimizu T, Kono
N, Aoki J. Identification andcharacterization of LPLAT7 asan sn-1-specificlysophospholipid
acyltransferase. J Lipid Res.
63:100271 (2022).
Shibata T, Kawana H, NishinoY, Ito Y, Sato H, Onishi H,
Kano K, Inoue A, Taketomi Y,
Murakami M, Kofuji S, Nishina
H, Miyazawa A, Kono N, Aoki
J. Abnormal male
reproduction and embryonicdevelopment induced bydownregulation of aphospholipid fatty acidintroducing enzyme Lpgat1 inzebrafish. Sci Rep. 2022
12:7312 (2022).

Biological membranes are composed of more than 1,000 lipid molecular species, and each of them isthought to have a specific function. Recently, some functions of lipids have been elucidated, and it is
becoming clear that lipid molecules play essential roles in physiological situations such as reproduction,
development, angiogenesis, and cell proliferation, and in pathological processes such as cancer andfibrosis development. On the other hand, the recent progress of mass spectrometry has revealed that
there are more lipid molecules with unknown functions in the body. Unlike proteins, lipid molecules are
not encoded by genes and lipid synthesis usually involves multiple proteins. Therefore, investigating thefunction of lipids is much more complicated than that of proteins. We are tackling to clarify the functionsof various phospholipids by using the latest technologies including mass spectrometry and mass
spectrometry imaging.
Our research results are promising to be applied to drug discovery and biomarker discovery.

Okasato R, Kano K, Kise R,
Inoue A, Fukuhara S, Aoki J.
An ATX- LPA6-Gα13-ROCKaxis shapes and maintains
caudal vein plexus inzebrafish. iScience. 2021
24:103254 (2021).

23

Laboratory ofPhysiological ChemistryProf.
D. Kitagawa
Lecturer M. Fukuyama
Project Lecturer S. Hata
Assist. Prof. T. Chinen
Assist. Prof. S. Yamamoto
http://www.f.u-tokyo.ac.
jp/~seiri/index_e.html

Mechanisms of cell division and their application to drug
development

Research Topics
1. M
 echanisms of centrosome duplication and its theoretical model
2. M
 echanisms of cell division regulated by divergent molecular machineries
3. Identification and characterization of non-coding RNAs that regulate cell division

Harada T., Hata S., Takagi R.
Komori T., Fukuyama F.,
Chinen T., Kitagawa D., An
antioxidant screen identifies
ascorbic acid for prevention oflight-induced mitotic
prolongation in live cell
imaging. Commun Biol 6,1107. doi: org/10.1038/
s42003-023-05479-6. (2023)

4. C omparative cancer cell biology and its application to anticancer drug
development

Ito K.K., Watanabe K., IshidaH., Matsuhashi K., Chinen T.,
Hata S., Kitagawa D. Cep57
and Cep57L1 maintaincentriole engagement ininterphase to ensure centriole
duplication cycle. Journal of
Cell Biology, 220, e202005153(2021)

interested in elucidating how divergent molecular

Chinen T., Yamamoto S.,
Takeda Y., Watanabe K.,
Kuroki K., Hashimoto K.,
Takao D., Kitagawa D. NuMA
assemblies organize
microtubule asters to establish
spindle bipolarity inacentrosomal human cells.
EMBO journal, doi: 10.15252/
embj.2019102378. (2020)
Yamamoto S., Kitagawa D.
Self-organization of Plk4
regulates symmetry breaking
in centriole duplication.
Nature Communications, doi:
10.1038/s41467-019-09847-x.
(2019)
Watanabe K., Takao D., Ito
K.K., Takahashi M., Kitagawa
D. The Cep57-pericentrin
module organizes PCM
expansion and centriole
engagement. Nature
Communications,doi: 10.1038/
s41467-019-08862-2.(2019)

24

5. F
 orward genetic analysis of cell-cell communication with human cells
Our laboratory mainly focuses on understanding
the mechanisms of cell division, with a particularemphasis on the molecular basis and theoreticalmodel of centrosome duplication. We are also
machineries, including a protein complex andprotein-lncRNA complex, regulate somatic andmeiotic cell division. Based on these studies, wethen explore a new approach to develop a novel

Bipolar spindle formation in mitotic HeLa cells. Control(left panel) and a cell defective in forming a proper mitotic
spindle and chromosome segregation (right panel).

anti-cancer therapy. To this end, we currently use
the combination of innovative and multi-disciplinary
methods including molecular biology, biochemistry,
biophysics, structural biology, genetics, computer
simulation and cell biology.
Furthermore, to understand molecular mechanisms
and basic principles underlying a wider range of
biological phenomena in vivo, we are also trying toestablish a forward genetic approach with in vitro
reconstitution of human cell-cell communication.

Centriole duplication and structure. An image obtained bysuper-resolution microscopy: centriole wall in green,
cartwheel structures in red.

Molecular Biology
Laboratory

Laboratory ofProf. Y. Gotoh

Assoc. Prof. D. Kawaguchi
Project Assoc. Prof. K. Oishi
Assist. Prof. T. Kuniya

Prof. Y. Gotoh

http://molbio.f.u-tokyo.ac.jp/

Molecular
studiesBiologyof brain development,
Molecular
homeostasis and disease
Molecular studies of brain development,
Research
Topicshomeostasis
and disease

Assoc. Prof. D. Kawaguchi 1. Molecular mechanisms responsible for the regulation of neural stemprogenitor cell fate during development and adulthood
Project Assoc. Prof. K. Oishi
Harada, Y., Yamada, M.,
Assist. Prof. T. Kuniya
Research
Topics of cell fate determination
regulation
2. Epigenetic
Imayoshi, I., Kageyama, R.,
Assist. Prof. L. Fang
Suzuki, Y., Kuniya, T.,
1. M
 olecular of
mechanisms
responsible forthe regulationneural stem-progenitor
neural development
associatedwith ofneurodevelopmental
disorders
3. Dysregulation
Furutachi, S.,
Kawaguchi, D.
http://molbio.f.u-tokyo.ac.jp/
cell fate during development and adulthoodand Gotoh, Y. Cell cycle
arrest determines adult neural
2. E pigenetic regulation of cell fate determination
stem cell ontogeny
byN,anKuwayama
Kujirai T, Kishi How does a cell determine its fate? This is a fundamental question in understanding multicellular
3. D ysregulation of neural development associated with neurodevelopmental
embryonic NotchY, Hirano R, Echigoya K, Fang
disordersorganisms. Our laboratory aims to understand development of the mammalian brain from theL, Watanabe
S, Nakao M,
nonoscillatory
Hey1 module.
Y, Ishiguro
KI,Nat. Comm.Suzuki
12, 6562(2021).
viewpoint of cell fate determination at the molecular level. The brain, the organ responsible for our
How does a cell determine its fate? This is a fundamental question in understanding multicellular
Kurumizaka H, Gotoh, Y.
Yuizumi, N.,HMGA2
HaradaY.,
thoughts
and actions,processes
extremely
complexneuralcircuits.
directly mediates
organisms.
Our laboratory
aimssophisticatedto understandinformation
developmentthroughof the mammalian
brain
from theviewpoint
Kuniya T., Sunabori
Koike
chromatin T.,
condensationin
The mammalianbrain is formed
duringdevelopmentby theproliferationanddifferentiationof cell fate determination
at themolecularlevel. The brain,
therepeatedorgan responsible
for ourthoughts
andM., Wakabayashi
M., with neuronal fateassociationof neural
stem-progenitor
cells (NSCs),
which throughgive rise
to various
typesneuralof neurons
glial cells, andactions,
processes sophisticatedinformation
extremely
complexcircuits. and
The mammalianIshihama Y.,
Suzuki Y.,
regulation.
Nat. Comm. 14,
Kawaguchi 3420
D.and
Gotoh Y.
(2023)
is formed
during ofdevelopmentby the cells
repeatedand differentiationof neuralstemby thebrain
properpositioning
these progeny
and proliferation
circuit maturation.
The brain
contains
many
Maintenance of neural stem
cells different(NSCs), whichgive rise
to NSCsvariousare
types
of neuronsfor
andtheglial
cells, and andby theproperHarada, Y., Yamada, M.,regionsprogenitor
that performfunctions,andresponsible
generation
construction- progenitor cells by the
Imayoshi, I., Kageyama, R.,
positioningof
theseprogenycells
andcircuitmaturation.
The
brain
contains
many
regions
that
perform
lysosomal biosynthesisof functional elements specific to each region. In addition, a specific subset of NSCs persists in the
Suzuki, Y., Kuniya, T.,
regulators TFEB and TFE3 in
different functions, and NSCs are responsible for the generation and construction of functional elements
Furutachi, S., Kawaguchi, D. adult mousebrain and continues to produce neurons throughout life, with these neurons being thought
the embryonic mouse
specific to each region. In addition, a specific subset of NSCs persists in the adult mouse brain andand Gotoh, Y. Cell cycle arrest
telencephalon.
Stem Cells 39,
essential roles in learning, memory, recovery from stress, and innate behaviors. We aredetermines adult neural stem to playcontinues
to produce neurons throughout life, with these neurons being thought to play essential roles in
929-944 (2021).
cell ontogeny by an embryonic particularly interested in temporal and spatial cues as well as epigenetic regulation of gene expression
learning,
memory,recovery from stress, and innate behaviors. We are particularly interested in temporal
NotchEto, H., Kishi,Y., nonoscillatory
Yakushiji- Hey1
andnuclearchromatinthat underlie
development
andfunction.architecture
For example,
and spatial cues asarchitecture
well as epigenetic
regulationproperof genebrain
expression
and nuclear
chromatinNat. Comm.
Kaminatsu,module.
N., Sugishita,
H., 12, 6562
(2021).
we arethatcurrently
investigating
the contributionof chromatin
epigenome
regulation theto theunderlie proper
brain development
and function.
For example,and
we arecurrently investigating
Utsunomiya, S., Koseki, H.
and Gotoh,Eto,
Y. ThePolycomb
H., Kishi,Y., Yakushijicontributionof chromatin and epigenome
developmental
stage–dependent control
of ofdevelopmental
stage–dependent
control of regulation
NSC fatetoasthe
well
as to the history-dependent
plasticity
group protein
Ring1 regulates
Kaminatsu,
N., Sugishita, H.,
fate asto thehistory-dependent
plasticity ofbasis
neuralofcircuits.
We are also investigating
the withneural NSC
circuits.
Wewellareasalso
investigating
the molecular
neurodevelopmental
disorders
Utsunomiya,dorsoventral
patterningS.,
ofKoseki,
the H.
molecular
basis
ofneurodevelopmental
disorders
with
the
use
of
mouse
models.
Wehopetocontributeand Gotoh, Y.Nat.
The Polycomb the use of mouse models. We hope to contribute to a better understanding of the principles of normalmouse telencephalon.
Ring1 regulatesComm. 11, group5709 protein(2020).
to a better understanding of the principles of normal brain development and of the pathogenesis of
dorsoventral patterning of the brain development and of the pathogenesis of developmental brain abnormalities.

Tsuboi, M.,mouse
Kishi, telencephalon.
Y.,Nat.
Kyozuka, W.,
Koseki,H., (2020).
Comm.
11, 5709
Hirabayashi, Y., and Gotoh,
Tsuboi,independent
M., Kishi, Y., Kyozuka,
Y. Ubiquitination
W., Koseki, H., Hirabayashi, Y.,
repression of PRC1 targets
and Gotoh, Y. Ubiquitination
during neuronal fateindependent repression of
restriction in the developing
PRC1 targets during neuronalmouse neocortex. Dev. Cell
fate restriction in the47, 758-772 (2018).

developing mouse neocortex.
Dev. CellD.,
47,Pior,758-772
Lanjakornsiripan,
B. (2018).

J., Kawaguchi,D., Furutachi,
Lanjakornsiripan,
D., Pior, B.
S., Tahara, J.,
T.,Kawaguchi,
Katsuyama,
D.,Y.,
Furutachi,
Suzuki, Y., S.,
Fukazawa,
andTahara, T.,F.,
Katsuyama,Y.,
Gotoh, Y. Layer-specificSuzuki, Y., Fukazawa, F., andheterogeneityof astrocytes
Gotoh,
Y. Layer-specificand its dependence
on of astrocytes
heterogeneity
neuronal layers.
and itsNat.
dependence onlayers. Nat.Commun.
Commun. 9,neuronal
1623 (2018).
9, 1623 (2018).

developmental brain abnormalities.

