‘Being integrated in the international biomedical research and biobanking world’
Prof. Philip Meuleman - UGent
CMI
Center for Medical Innovation

Cardiovascular diseases
Metabolic disorder s
Viral infectious diseases
Immune mediated inflammation
Oncology
Neurodegenerative diseases
COPD/Asthma
Reproductive medicine
Rare diseases
Ageing
5 selected focus biobanks
• Diabetes
• Rheumatic arthritis
• Inflammatory bowel disease
• Sudden cardiac death xx biobanks
• Hepatotropic disorders proposed for later integration
Other
CMI
Center for Medical Innovation

Focus biobank hepatotropic disorders
• Diabetes
5 selected focus biobanks
• 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
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Center for Medical Innovation

• 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

me
5
Bi me tra is the Clinical Research Center from Ghent
University Hospital in collaboration with Ghent
University .
Bi me tra 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

me
CPOC
CMI
Center for Medical Innovation
6 sofie.bekaert@ugent.be - © 2014

Validation
Valorisation
Research






Research funding
Valorisation (economical and societal)
Biobank and translationeel data mgmt
Reinforcing clinical trials
Inventorizing and reinforcing translational competences ( intra / extra muros )
Reporting performances
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infrastructure
Algemeen UZG plan, situering biobank
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Bimetra biobank
CMI
Center for Medical Innovation

infrastructure
25.000 l storage capacity:
-80°C + LN2
Lab facility
Invoegen algemeen grondplan met zonering uit iDOCs
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Center for Medical Innovation

infrastructure
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Center for Medical Innovation

Biobank Bimetra:
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Hepatitis viruses in Belgium - HCV
HCV
Incidentie
Seroprevalentie In 1993-94 0.87-1 %
Recentere studie (2007) op speekselstalen 0.12%
of
10 000 – 75 000 chronische
HBV patiënten in België
1.23%
Figuur en Tabel uit KCE rapport 173A
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Center for Medical Innovation
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Focus biobank hepatotropic disorders
UGENT/UZGENT
- G. Leroux-Roels
- P. Meuleman
- I. Desombere
- H. Van Vlierberghe
10/12/2014
KULeuven
- M. Van Ranst
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Center for Medical Innovation
13

Focus biobank hepatotropic disorders
UGENT/UZGENT
- G. Leroux-Roels
- P. Meuleman
- I. Desombere
- H. Van Vlierberghe
- L. Padalko
UA/UZA
- P. Michielsen
- T. Vanwolleghem
ITG
- P. Van Damme
10/12/2014
KULeuven
- M. Van Ranst
- F. Nevens
- T. Roskams
UHasselt-Genk (ZOL)
- G. Robaeys
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14

Focus biobank hepatotropic disorders
10/12/2014
Patient
-prevention
-personalized therapy
Society
-safe and affordable healthcare
Clinicians
-diagnostic markers
-epidem data
-post transplant parameter
Researchers
-access to phenotypes
-underlying mechanisms
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15

