The University of Tokyo (UTokyo)

and the Institute of Medical Science (IMSUT)

The University of Tokyo (UTokyo):Designated Univ., Japan

- Established in 1877

- No. of Personnel: Academic Staff 3,931

Other staffs 3,901

- No. of Students: Undergraduates 14,050

Graduates 13,887 incl. 2,635 from overseas

- Organization

10 Faculties

15 Graduate Schools

11 Research Institutes

The Institute of Medical Science (IMS)

Biomedical

Sci.

Bioinformatics

Translational

Research

President

Dr. Makoto

Gonokami

- 36 Full Professors

- 55 Principal Investigators

- 249 Academic Staffs

- 177 Medical Staff Members

- 258 Graduate Students

- 75 Published Papers with IF>10

in 2016

The University of Tokyo (UTokyo)

and the Institute of Medical Science (IMSUT)

The University of Tokyo (UTokyo):Designated Univ., Japan

- Established in 1877

- No. of Personnel: Academic Staff 3,931

Other staffs 3,901

- No. of Students: Undergraduates 14,050

Graduates 13,887 incl. 2,635 from overseas

- Organization

10 Faculties

15 Graduate Schools

11 Research Institutes

The Institute of Medical Science (IMS)

Biomedical

Sci.

Bioinformatics

Translational

Research

President

Dr. Makoto

Gonokami

- 3 Basic Departments

Immunology, Oncology etc.

- 8 Research Centers

Human Genome Center

Center for Regenerative Med.

- IMSUT-Affiliated Hospital

for translational research

Collaboration between Universities in Norway & IMSUT

Generation of iPS cells derived from specific patients for disease modeling

(2016-)

IMSUT

A Prof. Beate Heissig

University of Bergen

Prof. Helge Raeder

Prof. Kamal B. E. Mustafa

Delegation of University of Bergen

to IMSUT (20180129)

Molecular aberrations involved

In cancer metastasis (2011-2016)

Dean.

Prof. Per Bakke

Dean.

Prof. Yoshi MurakamiProf. Johan Lillehaug

Univ. Bergen

Prof. Yoshi Murakami,

IMSUT

Personalized Medicine & Precision Medicine in Japan

Precision Medicine Initiative

$215 Million Dollars, Jan 30, 2015,

Disease Resources required Target/Methods Projects in Japan

・ Monogenic Disease-oriented Causal gene IRUD (Initiative on rare

disorders cohort WES/WGS & undiagnosed diseases)

・ Polygenic Disease-oriented Associated gene Japan genomic medicine

disorders cohort GWAS, WGS /WES program/Biobank Japan

(65% of adult)

・ Cancer Clinical biobank Therapeutic target Core hospitals for cancer

(50% in life time) Panel, WES genomic medicine/UTokyo

Genome

structure

Genome

biology

Disease

biologyMedical

careHealth

care

1990-2003

Human Genome Pr.2004-2010

Hap Map Project

2011-2020

2021-

E D. Green et al. Nature, 2011

Shift of paradigm in medical science

Roles of population-based cohort & patient-oriented cohort for personalized prevention and personalized medicine

Personalized Prevention: Improve health care on the basis of genes associated with disease onset

Personalized Medicine: Improve medical care on the basis of genes associated with drug responses and progression

Delay onset

Stop

Improvement

Disease

Onset

Progression

Death

Low risk

individuals

Early

Diagnosis,

lifestyle

modification

Pro

gre

ss

ion

Age

Complication

Genes

associated

with

disease

onset

Genes

associated

with drug

response Improvement

Appropriate Treatment

Avoid drug ADR

Healt

hy s

tate

Optimized Health

Care

Optimized Medical

Care

A large number of samples are required to obtain significant results.

BioBank Japan: Infrastructure for Genomic Research (2003-)

- Stocks ~267,000 patients

- Targets 51 common diseases, including 14 cancers

- Follow-up of participants for average 9.7< years

- Associated with the genome research facilities at RIKEN & IMSUT

- Provides samples to researchers/companies

Purposes of Biobanking

- Identification of causal genes of rare disorders

- Identification of susceptibility genes associated with polygenic disorder

- Identification of genes associated with drug response

- Elucidation of genome/environment interaction of diseases

- Analysis of somatic alterations in cancer genome

- Scale merit

- Standardized

quality

50< Hospitals

330< novel disease susceptibility loci

were identified by GWAS

8

Samples collected in BioBank Japan(267,000 patients, 430,000 cases)

Disease N Disease N Disease N

Hyperlipidemia 65,960 Hay fever 6,282 Hepatitis B 1,508

Diabetes 55,969 Glaucoma 6,135Hematological neoplasia

1,478

Cataract 26,067 Prostate cancer 5,694 Esophageal cancer 1,453

Brain infarction 20,917 Unstable angina 5,286 Uterine cervical cancer 1,258

Arrhythmia 23,693 Rheumatoid arthritis 4,449 Nephrotic synd. 1,180

Stable angina 17,655 Lung cancer 4,396 Interstitial lung disease 1,158

Myocardial infarction 13,988 Periodontitis 3,958 Uterine corpus cancer 1,087

Heart failure 10,063 ASO 3,824 Pulmonary tbc 1,011

Bronchial asthma 9,561 COPD 3,504 Ovarian cancer 928

Osteoporosis 8,376 Liver cirrhosis 3,348 Keloid 896

Colorectal cancer 7,638 Atopic dermatitis 3,002 ALS 785

Gastric cancer 7,166 Brain aneurysm 2,999 Drug eruption 740

Urolithiasis 7,028 Epilepsy 2,727 Pancreatic cancer 569

Breast cancer 6,629 Basedow disease 2,494 Gallbladder cancer 504

Hepatitis C 6,392 Liver cancer 2,509 Febrile seizure 341

Uterine fibroid 6,217 Endometriosis 1,907 (as of Oct. 2013)(as of Jan. 2018)