Embryonic/Postnatal stage（Early life）

Adulthood（Late life）

Brain development
Embryonic

Neural stem cell

Stem cell pool/
Fate determination/
Migration/Maturation/
Circuit formation/
Plasticity

Brainfunction

Adult

Neural stem cell

Genetic and environmental
factors

Autism spectrum disorder
Schizophrenia
Major depressive disorder
etc

25

25

Laboratory of

Genetics

Prof. M. Miura
Lecturer Y. Nakajima
Assist. Prof. S. Kashio
Assist. Prof. N. Shinoda
https://idenut.f.u-tokyo.ac.jp

Molecular logic underlying the formation andmaintenance of cell society in the bodyResearch Topics
1. R egulatory mechanisms of non-apoptotic caspase
2. M etabolic regulation of development, regeneration, growth and aging

Fujita, S., Takahashi, M., Kumano, G.,
Kuranaga, E., Miura, M., andNakajima, Y.: Distinct stem-like cell
populations facilitate functional
regeneration of the Cladonema
medusa tentacle. PLOS Biol. 21:
e3002435 (2023)
Kosakamoto, H., Obata, F., Kuraishi,J., Aikawa, H., Okada, R., Johnstone,
J.N., Onuma, T., Piper, M.D.W., andMiura, M.: Early-adult methionine
restriction reduces methionine
sulfoxide and extends lifespan in
Drosophila. Nature Comm. 14: 7832
(2023)
Nagai, H., Nagai, LAE., Tasaki, S.,
Nakato, R., Umetsu, D., Kuranaga,E., Miura, M., and Nakajima, Y.:
Nutrient-driven dedifferentiation ofenteroendocrine cells promotes
adaptive intestinal growth inDrosophila. Dev. Cell 58: 17641781(2023)

3. M olecular mechanisms of phenotype expressivity
4. M
 echanisms of tissue size control during development
5. C ellular plasticity in tissue homeostasis and environmental responses
Programmed cell death functions in dynamic tissue formation and remodeling. We have revealed that in
the embryonic development, or aging process, caspases are activated by physiological stresses andexert not only apoptosis but also regulatory functions. We aim to reveal how caspase and metabolisms
are involved in the determination of phenotype expressivity during development, growth, regeneration
and aging. We also study the mechanisms of tissue size control during development and cellular plasticity
in tissue homeostasis and environmental responses. We believe that our research would stimulate andencourage students and researchers to have the breadth of vision for life science research and provide
new insights into the molecular logic underlying the formation and maintenance of cell society in thebody.
Drosophila pupal notumn

Kashio, S., Masuda, S., and Miura,
M.: Involvement of neuronaltachykinin-like receptor at 86C in
Drosophila disc repair via regulationof kynurenine metabolism. iScience
26: 107553 (2023)

Drosophila adult midgut

Cladonema medusa tentacle

Shinoda, N., Horikoshi, M., Taira,Y.,
Muramoto, M., Hirayama, S., Murata,S., and Miura, M.: Caspase cleaves
Drosophila BubR1 to modulate
spindle assembly checkpoint function
and lifespan of the organism. FEBS J.
290: 4200-4223 (2023)
Nakano, S., Kashio, S., Nishimura,K., Takeishi, A., Kosakamoto, H.,
Obata, F., Kuranaga, E., Chihara, T.,
Yamauchi, Y., Isobe, T., and Miura,
M.: Damage sensing mediated byserine proteases Hayan and
Persephone for Toll pathway
activation in apoptosis-deficient flies.
PLOS Genet. 19: e1010761(2023)

26

Non-apoptotic caspase activation
during cell delamination

Multipotent stem cells during homeostasis
and environmental responses

FigureConfocal stack image of the Drosophila pupal notumn. In this picture, caspase-3 activated cells(magenta) are observed in the midline (left picture). Visualization of tissue stem cells in Drosophila adultmidgut and Cladonema medusa tentacle. Multipotent stem cells contribute to tissue homeostasis andenvironmental responses (right picture).

Laboratory

Laboratory of

Cell Signaling

From signal transduction to drug discovery
Assoc. Prof. I. Naguro
Assist. Prof. T. Fujisawa
Assist. Prof.
S. Yamauchi
http://saijyou.f.u-tokyo.ac.
jp/index.html

Research Topics
1. S
 ignal transduction and functions of ASK family proteins
2. E
 xploration of novel signaling molecules involved in cell death and stressresponses
3. M
 olecular mechanisms of pathogenesis induced by dysfunction of stresssignaling

Morishita, K., Watanabe, K.,
Naguro I. and Ichijo H.
Sodium ion influx regulates
liquidity of biomolecularcondensates in hyperosmotic
stress response. Cell Rep.
42,112315 (2023).

The Laboratory of Cell Signaling has been focusing on analyses of the intracellular signal transduction,

Watanabe, K., Morishita, K.,
Zhou, X., Shiizaki, S.,
Uchiyma, Y., Koike, M.,
Naguro, I. and Ichijo, H. Cells
recognize osmotic stressthrough liquid–liquid phaseseparation lubricated withpoly(ADP-ribose). Nat.
Commun., 12,1353 (2021).

analytic technologies such as mass spectrometry-based proteomic analysis and genome-wide RNAithrough which we seek to elucidate molecular basis of human diseases and identify novel drug targets.
Our current research mainly focuses on the pathophysiological roles of stress responsive signals invarious diseases such as cancers, immune disorders, cardiovascular diseases and neurodegenerative
diseases. In addition to molecular genetic tools such as mice, flies and worms as well as basic
experimental techniques from molecular cloning to protein biochemistry, we always incorporate novel
screening systems into our research exploring “target molecules and molecular mechanisms”. By taking
advantage of such experimental approaches, we aim to open up new fields in pharmaceutical scienceswith paying attention to whole body physiology, diseases and drug discovery.

Ogawa, M., Kawarazaki, Y.,
Fujita, Y., Naguro, I. andIchijo, H. FGF21 induced by
the ASK1-p38 pathway
promotes mechanical cellcompetition by attracting
cells. Curr. Biol., 31, 1-10(2021).
Nakamura, T., Ogawa, M.,
Kojima, K., Takayanagi, S.,
Ishihara, S., Hattori, K.,
Naguro, I. and Ichijo, H. The
mitochondrial Ca2+ uptake
regulator, MICU1 is involvedin cold stress-induced
ferroptosis. EMBO Rep., 22,e51532 (2021).
Watanabe, K., Umeda, T.,
Niwa, K., Naguro, I. andIchijo, H. A PP6-ASK3
module coordinates thebidirectional cell volume
regulation under osmotic
stress. Cell Rep., 22, 28092817 (2018).

27

Laboratory ofProtein Metabolism

Prof. S. Murata
Assist. Prof.
J. Hamazaki
Assist. Prof.
S. Hirayama
https://tanpaku.f.u-tokyo.
ac.jp/indexe.html

Elucidating various biological phenomena controlled byproteolysis

Research Topics
1. T he action mechanisms of the proteasome, a multisubunit macromolecularcomplex responsible for regulated protein degradation in eukaryotic cells
2. P roteasome dysfunction in human diseases (senescence, malignant tumors,inflammation, neurodegeneration)

Hashimoto E, Okuno S, Hirayama S,
Arata Y, Goto T, Kosako H,
Hamazaki J, Murata S. Enhanced
O-GlcNAcylation mediates
cytoprotection under proteasome
impairment by promoting
proteasome turnover in cancer cells.
iScience 23 (2020)
Tomita T, Hirayama S, Sakurai Y,
Ohte Y, Yoshihara H, Saeki Y,
Hamazaki J, Murata S. Specific
Modification of Aged Proteasomes
Revealed by Tag-Exchangeable
Knock-In Mice. Mol Cell Biol 39:
e00426-18 (2018)
Murata S, Takahama Y, Kasahara
M, Tanaka K. The
immunoproteasome andthymoproteasome: functions,evolution and human disease. Nat
Immunol 19: 923-931 (2018)
Hirayama S, Sugihara M, Morito D,
Iemura SI, Natsume T, Murata S,
Nagata K. Nuclear export ofubiquitinated proteins via the UBINPOST system. Proc Natl Acad Sci
U S A 115: E4199-4208 (2018)
Uechi, H., Kuranaga, E., Iriki, T.,
Takano, K., Hirayama, S., Miura, M.,
Hamazaki, J., Murata, S. UbiquitinBinding Protein CG5445
Suppresses Aggregation and
Cytotoxicity of Amyotrophic
Lateral Sclerosis- linked TDP-43 in
Drosophila. Mol Cell Biol 16:
300195 (2018)
Koizumi S, Irie T, Hirayama S,
Sakurai Y, Yashiroda H, Naguro I,
Ichijo H, Hamazaki J, Murata S. The
aspartyl protease DDI2 activatesNrf1 to compensate for proteasome
dysfunction. Elife. 5: e18357 (2016)

28

3. T
 he mechanism of maintenance of protein homeostasis by the ubiquitinproteasome system
The proteasome is a supramolecular proteolytic apparatus that exists in all eukaryotic cells. The
proteasome plays pivotal roles in various cellular functions by selectively degrading ubiquitinated proteins.
It is also central to the maintenance of protein homeostasis (proteostasis). In recent years, it has become
evident that the impairment of proteostasis is a hallmark of senescence, and the decline of proteasomefunction is drawing attention as one of the primary factors. Indeed, it has been shown that age-associateddiseases develop as proteasome function declines with age, and that artificial increase in proteasome
activity prolongs the healthy lifespan in nematodes and Drosophila. However, in mammals, means toenhance proteasome function has not been established at present. This is because in mammals theproteasome is controlled more complicatedly and because the mechanisms by which the proteasomefunction decreases with aging and by which a decrease in proteasome function causes senescence are
not understood. On the other hand, it has become clear that inhibition of proteasome function is an
important therapeutic strategy in malignant tumors where proteasome hyperactivity is observed.
The ultimate goal of Laboratory of Protein Metabolism is to create a method of intervention in pathologies
involving proteasome dysfunction. To this end, we are researching detailed mechanisms of action andregulation of the proteasome by using techniques such as molecular and cell biology, comprehensive
gene screening, proteomics, and mouse genetics.

Laboratory

Laboratory of

Immunology and Microbiology

Prof. S. Hori
Assoc. Prof.
R. Setoguchi
Assist. Prof.
A. Nakajima
Project Assist. Prof.
R. Murakami
http://www.f.u-tokyo.ac.
jp/~bisei/

Understanding the principles of immunological tolerance
and homeostasis

Research Topics
1. M
 echanisms of immunological tolerance and homeostasis
2. M
 echanisms of regulatory T cell development and function
3. M echanisms of memory CD8 T cell maintenance
The immune system has evolved
the ability to distinguish “self” from

Nakajima, A., R. Murakami, andS. Hori. 2023. Functional
Analysis of Foxp3 and Its
Mutants by RetroviralTransduction of Murine Primary
CD4(+) T Cells. Methods Mol
Biol 2559:79-94.
Iriki, H., H. Takahashi, N. Wada,
H. Nomura, M. Mukai, A.
Kamata, H. Ito, J. Yamagami, T.
Matsui, Y. Kurebayashi, S.
Mise-Omata, H. Nishimasu, O.
Nureki, A. Yoshimura, S. Hori,and M. Amagai. 2021. Peripheral
tolerance by Treg via
constraining OX40 signal inautoreactive T cells against
desmoglein 3, a target antigen in
pemphigus. Proceedings of the
National Academy of Sciencesof the United States of America
118:e2026763118.

“non-self” to maintain homeostasisof the body. The immunological“self” is established in an adaptive
and acquired manner throughcontinuousinteractions

withchanging internal as well as
external

environments.

The

ultimate goal of this laboratory is
to elucidate, throughout multiple
layers, from molecules, cells, cell
populations, tissues, to individuals,

Fig. 1: Disintegration of immunological “self” underlies a variety of diseases

the principles that govern thedevelopment of such immunological “self” and its transformation during diseases. Towards this end, we
focus on a cell-extrinsic, dominant control mechanism of the immune system that depends on a
subpopulation of T lymphocytes called regulatory T (Treg) cells. As one approach, we elucidate how
mutations in the Foxp3 gene, encoding a transcription factor critical for Treg cell development andfunction, lead to a breakdown of immunological tolerance and homeostasis.

Hori, S. 2021. FOXP3 as amaster regulator of Treg cells.
Nat Rev Immunol 21:618-619.
Hori, S., and R. Murakami. 2021.
The adaptability of regulatory T
cells and Foxp3. International
Immunology 33:803-807.
Hayatsu, N., T. Miyao, M.
Tachibana, R. Murakami, A.
Kimura, T. Kato, E. Kawakami,
T.A. Endo, R. Setoguchi, H.
Watarai, T. Nishikawa, T. Yasuda,
H. Yoshida, and S. Hori. 2017.
Analyses of a Mutant Foxp3
Allele Reveal BATF as a Critical
Transcription Factor in the
Differentiation and Accumulationof Tissue Regulatory T Cells.
Immunity 47:268-283 e269.

Fig. 2: Foxp3-expressing regulatory T (Treg) cells are indispensable for
immunological tolerance and homeostasis

29

Laboratory of

Molecular Pharmacokinetics

Prof.
H. Kusuhara
Assist. Prof. H. Hayashi
Assist. Prof. T. Mizuno
http://www.f.u-tokyo.ac.
jp/~molpk/en/index.html

Elucidation of the mechanisms determining
pharmacokinetic properties of drugs that contributes todrug design, and safe and effective utilization of drugs
Research Topics
1. E
 stablishment of the methodologies for in vitro-in vivo extrapolation of drug
pharmacokinetics and pharmacological effect
2. E
 lucidation of molecular mechanisms determining the intestinal absorption ofdrugs, clearance of drugs from liver/kidney and drug transport at the barrier
organs such as blood-brain barrier

Maedera S, Mizuno T,
Kusuhara H. Investigation oflatent representation of
toxicopathological images
extracted by CNN model forunderstanding compoundproperties in vivo. Comput
Biol Med. 168:107748 (2024).
H ashimoto Y, et al.
Evaluation of the risk ofdiarrhea induced by
epidermal growth factor
receptor tyrosine kinase
inhibitors with cultured
intestinal stem cells
originated from crypts inhumans and monkeys.
Toxicol In Vitro. 93:105691(2023).
Tamura R, et al. Intestinal
Atp8b1 dysfunction causes
hepatic choline deficiency
and steatohepatitis. Nat
Commun. 14(1):6763 (2023).

