The successful model of NHRI virology contract
laboratory in EV71 outbreak leads to the network of
CDC virology laboratory in Taiwan, playing the key
role in surveillance of EV, SARS-CoV, and new H1N1
since 1999
EV71 outbreak in Taiwan, 1998
Antigenic
EV71 ( 1998-2008 )
EVmap
71 of
outbreak
3664 (B4)
7309 (C4)
Genotype B4/B1
7373(C4)
S0318-TW01 (B4)
1988 (C2)
2923(B4)
236-TW86 (B1)
7008-TW99 (B4)
N0692-TW08 (B5)
S0296-TW00 (B4)
N1796-TW99 (B4)
YFW
Genotype B5
12103 (B5)
1970 (C2)
N2838-TW03 (B5)
Genotype C4
N2121-TW04 (C4)
12121 (B5)
N1745-TW08 (B5)
M0448-TW08 (B5)
M0448-TW08 (B5)
BrCr (A)
S0584-TW04 (C4)
3877(B4)
7265(C4)
7773(C5)
4643-TW98 (C2)
2130(C4)
N1757-TW04 (C4)
7337(C4)
Genotype C2
3872(B4)
N2413-TW04 (C4)
6356-TW98 (C2)
N3340-TW02 (C4)
N1859-TW05 (C5)
By Wang JR &
Derek Smith
2003年2月舉辦國際病毒研討會，
適逢SARS疫情爆發
SARS發生，奉召任疾病管制局局長
SARS in 2003: the unpredictable life career
WHO SARS Conf. in Malaysia
2004年卸任前與疾病管制局一級主管
留影
Pandemic Influenza H5N1:
Control policy, education, and drug/vaccine development
2005.10 國家衛生研究院向媒體
說明禽流感藥物研發過程: Tamiflu
manufacturing in NHRI
2005.11
2006.04
(第一版)
(第二版)
2008.03
2009.05
(第三版)
(第四版)
New book on H1N1,
May, 2009
Establishing a NHRI Collaborative
virology laboratory in Children Hospital
No. 1 in HCMC,Vietnam (2006- )
NHRI Research Building on NCKU Campus for
Researches on Infectious Diseases and Cancers, 2006-
2003.09 .15
2006.11 .07
2005.03 .07
G.D. Hsiung Virology Laboratory and Monto Ho Auditorium
in the New Uni-President Health Research Building
Oct. 19, CHCH
HBV Hepatocarcinogenesis and
Chemoprevention for High Risk Chronic HBV
Hepatitis Patients
Ih-Jen Su
National Institue of Infectious Diseases and
Vaccinology, National Health Research Institutes;
Department of Pathology,
National Cheng Kung University Hospital
Ground Glass Hepatocytes ( GGHs ) Contain Pre-S Mutants
and Represent Pre-neoplastic Lesions in Chronic HBV Infection
Type II GGHs
Type I GGHs
Pre-S1 delection mutant
deletion region:
Pre-S2 delection mutant
( Fan et al., 2000; Fan et al., 2001; Wang et al., 2003;
Hung, 2005; Wang, 2005;Hsieh, 2006; Su IJ, 2008;
Yang, 2009)
HBV Pre-S2 Mutant Can Transform Hepatocytes And Induce
Tumor Formation in transgenic mice
(Cancer Sci 97: 1-6, 2006)
(HEPATOLOGY 41:761-770, 2005)
Yen et al ( 2007 ): male, 65%; female, 18% transgenic mice
of pre-S2 mutant develop HCC
VEGF-A/Akt/mTOR Signals Involve in
Oncogenic Pathways Induced by
ER-localized Pre-S Mutants in GGHs
Development of HCC in Transgenic Mice
ΔS2, 22M
HBx, 16M
HBx+ΔS2, 13M
Development of Functional Natural Products
Rich in PPAR Agonistic Activities for:
( 1 ) Cancer Chemoprevention; and
( 2 ) Metabolic syndrome and anti-ageing
Ih-Jen Su, MD, PhD
Professor and Director
National Institute of Infectious Diseases and Vaccinology,
National Health Research Institutes;
National Cheng Kung University Medical School,
Taiwan
引藻是小球藻中的獨特品種
CE3-3的高壓液態色層析分析:
10 種飽和及不飽和脂肪酸 ( Crypto-Chlorella )
**資料來自工研院
PPAR and 3D
Metamin 健康3D
3D and Metamin健康3D
• Do exercise (每天步行一萬步)
• Do healthy diet (天天五蔬果)
• Do control 3H (控制高血壓、糖尿病、高血脂)
運動可以增進肌肉中PPARs表現
蔬果中含植物性Omega-3,-6等高r-linolenic acid (GLA)的
PPAR活性劑。深海魚含EPA、DHA,也是PPAR活性劑
**有了Metamin健康3D 您再也不必每天擔憂
要 吃那麼多蔬菜及買不起深海魚,也不必憂
愁工作忙無法運動。
專業期刊投稿
主題：
紅麴、苦瓜、綠藻、大豆蛋白、與甘草抽出物複方對於改善代謝症候群患者之血
脂肪與代謝異常的功效
Chemoprevention target on mTOR signals and
lipid metabolism pathway by PPAR agonists
Proposed model of HBV-HCC progression:
PPAR-a/g and AKT/mTOR are the candidate targets for
chemoprevention in high risk HBV carriers
Chemoprevention
23
Tumor formation was reduced in x+D2 transgenic
mice receiving chemoprevention agents
24
Virus Cancers: from Pathopgenesis to prevention and therapy
Regulation of inflammation and cell proliferation via NFkB inhibition by
PPAR agonists and resveratrol
EBV- T cells
HBV
Pre-S mutants
LMP-1/TRAF
ER stress
TNF-a/ IFN-g
TNFR2/NFkB
Apoptosis blocked
Inhibition of caspases
PPAR
agonist &
resveratrol
Additional genetic
changes 9P& 6q25
Tumorigenesis
NFkB/COX-2
Cytokine
/VEGF
PPAR
agonist &
Resveratrol
+ Chemotherapy
ROIs
DNA damage
Genomic
Proliferation: instability
Akt/mTOR &
Raf-/MEK
Tumorigenesis
研究、績效及展望
國家衛生研究院
感染症與疫苗研究所
(National Institute of Infectious Diseases and
Vaccinology, NIIDV)
蘇 益 仁
所 長
26
Distribution of 4 main strains of M. tuberculosis in Taiwan:
Relevant to population migration and ethnic populations--Beijing
modern strain as the dominant circulating strain in Taiwan.
