Transcript CMI - Center for Medical Innovation

Focus Biobank :
hepatotropic
Disorders
‘Being integrated in the international biomedical research
and biobanking world’
Prof. Philip Meuleman - UGent
CMI Center for Medical Innovation
Several disease domains with unmet medical need
selected by academia/industry
Cardiovascular diseases
Metabolic disorder s
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5 selected
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Viral infectious diseases
Immune mediated inflammation
Oncology
Neurodegenerative diseases
COPD/Asthma
Reproductive medicine
focus
biobanks •
•
Diabetes
Rheumatic arthritis
Inflammatory bowel
disease
Sudden cardiac death
Hepatotropic disorders
xx biobanks
proposed for
later
integration
Other
Rare diseases
Ageing
CMI Center for Medical Innovation
[email protected] - © 2014
Focus biobank hepatotropic disorders
•
•
5 selected •
focus biobanks
•
•
Diabetes
Rheumatic arthritis
Inflammatory bowel
disease
Sudden cardiac death
Hepatotropic disorders
Selection criteria:
Need
Demonstrated scientific excellence
Industrial interest
Valorization potential
High quality samples
Links with data
Available patient populations
Research collaboration
CMI Center for Medical Innovation
Biobank initiatives: added value
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High quality repositories
Annotated samples
Collaborative model
Harmonized QA/QC
Economy of scale
Harmonized guidelines/rules
Drivers for translational research
= Biological back end of data driven collaborative translational
biomedical research
CMI Center for Medical Innovation
[email protected] - © 2014
Translational research @ UZGent:
Bimetra : mission
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Bimetra is the Clinical Research Center from Ghent
University Hospital in collaboration with Ghent
University.
Bimetra facilitates and integrates different aspects of
translational biomedical research acting as a central
point of contact (CPOC) to catalyze translational
research from bench to bedside and from bedside to
community and hence leveraging economical and
societal valorization.
CMI Center for Medical Innovation
[email protected] - © 2014
Bimetra = CPOC
CMI Center for Medical Innovation
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[email protected] - © 2014
Bimetra = integrative model
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Valorisation
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Validation
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Research
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Research funding
Valorisation (economical and societal)
Biobank and translationeel data mgmt
Reinforcing clinical trials
Inventorizing and reinforcing translational
competences (intra / extra muros)
Reporting performances
CMI Center for Medical Innovation
[email protected] - © 2014
Bimetra Biobank: infrastructure
Algemeen UZG plan, situering biobank
Bimetra biobank
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CMI Center for Medical Innovation
[email protected] - © 2014
Biobank Bimetra: infrastructure
25.000 l storage capacity:
-80°C + LN2
Lab facility
Invoegen algemeen grondplan met zonering uit iDOCs
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CMI Center for Medical Innovation
[email protected] - © 2014
Biobank Bimetra: infrastructure
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CMI Center for Medical Innovation
[email protected] - © 2014
Biobank Bimetra: cryoruimte (ULTs)
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CMI Center for Medical Innovation
[email protected] - © 2014
Hepatitis viruses in Belgium - HCV
HCV
Incidentie
Seroprevalentie
1.23%
In 1993-94
0.87-1 %
Recentere studie (2007) op
speekselstalen 0.12%
of
10 000 – 75 000 chronische
HBV patiënten in België
Figuur en Tabel uit KCE rapport 173A
CMI Center for Medical Innovation
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Focus biobank hepatotropic disorders
substrate for translational research: 2013
UGENT/UZGENT
- G. Leroux-Roels
- P. Meuleman
- I. Desombere
- H. Van Vlierberghe
KULeuven
- M. Van Ranst
10/12/2014
CMI Center for Medical Innovation
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Focus biobank hepatotropic disorders
substrate for translational research: 2014
UA/UZA
UGENT/UZGENT
- G. Leroux-Roels
- P. Meuleman
- I. Desombere
- H. Van Vlierberghe
- L. Padalko
- P. Michielsen
- T. Vanwolleghem ITG
- E. Vlieghe
- G. Ieven/H. Goosens
- P. Van Damme
KULeuven
- M. Van Ranst
- F. Nevens
- T. Roskams
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CMI Center for Medical Innovation
UHasselt-Genk (ZOL)
- G. Robaeys
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Focus biobank hepatotropic disorders
With a focus upon the needs of all stakeholders…
Patient
Society
-prevention
-safe and
affordable
healthcare
-personalized
therapy
Clinicians
-diagnostic
markers
-epidem data
-post
transplant
parameter
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CMI Center for Medical Innovation
Researchers
-access to
phenotypes
-underlying
mechanisms
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Focus biobank hepatotropic disorders
Prioritary themes = valorization potential
• Cell-cell transmission HCV and clinical implications:
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Intra host dynamics HCV
Link HCV, HCC, liver cirrhosis, and end-stage liver disease
Clinical implications reinfection in transplantation setting
Development of clinical tools for the prediction of response to therapy and therapy
decision guidelines
• In vivo evaluation of potential novel antiviral strategies
• B-cell mediated HCV transmission and clinical implications
• HCV and B lymphocytes
• Infecte dB lymphocytes and hepatocytes
• Epidemiological studies distribution of the different HCV genotypes.