3. P rediction of the effect of genetic polymorphisms of metabolic enzymes/transporters on the inter-individual variations of drug pharmacokinetics
4. E stablishment of the methodologies for the quantitative prediction of drug-druginteraction risks
5. E
 lucidation of mechanisms for the membrane trafficking of transporters
6. D evelopment of qualitative and quantitative prediction methods by in silico
analysis for pharmacokinetic properties of drugs
7. U nderstanding of drug effects by data-driven analysis
Pharmacological and adverse effects of drugs depend on their pharmacokinetic properties, which determine
their exposure to the targets. Our laboratory aims to establish methods for quantitative and theoreticalprediction of pharmacokinetic properties of new chemical entities in humans based on the molecularmechanisms. In particular, we investigate the impact of transporters on the elimination of drugs from theliver and kidney, the distribution of drugs into their target organs e.g., the brain, and drug absorption in
the small intestine, in order to develop drug screening systems and to elucidate the mechanisms of drugdrug interaction, and interindividual variation in pharmacokinetics of drugs. We have also started researchon the regulation of membrane trafficking of the transporters using low molecular weight compounds tocure transporter related-diseases. Research achievements in this laboratory contribute to predicting andevaluating rational pharmacokinetic properties in drug development, drug review and regulation, and inclinical use, and to developing medical therapy for transporter related-diseases.

Michiba K, et al. Usefulnessof Human Jejunal SpheroidDerived DifferentiatedIntestinal Epithelial Cells for
the Prediction of Intestinal
Drug Absorption in Humans.
Drug Metab Dispos.
50(3):204-213 (2022).
Mochizuki T, et al. Effect of
Cyclosporin A and Impact ofDose Staggering on
OATP1B1/1B3 Endogenous
Substrates and Drug Probes
for Assessing Clinical Drug
Interactions. Clin Pharmacol
Ther. 111(6):1315-1323(2022).

30

An example of a drug successfully designed to minimize
interindividual variation in pharmacokinetics byconsidering transporter characteristics.

As a high-throughput screening system for hepatobiliarytransport, uptake and efflux transporters are
simultaneously expressed in a single polarized cell(double transfectant).

Laboratory

Laboratory ofChemical Pharmacology

Prof. Y. Ikegaya
Assoc. Prof.
A. Nakashima
Assist. Prof.
N. Matsumoto
http://www.yakusaku.jp/
home_e.htm

Pharmacological approach toward the brain: frommolecule to animal

Research Topics
1. E
 xploring a new dimension of brain function via Brain-AI hybrid
2. S
 tudying brain network operation using multicellular activity recording
3. S tudying neuronal network formation during development

Pharmacology includes two aspects: 1) to analyze the biological action of drugs and 2) to search the
Ikegaya, Y., Matsumoto, N.
Spikes in the sleeping brain.
Science,366:306-307 (2019)

strategies for developing treatments for diseases. We conduct our pharmacological research by taking
advantage of state-of-the-art technologies and a wide range of knowledge from molecule to animal.
We focus on the roles of the cerebral limbic system and cerebral cortex, in particular, the hippocampus

Nakashima, A., Ihara, N.,
Shigeta, M., Kiyonari, H.,
Ikegaya, Y.,
Takeuchi, H. Structured spike
series specify gene
expression patterns forolfactory circuit formation.
Science, 365:eaaw5030(2019)

and amygdala, which are involved in learning, memory, and emotion.

Norimoto, H., Makino, K.,
Gao, M., Shikano, Y.,
Okamoto, K., Ishikawa, T.,
Sasaki, T., Hioki, H., Fujisawa,
S., Ikegaya, Y. Hippocampal
ripples down-regulate
synapses. Science, 359:15241527 (2018)

relevant neuronal circuits with immediate early genes with cellular and temporal resolution (Lower Figure).

Our experimental techniques cover from genetics, biochemistry, and cell biology to electrophysiology,
histochemistry, and behavioral pharmacology. Recent technical advances have allowed us to investigate
the neuronal network dynamics on far larger scales than hitherto. Functional multineuron calcium imaging
reveals the dynamics of network activity with single cell/synapse resolution (Upper Figure), through which
we elucidate the structural and functional relationship that generates spatiotemporally organized spikepatterns. We also address the mechanisms of learning and memory using in situ mapping learningWe believe that these novel approaches open up a new avenue for our mesoscopic understandings of
network function and malfunction associated with depression, stress-relevant disease, and epilepsy.

Takahashi, N., Kitamura, K.,
Matsuo, N., Mayford, M.,
Kano, M., Matsuki, N.,
Ikegaya, Y. Locallysynchronized synaptic inputs.
Science 335: 353-356 (2012)
Koyama, R., Tao, K., Sasaki,T., Ichikawa, J., Miyamoto, D.,
Muramatsu, R., Matsuki, N.,
Ikegaya, Y. GABAergic
excitation after febrile
seizures induces ectopic
granule cells and adultepilepsy. Nature Medicine 18:
1271-1278 (2012)
Sasaki, T., Matsuki, N.,
Ikegaya, Y. Action-potential
modulation during axonal
conduction. Science 311:
599-601 (2011)

Functional multineuron calcium imaging from neuron populations

31

Laboratory of

Neuropathology and Neuroscience

Prof. T. Tomita
Visiting. Prof. S. Torii
Assoc. Prof. Y. Hori
Assist. Prof. S. Takatori
Assist. Prof. T. Kimura
http://www.f.u-tokyo.ac.
jp/~neuropsc/

Nakamura R, Tomizawa I, etal. Photo-oxygenation ofhistidine residue inhibits
α-synuclein aggregation.
FASEB J. 37(12):e23311(2023)
Matsuzaki, M., Yokoyama, M.,
et al. ADAMTS4 is involved in
the production of the
Alzheimer disease amyloid
biomarker APP669-711. Mol.
Psychiatry 28(4):1802-1812(2023)
Ozawa, S., Hori, Y., et al.
Photo-oxygenation by abiocompatible catalyst
reduces Aβ levels in thebrains of Alzheimer diseasemodel mice. Brain
144(6):1884-1897 (2021)
Nagashima, N., Ozawa, S., etal. Catalytic
photooxygenation reduces
brain Aβ in vivo. Sci Adv
7(13): eabc9750, (2021)

From understanding the molecular pathogenesis ofneurodegenerative and psychiatric diseases todevelopment of therapeutics and novel basic science
Research Topics
1. R
 esearch on Aβ metabolism (production, secretion and clearance) and its
regulatory mechanisms
2. Understanding the cellular pathology after Aβ deposition towards thedevelopment of diagnostics
3. E
 lucidation of mechanism of amyloid formation deposited in the brains of patients
4. Investigation of the pathological function of microglia in Alzheimer disease
5. U nderstanding the molecular pathomechanisms of Parkinson disease
6. E
 lucidation of molecular mechanism of propagation of α-synuclein pathology
7. B iological and pathological roles of synaptic adhesion molecules in psychiatricdisorders
8. D evelopment of exercise program for dementia prevention
Aim of our laboratory is that understanding the molecular pathogenesis of neurodegenerative andpsychiatric diseases to develop novel approaches to therapeutic, prevention and diagnosis. Also, we are
pursuing novel basic science by understanding the molecular basis of diseases. Especially, we are
studying Alzheimer disease, autism spectrum disorder and schizophrenia to identify the pathologicalmechanisms and therapeutic targets of these diseases at molecular levels. To understand the disease
condition, we have to realize the basic mechanisms of cells and living organisms, and vice versa. We
believe that this disorder-to-normal cycle in research is a basis of modern disease and basic biology, andbolsters both scientific areas by novel knowledge and technology. From this standpoint, we proceed
disease-oriented molecular and cellular research in a multidisciplinary manner by mutual collaborations
with organic chemists, structural biologists, physicians and pharmaceutical companies.

Schweighauser, M., Shi, Y.,
Tarutani, A., et al. Structuresof α-synuclein filaments frommultiple system atrophy.
Nature 585(7825):464-469(2020)
Nakamura, A., Kaneko, N., etal. High performance plasma
Aβ-amyloid biomarkers for
Alzheimer’s disease. Nature554(7691):249-254 (2018)
Kidana, K., Tatebe, T., Ito, K.,
et al. Loss of astrocytederived kallikrein 7
exacerbates amyloid
pathology in Alzheimer
disease model mouse. EMBO
Mol Med. e8184 (2018)32

Molecular and cellular pathologies in Alzheimer disease

Laboratory

Laboratory of

Pharmaceutical Regulatory Science

Assoc. Prof.
S. OnoEstablishing scientific drug evaluation

Visiting Prof.
Y. Fujiwara
https://yakuhyou.f.u-tokyo.
ac.jp/study/eindex.html

Research Topics
1. A
 dvancing methods for rational drug evaluation
2. A
 nalyzing drug development behaviors and policies
3. E
 valuating drug regulation and guidelines
4. D eveloping systems to implement the above policies and guidelines
The goal of our research is to establish scientific principles and methods in drug evaluation with societal
perspectives in mind. Pharmaceutical research and development (R&D), clinical development in particular,
regulatory review and approval of new drugs, and post marketing activities are our research interests. We
provide evidence on R&D efficiency, performance and outcomes of regulations, and public health impact
through rigorous analysis based on economic models. Conflicts in global pharmaceutical R&D, including
recent launch delay of new drugs in Japan and so-called ethnic differences, are always high on our
agenda. Aside from the research activities, we also make efforts to develop human resources in bothSato, Y., Ono, S. Regulatory
Environment and Approvals in
Cell and Gene Therapy
Products between Japan, theUSA, and the EU. Therapeutic
Innovation & Regulatory
Science (2022)

private and public sectors with up-to-date knowledge, ethics, and philosophy, and rationale in drug
evaluation. We offer lectures for graduate and undergraduate students, and a half-year training course
for industry and regulatory professionals. We aim to secure transparency and social responsibility on
drug regulation through our research and educational programs.

Sugitani, Y., Ito, K., Ono, S.
Patient Preferences for
Attributes of Chemotherapy
for Lung Cancer.
Frontiers in Pharmacology
DOI: 10.3389/
fphar.2021.697711 (2021)
Harada, K., Toriyabe, K., Ono,
S. Survey of Japanese orphan
drug program:factors related to successful
marketing approval.
Journal of ClinicalPharmacology DOI: 10.1002/
jcph.1501 (2020)
Kaneko, R., Ono, S.
Exploratory analysis ofcomparative clinical trials
used for marketing approvalin patients with type 2
diabetes in Japan. SAGE
Open
Medicine DOI:
10.1177/2050312118823407(2019)

33

Laboratory ofMedicinal Plant Chemistry(Experimental Station for Medicinal Plant Studies)Prof. I. Abe
http://www.f.u-tokyo.ac.
jp/~oriharay/index.htm

An overall analysis is made of the old-yet-new drugs
known as “medicinal plants” (crude drugs) to develop
new ways of using them (utilizing the resources in theExperimental Station for Medicinal Plant Studies)
Research Topics
1. T he cultivation of medicinal plants and tissue cultures
2. T he production of useful secondary metabolites, using plant tissue culture
technology
3. C hemistry and biosynthesis of plant-derived biologically active substances
Since prehistoric times, plants have been the principal material used as drugs by humankind. Many havefallen by the wayside through a long process of trial and error (human experiments), and the ones thatremain can be considered the crude drugs of the present day. In recent years, the percentage of all
drugs accounted for by antibiotics and biologics has increased, but the importance of plant-derived
pharmaceuticals is by no means diminished and has led to the discovery of new drugs such as Taxol andvinblastine. Thus, the study of medicinal plants is by no means completed, and is continuing to evolve.
The Experimental Station for Medicinal Plant Studies, formally established in 1973, is located adjacent to
the Kemigawa Athletic Ground. The saplings transplanted there back then have grown large and now
form a dense enclosure of trees around the garden.
At the research lab in Hongo, we conduct research on the production of useful secondary metabolites

Fukuyama, N., Shibuya, M.,
Orihara, Y. Antimicrobial
polyacetylenes from Panax
ginseng hairy root. Chem.
Pharm. Bull. 60(3): 377-380(2012)

using plant tissue culture technologies (from the induction of culture cells to the production of substances).

Fukuyama, N., Ino, C.,
Suzuki, Y., Kobayashi, N.,
Hamamoto, H., Sekimizu, K.,
Orihara, Y. Antimicrobial
sesquiterpenoids from Laurus
nobilis L. Natural ProductResearch 25(14): 1295-1303(2011)

plant tissue culture technologies.

