Organising technical infrastructures:

EATRIS Biomarker Platform Meeting

Amsterdam 26 November 2014

Professor in Personalized Healthcare Head Radboud Center for Proteomics, Glycomics and Metabolomics Coordinator Radboud Technology Centers

Head Biomarkers in Personalized Healthcare

Prof Alain van Gool

Radboudumc Technology Centers

My background

8 years academia (NL, UK)

(molecular mechanisms of disease)

13 years pharma (EU, USA, Asia)

(biomarkers, Omics)

3 years applied research institute (NL, EU)

(biomarkers, personalized health)

3 years university medical center (NL)

(personalized healthcare, Omics, biomarkers)

1991-1996 1996-1998 2009-2012

1999-2007 2007-2009 2009-2011

2011-now

2011-now

2

Radboud university medical center

• Nijmegen, The Netherlands

• Mission: “To have a significant impact on healthcare”

• Strategic focus on Personalized Healthcare through “the patient as partner”

• Core activities:

• Patient care

• Research

• Education

• 11.000 colleagues

• 52 departments

• 3.300 students

• 1.000 beds

• First academic centre outside US to fully implement EPIC

Takehome message

• Strategic focus on implementing Personalized Healthcare

• Strong technological and methodological infrastructure

• Continuous exploration of functional networks

Patient

Radboud Personalized Healthcare

A significant impact

on healthcare

Molecule

Population

5

Personalized Healthcare @ Radboudumc

People are different Stratification by multilevel diagnosis

+ Patient’s preference of treatment

Exchange experiences in care communities

Select personalized therapy

6

Translational medicine @ Radboudumc

Personalized genomic diagnostics

{Nature, July 17 2014, 511: 344-}

8

2012

Patient Targeted

Metabolic

screen

Targeted

gene

analysis

Diagnosis

+ follow-up

2013 / 2014

Patient

Whole

exome

sequencing Targeted

confirmatory

metabolite +

enzyme

testing

Diagnosis

+ follow-up

Targeted assays vs holistic approach

Next

generation

metabolic

screening

Times are changing… add functional genome diagnostics

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

Personalized metabolic diagnostics

Xanthine Uric acid

10

Full metabolite profile: Highly suspected of xanthinuria

Research Biomarkers Diagnostics

Integrated Translational Research and Diagnostic Laboratory 220 fte, yearly budget ~ 28M euro. Close interaction with Radboudumc scientists and external partners

Specialities: • Proteomics, glycomics, metabolomics • Enzymatic assays • Neurochemistry • Cellulair immunotherapy • Immunomonitoring

Areas of disease: • Metabolic diseases • Mitochondrial diseases • Lysosomal /glycosylation disorders • Neuroscience • Nefrology • Iron metabolism • Autoimmunity • Immunodeficiency • Transplantation

In development: • ~500 Biomarkers • Early and late stage • Analytical development • Clinical validation

Assay formats: • Immunoassay • Turbidicity assays • Flow cytometry • DNA sequencing • Mass spectrometry • Experimental human (-ized)

invitro and invivo models for inflammation and immunosuppression

Validated assays*: • ~ 1000 assays • 3.000.000 tests/year

Areas of application: • Personalized healthcare • Diagnosis • Prognosis • Mechanism of disease • Mechanism of drug action

Department of Laboratory Medicine

*CCKL accreditation/RvA/EFI

www.laboratorymedicine.nl

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

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 ?

Activities: • Make inventories on current state and desired future state. • Work with technology coordinators + departments (research, clinical, strategy,

communication , valorisation). • Include input from research themes. • Organize monthly full team meetings + many 1:1 meetings. • Discussed output with research institutes, executive board. • Implementation structure 1.0 by 1H2014. Improve in version 2.0 1H2015.

13

External role

Internal role

• Knowledge hub for technological expertise • Maximise use of available technical capabilities and knowledge (‘duurzaamheid’) • Advise scientists with technological expertise • Advise management on strategic investments and opportunities • Drive innovations by working with each other, theme’s and Valorisation

• Easy access to Radboudumc’s technological expertise • Represent Radboudumc as one in external technology networks • Increase funding (grants, contract research) with Valorisation

Internal / external role

Radboudumc Technology Centers

Technology Platforms UMC St Radboud

(Potential) Technology Platforms

Genomics

RPC

CMBI PRIME

MIC

CDL

CRCN

Radboud Biobank Malaria lab

Flow cytometry

TR&CT

TNU

MITeC

PDRC

(based on quick scan Radboudumc Technology Platforms, Sept 2013)

December 2013

Radboudumc Technology Centers

Genomics

Bioinformatics Animal studies

Flow cytometry

Translational neuroscience

Image-guided treatment

Imaging

Microscopy

Biobank

Data stewardship

Proteomics Glycomics

Metabolomics

Radboudumc Technology

Centers

GMP products

Clinical trials

January 2014

• Align with the needs of the Research and Education, and contribute to output and quality of those

• Organise each Technology Center as a single portal • Add other Technology Centers when needed and useful • Keep improving efficiency and funding

17

Radboudumc Technology Centers Form and improve organisation

www.radboudumc.nl/research/technologycenters

Genomics

Bioinformatics

Animal studies Translational

neuroscience

Image-guided treatment

Imaging

Microscopy

Biobank

Health economics

Mass Spectrometry

Radboudumc Technology

Centers Investigational

products

Clinical trials EHR-based

research

Statistics

Human physiology

Data stewardship

Molecule

Flow cytometry

(August 2014)

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• 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 • Radio-isotopes • Malaria parasites

• Management • Analysis • Sharing • Cloud computing

• DNA • RNA

• Internal • External

• HTA • Evidence-based

surgery • Field lab

• Statistics • Biological • Structural

• Preclinical • Clinical

• Economic viability

• Decision analysis

• Experimental design • Biostatistical advice

• Electronic Health Records • Big Data • Best practice

• In vivo • Functional

diagnostics

About 240 dedicated people working in 17 Technology Centers, ~1500 users (internal, external), ~130 consortia

www.radboudumc.nl/research/technologycenters/

Cross-technology interactions

Input-output Radboudumc Technology Centers

In

Scientist

Industry

Science Lectures

Papers

Grants

Funding

Valorisation

Diagnostics

Commercial

Patents

Out

Patient

Spin-off companies

21

www.radboudumc.nl/research/technologycenters/

Working together on the Radboud campus

(Spin-out) companies

23

Radboud Research Facilities

24

www.ru.nl/radboudresearchfacilities/

Working with other Technology Networks Region, nation, Europe, world

25

Working through multi-partner projects

Standardisation, harmonisation, knowledge sharing needed in:

1. Assay development

2. Clinical validation

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Example: Biomarker Development Center

Open Innovation Network !

Roadmap Molecular Diagnostics

PPP Grant 4.3M Euro

Next

• Keep improving Technology Center infrastructure • Technology • Collaborations • Impact (research, education, patient care) • Finances

• Continuous exploration of functional networks