How can we deal with ?
Risk factors of active tuberculosis: elderly
patients with diabetes mellitus
350
Multivariate
Rate ( per 100K)
300
250
200
150
Male gender
Age (per 1 yr)
Diabetes
COPD
Hypertension
Chronic kidney disease
HR
P value
2.759
1.042
1.246
1.464
0.785
1.212
<0.001
<0.001
0.001
<0.001
<0.001
0.005
95% CI
2.525
1.036
1.099
1.223
0.717
1.000
3.014
1.047
1.412
1.752
0.859
1.468
2005
2006
2007
2008
2009
2010
100
50
0
0-4
5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 ≧65
Age group (years)
Data from TCDC
Data from National Health Insurance Database
BCG and TB Vaccine Project



2011
Contract Manufacturing from Taiwan CDC
Ready for BCG production by 2015
Develop rBCG ( booster dose ) and TB Vaccine ( latency )
2012
2013
-Negotiation -Establishing -Technology
transfer
with Taiwan BCG
from CDC
CDC for
specific
contract
facility
-Scale-up &
manufactur
pilot scale
-Contract
ing
manuf.
signed by
CDC
-Prepare for
TFDA
-Technology
inspection
transfer
from CDC
2014
≧ 2015
-Establishing
Supply BCG for
consistent lots domestic market
manufacturing
Expansion
-BSL-2,3 animal
for
facility
certification
-TFDA
inspection
Global market
( WHO guideline )
Pipelines of NHRI Vaccine Development
Target
BCG production
Category 1:
Production contracts BCG efficacy
from Taiwan CDC
evaluation
Status
 Taking over Taiwan CDC orphan
2012 Funding
DOH/CDC
vaccine production
New development to Improve current
vaccine
rBCG Vaccine
Antivenin production
Antivenin development
Category 2:
Emergency
manufacture
Flu Vaccine
Flu - Clade 2 H5N1
Enterovirus : EV71 (B4)
EV –HFMD vaccine
Category 3:
Developing vaccine
with commercial
value
Meningoccoccal Group B
Vaccine
Category 4:
Novel vaccine and
technology
development
Dengue Vaccine
HPV Therapeutic Vaccine
RSV Vaccine
PELC adjuvant
Subunit
bacterial vaccine
Enhance national Bio-security and
DOH Regular
capability to produce vaccine under
Funding/ Industry
emergency and /or pandemic disease
New development to Improve current
vaccine
Complete product development up to MOEA/ Industry/
phase 2 clinical trial and then
DOH
technology and product transfer
Meningococcal group B using
lipoprotein technology is going to enter
into Phase I in 2012
Vaccine platform technology
development and novel vaccine R&D
to assist, reduce the cost and timelines
and enhance the product pipelines in
Basic R&D by
NSC/NHRI/PP
project
30
PPARg agonist
Resveratrol/Curcumin
PPAR agonist can enhance
b-amyloid clearance
through activating
PPARg:RXR
ApoE
b-Amyloid
clearance
References: 1. Cramer PE., et. al. Science 2012, 335:
1503-1506.
2. Demers A., et. al. PPAR research 2008,
article ID 364784, 9 pages.
Upregulation of ApoE and downregulation of mTOR by Curcumin+ PPAR agonists
Huh7
DMSO
Rapamycin
3D
Resveratrol
3DR
Curcumin
HepG2
-
+
-
+
+
+
+
DMSO
+
nM
200
300
μg/mL
20
μg/mL
400
15
400
μg/mL
15
μg/mL
Rapamycin
μg/mL3D
μM
Resveratrol
μg/mL
3DR
μg/mL
Curcumin
p-mTOR
p-mTOR
p-Akt
p-Akt
SIRT1
PGC-1α
SIRT1
PGC-1α
PPARα
PPARα
PPARγ
PPARγ
Apo E
Apo E
actin
actin
-
+
-
+
+
+
+
+
400
300
20
400
400
15
15
** Resveratrol (pure compound, merck)
Curcumin (pure compound, sigma)
The
Bali
Girl
人的一生能從事自己喜愛的
醫學研究，貢獻國家社會，
並進行社會改革，
是一個福氣。
Acknowledgments
My parents, teachers, relatives, and friends
National Health
Research Institues
NCKU Medical School
Hui-Ching Wang
Han-Chieh Wu
Juei-Chu Yang
Yuan-Ching Lo
Yi-Fen Fan
Jong-Ding Lay
Huai-Chia Chuang
Wen-Chuan Hsieh
Yi-Hsuan Hsieh
Wen-Ya Huang
Ming-Der Lai