Some of the research topics we are currently pursuing are the biosynthesis of diterpene constituentsfrom Gymnosperm plant cultured cells, the production and biosynthesis of diterpene alkaloids using
cultured tissue of monkshood, the production and biosynthesis of phenylethanoids using cultured cellsof olive, and the production of biologically active constituents of Egyptian medicinal plants by means of

Saimaru, H., Orihara, Y.
Biosynthesis of acteoside incultured cells of Olea
europaea. J. Nat. Med. 64:
139–145 (2010)
Orihara, Y., Hamamoto, H.,
Kasuga, H., Shimada, T.,
Kawaguchi, Y., Sekimizu, K.
Evaluation of therapeutic
effects of antiviral agentsusing a silkworm baculovirus
infection model. Journal of
General Virology 89: 188-194(2008)

34

Aconitum japonicum cultured root

The sweetener glycyrrhizin is contained in the roots andstolons of Glycyrrhiza uralensis Fisher

Laboratory

Laboratory ofApplied Immunology(IQB Laboratory of Immunology and Infection Control)
Prof.
R. Shinkura

Research on immunoglobulin diversification and gut
microbial regulation by intestinal IgA

Assist. Prof. N. Morita
Assist. Prof. P. Gao
http://www.iqb.u-tokyo.ac.
jp/shinkuralab/Research Topics
1. M
 echanism of gut microbial regulation by intestinal IgA
2. M
 olecular mechanism of somatic hypermutation of immunoglobulin genes
3. S
 earch for IgA class switch inducer
The immune response has evolved to protect us from pathogenic infectious agents and toxic foreign substances. In
acquired immune response, antigen stimulation of B cells induces two distinct genetic alterations in the immunoglobulin(Ig) loci: somatic hypermutation (SHM) and class switch recombination (CSR), both of which require an enzyme,
activation-induced cytidine deaminase (AID). After these processes, among diversified Ig repertoire, selected highaffinity Igs efficiently defend host. AID plays a crucial role in host defense but it introduces DNA cleavage into Ig loci andaberrantly into non-Ig loci causing lymphoma. Our aim is to answer ‘how AID’s activity targets Ig loci specifically’ using
AID mutant protein and mutant knock-in mice and to understand the precise molecular mechanism of SHM and CSR.
Recently dysbiosis (gut commensal microbial imbalance) is frequently reported to be associated with illnesses such as

Intestinal IgA as a modulatorof the gut microbiota. Okai S,
Usui F, Ohta M, Mori H,
Kurokawa K, Matsumoto S,
Kato T, Miyauchi E, Ohno H,
Shinkura R. Gut Microbes
2017 Sep 3;8(5):486-492. doi:
10.1080/19490976.2017.
1310357. Epub 2017 Apr 6.
High-affinity monoclonal IgA
regulates gut microbiota andprevents colitis in mice. Okai
S, Usui F, Yokota S, Hori-I Y,
Hasegawa M, Nakamura T,
Kurosawa M, Okada S,
Yamamoto K, Nishiyama E,
Mori H, Yamada T, Kurokawa
K, Matsumoto S, Nanno M,
Naito T, Watanabe Y, Kato T,
Miyauchi E, Ohno H, Shinkura
R. Nat Microbiol. 2016 Jul 4;
1(9):16103. doi: 10.1038/
nmicrobiol.2016.103.
Mice carrying a knock-in
mutation of Aicda resulting in
a defect in somatic
hypermutationhave impaired
gut homeostasis andcompromised mucosal
defense. Wei M, Shinkura R,
Doi Y, Maruya M, FagarasanS, Honjo T. Nat Immunol.
12(3), 264-270, 2011

inflammatory bowel disease (IBD), obesity, cancer, etc. We found that the high-affinity intestinal IgA produced by SHM
is important to control non-pathogenic gut bacteria as well as pathogens. Our main question is how intestinal IgA
recognizes and targets a huge variety of gut bacteria. We have isolated a useful monoclonal IgA to modulate gut
microbiota leading to symbiosis (balanced host-microbial relationship in gut). We aim at applying the findings of ourbasic research to practical medicine.
Major Research Topics
1. Mechanism of gut microbial regulation by intestinal IgA
We generated hybridomas from IgA producing cells in small intestine of wild type mice. We selected W27 monoclonal
IgA as a best gut microbial modulator because of its strong binding ability specifically against colitogenic bacteria. We
are analyzing the bacterial target molecule for W27 to control microbial community, and will elucidate the reason why
IgA selects that target in the point of physiological view. We aim at thedevelopment of therapeutic W27 IgA antibody.
2. Molecular mechanism of SHM
We have found that a N-terminal mutant AID (G23S; glycine to serine
mutation at the 23rd AA) showed defective SHM but relatively intact
CSR both in vitro and in vivo, suggesting the N-terminus of AID may be
the domain responsible for SHM-specific co-factor binding. Throughthe search of SHM-specific co-factor, we will understand how AID
distinguishes SHM from CSR.
3. Search for IgA CSR inducer
Upon antigen stimulation B cells can undergo CSR to IgG, IgE or IgA
isotype. However, what induces B cells to each isotype specifically is
not completely understood. We focus on searching a novel IgA CSR
inducer, which may drive IgA CSR instead of IgE CSR at mucosal
surface, helping prevent allergy, as well as enhance the mucosal
immunity.

35

Laboratory of

Pathology and Development(Institute for Quantitative Biosciences)Prof. Y. Okada

Investigation of chromatin dynamics in germ cells

Assist. Prof. Y. Fujiwara
Assist. Prof. M. Hada
https://webpark2349.
sakura.ne.jp/okadalab/Research Topics
1. P rofiling sperm-retained histones
2. E lucidating the sperm chromatin structure

Fujiwara Y, Hada M, Fukuda Y, Koga C, Inoue E,*Okada Y. Isolation of stage-specific spermatogenic
cells by dynamic histone incorporation and removal inspermatogenesis. Cytometry A. 2023 Dec 12. doi:
10.1002/cyto.a.24812. Epub ahead of print. PMID:
38087848.
*Okada Y. “Sperm chromatin structure: Insights from invitro to in situ experiments”. Curr Opin Cell Biol. 2022
Apr;75:102075. doi: 10.1016/j.ceb.2022.102075. Epub
2022 Mar 25. PMID: 35344802.

3. Investigation of the machamism of histone retentaion in sperm during histoneprotamine exhange“Neuronal cells are who you are, while germ cells are where you came from.”- This is the word by aleading scientist in the field of germ cell research. Somatic cells including neuronal cells compose
ourselves, while germ cells play transgenerational roles. Recently, scientists demonstrated that not only
DNAs but also certain non-DNA factors can be transgenerationally transferred from ancestors toprogenies. The substance of this is non-DNA material is supposed to “epigenome” such as chromatin
and small RNAs, although the real entity hasn’t been determined. For now, the most possible idea is thatthe parental epigenetic information in their germ cells is altered upon stress responses and transferred to

Fukuda Y, Shintomi K, Yamaguchi K, Fujiwara Y,*Okada Y. “Solubilization of Mouse Sperm Chromatinfor Sequencing Analyses Using a Chaperon Protein”.
Methods Mol Biol. 2023;2577:161-173. doi:
10.1007/978-1-0716-2724-2_11. PMID: 36173572

the progeny by fertilization.

Fujiwara Y, Horisawa-Takada Y, Inoue E, Tani N,
Shibuya H, Fujimura S, Kariyazono R, Sakata T, Ohta
K, Araki K, Okada Y, *Ishiguro KI. “Meiotic cohesins
mediate initial loading of HORMAD1 to thechromosomes and coordinate SC formation during
meiotic prophase”. PLoS Genet.2020 Sep
15;16(9):e1009048. doi:10.1371/journal.pgen.1009048.
PMID: 32931493; PMCID: PMC7518614..

and genomic approaches. In addition, we are trying to utilize our research outcome for sperm quality

In our laboratory, we are investigating how epigenetic information is established in germ cells (especiallyin male germ cells) and altered upon various stress responses using biochemical, molecular biological,
control in Assisted Reproductive Technologies (ART).

Kim CR, Noda T, Kim H, Kim G, Park S, Na Y, Oura S,
Shimada K, Bang I, Ahn JY, Kim YR, Oh SK, Choi HJ,
Kim JS, Jung I, Lee H, Okada Y, *Ikawa M, *Baek SH.
“PHF7 Modulates BRDT Stability and Histone-toProtamine Exchange during Spermiogenesis”.Cell
Rep. 2020 Jul 28;32(4):107950. doi:10.1016/ j.
celrep.2020.107950. PMID: 32726616.
Makino Y, Jensen NH, Yokota N, Rossner MJ, Akiyama
H, Shirahige K, *Okada Y. “Single cell RNAsequencing identified Dec2 as a suppressive factor for
spermatogonial differentiation by inhibiting Sohlh1
expression”. Sci Rep. 2019 Apr 15;9(1):6063. doi:
10.1038/s41598-019-42578-z. PMID: 30988352;
PMCID: PMC6465314.
Yamaguchi K, Hada M, Fukuda Y, Inoue E, Katou Y,
Shirahige K, *Okada Y. “Re-evaluating the localizationof sperm-retained histones revealed the modificationdependent accumulation in specific genome regions”.
Cell Rep. 2018Jun 26;23(13):3920-3932. doi:
10.1016/j.celrep.2018.05.094. PMID: 29949774.

36

An example of our research achievement. Mammalian sperm nuclei are tightly condensed due to the highly basic
proteins called protamines. This unique chromatin structure prevents us from performing various kinds of biochemical
approaches to investigate the characteristics of sperm chromatin. In order to overcome this problem, we developed a
new method to artificially remove protamines from sperm chromatin by treating them with nucleoplamin (left figure).
This treatment enabled us to extract histone-DNA complex from sperm chromatin, then we performed Chromatin
Immunoprecipitation-Sequencing (ChIP-seq) to determine where histones are retained in sperm genome. The result
tells us that histones are scattered across the genome and exhibit modest enrichment in repeat regions. Interestingly,
post-translationally modified histones are retained in specific genome elements depending on the patterns of theirmodifications (right figure). Recently, paternal lifestyle and habits are supposed to be transferred to their children
through sperm. This phenomenon is called “epigenetic inheritance”, and our research outcome is expected to provide
a useful knowledge for understanding its molecular mechanisms.

Laboratory

Laboratory of

Molecular Neurobiology

Assoc. Prof.
Y. KishiUnderstanding how the brain functions throughepigenetic analysis

Assist. Prof. M. Bilgic
https://www.iqb.u-tokyo.
ac.jp/lab/kishi/

Research Topics
1. E
 pigenetics analysis of brain cells to understand alterations in brain function
under aging, stress, and psychiatric disorder conditions
2. E
 pigenome editing of neurons to improve brain function
Our genetic information is encoded in our genomic DNA. Several mechanisms are used to properly
identify and access the necessary genetic information contained within our three billion base pairs ofDNA. One of these mechanisms is epigenetic regulation. Through epigenetic regulation, chemical
modifications on DNA and histones—such as methylation and acetylation—function as “bookmarks,”
resulting in the expression of only the necessary genes.
These epigenetic “bookmarks” are modified in response to the cell’s previous exposures to stimuli andexperiences. In other words, epigenetic regulation functions as the memory system of cells. The question
then becomes, what role does epigenetics play in the brain, which is the memory system of individuals?
In our laboratory, we are working to understand the mysteries of the brain through epigenetic analysis bycombining the biochemical, molecular biological, and bioinformatics technologies needed to carry out
the latest genomic analysis with the genetic and neuroscience technologies necessary to analyze brain
function. Through this research, we aim to understand the basis of changes in brain function caused by

Tanita Frey, Tomonari
Murakami, Koichiro Maki,
Takumi Kawaue, Ayaka Sugai,
Naotaka Nakazawa, Taiji
Adachi, Mineko Kengaku,
Kenichi Ohki, Yukiko Gotoh,
and Yusuke Kishi. Ageassociated reduction of
nuclear shape dynamics inexcitatory neurons of thevisual cortex. Aging Cell,
e13925, 2023

aging, stress, and psychiatric disorders.

