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European Perspectives in Cardiology
Spotlight: Christian Weber, MD, FESC
Aiming to Selectively Target Platelet Chemokine Heteromers
and Macrophage Migration Inhibitory Factor Receptors to
Diagnose, Treat, and Prevent Atherosclerosis
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I
Christian Weber, professor, chair, and director of the Institute for Molecular
Cardiovascular Research, Preventive Cardiology, Rheinisch-Westfälische Technische
Hochschule Aachen University, Aachen, orth Rhine-Westphalia, Germany, and
visiting professor at the Cardiovascular Research Institute Maastricht, University of
Maastricht, the etherlands, talks to Jennifer Taylor, BSc, MSc, MPhil.
dentifying macrophage migration inhibitory factor (MIF)
receptors was one of those eureka moments that create
some of the happiest times at work, says Christian Weber,
MD, PhD, FESC, professor, chair, and director at the
Institute for Molecular Cardiovascular Research, Preventive
Cardiology, Rheinisch-Westfälische Technische Hochschule
Aachen University, Aachen, North Rhine-Westphalia,
Germany, and visiting professor at the Cardiovascular
Research Institute Maastricht, University of Maastricht, the
Netherlands. The identification of the CXC chemokine
receptor 2 (CXCR2) and CXCR4 as the first signaling
receptors for MIF has been Professor Weber’s most important work; for him, by definition, it has also been some of
the most enjoyable. “There is a lot of science that tries to
reproduce things, but instead we were out on the challenge
of finding new molecules, new molecular interactions,
which is what we think is important. And that’s where the
fun for my group and myself really comes in. The more
challenging and the more important we think things are, the
more enjoyable it gets.”
Providing Evidence That Heteromer Formation of
Platelet Chemokines Is Relevant in Atherosclerosis
Also important—and fun—was discovering the role of
the deposition of platelet chemokines and the functional
On other pages...
Team 2009:
Institute for Molecular Cardiovascular Research,
Rheinisch-Westfälische Technische Hochschule
Aachen University, Aachen,
orth Rhine-Westphalia, Germany
Professor Weber describes the team and its work.
Page f142
heteromerisation of chemokines in atherogenic recruitment
and atheroprogression.“MIF is an atypical cytokine that
was known since the early 1960s, long before the term
cytokine was even created,” he says. “Yet despite this long
time, no receptor had been identified, so that was a great
moment.” His team discovered CXCR2 and CXCR4 as the
first signaling receptors for the pleiotropic cytokine MIF.
In close cooperation with Jürgen Bernhagen, PhD—a
biochemist whom Professor Weber describes as “a very
close friend and collaborator here in Aachen”—the team’s
2007 article in ature Medicine1 unveiled MIF as a noncanonical and dual ligand for CXCR2 and CXCR4. He
says, “This explained its chemokine-like functions in
leukocyte recruitment in atherogenesis and inflammation
and opened a novel option to achieve therapeutic regression by its blockade. The activity of MIF as a functional
CXCR2 agonist is mediated by a pseudo-ELR (glutamic
acid-leucine-arginine) motif, which is structurally related
to critical N-terminal motifs in ELR-CXC chemokines.”
More recently, in 2009 the team published a landmark
article in ature Medicine,2 revealing a structural model of
the prototypic chemokine heteromer chemokine CXC ligand 4–chemokine CC ligand 5, also known as regulated
on activation normal T-cell expressed and secreted
(RANTES), including its affinity. Stable cyclic peptides that
Initiatives in Cardiovascular Research:
The Euregio Cardiovascular Research School
Professor Weber describes this innovative “school” he has set up
with Mat Daemen, MD, PhD, scientific director of CARIM,
Maastricht, the Netherlands, and says it “brings 2 academic cultures
together and fosters an international scientific atmosphere.”
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selectively disrupted the heteromer without side effects on
the immune system led to a reduction of atherosclerosis.
This finding indicates that heteromer formation of platelet
chemokines is functionally relevant in vivo, allowing for
their selective targeting in therapy and prevention but also
for use in molecular diagnostics and imaging.