• Optimization and clinical validation of novel serological assays, Q-PCR
assays and genotyping assays in support of good diagnostical tools
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CMI Center for Medical Innovation
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Focus biobank hepatotropic disorders
Research objectives= valorization potential
Project 1:
Project 2:
Identification
‘immune
correlates’ for
clearance/prot
ection of HCVinfection
HEV research:
characterizati
on and
invivo/in vitro
models
Project 3:
Project 4:
Hepatocellular
carcinoma and
cirrhosis:
prognostic
markers
HCV DAA
therapy:
identification,
mode of action,
success rate +
alternatives
Project 5:
epidemiology:
distribution of
HCV
genotypes
10/12/2014
Project 6:
China in
Antwerp,
CMI Center for Medical Innovation
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Focus biobank hepatotropic disorders
Enrichment projects = valorization potential
Project 1:
Project 2:
Identification
‘immune
correlates’ for
clearance/prot
ection of HCVinfection
HEV research:
characterizati
on and
invivo/in vitro
models
Project 3:
Prioritized
research topics
Project 5:
epidemiology:
distribution of
HCV
genotypes
10/12/2014
Project 4:
Hepatocellular
carcinoma and
cirrhosis:
prognostic
markers
HCV DAA
therapy:
identification,
mode of action,
success rate +
alternatives
Project 6:
China in
Antwerp,
CMI Center for Medical Innovation
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Biobank Bimetra: translational data mgmt
MDS: minimale dataset
EDS: extended dataset per focusbiobank
PDS: project dataset per project
Docs
Anonieme
gebruiker
Overzicht van de
focusbiobanken
Metadata
over de
variabelen
van de PDS
BACKBONE
Anonieme
gebruiker met
bestaand
emailadres
Metadata
over de
variabelen
van de MDS
Metadata
over de
variabelen
van de EDS
CRC Y
#
OPAL SERVER
enkel
aantallen
X
Geen identificeerbare gegevens!
#
Query
?
CRC UZ GENT
Niet identificeerbare gegevens
M
D
S
EDS
EDS
PDS 1
PDS 2
X
X
Databanken
Identificeerbare gegevens
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EDS
EDS
PDS 7
PDS 8
PDS 9
PDS 1
PDS 2
PDS 5
PDS 6
EDS
EDS
EDS
CRC X
Niet identificeerbare gegevens
OPAL SERVER
M
D
S
EDS
M
D
S
EDS
EDS
PDS 1
PDS 3
PDS 4
PDS 7
X
Geen identificeerbare gegevens!
Niet identificeerbare gegeven s
EDS
PDS 8
EDS
Niet identificeerbare gegeven s
M
D
S
M
D
S
Geen identificeerbare gegevens!