Miho Koizumi, Hikaru Eto,
Mai Saeki, Masahide Seki,
Tsuyoshi, Fukushima,
Shoichiro Mukai, Hisamitsu
Ide, Yasuyuki Sera, Masayuki,
Iwasaki, Yutaka Suzuki,
Atsushi Tohei, Yusuke Kishi,
and Hiroaki Honda. UTX
deficiency in neural stem/
progenitor cells results in
impaired neural development,
fetal ventriculomegaly, andpostnatal death. FASEBJournal, 36(12):e22662, 2022

37

Laboratory of

RNP Synthetic Biology and Biotechnology(Institute for Quantitative Biosciences)Prof. H. Saito

Empowering new life systems through synthetic biology
and bioengineering

Lecturer T. Yoshii
Assist. Prof. H. Ono
https://www.iqb.u-tokyo.
ac.jp/lab/saito/

Research Topics
1. B asic biology and drug discovery based on RNA and RNP
2. S
 ynthetic biology and bioengineering for gene expression and cell-fate control
3. C reation of artificial biomolecules and living matters for medical applications
In our laboratory, we delve into the fascinating world of RNA and RNA-Protein complexes (RNPs), pivotal
elements in myriad life processes. Our research is dedicated to unraveling the mysteries of RNA and RNP
interactions, aiming to deepen our understanding of life systems, discover new biological phenomena,and pioneer groundbreaking technologies.
RNPs, formed through the recognition of RNA sequences and structures by proteins, are central to thecellular mechanisms controlling gene expression and intracellular localization. By elucidating thesequences and structures involved in RNP interactions, along with their molecular mechanisms, we

1. Sumi S, Hamada M*, andSaito H*: Deep generative
design of RNA family
sequences. Nature
Methods, in press
2. Kawasaki S*, Ono H,
Hirosawa M, Kuwabara T.,
Sumi S., Lee S, Woltjen K.,
and Saito H*:
Programmable mammaliantranslational modulators by
CRISPR-associatedproteins. Nature Commun,
2023;2243.
3. Fujita Y*, Hirosawa M,
Hayashi K, Hatani T,
Yoshida Y, Yamamoto T,
Saito H*: A versatile androbust cell purification
system with an RNA-only
circuit composed of
microRNA-responsive ON
and OFF switches.
Science Adv., 2022 Jan
7;8(1):eabj1793.
4. Wroblewska L, Kitada T,
Endo K, Siciliano V, Stillo B,
Saito H*, Weiss R*:
Mammalian synthetic
circuits with RNA binding
proteins for RNA-only
delivery. Nature
Biotechnol,
2015;33(8):839-41.

38

unlock the potential to artificially modify the functions and formations of RNA and RNP complexes. This
capability opens up exciting possibilities for manipulating cellular functions at will, creating artificial RNAsand RNPs with novel functions, and exploring the interactions between RNA and various molecules “X”(RNX) as a foundation for understanding and creating new biomolecules and life systems (RNX Synthetic
Biology).
We believe in the importance of integrating interdisciplinary technologies and developing new ones toforge new research fields. By merging techniques and knowledge from synthetic biology, evolutionary
engineering,

informatics,

andbiophysical chemistry, we aim tomRNA-based cell programming in vitro and in vivo

develop new technologies forunderstanding and controlling life
systems. Leveraging our unique
technologies, we strive to elucidate
the mechanisms behind RNAbased life systems, contributing to
the life sciences and paving the
way

for

new

pharmaceuticaldevelopments. Our lab is not just aplace of research but a crucible ofinnovation, where we challenge
the boundaries of science tocreate a future where the mysteriesof life are not just understood but
harnessed.

miRNA-OFF and ON switches for cell specific regulation

Laboratory

Laboratory ofStem Cell Regulation and Drug Discovery(Institute of Medical Science)Prof.
E. Nishimura
Assist. Prof. Y. Mohri
Assist. Prof.
K. Asakawa
https://www.ims.u-tokyo.
ac.jp/aging-regeneration/
Yang J H＊, Hayano M, Griffin P T, Amorim
J A, Bonkowski M S, Apostolides J K,
Salfati E L, Blanchette M, Munding E,
Bhakta M, Chew Y, Blanchette M, Munding
E M, Bhakta M, Chew Y C, Guo W, Yang X,
Maybury-Lewis S, Tian X, Ross J M,
Coppotelli G, Meer M V, Rogers-Hammond
R, Vera D L, Lu Y R, Pippin J W, Creswell
M L, Dou Z, Xu C, Mitchell S J, Das A,
O’Connel B L, Thakur S, Kane A E, Su Q,
Mohri Y, Nishimura EK, Schaevitz L, Garg
N, Balta A-M, Rego M A, Gregory-Ksander
M, Jakobs T C, Zhong L, Wakimoto H,
Andari J E, Grimm D, Mostoslavsky R,
Wagers A J, Tsubota K, Bonasera S J,
Palmeira C M, Seidman J G, Seidman C E,
Wolf N S, Kreiling J A, Sedivy J M, Murphy
G, Green R E, Garcia B A, Berger S L,
Oberdoerffer P, Shankland S J, Gladyshev
V N, Ksander B R, Pfenning A R, Rajman L
A, Sinclair D A＊.
Loss of epigenetic information as a causeof mammalian aging.
Cell, 186(2):305-326, 2023

Study of skin stem cell dynamics and aging as a clue forthe serach of therapeutic drugs for age-associateddiseases
Research Topics
1. E
 lucidation of the mechanism of self-renewal of tissue stem cells and their quality
control
2. E
 lucidation of the mechanism of tissue aging, diseases and systemic frailty
3. D evelopment of therapeutic drugs using stem cell technology.
Many of the tissues and organs that make up our bodies form a tissue stem cell system, maintaining their
homeostasis. Tissue stem cells are the backbone cell population for maintaining homeostasis, such as
tissue regeneration, but they gradually undergo changes due to aging and various environmental
stresses, leading to the onset of many age-related diseases, including cancer. We believe that in treating
age-related diseases, it is essential to clarify the aging processes and mechanisms leading to their onset,
explore the key cell populations and molecules to be targeted, which can contribute to new drug
development. Based on this approach, we are developing stem cell control technology targeting stem
cells, searching for substances that enable tissue regeneration and control tissue aging and diseases.

Karigane D, Haraguchi M, ToyamaSorimachi N, Nishimura EK, Takubo K.
Mitf is required for T cell maturation by
regulating dendritic cell homing to thethymus.
Biochem Biophys Res Commun., 596:
29-35, 2022
Nanba D, Toki F, Asakawa K, Matsumura
H, Shiraishi K, Sayama K, Matsuzaki K,
Toki H, Nishimura EK.
EGFR-mediated epidermal stem cell
motility drives skin regeneration through
COL17A1 proteolysis.
J Cell Biol., 220(11): e202012073, 2021
Eshiba S, Namiki T, Mohri Y, Aida T,
Serizawa N, Shibata T, Morinaga H, Nanba
D, Hiraoka Y, Tanaka K, Miura K, Tanaka
M, Uhara H, Yokozeki H, Saida T,
Nishimura EK＊.
Stem cell spreading dynamics intrinsicallydifferentiate acral melanomas from nevi.
Cell Reports, 36(5):109492, 2021

Stem cell system

Stem cell clone analysis
Spatial Single Cell Omics

Stem cells

Mechanisms ofStem cell self-renewal

幹細胞

Organ netwrok

Differentiated cells

Science &Evidence

Protects one from the outside world
as a barrier

Frail network
Mechanisms ofsystemic fraily

Stem cell
Collagen XVII

Niche

Stem cell control technology

Overcoming
Aging-Related Diseases

Meeting Unmet Medical Needs
Extention of healthy lifespan

In our laboratory, we focus on elucidating the mechanism of stem cell self-renewal and quality control, utilizing
techniques such as single-cell omics analysis of skin, tracking the fate of stem cells in epithelial organoids and in vivo,
and analyzing interactions with surrounding cells and other organs to elucidate the breakdown mechanism and thediseases.

39

Laboratory ofProtein Dynamics(Division of Protein Metabolism, The Institute of Medical Science)Prof. Y. Saeki
Assoc. Prof.
T. Kobayashi
Assist. Prof.
T. Tomita
https://www.ims.u-tokyo.
ac.jp/prometa/

Understanding diverse cellular functions through protein
dynamics

Research Topics
1. R egulation of Cellular Functions by the Ubiquitin Code
2. S tress adapation mechanisms by liquid-liquid phase separation
3. P roteostasis of adult neural stem cells

The Laboratory of Protein
Dynamics studies how thecellular proteome is shaped
and maintained in responseto changes in the cellularenvironment. It has become
clear that dysregulation ofproteostasis has emerged
as a key factor contributing
to a range of pathologies,
Yasuda, S., Tsuchiya, H.,
Kaiho, A., Guo, Q., Ikeuchi,
K., Endo, A., Arai, N., Ohtake,F., Murata, S., Inada, T.,
Baumeister, W., FernandezBusnadiego, R., Tanaka, K.,
Saeki Y. Stress- andubiquitylation-dependent
phase separation of theproteasome. Nature, 578,
296-300 (2020)
Kobayashi, T., Piao, W.,
Takamura T., Kori, H.,
Miyachi, H., Kitano, S.,
Iwamoto, Y., Yamada, M.,
Imayoshi, I., Shioda, S.,
Ballabio, A., Kageyama, R.
Enhanced lysosomal
degradation maintains thequiescent state of neuralstem cells. Nat. Commun.,10, 5446 (2019)
Tsuchiya, H., Burana, D.,
Ohtake, F., Arai, N., Kaiho, A.,
Komada, M., Tanaka, K.,
Saeki Y. Ub-ProT reveals
global length andcomposition of protein
ubiquitylation in cells. Nat.
Commun., 9, 524 (2018)40

including neurodegenerative
diseases.

Theubiquitin

system plays a pivotal roleinproteostasis

proteome

remodelingandRegulation of Cellular Functions by the Ubiquitin Codebyspatiotemporally regulating diverse biological phenomena such as protein degradation, cellular
localization, and protein-protein interactions. Behind the diverse functions of ubiquitin modifications, wehave shown that higher-order structures of ubiquitin chains act as “ubiquitin code”. More recently, we
have also discovered a ubiquitin code drives liquid-liquid phase separation with specific ubiquitin
decoders. Additionally, our laboratory focuses on neural stem cell proteostasis, in which protein
degradation plays a crucial role in reactivating neural stem cells from dormancy to proliferation. Thus, ourgoal is to uncover the impact of proteome remodeling and proteostasis on disease pathogenesis andcontribute to drug discovery.

Proteostasis of adult neural stem cells

Laboratory

Laboratory of

Nucleic Acids ResearchProf.
N. Akimitsu
Project Assoc. Prof.
K. Taniue
Assist. Prof. K. Tao
Project Assist. Prof.
R. Onoguchi-Mizutani
Project Assist. Prof.
K. Kawata
https://akimitsu.ric.u-tokyo.
ac.jp/en/

Investigation of the molecular functions of nucleic acids(especially, RNA), and development of nucleic acidtherapeutics
Research Topics
1. Investigation of molecular mechanisms of noncoding RNAs for the gene
regulation.
2. Investigation of physiological and pathological roles of membrane-less organelle.
3. D evelopment of basic technology to control nucleic acid medicine.
Nucleic acids such as DNA and RNA play a central role in gene expression flow. This laboratory has been
focusing on investigation of roles of nucleic acids. We have revealed that long noncoding RNAs regulate
the cellular responses against stresses such as pathogenic infection, heat shock, and DNA damage. We
also investigate physiological and pathological roles of membrane-less organelle formed by nucleic acids
and RNA binding proteins. In addition, we have revealed the biological significances of RNA turnoverregulated by RNA binding proteins through omics-based approaches. Based on these achievement, we
also develop technologies for nucleic acid therapeutics.

1. Kurosaki T., Imamachi N.,
röschel C., Nagao R.,
Mitsutomi S., Akimitsu N. and
Maquat LE. (2020) Loss of thefragile X syndrome protein
FMRP results in misregulationof nonsense-mediated mRNA
decay. Nature Cell Biol. 23,
40-48.
2. Yamada T., Imamachi N.,
Imamura K., Taniue K.,
Kawamura T., Suzuki Y.,
Nagahama M., Akimitsu N.
(2020) Systematic Analysis ofTargets of Pumilio-mediatedmRNA Decay Reveals that
PUM1 Repression by DNA
Damage Activates
Translesion Synthesis, Cell
Rep.31, 107542.
3. Imamura K., Takaya A.,
Ishida Y., Fukuoka Y., Taya
T., Nakaki R., Kakeda M.,
Imamachi N., Sato A.,
Yamada T., OnoguchiMizutani R., Akizuki G., Tanu
T.,Tao K., Miyao S., Suzuki
Y., Nagahama M., YamamotoT., Jensen TH. and AkimitsuN., (2018) Diminished nuclear
RNA decay upon Salmonella
infection upregulates
antibacterial noncoding
RNAs, EMBO J. 37, e97723

Discovery of novel nuclear body involved in heat shock response.
HiNoCo-body, a novel nuclear body containing long noncoding RNA, is formed in
response to heat shock through liquid-liquid phase separation. HiNoCo-body controls
heat-induced 4D-genome organization and gene expression.

Network-based study of gene expression.
Gene expression is precisely regulated by many steps, such as transcription, RNA processing, and RNA decay. We
study the regulatory network of gene expression flow based on molecular biology, biochemistry, genomics, andmulti-omics. In addition, we develop novel technologies contributing on development of nucleic acids therapies.