The discoveries have culminated in the foundation of a
small biopharmaceutical company, Carolus Therapeutics
Inc, and have defined its 2 pipelines—MIF antagonists and
interceptors for the platelet chemokine heteromer complexes. Professor Weber explains, “We didn’t write a business plan and shop around for venture capital, it was just
the reverse. One of the major San Diego, Calif-based venture capital funds was doing active research and it came
across these papers and patents.” His laboratory provides
the intellectual property, whereas the venture capitalists
provide the money and manpower. The company is based
in San Diego, but the local touch comes from its name,
which is in honour of Charlemagne, a historic local patron
and the first sovereign to pursue a unified European community. Plans include setting up a branch in Maastricht, the
Netherlands, which is 30 km from Aachen. The company
has allowed Professor Weber’s group to transform its findings into biopharmaceutical drug development.
A Review Article About a Refinement of the
Inflammatory Pathogenesis of Atherosclerosis Was a
“Manifesto of Our Shared Interests”
Early on in his career, Professor Weber contributed to the
identification of important and direct antiinflammatory
effects and antiadhesive mechanisms exerted by aspirin3
and statins.4 He later developed the concept of a thromboinflammatory nexus through the discovery of a functional
deposition of chemokines, namely RANTES, from the αgranules of activated platelets on inflamed endothelium,
which subsequently trigger atherogenic recruitment of
monocytes. Based on this article,5 further studies in collaboration with Klaus Ley, MD, in San Diego revealed an
important and active role of platelets in exacerbating primary atherosclerosis as a result of complex formation with
monocytes and deposition of platelet chemokines. Since
then, they have identified the important role of the
chemokine stromal cell-derived factor-1, which can be presented by platelets, and its CXCR4 in promoting neointimal
hyperplasia and progenitor cell recruitment after arterial
injury, but also in controlling the delicate balance of
haematopoietic and vascular progenitor cell homeostasis
and thereby limiting atheroprogression and plaque instability.
Professor Weber’s work on chemokines began when he
was still a medical student at Ludwig Maximilians
University, Munich, Germany, where he devoted more time
than his peers to research. His MD thesis was supervised by
Peter C. Weber, MD, director of the Institute for
Preventative Cardiovascular Medicine. Professor Weber
was a pioneer in polyunsaturated fatty acids and eicosanoid
metabolism, and his published articles showed that the
body can produce Ω-3 derivatives from ingesting fish oil.
“He was really excellent in generating independence of
thought, and he gave me the freedom to pursue what I
thought was interesting,” says Professor Weber. He was
also the source of sharp and constructive feedback. The fact
that they shared the same name and looked alike was a
source of amusement, but they are not related.
After receiving his MD in 1994, Professor Weber applied
for a grant on the basis of his work as an MD student, and he
received a postdoctoral scholarship from the German
Research Foundation (Deutsche Forschungsgemeinschaft
[DFG]), which allowed him to choose a laboratory in which to
work. He chose the laboratory of Tim Springer, PhD, at the
Center for Blood Research at Harvard Medical School,
Boston, Mass, where he stayed from 1995 to 1997. He says, “I
had an interest early on in adhesion, and the field of
chemokines picked up at the time. Tim Springer was the right
person to let me study the control of adhesion by
chemokines.” An immunologist and biochemist, Dr Springer
was “a brilliant, universally gifted scientist” who taught Weber
the need for hard meticulous work, rigorous controls, and precise writing. He was a challenging supervisor who directly
supervised 20 to 30 postdocs—a situation that fostered
quality because only the best work caught his attention.
In Boston, Weber also encountered Peter Libby, MD,
“an encyclopaedically educated and interested doctor and
scientist, a true ‘renaissance man’ and role model.” They
became close simply by mutual interests, and they still
meet face to face. In 2008, they wrote a review article for
ature Reviews Immunology about a refinement of the
inflammatory pathogenesis of atherosclerosis. “That’s the
manifesto of our shared interests,” says Professor Weber.
“The DFG Is a Truly Unique Funding Organisation:
…and I Owe a Lot to It in My Scientific Career”
On his return to Munich in 1997, Professor Weber set up
his own research laboratory in Professor Peter Weber’s
institute. Thus, he got his own position and the independence that came with it, plus a postdoc, 2 PhD students, and
a technician, all funded by the DFG. He continued his interest in chemokines and adhesion molecules, but he decided
to put that to use in atherosclerosis research and to learn
more about the pathogenesis of inflammation.
