DEPARTMENT OF CLINICAL
RESEARCH
www.dkf.unibe.ch
JahrAensbneurailchRtep2o01rt22012
50 µm
Contact
Basak Ginsbourger
Administrator
Department of Clinical Research
University of Bern
Murtenstrasse 35
3010 Bern
Switzerland
Phone: +41 31 632 3552
Fax: +41 31 632 0946
Email: basak.ginsbourger@dkf.unibe.ch
Members of the University of Bern and Inselspital can obtain
a copy of this report online at: www.dkf.unibe.ch
Cover:
Human cardiomyocytes derived from induced pluripotent stem
cells (iPSC) were allowed to self-aggregate in hanging drops.
After spontaneously contracting spheroids had formed, the micro-
tissue was fixed, immunostained for the muscle protein myomesin
(red), connexin-43 (green) and DNA (blue), and images were
obtained using confocal microscopy at different magnifications.
Image: Dr. Christian Zuppinger
Contents
The DCR at a Glance / Das DKF auf einen Blick 2
Foreword – Director’s Report 3
Vorwort – Bericht des Direktors 4
Organisation 5
Organigram 6
DCR Sites 7
Key People 8
Technology Core Facilities 10
Technology Core Facilities / DCR Internal Research Groups 12
DCR Internal Research Groups 16
DCR Research Groups from the Inselspital 28
Key Events 63
Personnel Update 64
The DCR at a Glance / Das DKF auf einen Blick
The DCR at a Glance Das DKF auf einen Blick
The Department of Clinical Research (DCR) is a research Das Departement Klinische Forschung (DKF) ist ein For-
department of the Faculty of Medicine at the University schungsdepartement der Medizinischen Fakultät der
of Bern. Universität Bern.
Founded in 1994, its mission is to provide the best Es wurde 1994 mit dem Auftrag gegründet, Forschen-
possible environment and infrastructure to researchers at den vom Inselspital, Universitätsspital Bern und von der
the Inselspital, Bern University Hospital and at the Faculty Medizinischen Fakultät eine optimale Infrastruktur zur Ver-
of Medicine. In 2012, 51 independent research groups, fügung zu stellen. 2012 waren 51 unabhängige Forschungs-
covering almost all fields of biomedical research, were gruppen dem DKF angeschlossen, die zusammen fast alle
affiliated with the DCR. Bereiche der biomedizinischen Forschung abdecken.
The main goal of the DCR is to establish a bridge Das Ziel vom DKF ist es, durch die wissenschaftliche
between laboratory-based biomedical and patient-orient- Unterstützung seiner Forschungsgruppen, sowie den Betrieb
ed clinical research, by offering scientific support to its von, dem neusten Stand der Technik entsprechenden, Tech-
groups and by operating state-of-the-art technology core nologie Core Facilities und spezialisierten Tier Core Facilities,
facilities and specialised animal core facilities. Brücken zu schlagen zwischen laborbasierter biomedizini-
scher und patientenorientierter klinischer Forschung.
4 DCR Annual Report 2012 / DKF Jahresbericht 2012
Foreword – Director’s Report
Foreword – Director’s Report
Dear readers and colleagues, Another very positive point that will on ribosomes. Noteworthy also is that
significantly help many DCR scientists, during the day, we had the first site
Looking back at 2012, we can say that is the approval given by the Inselspital visit of the DCR External Advisory
this was a very positive year for the to fund the development of the bio Board. Not only were the four scien-
DCR! Many of the achievements of the informatics support for clinical projects. tists able to attend the meeting but
past year will have a significant impact With this five-year funding, the DCR they also had the opportunity to listen
and improve the breadth of research will be able to hire two bioinformati- to presentations by the heads of the
that can be performed at the DCR. cians and purchase the needed bio DCR Animal and Technology Core
As you may know, one of the core informatics infrastructure to help de- Facilities. We received much interest-
activities of the DCR is to operate tech- velop clinical bioinformatics projects ing and constructive feedback from
nology core facilities, allowing DCR at the Inselspital. This venture will be this new board.