41

Laboratory ofClinical Pharmacokinetics(The University of Tokyo Hospital)
Prof.
T. Takada

Systems-pharmacological studies for drug developmentin the next-generation

Lecturer Y. Yamanashi
http://plaza.umin.ac.
jp/~todaiyak/

Research Topics
1. T herapies for lifestyle-related diseases based on the comprehensive
understanding of molecular mechanisms that control the transport of endogenous
small molecules
2. T herapies for bone metabolism diseases based on the comprehensive
understanding of the dynamic control mechanisms of signal molecules involved inbone resorption and formation

Miyata, H., Toyoda, Y., Takada,T., Hiragi. T., Kubota. Y.,
Shigesawa. R., Koyama. R.,
Ikegaya. Y., Suzuki, H.
Identification of an exporterthat regulates vitamin C supply
from blood to the brain.
iScience. 25(1): 103642 (2022)
Toyoda, Y., Takada, T.,
Miyata, H., Matsuo, H.,
Kassai, H., Nakao, K.,
Nakatochi,M., Kawamura, Y.,
Shimizu, S., Shinomiya, N.,
Ichida, K., Hosoyamada, M.,
Aiba, A., Suzuki, H.
Identification of GLUT12/SLC2A12 as a uratetransporter that regulates the
blood urate level inhyperuricemia model mice.
Proc Natl Acad Sci USA.
117(31):18175-18177 (2020)
Ikebuchi, Y., Aoki, S., Honma,
M., Hayashi, M., Sugamori, Y.,
Khan, M., Kariya, Y., Kato, G.,
Tabata, Y., Penninger, J.M.,
Udagawa, N., Aoki, K., Suzuki,
H. Coupling of bone resorption
and formation by RANKL
reverse signalling. Nature.
561(7722):195-200 (2018)
Takada, T., Yamanashi, Y.,
Konishi, K., Yamamoto, T.,
Toyoda, Y., Masuo, Y.,
Yamamoto, H., Suzuki H.
NPC1L1 is a key regulator ofintestinal vitamin K absorption
and a modulator of warfarintherapy. Sci Transl Med.
7(275):275ra23 (2015)

42

3. Q
 uantitative understanding of the pharmacological and toxicological effects ofmolecular targeted anti-cancer drugs to establish clinical applications and new
drug discovery techniques
4. L arge-scale omics analysis to establish methods of preventing and treating
adverse drug reactions based on the quantitative understanding of underlying
molecular mechanisms
5. C linical pharmacokinetics based on detailed quantification of related molecularfunctions
It has been recognized very well that we need to describe / predict the functions of cells, tissues andorganisms from the function of each constituent molecule in a quantitative manner in order to understandthe life activities. Although we have used such approach in analyzing and predicting the drug dispositionin humans, it is quite important for us to expand the concept to the analysis of pharmacological /toxicological actions of drugs in humans. We are using such "systems-pharmacological" methods tosolve many kinds of problems that remain great challenges in drug discovery, such as how to identify themost effective target molecules among numerous candidates, and how to comprehensively predict theadverse drug reactions in humans.

Laboratory

Endowed Laboratory ofDrug Lifetime Management

Visiting Prof.
Y. Sawada
Project Assoc. Prof.
H. Satoh
Project Assist. Prof.
N. Yanagi
http://www.f.u-tokyo.ac.
jp/~druginfo/
Tanaka, S., Kanagawa, T.,
Momma, K., Hori, S., Satoh, H.,
Nagamatsu, T., Fujii, T., Kimura,T., Sawada, Y. Prediction ofsustained fetal toxicity inducedby ketoprofen based on PK/PD
analysis using human placental
perfusion and rat toxicity data.
Br J Clin Pharmacol. 83(11):2503-2516 (2017)
Park, H., Miki, A., Satoh, H.,
Sawada, Y. Survey on theattitudes and concerns offee-based elderly nursing
homes staff regarding
medication assistance in Japan:
a questionnaire survey. Jpn J
Drug Inform. 19(3): 133-141(2017)
Miyazaki, S., Satoh, H., Ikenishi,
M., Sakurai, M., Ueda, M.,
Kawahara, K., Ueda, R., Ohtori,T., Matsuyama, K., Miki, A.,
Hori, S., Fukui, E., Nakatsuka,
E., Sawada, Y. Pharmacokinetic
model analysis of interaction
between phenytoin andcapecitabine. Int J Clin
Pharmacol Ther. 54(9): 657-665(2016)

Drug lifetime management for development of excellent
drugs, proper use of drugs, and evolution of drugs

Research Topics
1. D evelopment and practice of methodologies for the collection, evaluation,
analysis, and distribution of drug post-marketing information
2. C reation of programs for promoting proper use and evolution of drugs incommunity healthcare
3. D evelopment of new features in the community pharmacy to practice the abovementioned 2
4. S
 pecification, standardization, and digitization of drug information, and theirclinical applications
5. Q uantitative prediction of the effects of biodisturbance factors on
pharmacokinetics and drug effects
Our university’s Faculty of Pharmaceutical Sciences bears the social mission of promoting drug discovery
and the proper use and evolution of drugs while improving the quality of drug therapies. To these ends,
this course in Drug lifetime management pursues various research to ensure that the developed drugs
can amply exhibit their effects and lead a substantial “drug life.”
The research topics of this course are that (1) the proper collection of drug information (DI), (2) evaluation/
analysis of DI based on pharmacokinetics and pharmacodynamics and quantitative prediction of changes
in pharmacokinetics and drug effect due to various risk factors, (3) Qualitative evaluation and analysis of
the individual cases, (4) Creation of archive based on the optimal specification/standardization/digitizationof DI, and (5) their proper provision to the clinical field. Concretely speaking, the content of our researchis to seize drug post-marketing problems (including trouble and needs related with drugs), to make aproposal, to the pharmaceutical field, for evolving drugs and their information in order to solve theproblems, and to feedback them to the clinical field.

Matsuo, N., Hori, S., Suehira,M., Satoh, H., Miki, A., Sawada,
Y. Sisters who developed
piloerection after administrationof milnacipran. Int J Clin
Pharmacol Ther. 54(3): 208-211(2016)
Park, H., Satoh, H., Miki, A.,
Urushihara, H., Sawada, Y.
Medications associated withfalls in older people: systematic
review of publications from a
recent 5-year period. Eur J Clin
Pharmacol. 71(12): 1429-1440(2015)

The central dogma of pharmaceutical development
consists of the cycle of drug discovery → proper use ofdrugs → post-marketing drug development → drug
discovery and so on

Collection of drug post-marketing information withappropriate method (from whom? from where? How?).

43

Endowed Laboratory of

Health Economics and Outcomes
Research
Prof. Y. Urano
Project Assist. Prof.
L. Teng
http://www.f.u-tokyo.ac.
jp/~uthta/

Maximizing and evaluating true "value" of various
medical interventions, not only its impact for health carebudgets but for health outcomes, to maintain andimprove public health care system.
Research Topics
1. H ealth Technology Assessment (HTA)
2. H
 ealth economic analyses for drugs / medical devises
3. S
 urveys on public healthcare system / reimbursement system
4. R
 esearch on QOL (Quality of Life) instruments
There are growing concern about the cost issue of medical care interventions, as the sustainability ofuniversal health coverage system is threatened with the increase of health care budget, in particular withintroduction of expensive medications, such as drugs for cancer, hepatitis or life style diseases. Many
stakeholders in Japan, not only health economists but also physicians, governmental decision makers,
and industry officers have keen interest on health economics and outcomes research (HEOR), including
QOL survey.
Efficiency data, or cost-effectiveness data, would play more role in decision making process, as well as
efficacy and safety data would do.
We define the word "HEOR" with broader definition; any kind of researches which can maximize/quantify
the value of particular medical interventions and/or disease area. Then, our research topics would range
from narrower ones, like cost-effectiveness analyses of particular products to broader ones, like
conceptual research for QOLs and the analytical methods.

44

Laboratory

Social Cooperation Program ofTargeted Protein Degradation

Project Prof.
M. Naito

Inducing targeted protein degradation by chemicalcompounds

Prof. S. Murata

Research Topics
1. D evelopment of new technologies to induce protein degradation
2. D evelopment of SNIPER compounds that degrade disease causative proteinsAs the mechanisms of various diseases are better understood at the molecular level, it will become
possible to develop molecular target drugs that specifically inhibit pathogenic proteins. With the current
drug discovery technologies, however, it is not possible to develop such drugs against all pathogenic
proteins. Especially, most of the intracellular proteins without enzymatic activity have been considered
undruggable.
Akizuki Y, Morita M, Mori Y,
Kaiho-Soma A, Dixit S, Endo
A, Shimogawa M, Hayashi G,
Naito M, Okamoto A, Tanaka
K, Saeki Y, and Ohtake F:
cIAP1-based degradersinduce degradation via
branched ubiquitin
architectures. Nat Chem Biol19, 311-322 (2023)

Targeted protein degradation is a promising approach for suppressing such undruggable targets.
Chimeric compounds such as PROTACs and SNIPERs are attracting attention because they allow us todevelop novel drugs that degrade proteins of your interest.
In our laboratory, we have developed a series of SNIPER compounds that degrade various target
proteins. SNIPERs recruit IAP ubiquitin ligases to target proteins for ubiquitylation and proteasomal
degradation. We are currently developing new technologies to induce protein degradation, which include
cancer-specific or tissue-specific degradation of target proteins. We are also developing new compounds
that degrade disease causative proteins.

Naito M: Targeted protein
degradation and drug
discovery. J Biochem 172,
61-69 (2022)
Kaiho-Soma A, Akizuki Y,
Igarashi K, Endo A, Shoda T,
Kawase Y, Demizu Y, Naito M,
Saeki Y, Tanaka K, andOhtake F: TRIP12 promotes
small-molecule-induced
degradation through K29/
K48-branched ubiquitin
chains. Mol Cell 81, 14111424 e1417 (2021)
Naito M, and Murata S:
Gluing Proteins for Targeted
Degradation. Cancer Cell 39,
19-21 (2021)

SNIPER compounds induce ubiquitylation and proteasomal degradation of target proteins.

Shibata N, Ohoka N, Tsuji G,
Demizu Y, Miyawaza K, Ui-Tei
K, Akiyama T, and Naito M:
Deubiquitylase USP25
prevents degradation of
BCR-ABL protein andensures proliferation of
Ph-positive leukemia cells.
Oncogene 39, 3867-3878(2020)

45

Social Cooperation Program of

Molecular Pharmacology of Malignant
DiseasesProf. S. Hori
Project Assoc. Prof.
Y. Enomoto
Researcher
T. Kitamura

Research on hematopoietic stem cells and hematopoietic
malignancies toward the development of new therapeutic
approaches
Research Topics
1. E
 lucidation of the mechanism of drug resistance
2. D evelopment of drug combination therapies
3. T herapy with immune activation in the treatment of hematopoietic malignancies
4. E
 lucidation of T cell function in clonal hematopoiesis
We aim to elucidate the mechanisms of drug resistance and to develop combination therapies in orderto overcome drug resistance of hematopoietic malignant cells. To determine which genes contribute to
becoming drug resistance, we utilize genome-wide libraries for Crispr-A system and culture cells
transduced with each sgRNA in the presence of drugs. In addition, pathway analysis of the gene groups
identified by this method will reveal the mechanism of drug resistance and the mechanism of action.
We will then devise drug combination therapies by revealing
the mechanisms of drug resistance. We have obtainedinteresting research results on HDAC inhibitors and DNA
methyltransferase inhibitors. In the future, we will also
investigate other drugs and expand the scope of our research.
Immune checkpoint inhibitors have attracted attention for theirefficacy in the treatment of malignant tumors. By using G0marker mice, our group has reported that 1) leukemic stem
cells of chronic myeloid leukemia (CML) after the treatment are
in G0 phase and express PD-L1, 2) IRAK inhibitors suppress
PD-L1 expression and augment the therapeutic effect oftyrosine kinase inhibitors (TKIs), and 3) the combination therapy
with TKIs and anti-PD-L1 antibody has a dramatic synergistic
effect on murine CML models. Immune activation is a crucial

Fig. 1 Principle of the SunTag method, atype of Crispr-A.
Cells expressing 1) complex of dCAS9,which lacks its DNA cleavage activity, andpeptides containing multiple repetitive
sequences (red part), and 2) a fusion of asingle chain antibody that recognizes therepetitive sequences and a tetramer of thetranscriptional activator VP16 (VP64) canartificially overexpress any gene with asingle-guide RNA that recognizes thepromoter region (Marvin et al. Cell 2014).

strategy for the treatment of malignant tumors, and we aim todevelop new effective therapies, including drug combination
Yabushita T, Chinen T,
Nishiyama A, Asada S,
Shimura R, Isobe T,
Yamamoto K, Sato N,
Enomoto Y, Tanaka Y,
Fukuyama T, Satoh H, Kato K,
Saitoh K, Ishikawa T, Soga T,
Nannya Y, Fukagawa T,
Nakanishi M, Kitagawa D,
Kitamura T, Goyama S. :Mitotic perturbation is a key
mechanism of action ofdecitabine in myeloid tumor
treatment. Cell Reports
42(9):113098 (2023)

46

therapies.
On the other hand, it has received attention that approximately
10% of healthy elderly people have clonal hematopoiesis (CH)with one leukemia-related gene mutation. People with CH havea 10-fold higher incidence rate of hematopoietic malignancies
than healthy people without CH. Therefore, CH can beassumed to be a preleukemic state. Interestingly, the incidence
rate of atherosclerotic disease is about twice as high in people
with CH, one in four cancer patients has CH, and cancer
patients with CH have significantly worse prognosis. We
assume that those high incidence rate and worse prognosis
can be caused by abnormal function of T cells with CH.