The institute had no animal facility, so the next few years
were spent developing mouse models. Today, they generate
their own transgenic mice, a process that takes about 2
years—“a very tedious process,” according to Professor
Weber, who wishes they had been able to generate the mice
more quickly because of the competitive environment. He
adds, “Sometimes you may be at the right conferences and
talk to the right people, but you still may not find out what
they’re doing.” The trick is to have several projects ongoing,
a system he starts at the level of PhD students, who always
have a backup project in case something does not succeed.
Professor Weber has received most of his funding from
the DFG. He says, “The DFG is a truly unique funding
organisation. It is as unbiased, independent, and stringent as
possible in its scientific peer review, and I owe a lot to it in
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my scientific career.” He is currently a spokesperson for the
Euregio Cardiovascular Research School (EuCAR) and for
the programme project grant FOR809, “Chemokines and
adhesion molecules in cardiovascular pathogenesis,” which
are both funded by the DFG
During his career, Professor Weber has been frustrated
by the German university administration system and its
recruitment and tenure policies. The recruitment process
does not prioritise performance and merit, he says, in contrast to the Anglo-Saxon system, where powerful deans
decide to recruit people and are then held accountable for
that decision. “We have a very egalitarian culture, and with
the reunification of Germany that’s even more promoted,”
says Professor Weber. “The problem is that we cannot
recruit a person simply because we think he or she is an
absolutely great, outstanding, and brilliant scientist. That
always has to go through a pseudo-democratic caucus
process, and in the end everyone has to concur. You will
find that the majority of people who are rather settled in their
mainstream positions will not be happy with recruiting the
best people.”
Professor Weber is also frustrated by the lack of a tenure
track system. This means that people who want to become
professors or improve their conditions cannot stay at the
institution where they have established good work. They
have to be recruited to another place or at least have a
recruitment offer. “It takes a lot of energy to do that. They
simply don’t rely on the quality of work that you do, and I
think that should speak for itself.”
“We Have a Couple of Markers That We Want to Test in
the Clinic That May Be the [ew] CRP in 10 or 20 Years”
Professor Weber’s research has won numerous prizes,
including the GlaxoSmithKline Basic Research Award in
2003; the Arthur Weber Award, one of the highest awards
from the German Cardiac Society, in 2004; and, in 2005,
the Forßmann Award, a cardiology award in Germany
named after the Nobel laureate who developed vascular
catheterisation in 1929. In 2008, together with Professor
Bernhagen, he was presented with the Paul Martini Award
for the ature Medicine MIF article, and he recently
received a European Society of Cardiology Outstanding
Achievement Award.
In the future, Professor Weber wants to continue to
maintain a balanced private life while recruiting excellent
young scientists and peers to work with him. Personally, he
is always striving to become a better scientist, both conceptually and technically. As for scientific developments, he
believes that individualised medicine will become increasingly important with the use of genome-wide screening and
molecular imaging. The combinatorial diversity of protein
interactions will also allow for the development of tailored
drugs that can treat and prevent atherosclerosis without
side effects. He also believes that the generation of biofunctionalisation of surfaces or interfaces of biomaterials
will be an important and expanding area (eg, for the further
optimisation of stents, vascular grafts, or implants). In his
Circulation: European Perspectives
Circulation June 23, 2009
Working on MIF receptors—from right to left, Professor Bernhagen,
Professor Weber, and PhD student Maik Drechsler. Photograph
courtesy of Professor Weber.
own laboratory, exciting developments in biomarkers for
cardiovascular risk prediction will be tested in patients. “Creactive protein was 10 years ago,” says Professor Weber.
“We have a couple of markers that we want to test in the
clinic that may be the [new] C-reactive protein in 10 or 20
years and may be even more specific and have even more
precision in the prediction of cardiovascular risk.”
References
1. Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR,
Dewor M, Georgiev I, Schober A, Leng L, Kooistra T, Fingerle-Rowson
G, Ghezzi P, Kleemann R, McColl SR, Bucala R, Hickey MJ, Weber C.
MIF is a non-cognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. ature Med. 2007;13:587–596.
2. Koenen RR, von Hundelshausen P, Nesmelova IV, Zernecke A, Liehn
EA, Sarabi A, Kramp BK, Piccinini A, Kowalska A, Kungl AJ, Hackeng
TM, Mayo KH, Weber C. Disrupting functional interactions between
platelet chemokines inhibits atherosclerosis in hyperlipidemic mice.
ature Med. 2009;15:97–103.