researchers to perform cutting-edge carried out in close collaboration with Again, as you can see, 2012 was
science. Early in 2012, we created a the newly created “Interfaculty Bioin- a year full of activities and develop-
new core facility, located at the Murten- formatics Unit” at the University of ments! It is certainly extremely reward-
strasse 50 division. The “Live Cell Im- Bern, headed by Dr. Rémy Bruggmann. ing to be able to head this department.
aging (LCI) Core Facility” is an offshoot As for the organisation of the This is also the reason why I would
of the DCR “Confocal Microscopy DCR, groups of the DCR were given like to warmly thank all the DCR em-
Core Facility”, which was headed for the possibility in 2012 to form “Re- ployees for the outstanding spirit and
many years by Prof. Shida Yousefi. search Clusters”. With these clusters, excellent work done for the depart-
We thank her for her commitment in the DCR aims to support bottom-up ment and the research community at
running this former facility and, at the initiatives of several DCR research the University of Bern.
same time, wish Dr. Fabian Blank, who groups to collaborate and organise
will head the new facility, all the best. educational activities together. At the Prof. Dr. Hugues Abriel, MD PhD
One first outstanding accomplishment present time, two clusters have for-
of the LCI Facility is the approval of mally started their activities: “Regen-
an SNSF R’Equip project permitting the erative Neuroscience” and “Signal
purchase of a Zeiss LSM 710, one of Transduction in Disease”. The creation
the best confocal microscopes availa- of more research clusters in 2013 is
ble. This microscope will be available under discussion.
to all members of the DCR and will As you know, every year the DCR
also be part of the Microscopy Imag- awards a research prize of CHF 30,000
ing Center (MIC) at the University of to support a promising project pro-
Bern. Here, we also thank the Fund of posed by a young investigator. In 2012,
the Chefärzte of the Inselspital for we had the great luck to reach an
providing matching financial support. agreement with the Johanna Dürmül
The DCR Cytometry Laboratory ler-Bol Foundation, who will finance
also obtained an SNSF R’Equip grant. this prize from now on. The award
This grant allowed the purchase of a will be re-named “Johanna Dürmül
new type of cytometer, ImageStreamX, ler-Bol DCR Research Award” in 2013
which combines the speed and power but the aim of the prize will remain
of flow cytometry with high-resolution unchanged. I take this opportunity to
single-cell microscopy. The newly warmly thank the Foundation Board
created “Genomics Core Facility” was for this very generous support.
likewise able to purchase an Ion Torrent On 14 November, the DCR again
PGM next-generation sequencing held a truly remarkable Day of Clinical
machine in 2012. This machine, which Research. Particularly unforgettable
allows medium throughput sequenc- was the exciting lecture given by
ing, is located at Murtenstrasse 31. Prof. Ada Yonath, Nobel Prize recipient,
5 DCR Annual Report 2012 / DKF Jahresbericht 2012
Vorwort – Bericht des Direktors
Vorwort – Bericht des Direktors
Liebe Leserinnen und Leser neuen Typs von Zytometer, dem jungen Forschers. 2012 konnten wir
Liebe Kolleginnen und Kollegen ImageStreamX, der die Geschwindig- eine Vereinbarung mit der Fondation
keit und die Leistung der Durchfluss Johanna Dürmüller-Bol, die ab 2013
Im Rückblick auf das Jahr 2012 dürfen zytometrie mit der Möglichkeit der den Preis finanzieren wird, unterzeich-
wir sagen, dass es ein sehr positives hochauflösenden Single-Cell-Mikrosko- nen. Die Auszeichnung wird im 2013
Jahr für das DKF war. Viele Errungen- pie kombiniert. Aus fakultären Mitteln umbenannt in „Johanna Dürmüller-Bol
schaften des letzten Jahres werden konnte die neu geschaffene „Genomics DKF Forschungspreis“. Das Ziel des
in der nahen Zukunft positive Auswir- Core Facility“ 2012 ein Ion Torrent Preises bleibt unverändert. Ich nutze
kungen auf die Möglichkeiten der For- PGM Next-Generation Sequenziergerät diese Gelegenheit und bedanke mich
schungsgruppen des DKF entwickeln. anschaffen. Das Gerät für Sequencie- herzlich beim Stiftungsrat für diese
Eine der Kernaufgaben des DKF rungen für mittleren Durchsatz befindet grosszügige Unterstützung.