Fig. 2 Clonal hematopoiesis: CH
The incidence rate of hematopoietic
malignancies is about 10 times higher andthe incidence rate of myocardial infarction
and cerebral infarction is about twice as
high. The latter diseases are the reason
why people with CH have worse
prognosis.

Laboratory

Social Cooperation Program of

Health Policy and Public Health

Project Assoc. Prof.
A. Igarashi
Project Assist. Prof.
A. Shoji

The generation and application of evidence tailored toclinical needs, and the proposal of value-based healthpolicies.
Research Topics
1. B uilding an evidence foundation in the field of infectious diseases that can
respond to both normal and emergency situations
2. P
 roposal for a sustainable Value-Based Healthcare System from the perspectivesof both innovation and social security systems

Igarashi A, Nakano Y,
Yoneyama-Hirozane M.
Public preferences andwillingness to accept ahypothetical vaccine toprevent a pandemic in Japan:
a conjoint analysis. Expert
Rev Vaccines. 2022:1-8.
Sekiguchi M, Igarashi A,
Mizuguchi Y, et al. Costeffectiveness analysis ofendoscopic resection forcolorectal laterally spreading
tumors: Endoscopic
submucosal dissection versus
piecemeal endoscopic
mucosal resection. Dig
Endosc. 2021.
Ashizawa T, Igarashi A,
Sakata Y, et al. Impact of the
Severity of Alzheimer's
Disease on the Quality of Life,
Activities of Daily Living, andCaregiving Costs for
Institutionalized Patients on
Anti-Alzheimer Medications inJapan. J Alzheimers Dis.
2021;81(1):367-74.
Ikeda T, Igarashi A, Odani S,
et al. Health-Related Qualityof Life during COVID-19
Pandemic: Assessing Impactsof Job Loss and Financial
Support Programs in Japan.
Appl Res Qual Life. 2021 Jan
30:1-17.

Following the pandemic and the increasing medical and pharmaceutical expenses, “optimal allocation of
medical resources based on evidence” has become an important issue to maintain the sustainability ofboth the public healthcare system and innovation.
We aim to contribute to the promotion of researchers and the improvement of policy-making / publichealth by simultaneously: i) creating a system for evaluating therapeutic and preventive interventions frommultiple perspectives in various disease areas, ii) building a composite database capable of generating
evidence over time in response to environmental changes , and iii) developing frameworks for the social
implementation of the evidence obtained through SIB/PFS and proposals for healthcare policies.

Scientificspillovers

Qualityadjusted
life-years（QALYs）
gainedNet costs

Productivity

Equityvalue

Real optionvalue

FamilyspilloverReduction in
uncertainty

Value of hope

Severity of
diseaseInsurance
value

Fear ofcontagion

The concept of the Value Flower developed by the ISPOR (International Society for Pharmacoeconomics and Outcomes
Research) Task force

Tan RL, Yang Z, Igarashi A, etal. How Do Respondents
Interpret and View the
EQ-VAS? A Qualitative Studyof Three Asian Populations.
Patient. 2021 Mar;14(2):28393.

47

One-Stop Sharing Facility Center for Future Drug Discoveries
Sharing research facilities to promote research for drug discoveries
https://onestop.f.u-tokyo.ac.jp/
Professor (concurrent)   S. Murata

The One-Stop Drug Discovery Facility Center offers a variety of advanced facilities for mass spectrometry, structural analysis,
and biofunctional analysis. These tools allow for detailed investigation of drug candidates and targets, including structure
elucidation and assessment of drug effects through precise intracellular imaging. The Center employs mass spectrometers,
NMR, confocal microscopes, and cell image analyzers.
This initiative aims to enhance collaboration between industry and academia in drug discovery, promote cross-disciplinary
integration, support start-up ventures, and provide a research environment for emerging scientists and students throughresource sharing.
Moreover, the Center encourages the communal use of its facilities to foster a collaborative spirit. The Center regularly updates
its website with relevant information, presents its capabilities at the Pharmaceutical Sciences Foundation of Japan’s FDD
Seminar, and collaborates with the WINGS-LST International Graduate Program at the University of Tokyo. A descriptive
video about the Center can be found on its website.
Additionally, the Center hosts One-Stop Technology Seminars, which provide hands-on experience with state-of-the-art
equipment tailored to meet evolving technological needs.

48

Drug Discovery Initiative
Support for Drug Discovery

https://www.ddi.f.u-tokyo.ac.jp/en/

Director Prof.

Y. Urano

Project Lecturer

R. Imamura

Duputy Director Project Prof.

H. Kojima

Project Lecturer

K. Kanamitsu

Visiting Prof.

T. Okabe

Project Lecturer

M. Takamiya

Project Assoc. Prof.

T. Iijima

Project Lecturer

K. Kanai

Project Assoc. Prof.

K. Yasuda

Drug Discovery Initiative, DDI, was established to contribute to our health through the elucidation of life phenomena andthe discovery of new drug leads. DDI is a hub of national collaborative research networks for drug discovery based on our
public chemical library. DDI promotes open innovation by providing advice, technical support and chemical samples to theresearchers who need to screen chemical samples. DDI also provides chemical synthesis and pharmacokinetic research support
for lead compound generation.

49

Education Center for Medical Pharmaceutics

Director
Prof. Y. Urano
Vice Director
Project Prof. H. Hosono
Prof. T. Tomita
Prof. T. Takada
Visiting Prof. Y. Sawada
Assoc. Prof. U. Ohto
Project Assoc. Prof.
H. Satoh
Lecturer Y. Kariya

The center has been established in June, 2012.
The purpose of the establishment is to enhance the educational
research structure in those new educational programs, especially
6-year undergraduate program (Department of Pharmacy) and
4-year doctoral program (Department of Pharmacy).

Research Topics
1. D evelopment of educational program for practice for medical pharmaceutics
2. D evelopment of educational program of medical pharmaceutics
3. D evelopment of postgraduate educational program for training leading
pharmacists

We are in charge of the pre-clinical training, the administration of the Pharmaceutical Common
Achievement Tests for clinical pharmacy (CBT and OSCE), and the pharmacy practice experiences in
hospitals and pharmacies. Additionally, we conduct research aimed at developing educational programsfor clinical pharmacy. Pharmacy practice experiences are critical opportunities for students to engage
with patients directly, reflecting on how they can contribute as pharmacists within the multi-professionalteam care and what competencies they need to develop to make such contributions. In collaboration
with the University of Tokyo Hospital and local pharmacies, our education programs are designed tonurture a “pharmacist mindset” by encouraging students to identify and solve problems with maximum
support.
Clinical pharmacy, particularly closely related to the activities of pharmacists, is related to a broad rangeof research areas: one area includes basic and clinical research to understand how drugs move to theirtarget organs or molecules, exhibit their therapeutic effects, and potentially cause side effects, while
another area of focus is social pharmacy, which approaches the sustainable provision of better healthcare
through the appropriate use of medications and information. The medical field is inevitably uncertain andinvolves the responsibility of patient care, making research in all these areas crucial for acquiring theinformation required by healthcare professionals. By advancing clinical pharmacy research, we aim toequip students with the capability to gather and disseminate information, connect people througheffective communication, and solve problems. Our programs also prepare them to become pharmacists
with a “research mindset,” capable of adapting to the evolving landscape of healthcare and unprecedented
societal changes.

50After Graduating from
Graduate School of Pharmaceutical Sciences
Graduates of Faculty of Pharmaceutical Sciences, who haveacquired a comprehensive fundamental understanding andapplied knowledge of the field, receive extremely high respect,
resulting in relative easiness to find a job. Over 90 percent ofgraduates choose to move forward to Graduate School of
Pharmaceutical Sciences, the University of Tokyo. An increasing
number of applications from the University of Tokyo, otheruniversities, and foreign universities take an annual entrance examin August.
We have seen more and more of a social trend that prefers an

B.S. Graduates
Department ofPharmaceutical Sciences
Other advanced degrees in different schools 0%

1%
5%

individual with a researcher background and research experiencehigher than a Master’s level. Our graduates who completed either
undergraduate or graduate courses find positions in a wide arrayof fields, such as pharmaceuticals, chemical, and food relatedcompanies, universities, as well as government agencies.
Half of graduate students opt for the doctoral course. Afteracquiring a PhD., they find vast opportunities not only in theacademic field, such as universities and public research agencies,
but in researching departments of companies, as leaders ofprojects.

M.S. Graduates

PhD. Graduates

Department ofPharmacy
Other advanced degrees in different schools 0%

25%

2022

4%
1%

12%

2022

43%

10%

2022

2%

2022
25%

94%

5%

4%
1%

63%

20%

10%

2021

2021
90%

4%

6%
2%

10%

48%

4%

23%

45%

11%

2020

22%

8%

2021

2%

2021

6%

60%
Other advanced degrees in different schools 0%

63%

25%

1%

45%

23%

2020

29%

61%

8%

2020

2%

2020

6%
88%

67%

25%

1%

Graduate School of Pharmaceutical Sciences,
The University of Tokyo(Master's Program)

Graduate School of Pharmaceutical Sciences,
The University of Tokyo(Doctoral Program)

Graduate School of Pharmaceutical Sciences,
The University of Tokyo (Doctoral Program)

Other advanced degrees in different schools

Other advanced degrees in different schools

Other advanced degrees in different schools

Government agencies and private enterprises

Government agencies and private enterprises

Research labs of private enterprises

OthersOthers

Universities and government agencies
Others29%

61%

JSPS Research Fellow
Research labs of private enterprises
Universities, government agencies,
public research labs, andoverseas postdoctral research fellow
Others51

Life on Campus
Undergraduate
There are roughly 80 students in each grade at the Faculty of
Pharmaceutical Sciences, and this is one of the smallest faculties
at the University of Tokyo. New students form close friendships
in no time after starting their first year. They attend lectures andengage in pharmaceutical training, all the while maintaining close
relationships with faculty members. Lectures encompass a broad
range of academic fields closely related to real life medicine.
Assistant professors and graduate students as teaching assistantsalso take part in the pharmaceutical training classes.
Second-year students begin to attend lectures on specialized topics
for three days at the Hongo campus in the fall after receiving
liberal arts education at the Komaba campus.
In the third year, students sit in on lectures in the morning andengage in pharmaceutical training in the afternoon. Lectures
become more specialized, and during training sessions students
work in groups of two to four.
Fourth-year students work in the laboratory of their choice, andthey begin to focus less on classes and more on their seniorresearch project.
Students must choose either the four-year program of the
Department of Pharmaceutical Sciences or the six-year programof the Department of Pharmacy in their fourth year. Students
who choose the Department of Pharmaceutical Sciences mustcomplete a year-long senior research project in order to complete
their degree. Those who decide on the Department of Pharmacy
begin to work in the laboratory while they receive laboratory

52

training for clinical pharmacy. At the end of the fourth year,
students are expected to go through the Pharmaceutical Common
Achievement Tests for clinical pharmacy. In the fifth year,
students receive training for clinical pharmacy, and work in theirlaboratories. In the sixth year, students dedicate their time toworking on their senior research project until graduation.

Postgraduate
Each laboratory and related laboratories (Institutes) of the
Graduate School of Pharmaceutical Sciences and the Departmentof Pharmacy of the University of Tokyo Hospital conducts
leading research in their specialized areas of focus. Students at thestart of their graduate studies begin their research career byattending seminars and conducting experiments inworld-renowned laboratories which are equipped withstate-of-the-art facilities.

Campus Social Events
All the members form close-knit friendships, and this is not justbecause it is a relatively small department. The department hosts a
slew of social events that include but are not limited to sports
events, and activities with international students and researchers.
These events contribute to the growth of friendships and close
bonds outside of academic life. The close bonds of the students
and researchers in this department foster collaboration, and thisleads to a wider spectrum of academic insights and new
developments in research.

Message from Student and Graduate
Shiseido global innovation center
Shiseido Company, Limited

Boston Consulting Group

Xiaomin Li

Luo, Cong

M.S. Completed in September 2017
Laboratory of Bioanalytical ChemistryWith the dream of doing cosmetic research in Japan, I decided
to take a master’s degree in Japan after graduating from Beijing
University of Chemical Technology. Fortunately, with theacceptance of Pro. Funatsu, I won the opportunity to join the
Laboratory of Bioanalytical Chemistry.
In the first year, as a research student, I started my research
while preparing for the entrance exam of the Graduate School of
Pharmaceutical Sciences. At first, I was a little uneasy because of
the different major and new language environments. However,with the kind help from members of my laboratory, I quickly
adapt to life at the University of Tokyo.
In the second year, I passed the entrance exam successfully andbecame a master student. During my master’s degree, I did two
research projects, but one of the projects did not go well at first.
Even so, my mentors and seniors continued giving me usefulguidance, which encouraged me a lot. Then we started tocollaborate with the Laboratory of Advanced Elements Chemistry
and Ajinomoto. Finally, we completed the research successfully.
Though the research experience, I began to rea lize theimportance of cooperation because it allows us to analyze
problems from multiple perspectives and find solutions more
effectively.
In addition to laboratory life, I had many unforgettable
experiences at the University of Tokyo. ISAR organized a varietyof activities, such as international student trips, dumpling parties,
and various Japanese cultural experience activities, which enabled
me to enhance communication and understand different
cultures. Also, ISAR provided Japanese classes and helped me toapply for a dormitory and scholarship. I appreciate all membersof ISAR, especially, my Japanese teacher Ezure-sensei. She not
only taught me Japanese but also gave me much good advice on
my life and career plan. Thanks to these supports, I was able tocomplete my studies and found my ideal job.
After graduation, I entered a cosmetics company as I wish. My
main job is to develop new skincare products. I have beenworking for two years and a half. However, I still miss lovely
people, beautiful campus, and delicious Akamon Ramen of the
University of Tokyo. I hope you can come here to pursue yourdreams, and I believe this university can help you to make yourdream come true!