3. Weber C, Erl W, Pietsch A, Weber PC. Aspirin inhibits nuclear factorkappa B mobilization and monocyte adhesion in stimulated human
endothelial cells. Circulation. 1995;91:1914–1917.
4. Weber C, Erl W, Weber KSC, Weber PC. HMG-CoA reductase inhibitors
decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes
isolated from hypercholesterolemic patients. J Am Coll Cardiol.
1997;30:1212–1217.
5. von Hundelshausen P, Weber KSC, Huo YQ, Proudfoot A, Nelson PJ,
Ley K, Weber C. Deposition of RANTES by platelets triggers monocyte
recruitment on inflamed and atherosclerotic endothelium. Circulation.
2001;103:1772–1777.
Jennifer Taylor is a freelance medical journalist.
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Team 2009: Institute for Molecular Cardiovascular
Research, Aachen, Germany
“Mutual Help and Synergy Is the Concept”
A
Christian Weber, MD, PhD, FESC, professor, chair, and director of the Institute
for Molecular Cardiovascular Research, Preventive Cardiology, RheinischWestfälische Technische Hochschule Aachen University, Aachen,
orth Rhine-Westphalia, Germany, describes the team and how it works
to Jennifer Taylor, BSc, MSc, MPhil.
s the chair and director of the Institute for Molecular
• Elisa Liehn, MD, PhD, is currently training to become a
Cardiovascular Research (IMCAR), Professor Weber
cardiologist and heads up the molecular cardiology
heads up a 70-strong team with 8 group leaders:
group, which studies chemokines in myocardial infarc• Andreas Schober, MD, a cardiologist, leads the cardiotion and ischaemia reperfusion.
vascular medicine group, which works on mechanisms
of arterial remodelling and the role of chemokines,
Group Leaders Are Either Working on Their
lipids, hypoxia-inducible factor 1, and microRNA.
Habilitation or Have Associate Professor Positions
• Esther Lutgens, MD, PhD, a pathologist from
To become a group leader, a researcher must have funding
Maastricht, the Netherlands, who recently joined
in place, and the number of leaders varies. “If someone
IMCAR through a prestigious Sofia Kovalevskaja
grows into the position of a group leader, I don’t wait until
award funded by the German Humboldt Foundation,
someone is leaving,” explains Professor Weber. Equally, if
heads up vascular pathology and works on immunomodsomeone leaves and there is no one mature enough to follow,
ulation of atherosclerosis and costimulatory molecules
the place remains vacant—apart from associate professor(eg, the CD40/CD40
ship positions, which
ligand axis).
must be filled.
• Marc van Zandvoort,
Group leader meetPhD, a biophysicist,
ings take place weekly.
leads biophysics and
“Everything is exfocuses on 2-photon
tremely cooperative,”
microscopy and molesays Professor Weber.
cular imaging probes
“Mutual help and
for arterial pathology.
synergy are the con• Alma Zernecke, MD,
cepts. Ultimately, the
leads work on vascular
whole is larger than
immunology, which
the sum of its parts,
covers the cellular
and all individuals
immunopathogenesis
benefit from the
of atherosclerosis.
results.” There are
• Rory Koenen, PhD, “a
also weekly semihome-grown talent”
nars with progress
who has been instru- Trying to fit everyone into one boat during an outing. The IMCAR team in Brugge, reports, journal clubs
mental in the work at Belgium. Professor Weber at the back of the boat wearing a cap. Photograph for the postdoctoral
IMCAR, is a chemist courtesy of Professor Weber.
researchers and stuwith an interest in biochemistry and peptide chemistry. He
dents, and regular individual, project-related, and focused
leads these 2 areas and looks at structure–function analysis
meetings with relevant laboratory and group members and
for the interactions of platelet chemokines and adhesion
supervisors.
molecules in vascular recruitment.
For leisure, the team often plays and watches soccer
• Oliver Soehnlein, MD, PhD, has yet to specialise. He leads
with the IMCAR team AC/FC Bayern Aachen.
the vascular medicine/biology group, which studies the role
The team’s mix of skills fosters the multidisciplinary
of neutrophils and monocyte subsets in atherosclerosis.
atmosphere essential for high-level science. Professor
• Mihail Hristov, MD, is skilled in medical theory and
Weber says, “They share ideas and they share technology.
also leads the vascular medicine/biology group, but he
The problem is that with these demanding projects, you
focuses on the role of vascular progenitor cells in cardioneed quite a bit of technology and technical expertise that
vascular remodelling and risk prediction.
cannot be provided by 1 single person or 1 single group.”
