the university of tokyo...
TRANSCRIPT
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