PDS 3
PDS 4
Geverifieerde
gebruiker /
partner
In 1 WG
OPAL SERVER
SLIMS SERVER
Identificeerbare gegevens
Niet id en tificeerbare gegeven s
Result
M
D
S
EDS
EDS
PDS 2
PDS 3
PDS 4
PDS 5
PDS 8
Export van
de datasets
van de
focusbiobanken
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Enrichment projects 1, 4, 6: retrospective data
#historische stalen Type
stalen
DataSet (local Opal server)
HCV stalen
(CEVAC)
~ 4000
~ 640/jaar ’00-’13
Serum
Minimal DS
+ RNA qual/quant
HBV stalen
(Gastro-enterology)
~ 140
Serum
DNA
Project DS (max 150 velden),
Extended DS, Minimale DS
HCV stalen
(Gastro-enterology)
~ 600
Serum
DNA
Project DS (max 170 velden),
Extended DS, Minimale DS
HCC - Hepatocellular
carcinoma
~ 60
Serum
DNA
Extended DS,
Minimal DS
NASH –
Niet Alcoholische
Steatose Hepatitis
~ 100
Serum
DNA
Minimal DS
10/12/2014
CMI Center for Medical Innovation
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Enrichment project 1: prospective sample /
data collection
Isabelle Desombere/Philip Meuleman/Geert Leroux-Roels
Ghent University Hospital
Geert Robaeys
UHasselt
© 2013 Universitair Ziekenhuis Gent
Focus biobank hepatotropic disorders: Project 1
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Identification ‘immune correlates’ for clearance/protection of HCV-infection
(lead CRC Gent)
• Multicentric approach
• De novo HCV-infections in MSOC centra (IDU) and follow-up (several samples
/year)
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Outcome: spontaneous clearance or chronic carriers
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Approach:
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serum, plasma, PBMC collection
1 coordinating trial nurse
Harmonization protocols and SOPs
Decentral collection of samples (CMI biobanks)
Collaborative research projects
• Starting point: MSOC centra Ghent and Hasselt
• Stepwise extension towards other MSOC (other regions in Flanders)
10/12/2014
CMI Center for Medical Innovation
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Focus biobank hepatotropic disorders: Project 1
Patiënten en humaan biologisch materiaal
CRC Gent
Patiënten
MSOC
Bloed stalen
CRC UHasselt
Patiënten
MSOC
Bloed stalen
Prospectief (1 jaar,
verrijking)
Screening 220 injecterende
druggebruikers (IDU) ter
detectie van vroege fase de
novo HCV infectie : zelf
klarend (15 %) versus
chronisch (85%)
660 serum (3x/jaar,
serieel), + 30 PBMC
retrospectief
Kost prospectief
1326 serum
Afname en transport:
12*85€ + 30*10€
Prospectief (1 jaar,
verrijking)
Screening 300 injecterende
druggebruikers (IDU) ter
detectie van vroege fase de
novo HCV infectie : zelf
klarend (15 %) versus
chronisch (85%)
retrospectief
Kost prospectief
idem
idem
900 serum (3x/jaar, serieel),
+ 90 PBMC
CMI Center for Medical Innovation
Enrichment project 6:
‘China aan de Schelde’ –China in
Antwerp
Viral hepatitis within Chinese community in clinic and laboratory
Gastroenterology and hepatology UZA
CMI Center for Medical Innovation
China aan de Schelde: een complexe samenwerking
CMI Center for Medical Innovation
Focus biobank hepatotropic disorders
Enrichment project 6 = “China aan de Schelde” (lead: CRC Antwerp)
Population migrants form endemic regions : important risk groups for viral hepatitis
infections:
• Screening viral hepatitis B and C:
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Chinese population in Antwerp
Bulgarian/Turkish population in Ghent
Turkish population in Limburg
Holistic clinical characterization and follow-up
Mapping gentic variants and linked patterns of clearance or chronic carriers
Approach:
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Blood samples (liver biopsies: optional)
Prospective collected samples in CMI biobanks
Harmonization protocols, methods, SOPs
• Starting point: China in Antwerp: prevalence study: prospective collection 500
volunteers (up to date: ~153)
• Stepwise extension towards Ghent, Hasselt, other
10/12/2014
CMI Center for Medical Innovation
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Focus
hepatotropic
disorders:
China
aanbiobank
de Schelde:
screeningsmethodes
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Prevalence study: Prospective screening 500 persons
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•
Project 1
Comparison screening methods (cfr Protocol plan federal
Government)