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Team 2009. The IMCAR team in May 2009—a young multidisciplinary group of 60–70 scientists from 16 nations. Photograph courtesy of
Professor Weber.
It is therefore advantageous to share each other’s expertise, which means that groups appear as authors on other
groups’ articles. “That’s what makes it a very synergistic
and very lively system. They are definitely not groups that
are separated against each other, it’s rather the opposite.
It’s trying to define expertise and then let them work
together.”
To avoid unhelpful competition and friction, it is essential to define distinct group interests. For example, the
inflammatory pathogenesis of atherosclerosis of vascular
progenitor cells is one subject, and specific cell types or
molecular families need to be assigned to particular groups.
“Alma will work on dendritic cells and T cells, and Oliver
will work on neutrophils and monocytes,” says Professor
Weber. “So then you can simply say in the end, these cells
in the blood work together, but for a starting point we can
have a topical definition of not the expertise but the content
that the groups are working on.” He says that discussing
science, results, and projects with postdoc, PhD, MD, and
MD/PhD students on an individual or a small-group basis
is rewarding because it allows for interactive, stimulating,
and creative processes.
“A Conductor of an Orchestra With Excellent Soloists”
Encountering and discovering talented young scientists for
mutual collaboration, learning, and inspiration is something
Professor Weber views as a privilege and an enjoyable part
of his work, along with promoting the scientists’ development and careers. Professor Weber sees his role as that of
“a conductor of an orchestra with excellent soloists.” He
says, “You need to have a scientific vision and to provide a
strategy and advice, but you also need to carefully listen to
all players to coordinate and balance all groups to create
rhythm and harmony.”
The team has been the source of numerous important
articles, including one in Circulation in 2003 that identified
the role of the chemokine stromal cell-derived factor-1α in
promoting neointimal hyperplasia, smooth muscle cell
content, and progenitor cell recruitment after arterial
denudation injury in atherosclerosis-prone mice.1
An article in Blood in 2005 demonstrated a heterophilic
interaction of the platelet chemokines RANTES and
platelet factor 4, which may explain the synergistic
enhancement of atherogenic monocyte arrest in the presence of both chemokines.2
In Circulation Research in 2008, the team demonstrated
that the stromal cell–derived factor-1/CXC chemokine
receptor 4 ligand–receptor axis protects against atherosclerosis by controlling the homeostasis of neutrophils, thereby
identifying the unexpected involvement of neutrophils in
atherosclerosis.3
It is the collaboration among such a diverse group of
people—biochemists, immunologists, and so on—that
makes the work possible, says Professor Weber. “That’s
also something that creates this fun or the happy moments.
For all of these articles, you need a highly multidisciplinary
effort, and only by bringing these together can you create
the high-impact articles.”
References
1. Schober A, Knarren S, Lin E, Lietz M, Guttenbach M, Weber C. Crucial
role of stromal cell-derived factor-1alpha in neointima formation after
arterial injury in apolipoprotein E–deficient mice. Circulation.
2003;108:2491–2497.
2. von Hundelshausen P, Koenen RR, Sack M, Mause SF, Proudfoot AEI,
Adriaens W, Hackeng TM, Weber C. Heterophilic interactions of
platelet factor 4 and RANTES promote monocyte arrest on endothelium.
Blood. 2005;105:924–930.
3. Zernecke, Bot I, Djalali Talab Y, Shagdarsuren E, Meiler S, Liehn EA,
Schober A, Soehnlein O, Sperandio M, Tacke F, Biessen EA, Weber C.
Protective role of Cxcr4/Cxcl12 unveils the importance of neutrophils
in atherosclerosis. Circ Res. 2008;102:209–217.
Jennifer Taylor is a freelance medical journalist.