IMSUT

Biobank Japan ・ Patient-oriented biobank

・ Store and distribute DNA, serum, plasma and

tissue

Research infrastructure of the Biobank Japan project

DNA bank Tissue bankSerum/plasma bank

LN2 tank

(47→58)

Capacity:

2.7M→3.34M

Automated

LN2 tank (12)

Capacity: 0.5M

Automated

system

Capacity:

1M→2M

Inst Med Sci, UTokyo (IMSUT)

NextSeq500 (1)HiSeq2500 (2) MiSeq (2)

RIKENCenter for Integrative Medical Sciences

HiSeq2500 (10) MiSeq (5)Omni Micorarray

・ GWAS

・ Sequencing

Tight collaboration

- Genotyping at 900,000 SNPs 180,000 cases

- Whole genome seq. 3,000 cases

- Target seq. for breast ca. by Riken 30,000 cases

Distributed: DNA x 16,000 cases

Serum x 10,000 cases

Data sharing

(2018.12.-)

in NBDC, Japan

Published papers from the BioBank Japan Projectin collaboration with Riken CIMS

BioBank Japan Project

- has identified 330< SNPs associated with disease onset or drug

response

- has published 310< papers to representative academic journals,

including 9 from Nature and 43 from Nature Genetics (As of Mar 2018)

(by RIKEN CIMS and IMSUT)

1 3 9 1121

35

62

99

152

201

240

265

295

336

385

0

50

100

150

200

250

300

350

400

450

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

0

20

40

60

80

100

120

140

160

180

200

なし

タバコ

アルコール

アルコール＋タバコ

0

20

40

60

80

100

120

140

160

180

200

なし

タバコ

アルコール

アルコール＋タバコ

None

Smoking

Alcohol

Alcohol+Smoking

None SNP1 SNP2 SNP1+2

1

189

3.44 6.79

SNP1: ADH1B

SNP2: ALDH2

ADH1B1 x ALDH2 x Smoking x Alcohol drinking

increases Esophageal Cancer Risk up to 190 folds

Risk of esophageal cancer by additive effects

of 2 genetic and 2 environmental factors

(Cui R. Matsuda K et al.,

Gastroenterology 2009)

Ethanol

Acetaldehyde

Acetate

ADH1B

ALDH2

toxic

Global Network of

Genome Science

Bioinformatics

Sequencing

ICGC-TCGA

Liver Cancer in Japan

Director

Prof. Satoru Miyano

Prof. Tatsuhiro

Shibata

Banking

Prof. Yoshinori

MurakamiProf. Koichi

Matsuda (GSFS)

１PB １PB １PB

１PB １PB １PB

Chicago Sanger DKFZ

Barcelona IMSUT Seoul

Biobank Japan

Serum & DNA

x 270,000 Pts

Super

-computer

Next Generation of Human Genome Science in Human Genome Center, IMSUT

Clinical Sequencing & AI-assisted Diagnosis and Treatment

of Hematological Malignancies at IMSUT Hospital

Human Genome

Center

IMSUT

Hospital

Prof. Arinobu TojoDirector of Hospital

AI

IBM Watson

Prof.

Satoru Miyano

Prof.

Seiya

Imoto

Prof.

Yoichi

Furukawa

AI

Genomon

Self Approval Estimate disease

risk

Optimized

prevention

Self Approval Personal data input Estimate treatment risk Optimized treatment

Health Record

Genetic information

Risk of developing stomach cancer

15％

Drug A→ Side effects

Drug B→ Effective

Prescribe Drug B

**mg/day

You have a higher risk for stomach

cancer. Be careful not to take ****.

Personalized Prevention

SNP 1SNP 5SNP 8

…..

SNP 2SNP 9SNP1

1..

Genetic Info. DB

Clinical Info. DB

Large-scale population /

patient-based cohorts

Personalized Medicine

SNP・Clinical information

SNP・Health record

Current & Future of Personalized Medicine and Prevention

Genetic information

Clinical Information

Personal data

input

Estimate individual genetic risk

Prevention/Intervention method for genetic risk

Acknowledgement

University of Tokyo

Institute of Medical ScienceYusuke Nakamura

Koichi Matsuda

Kaori Muto

Takayuki Morisaki

Yoichi Furukawa

Tatsuhiro Shibata

Koichiro Yuji

Makoto Hirata

Yasushi Yamashiata

Graduate School of Medicine

Masashi Fukayama

Tsuyoshi Sasaki

RIKEN

Center for Integrative Medical ScienceMichiaki Kubo

Taisei Mushiroda

Yukihide Momozawa

Yoichiro Kamatani

Japan Pathological Society

Yoshinao Oda

Collaborative Hospital

Iizuka Hospital

Iwate Medical Univ

Osaka Ctr for Adult Dis.

Cancer Inst Ariake Hospital

Double Corss Hospital

Osaka Medical Ctr

Shiga Medical University

Juntendo University

Tokyo Metropolitan Inst of Gerontology

Tokushukai Hospital

Nihon Medical University

Nippon University

Clinical Study Group JCOG

JCCG

NHO

Tokyo Medical & Dental Univ Johji Inazawa

University of Tokyo Takashi Kadowaki

Kyoto Prefecture Med Univ Mayumi Yoshida

Keio University Toshiaki Kabe

Natl Cancer Res Inst Teruhiko Yoshida

Natl Ctr Neuro Psy Yuichi Goto

Natl Ctr Child Health Dev Yoichi Matsubara