Virus-host interactions and natural history studies via
collection of mRNA en PBMC
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Assessment of HBsAg, anti-HBc, anti-HCV via Roche Elecsys
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Golden standard: serum
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Saliva (OraSure Intercept i2)
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Dried Blood Spot testing (Whatman 903 Protein Saver card)
CMI Center for Medical Innovation
Focus
hepatotropic
disorders:
Project
China
aanbiobank
de Schelde:
verwerking, workflow
en opslag
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Serologie: labo UZA in samenwerking met biobank en ICT
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mRNA: afname in Tempus tube, opslag in biobank (-80°C)
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PBMC: labo LEMP in samenwerking met biobank

Ter plekke centrifugatie met scheiding PBMC (BD
Heparine CPT
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Day 0 verwerking en temporary storage in LEMP
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Long term opslag in biobank (-150°C)
CMI Center for Medical Innovation
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Focus
hepatotropic
China
aanbiobank
de Schelde:
mRNA
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•
disorders: Project 1
example: assessment gene expression in HCV

Profiling via microarray analysis
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Prediction of interferon-alpha therapy outcome at baseline

Comparison transcriptome of ‘cured’ patients vs. healthy
controls
Hou et al. J Virol. 2014 Nov 1;88(21):12254-64. doi:
10.1128/JVI.00775-14. Epub 2014 Aug 6.
CMI Center for Medical Innovation
Focus
hepatotropic
China
aanbiobank
de Schelde:
stand van zakendisorders:
•
•
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Project 1
Status december 2014:
2 screening sessions (25/10 en 19/11): 153 volunteers
screened
153 sets PBMC (cryovials 2 mL) and mRNA (Tempus) in
biobank (CRC Antwerp)
153 sets residuary serum in biobank
Future research projects:
Extension towards other regions:
•
Bulgarije a/d Leie
•
Turkije a/d Demer
CMI Center for Medical Innovation
GlycoCirrhoTest as a prognostic marker for
HCC development in liver cirrhosis
enrichment project 4
Hans Van Vlierberghe, MD, PhD
Dept of Gastroenterology and Hepatology
Ghent University Hospital
© 2013 Universitair Ziekenhuis Gent
Focus biobank hepatotropic disorders
• Project 4: Hepatocellular carcinoma and cirrhosis: research for prognostic markers
(lead CRC Gent)
• HCC is 3rd most frequent causes of cancer associated mortality
• Search for prognostic markers for early markers for detection and validation of
biomarkers: “glycomics”
• Enrichment of retrospective collections
• Uploading retrospective data (MDS)
10/12/2014
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Patients with cirrhosis can develop a primary hepatocellular carcinoma,
however few variables are predictive for this complication.
Preliminary data suggest that glycomics can be a predictive marker
© 2013 Universitair Ziekenhuis Gent
CMI
Center for Medical Innovation
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Samples needed.
1) Patients with cirrhosis
1)
2)
Developing a HCC (n=125)
Not developing a HCC (n=125)
2) Combination of retrospective (n=50) and prospective
samples.
3) On serum: glycomic profile will be analysed.
© 2013 Universitair Ziekenhuis Gent
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Focus biobank hepatotropic disorders
Valorisation
criteria:
• Demonstrated scientific excellence
• Industrial interest
• Valorization potential
• High quality samples
• Links with data
• Available patient populations
• Research collaboration
Usage phenotypes:
• Actualisation epidemiologicale data Hepatitis (A, B, C, D, E)
• Biomarkers acute  chronical infection process
• Development innovative therapy: chronic HBV, re-infection LTX
10/12/2014
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Focus biobank hepatotropic disorders
• Coordinators:
• Prof. Geert Leroux-Roels (UZGent)
• Prof. Marc Van Ranst (KULeuven)
• Coordinating CRC:
• Prof. Sofie Bekaert (Bimetra – CRC Gent)
http://www.bimetra.be
10/12/2014
CMI Center for Medical Innovation
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