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Initiatives in Cardiovascular Research:
The Euregio Cardiovascular Research School
“It Brings 2 Academic Cultures Together and Fosters an
International Scientific Atmosphere”
T
Christian Weber, MD, PhD, FESC, director of the Institute for Molecular
Cardiovascular Research, Rheinisch-Westfälische Technische Hochschule Aachen
University, Aachen, orth Rhine-Westphalia, Germany, talks to Jennifer Taylor,
BSc, MSc, MPhil, about the Euregio Cardiovascular Research School.
he Euregio Cardiovascular Research School (EuCAR) is
Ten PhD students started in October 2008, and in early
an international school jointly based at the Institute for
2010, another round will start. Each PhD student has 2
Molecular Cardiovascular Research (IMCAR) in Aachen,
supervisors, 1 each from the Dutch and German sides, plus a
North Rhine-Westphalia, Germany, and the Cardiovascular
third person who is not yet at the professor level and proResearch Institute Maastricht (CARIM) in Maastricht, the
vides day-to-day supervision. Together they form the thesis
Netherlands. Euregio refers to the Belgian, Dutch, and
committee. A joint curriculum means that students can attend
German triangle in Europe, and CAR is the common denomlectures and seminars at both IMCAR and CARIM. Each
inator of IMCAR and CARIM. With just 30 km between
student has a log book for accruing credit points from the
Aachen and Maastricht, PhD students can commute between
teaching they attend. “The fun part about this is that people
cities for teaching and scientific collaboration.
who are mainly on the Dutch side need to obtain 30% of
Mat Daemen, MD, PhD, scientific director of CARIM,
their credit points here on the German side and vice versa,”
has been a friend of Professor Weber’s since his arrival in
says Professor Weber. “That’s also some guarantee that peoAachen, and in 2006, Professor Weber became jointly affilple really exchange and move between the programme.”
iated as a visiting professor at
The research programme
CARIM. Professor Weber realised the
focuses on arterial remodelling,
possibility of a collaboration when he
and each centre contributes its
obtained a centre grant from the
own expertise. IMCAR has
German
Research
Foundation
expertise in primary atherosclero(Deutsche Forschungsgemeinschaft
sis, neointimal hyperplasia, mouse
[DFG]), the “Forschergruppe 809
models with miniaturised stents as
Chemokines and Adhesion Molecules
models for restenosis, and arterial
in Cardiovascular Pathogenesis,” Professor Weber (right) and Professor Daemen (left), tissue engineering. CARIM has a
which funds consumables and post- are the spokespeople for EuCAR. Steering committee stronger focus on plaque instadoctoral researchers rather than PhD members are Jürgen Bernhagen, PhD, a biochemist at bility and imaging and also works
IMCAR, and Tilman Hackeng, PhD, a biochemist at
students. The DFG’s ideal scenario is
on primary atherosclerosis. Instead
CARIM. Photograph courtesy of Professor Weber.
for groups to have a centre grant, on
of arterial injury, it specialises in
one hand, and a research and training grant, on the other
the processes that lead to plaque rupture and plaque instabilhand, to complement it. Professor Weber says, “Because
ity and has the corresponding models for these processes.
we had the Forschergruppe, the next logical step was to
Professor Weber says the international graduate school
complement it with a research training group.”
“brings 2 academic cultures together and fosters an internaApplying for an international graduate school offered
tional scientific atmosphere.” It accepts the best applicants,
the potential for higher funding, but it required a parallel
regardless of where they come from, so the students have a
grant application and peer review in both countries by the
range of nationalities, including Dutch, German, Belgian,
DFG and the Netherlands Organisation for Scientific
Russian, Indian, Chinese, and Iranian. English is the lingua
Research (NWO). It was an all-or-none situation—either
franca. “But subtle differences exist in the cultures
they both said yes or the whole plan was rejected. They
[between Aachen and Maastricht],” says Professor Weber.
went for it and in 2008 received funding for 5 years, with a
“Different people, different ways of operating a lab—and
chance for renewal for another 5 years, which, roughly
so they experience both, and I think that’s an asset.”
speaking, means 2 rounds of PhD students.
Jennifer Taylor is a freelance medical journalist.
Editor: Helmut Drexler, MD, FESC
Managing Editor: Lindy van den Berghe, BMedSci, BM, BS
We welcome comments. E-mail [email protected]
The opinions expressed in Circulation: European Perspectives
in Cardiology are not necessarily those of the editors or of
the American Heart Association.
European Perspectives
Circulation. 2009;119:f139-f144
doi: 10.1161/CIRCULATIONAHA.109.192208
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Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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