2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool
-
Upload
alain-van-gool -
Category
Health & Medicine
-
view
155 -
download
0
Transcript of 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool
![Page 1: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/1.jpg)
‘Personalized Health(care) doe je samen’
Prof Alain van Gool +
Radboud Grand Round 22 Augustus 2016
![Page 2: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/2.jpg)
My path 1989-now
• Molecular biology
• Mechanisms of disease
• Biomarkers
• Omics / technologies
• Translational medicine
• Personalized healthcare
Senior Scientist Integrator Biomarkers
Scientific lead DTL-Technologies
Head EATRIS Biomarker Platform
Professor of Personalized Healthcare Head Radboud Center for Proteomics, Glycomics & Metabolomics Coordinator Radboud Technology Centers
2 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 3: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/3.jpg)
Consider individual differences in life science research
3
3 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 4: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/4.jpg)
Source: Chakma, Journal of Young Investigators, 16, 2009
Principle of Personalized Medicine
4
• The right drug for right patient at right dose at right time • Molecular biomarkers as key drivers of patient selection • = Precision medicine or Targeted medicine
4 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 5: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/5.jpg)
Example: Personalized medicine in melanoma
B-RAFV600E mutation Strong growth of cell Growth of tumor
• B-RAFV600E cells always grow and become cancer cells
• RAF inhibitors will block pathway, block cell growth and inhibit cancers that have a B-RAFV600E mutation
• 60% of melanoma patients have B-RAFV600E mutation
• Basis for a personalized medicine !
5 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 6: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/6.jpg)
Personalized medicine in melanoma
Treat patients with
B-RAFV600E mutation Inhibit growth of cell
Patients live longer Tumors disappear Cells stop growing
B-RAF inhibitor
6 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 7: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/7.jpg)
Emerging Personalized / Precision / Targeted Medicine
2010:
5% of drugs in pipeline had companion diagnostic biomarker test
2015:
80%
50%
7 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 8: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/8.jpg)
8
Optimal Personalized / Precision / Targeted Medicine
![Page 9: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/9.jpg)
People are more than linear pathways
{Source: Barabási 2007 NEJM 357; 4}
• People are different • Different systems and networks • Different risk factors • Different preferences
9 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 10: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/10.jpg)
Societal need in efficient personalized health(care)
{Source: prof Jan Kremer}
Towards cost effective care, less cure
10 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 11: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/11.jpg)
Highest need in efficient personalized health(care)
It’s personal !
‘I want to stay healthy.’ ‘If not, how do I get healthy?’
11 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 12: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/12.jpg)
3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
12 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 13: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/13.jpg)
1. What to measure?
Exponential technological developments • Next generation sequencing
• DNA, RNA
• Risk analysis and therapy selection
• Mass spectrometry • Proteins, metabolites • Monitoring of disease and treatment effects
• Imaging • Non invasive images, real time • Spatial view of intact organs and organisms
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
13 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 14: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/14.jpg)
Crash course in molecular biology
DNA, protein, cell, tissue, system biology
14 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 15: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/15.jpg)
Advances in mass spectrometry • Mass spectrometry analysis of glycoproteins in human plasma • 0,05 microliter analysis: detection of 1.000.000 signals in one scan (1,4 Gb) • ~40.000 peptides of which >80% contain sugar modification • Diagnose patients and identify new biomarkers
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
Proof of principle study:
{Hans Wessels, Monique van Scherpenzeel, Dirk Lefeber, Alain van Gool} Biomarkers !?
15 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 16: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/16.jpg)
Innovation in protein biomarker diagnostics
Current diagnostic protein assays:
• Mostly protein abundance
Emerging:
• Post-translational modifications
• Intact proteins
• Protein complexes
16 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 17: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/17.jpg)
New diagnostic glycoprotein biomarker
• Rare metabolic disease cases (liver disease and dilated cardiomyopathy)
• Combination glycoproteomics and exome sequencing
• Identification of deficient enzyme in glycosylation pathway
• Outcome 1: Explanation of disease
• Outcome 2: Dietary intervention as succesful personalized therapy
• Outcome 3: Glyco -transferrin profile developed as diagnostic mass spec test
{Monique van Scherpenzeel, Dirk Lefeber}
17 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 18: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/18.jpg)
18 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
Intact protein analysis
Bottom-up proteomics
Top-down proteomics
{Hans Wessels, Alain van Gool}
![Page 19: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/19.jpg)
Intact complexome proteins as new biomarker?