Focus biobank hepatotropic disorders
• Cell-cell transmission HCV and clinical implications:
• 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
10/12/2014 CMI
Center for Medical Innovation
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Focus biobank hepatotropic disorders
Project 1:
Identification
‘immune correlates’ for clearance/prot ection of HCVinfection
Project 3:
HCV DAA therapy: identification, mode of action, success rate + alternatives
Project 2:
HEV research: characterizati on and invivo/in vitro models
Project 4:
Hepatocellular carcinoma and cirrhosis: prognostic markers
Project 5: epidemiology: distribution of
HCV genotypes
Project 6:
China in
Antwerp,
10/12/2014 CMI
Center for Medical Innovation
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Focus biobank hepatotropic disorders
Project 1:
Identification
‘immune correlates’ for clearance/prot ection of HCVinfection
Prioritized research topics
Project 3:
HCV DAA therapy: identification, mode of action, success rate + alternatives
Project 2:
HEV research: characterizati on and invivo/in vitro models
Project 4:
Hepatocellular carcinoma and cirrhosis: prognostic markers
Project 5: epidemiology: distribution of
HCV genotypes
Project 6:
China in
Antwerp,
10/12/2014 CMI
Center for Medical Innovation
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Biobank Bimetra:
MDS: minimale dataset
EDS: extended dataset per focusbiobank
PDS: project dataset per project
Anonieme gebruiker
Anonieme gebruiker met bestaand emailadres
Overzicht van de focusbiobanken
Metadata over de variabelen van de MDS
BACKBONE
Metadata over de variabelen van de EDS
# enkel aantallen
Docs
Metadata over de variabelen van de PDS
CRC Y
OPAL SERVER
X
Geen identificeerbare gegevens!
Niet id en tificeerbare gegeven s
M
D
S
EDS
EDS
EDS
PDS 1
PDS 2
PDS 5
PDS 6
SLIMS SERVER
Identificeerbare gegevens
Niet identificeerbare gegevens
M
D
S
EDS
EDS
PDS 1
PDS 2
PDS 3
PDS 4
Databanken
Identificeerbare gegevens
Niet identificeerbare gegeven s
M
D
S
EDS
EDS
PDS 7
PDS 8
PDS 9
# Result
Query
CRC UZ GENT
?
X
OPAL SERVER
X
Geen identificeerbare gegevens!
Niet identificeerbare gegevens
M
D
S
EDS
EDS
M
D
S
EDS
EDS
PDS 1
PDS 3
PDS 4
PDS 7
PDS 8
Export van de datasets van de focusbiobanken
Geverifieerde gebruiker / partner
In 1 WG
CRC X
OPAL SERVER
X
Geen identificeerbare gegevens!
Niet identificeerbare gegeven s
M
D
S
EDS
EDS
EDS
PDS 2
PDS 3
PDS 4
PDS 5
PDS 8
10/12/2014 CMI
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Enrichment projects 1, 4, 6: retrospective data
HCV stalen
(CEVAC)
HBV stalen
(Gastro-enterology)
HCV stalen
(Gastro-enterology)
HCC - Hepatocellular carcinoma
NASH –
Niet Alcoholische
Steatose Hepatitis
10/12/2014
#historische stalen Type stalen
DataSet (local Opal server)
~ 4000
~ 640/jaar ’00-’13
~ 140
Serum Minimal DS
+ RNA qual/quant
Serum
DNA
Project DS (max 150 velden),
Extended DS, Minimale DS
~ 600
~ 60
~ 100
Serum
DNA
Project DS (max 170 velden),
Extended DS, Minimale DS
Serum
DNA
Serum
DNA
Extended DS,
Minimal DS
Minimal DS
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Isabelle Desombere/Philip Meuleman/Geert Leroux-Roels
Ghent University Hospital
Geert Robaeys
UHasselt
© 2013 Universitair Ziekenhuis Gent

• 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)
• Outcome: spontaneous clearance or chronic carriers
• Approach:
• 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
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
CRC UHasselt
Patiënten
MSOC
Bloed stalen
Prospectief (1 jaar, verrijking)
Screening 300 injecterende druggebruikers (IDU) ter detectie van vroege fase de novo HCV infectie : zelf klarend (15 %) versus chronisch (85%)
900 serum (3x/jaar, serieel),
+ 90 PBMC retrospectief idem
1326 serum retrospectief idem
Kost prospectief
Afname en transport:
12*85€ + 30*10€
Kost prospectief
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Center for Medical Innovation

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
“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:
• 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:
• 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
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•
Focus biobank hepatotropic disorders: Project 1
Prevalence study: Prospective screening 500 persons
•
Comparison screening methods (cfr Protocol plan federal
Government)
•
Virus-host interactions and natural history studies via collection of mRNA en PBMC
•
Assessment of HBsAg, anti-HBc, anti-HCV via Roche Elecsys
•
Golden standard: serum
•
Saliva (OraSure Intercept i2)
•
Dried Blood Spot testing (Whatman 903 Protein Saver card)
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Focus biobank hepatotropic disorders: Project 1
•
•
Serologie: labo UZA in samenwerking met biobank en ICT mRNA: afname in Tempus tube, opslag in biobank (-80
°
C)
•
PBMC: labo LEMP in samenwerking met biobank
 Ter plekke centrifugatie met scheiding PBMC (BD
Heparine CPT


Day 0 verwerking en temporary storage in LEMP
Long term opslag in biobank (-150
°
C)
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Center for Medical Innovation

Focus biobank hepatotropic disorders: Project 1
•
• example: assessment gene expression in HCV
 Profiling via microarray analysis


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.
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Focus biobank hepatotropic disorders: 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

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 3 rd 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 CMI
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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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1) Patients with cirrhosis
1) Developing a HCC (n=125)
2) 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 35

Focus biobank hepatotropic disorders
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
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Center for Medical Innovation
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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
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Center for Medical Innovation
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