M. S. Completed in March 2017
Laboratory of Chemical Pharmacology

I obtained a bachelor’s degree from the Department ofPharmaceutical sciences of the Univ. of Tokyo and a master’s
degree from the Graduate School later. In these few years, I have
not only achieved academic achievements, but also spent a
wonderful university life. I sincerely thank all the mentors andclassmates for their the great support and generosity. At the sametime, as an international student, I must give special thanks to
ISAR, who have been so supportive to all international students
including myself.
I entered the Univ. of Tokyo in 2011. I chose pharmaceuticalscience as my major because of my interest in biology and thewilling to contribute to medical development that can cure andsave people. During in-depth study, I also found my interest inneurology and central nervous disease given that various diseasedin this area have not been clearly understood by human-beings
ever before. Thus I entered the Chemistry Pharmacology
laboratory and researched key topics such as Neurogenesis and
Neuron-Glia interaction. With the help of my supervisors, Prof.
Koyama, Prof. Ikegaya, and my lab mates, I successfully published
my scientific findings in academic societies and international
journals. I feel very fortunate for the high academic competencies
and the environment that professors and students are so supportive
to each other.
In the study and life of the Department of Pharmacy of the
University of Tokyo, ISAR teachers have always given us a lot ofcare and help to the international students. Whether it isconsulting and helping with various issues such as studying
Japanese, applying for scholarships, or various travel and social
activities to enrich our life in Japan. It can be said that ISAR
makes us feel like home here.
After graduation, I entered a pharmaceutical company to engage
in drug research and development. I sincerely feel that the
professional knowledge and general education I learned at the
University of Tokyo have benefited me a lot. Now I am in the fieldof management consulting, I continue to investigate and research
the medical and pharmaceutical industry from a businessperspective. Life is a journey of continuous learning and growth. I
am deeply honoured to be able to study at the University of Tokyo
in the early stages of my life.

53College of Pharmacy, Kyung Hee University

Dong-Soon Im
Ph.D. Completed in September 1996
Laboratory of Physiological Chemistry

In March of 1993, I came to Japan as a research student in
Department of Physiological Chemistry, the University of Tokyo.
From October of 1993 to September of 1996, I had worked as a
PhD student under supervision of Drs Michio Ui and Toshiaki
Katada. It was a huge challenge to study in foreign country. In
the years, I have not only achieved scientific achievements but
also had a wonderful university life. Honestly, I went out tosightsee the Tokyo after lab meeting on every Saturday for the
initial several months. Later, I found other lab members were
working hard after the meeting. Given that my experience in themaster degree wasn’t good enough to do my own research as a
PhD student, the first year was a period of learning techniques.
In the second year, I had a great chance to meet Dr Fumikazu
Okajima at Gunma University. As a mentor, he taught me a lotof things a nd ra ise me a scientist. It wa s fa nta stic a nd
unforgettable of me to do research under his supervision. I’d likealso to express special thanks to the ISAR staff for her full
supports. She made me to feel comfortable in the campus andhelped me to establish my life in Japan, in addition to advices
and helps of many Japanese lab mentors and members. ISAR
organized many activities for international students, mostmemorable of which were the yearly visiting places around Tokyo
like hot spring and sumo wrestling.
Right after finishing my PhD, I went to the University ofVirginia as a postdoctoral fellow in Pharmacology. At the time,
my supervisor wanted me to translate patents applications inJapanese to English. It was my pleasure to translate Japanese to
English, and I realized that there are huge differences between
Japanese ways of thinking and American ways of strategies inscience. In 2002, I moved back to my home country (Korea) as
an assistant professor. Since 2020, I have been the Dean, Collegeof Pharmacy, Kyung Hee University (Seoul). I am confident thatmy experiences in Japan and the ways of thinking during my
PhD study at the University of Tokyo made me to grow up andbe present myself. In the young ages, you have dreams, facechallenges, and make experiences, which make your dreams
come true. I strongly recommend you to join this university andpursue your dreams!

54

Daiichi Sankyo Company, Limited

Zekun Yang
PhD completed in September 2020
Advanced Elements Chemistry Laboratory

Seven years ago, thanks to the opportunity provided by Prof.
Uchiyama, I came to the University of Tokyo after graduatingfrom Fudan University (China). To this day, I still clearly
remember the tension and excitement when I first entered Japan
from the Narita Airport.
In the first year, I learned the basics of scientific research whilestrengthening my Japanese ability as a research student at theAdvanced Elements Chemistry Lab (the Uchiyama Lab.). Duringthat hard period, my supervisors, seniors, and ISAR teachers had
helped me a lot. In particular, the basic literacy of scientificresearch taught by Assistant Prof. Wang and Japanese conversation
skills taught by Hirayama-sensei had become the most solid
foundation and support my future life in Japan.
After entering the master course in the second year, I started theresearch project about organometal chemistry. Thanks to theperfect research conditions of the University of Tokyo and theprofessional supports of my lab mates, the project was carried out
smoothly and several interesting results were obtained, which
greatly increased my enthusiasm for scientific research. Also, with
the improvement of Japanese speaking, communicating with lab
mates had become more frequently. Through the conversation, I
had a deeper understanding of Japanese society. Also, ISAR
teachers had always given me a lot of care, consulting, and helping
with various issues, such as Japanese studying, scholarships, orvarious travel and social activities to enrich my life in Japan.
After obtained the master’s degree, I chose to enter the Ph.D.
course. With the help from my supervisors and seniors. I luckily
became the JSPS Research Fellow DC1, which not only financiallybut also mentally supported me. The Ph.D. life was exhilarating
and fulfilling, Prof. Uchiyama gave me a lot of freedom to explore
topics that interested me, which was a very precious and rewarding
experience. After graduation, I entered a pharmaceutical company
in Japan to engage in medical research. There are bound to be
more challenges in the future, and the seven years of experience at
the University of Tokyo gives me strong confidence and sufficientcourage to face them. Thanks to every person who appeared in mylife and gave their kindly help to me.

International Student Advising RoomThe International Student Advising Room (ISAR), established in
1994, provides a variety of services to support international students
and researchers. https://israr.f.u-tokyo.ac.jp/en/isar/index.html
ISAR offers:• Advisory assistance and a counseling service• Information for prospective international students• Event planning• Inter-university academic exchange program• Information services

Lecturer E. Gosho
International Student Adviser

Academic Exchange Agreements between Universities
USA

SwedenGermany

P.R.China

Republic of Korea

The University of Texas M. D.
Anderson Cancer Center

The Sahlgrenska Academy,
University of Göthenburg

Research Training Group 1873
The University of Bonn

Shenyang Pharmaceutical
University

School of Pharmacy,
Sungkyunkwan University

Thailand
Chulalongkorn
University

The Netherlands
Leiden University

UK

Belgium

University of Cambridge

The Faculty of Science,
KU Leuven

55

FACILITIES
Experimental Station for Medicinal Plant Studies
Hanamigawa-ku, Chiba-shi, Chiba
The Experimental Station for Medicinal Plant Studies islocated about 30 km east of the Hongo Campus. Its 6,123
m2 plant specimen garden includes the medicinal plants thatare considered important for the students’ education. Thisgarden serves a variety of purposes, including maintenance ofplant lineages; research on plant breeding and cultivation;collection and cultivation of medicinal plants native to Japan
as well as introduced from overseas; research on medicinal
plant ingredients from the standpoints of chemistry,
pharmacology, biosynthesis, plant physiology, andpharmacognosy; and research on the medicinal plantc u l t i va t i o n a n d m a i n t e n a n c e . Th e g ro u n d s o f t h eExperimental Station also encompass a greenhouse,
administration building, and laboratory building.
At present, about 250 varieties of plants are undercultivation. Each year, 3rd-year students receive practicaltraining in the plant specimen garden during the summer
session. In 1982, the laboratory for medicinal plant studies
was set up within the building in Hongo Campus and havecontinued research until now.
The University Museum, The University of Tokyo (Hongo
Campus) houses a Pharmaceutical Sciences Division on its
first floor, where a large number of specimens – mainly crude
drugs and medicinal plants – are stored and managed.
In October 2004, the first rooftop herb garden, with an areaof approximately 100 m2, was created on the rooftop of theauditorium of Pharmaceutical Sciences Research Building forenabling the students to come into close contact withmedicinal plants. Several dozen varieties of medicinal plants
are cultivated in light soil with a depth of about 60 cm,
equipped with an automatic irrigation system.

Vanilla planifolia (Andr.) G.Jackson

Greenhouse

Magnolia obovata Thunb.

Roof Garden

Pharmaceutical Sciences LibraryBooks

Academic
Journals(titles)

JapanesebooksInternational
books

Total

14,79837,111

51,909Japanese
JournalsInternational
Journals

Total

414

427

841
(As of March, 2023)

56

Main Entrance

Reading Room

Access Map

Dr. Leopold Müller

In 1869, Meiji government decided to adopt German medicine and asked the minister of the North
German Federation to send 2 instructors. In 1871, Müller (chief Army physician/staff surgeon) andHoffman (Navy physician/staff internist) arrived in Japan and assumed their duties at the University
East Building (Tôkô) in Shitaya Izumibashi (precursor of the Faculty of Medicine, University ofTokyo).
Müller and Hoffman, who were under the direct supervision of the Meiji Minister of Education,
had absolute authority over medical education in Japan. A new curriculum was established with 3
preparatory years (changed to 2 the following year) and a 5-year main program.
Müller and Hoffman regarded “pharmaceutical sciences” as an independent branch of the naturalsciences that was closely related to medicine, and they proposed the establishment of a pharmaceuticalinstitute. This took shape in 1873 as the Department of Pharmaceutical Manufacturing, establishedin The First University District Medical School. Müller returned to Germany in 1875. In Octoberof 1895, upon the third anniversary of his death, a bust of Müller was erected to honor him as abenefactor of Japanese medicine and pharmaceutical sciences.

Dr. Leopold Müller (1824 - 1893)

Dr. Junichiro Shimoyama

Dr. Shimoyama was born in Owari Inuyama in 1853. In 1873, after transferring to the Departmentof Pharmaceutical Manufacturing, The First University District Medical School (the precursor of theFaculty of Pharmaceutical Sciences, University of Tokyo), he graduated in 1878. He gave the “address
in reply” at the first degree-conferring ceremony held by the Faculty of Medicine.
In 1886, Dr. Shimoyama received the Doktor der Philosophie degree from Strasburg University inGermany and in 1899, he became the first person in Japan to be awarded a Doctor of Pharmaceutical
Sciences degree.
Dr. Shimoyama became a professor of the Department of Pharmacy in the Faculty of Medicine in
1887, and a professor of a laboratory of Pharmacognosy, the Department of Pharmacy in 1893. While
devoting great efforts to education and research, he also helped to cultivate successors through theestablishment of the Pharmaceutical Society of Tokyo (the present Pharmaceutical Society of Japan)
and the creation of a privately funded medicinal herb garden (Zekô Yakuen), etc.
Dr. Shimoyama died suddenly in February of 1912 while still in service as an educator. In
remembrance of him, a bronze statue was erected beside the Pharmaceutical Sciences Building in 1913.

Dr. Junichiro Shimoyama (1853 - 1912)

57

Hongo Campus

Pharmaceutical Sciences
Research Building

Pharmaceutical
Sciences Library

Pharmaceutical
Sciences
Building

Pharmaceutical
Sciences
South Building

Main
Entrance

Pharmaceutical Sciences BuildingWest Building

Graduate School of
Pharmaceutical Sciences
Faculty of Pharmaceutical Sciences

The University of Tokyo Hospital

Faculty of Science
Gotenshita Ground

YasudaAuditorium

Sanjo Conference
Hall
Sanshiro Pond

FacultyofEngineering

Facultyof
Law

FacultyofLetters
GeneralLibrary

Main Gate

MedicalLibrary

Administration
BureauTatsuoka
Gate

FacultyofMedicine

FacultyofFaculty EconomicsofEducation

KasugaGate

Kaitokukan

Red Gate(Akamon)Pharmatical Sciences Research Building

58

Left :
Liquid droplets of nuclear proteasomes ( green) that appear specifically in senescent cells and DNA (blue).
Right :
volcano plot of relative quantitative proteomics analysis
Graduate School of Pharmaceutical Sciences,
Faculty of Pharmaceutical Sciences, The University of Tokyo

7-3 -1 Hongo, Bunkyo -ku, Tokyo 113 - 0033, Japan http://www.f.u-tokyo.ac.jp/en/