• Native tissue biopsies
• Isolate intact membrane complexes
• Separate and isolate complexes using native gels
• LC-MS/MS analysis of intact proteins
• Data analysis
Tissue 1 (n=3)
Tissue 2 (n=3)
Subunit
Subunit – tissue 1
Subunit – tissue 2
• Identified protein sequence of subunit • Deduce simulated sequences from database • Determine fit with experimental data
19
{Hans Wessels, Susanne Arnold, Uli Brandt, Alain van Gool}
![Page 20: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/20.jpg)
Uric acid Human samples
Plasma, CSF (urine) Controls vs. patient
QTOF Mass Spectrometry
- Reverse phase liquid chromatography - Positive and negative mode - Features
XCMS Alignment Peak comparison > 10,000 Features
Next generation metabolic screening
Xanthine
Whole Exome Sequencing
{Leo Kluijtmans, Ron Wevers (TML) + Genetica}
![Page 21: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/21.jpg)
Challenge: translate laboratory to society
• Heart beat • Steps / movement • Glasses water/coffee • 1.000.000 molecules per analysis
21 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 22: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/22.jpg)
22
New data (generators, owners)
22 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 23: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/23.jpg)
What does my DNA tell me?
23% chance blond hair 3.1% Neanderthaler DNA
23 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 24: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/24.jpg)
Genetic risk lung cancer → don’t smoke !
What does my DNA tell me?
No expected adverse reaction to Warfarin
24 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 25: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/25.jpg)
![Page 26: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/26.jpg)
Need for optimal quality in health biomarker analyses
Test, interpret, advice
“Post-traumatic Test Syndrome” ?
26 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 27: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/27.jpg)
Try-outs at REshape Center of Health(care) Innovation
Lucien Engelen
![Page 28: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/28.jpg)
… but not all data is useful data !
![Page 29: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/29.jpg)
3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
29 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 30: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/30.jpg)
healthy disease disease + treatment
2. How much can it change?
Subgroups
100%
Individual
Population
30 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
Past
Present
Future
![Page 31: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/31.jpg)
Personalized health(care) model Personalized Intervention
of patients-like-me Personal thresholds of persons-like-me
Big Biomarker Data
Molecular Non-molecular Environment …
Ho
meo
sta
sis
A
llo
sta
sis
D
isease
Time
Disease
Health
Selfmonitoring
Adapted from Jan van der Greef, TNO
Personal profile
Personalized health
Personalized medicine
31 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 32: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/32.jpg)
3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
32 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 33: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/33.jpg)
3. What should be the follow-up for me?
Personal profile data
Knowledge
Understanding
Decision
Action
33 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 34: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/34.jpg)
Daily views of molecular system biologists β-cell Pathology
gluc Risk factor
{Source: Ben van Ommen, TNO}
therapy
34 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 35: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/35.jpg)
Translation is key in Personalized Healthcare !
“I’m afraid you’re
suffering from an
increased IL-1β and
an aberrant miR843
expression”
Adapted from:
?
35 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 36: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/36.jpg)
36 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
Translating Personalized Health(care) in society
![Page 37: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/37.jpg)
We need a personalized data-driven GPS for health
• Monitor on background
• Alert when you are at risk
• Advice what to do
37 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 38: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/38.jpg)
Translational medicine using simulation + feedback
Simulating YOUR health + Personalized advice + Feedback
38 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 39: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/39.jpg)
Personalized Healthcare @ Radboudumc :
Focus on the end user: the patient / citizen
39 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 40: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/40.jpg)
Patient
Radboud Personalized Healthcare
A significant impact
on healthcare
Molecule
Population
40 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 41: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/41.jpg)
Personalized Healthcare @ Radboudumc
People are different Stratification by multilevel diagnosis
+ Patient’s preference of treatment
Exchange experiences in care communities Select personalized therapy
Population
Man
Molecule
41 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016 www.radboudumc.nl/Research/Pages/PersonalizedHealthcare
![Page 42: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/42.jpg)
Be proud of what we achieve !
42 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 43: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/43.jpg)
Research themes and institutes
www.radboudumc.nl/Research/Themes/Pages/default.aspx
43
![Page 44: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/44.jpg)
Orientation across the spectrum from molecule to man to population
Ori
enta
tio
n a
cro
ss
the
spec
tru
m o
f d
isea
ses
PI
Research theme
Te
chn
olo
gy
C
ente
rs
Research support by Technology Centers
44
www.radboudumc.nl/research/technologycenters
![Page 45: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/45.jpg)
Radboudumc Technology Infrastructure
Get organised:
1. What technological expertise do we have and should we have ?
2. How should we organise this ?
3. How will we communicate this ?
45 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016
![Page 46: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/46.jpg)
www.radboudumc.nl/research/technologycenters 46
Genomics
Bioinformatics
Animal studies
Stem cells
Translational neuroscience
Image-guided treatment
Imaging
Microscopy
Biobank
Health economics
Mass Spectrometry
Radboudumc Technology
Centers
Investigational products
Clinical studies
EHR data analysis
Statistics
Human performance
Data stewardship
Molecule
Flow cytometry
3D lab
![Page 47: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/47.jpg)
About 280 dedicated people working in 19 Technology Centers, ~1800 users (internal, external), ~150 consortia www.radboudumc.nl/research/technologycenters/ 47
• Proteins • Metabolites • Drugs • PK-PD • Preclinical
• Clinical
• Behavioural • Preclinical
• Animal facility • Systematic review
• Cell analysis • Sorting
• Pediatric • Adult • Phase 1, 2, 3, 4
• Vaccines • Pharmaceutics • Cyclotron • Radio-isotopes • Malaria parasites
• Management • Analysis • Sharing • Cloud computing
• DNA • RNA
• Internal • External
• Early HTA • Evidence-
based surgery • Field lab
• Statistics • Biological • Structural
• Preclinical • Clinical
• Economic viability
• Decision analysis
• Experimental design • Biostatistical advice
• Electronic Health Records
• Transmural translation
• Best practice
• In vivo • Functional
diagnostics
• iPSC • Organoids
• 3D imaging • 3D printing • Virtual reality
![Page 48: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/48.jpg)
Working with/within other networks Region, nation, Europe, world
48
Peggy Manders Gerhard Zielhuis
Peter Friedl Otto Boerman
Alain van Gool (Scientific Lead Technologies)
RADBOUD RESEARCH FACILITIES
Otto Boerman (Head Imaging Platform) Alain van Gool (Head Biomarker Platform)
Via DTL
Grootschalige Wetenschappelijke Infrastructuur
![Page 49: 2016 08-22 Radboud Grand Round, Nijmegen, Alain van Gool](https://reader031.fdocument.pub/reader031/viewer/2022021918/589a501d1a28ab040e8b646d/html5/thumbnails/49.jpg)
Acknowledgements
Ron Wevers
Jolein Gloerich
Hans Wessels
Dirk Lefeber
Monique Scherpenzeel
Leo Kluijtmans
Lucien Engelen
Nathalie Bovy
Paul Smits
Maroeska Rovers
Bas Bloem
the Technology Centers
and many others
www.radboudumc.nl/personalizedhealthcare
www.radboudumc.nl/research/technologycenters
www.radboudresearchfacilities.nl
www.linkedIn.com
www.slideshare.net/alainvangool
Many collaborators and funders
Jan van der Greef
Ben van Ommen
Ivana Bobeldijk
Lars Verschuren
Marjan van Erk
Peter van Dijken
Heleen Wortelboer
Wessel Kraaij
Peter Wielinga
Ronald Mooij
Suzan Wopereis
and many others
CarTarDis
49 Alain van Gool, Radboudumc Grand Rounds, 22 Aug 2016