besteht im Betrieb von Technologie sich an der Murtenstrasse 31. Am 14. November konnte das DKF
Core Facilities, um den Forschenden Ein weiterer Punkt, von welchem wieder den vielbeachteten Tag der
im DKF den Zugang zu Spitzentech- viele DKF Wissenschaftler profitieren Klinischen Forschung durchführen.
nologien zu ermöglichen. Anfangs werden, ist die Zustimmung des Insel- Besonders in Erinnerung bleiben wird
2012 haben wir im Forschungsbereich spitals, die Entwicklung des Bioinfor- der spannende Vortrag über die Auf-
Murtens trasse 50 eine neue Core matik-Support für klinische Projekte zu klärung der Struktur der Ribosomen
Facility geschaffen. Die „Live Cell Ima- unterstützen. Diese Fünf-Jahres-Finan- der Trägerin des Nobelpreises von 2009,
ging (LCI) Core Facility“ ist die Weiter- zierung erlaubt dem DKF die Anstel- Frau Prof. Ada Yonath (Weitzman In-
führung der „Konfokalen Mikroskopie lung von zwei Bioinformatikern und die stitute, Rehovot, Israel). Erwähnens-
Core Facility“ des DKF, welche wäh- Anschaffung der nötigen Infrastruktur wert ist ebenfalls, dass am Tag der
rend vielen Jahren von Prof. Shida für Bioinformatik zur Entwicklung von Klinischen Forschung die erste Site-Visit
Yousefi geleitet wurde. Wir danken klinischen Bioinformatik-Projekten am des External Advisory Boards des DKF
Frau Prof. Yousefi für ihr Engagement Inselspital. Dieses Unternehmen wird in stattfand. Die vier Wissenschaftler
in der Führung dieser Einheit, und zur enger Zusammenarbeit mit der neu ge- konnten nicht nur diese Veranstaltung
gleichen Zeit wünschen wir Dr. Fabian schaffenen „Interfaculty Bioinformatics besuchen, sondern hatten auch die
Blank, der die Leitung der neuen LCI Unit“ der Universität Bern, unter der Gelegenheit den Präsentationen der
übernehmen wird, alles Gute! Eine Leitung von Dr. Rémy Bruggmann, Leiter der DKF Tier und Technologie
erste ausserordentliche Leistung konnte durchgeführt werden. Core Facilities zu folgen. Wir erhielten
die LCI Core Facility bereits verzeich- Was die Organisation des DKF be- eine sehr interessante und konstruktive
nen. Mit der Genehmigung eines SNF trifft, wird seit 2012 DKF Forschungs- Rückmeldung von diesem neuen Board.
R’Equip Projektes für ein Zeiss LSM gruppen die Möglichkeit geboten Wie Sie sehen, war auch das Jahr
710 Mikroskop, wird die Anschaffung sogenannte „Forschungscluster“ zu 2012 wieder ein Jahr voller Aktivitäten
eines der zurzeit besten Konfokalen bilden. Das Ziel ist es, mit diesen Clus- und Wachstum! Es ist für mich sehr be-
Mikroskope ermöglicht. Dieses Mikro- ters bottom-up Initiativen von DKF friedigend, dieses Departement leiten
skop wird den Mitarbeitenden des Forschungsgruppen zu Zusammen zu dürfen. Aus diesem Grund möchte
DKF zur Verfügung stehen und wird arbeiten und zur Organisation ge- ich mich ganz herzlich bei allen DKF
auch Teil des Microscopy Imaging meinsamer Weiterbildungsaktivitäten Mitarbeitenden bedanken für ihren be-
Centers (MIC) der Universität Bern sein. zu unterstützen. Aktuell sind zwei merkenswerten Elan und für die exzel-
An dieser Stelle bedanken wir uns Clusters aktiv: „Cluster für Regenera- lente Arbeit, die sie für das Department
beim Fonds für Infrastruktur der Chef tive Neurowissenschaft“ und „Cluster und die Forschungsgemeinschaft an
ärztinnen und Chefärzte des Insel Signal Transduction in Disease“. Die der Universität Bern geleistet haben.
spitals für die Bereitstellung eines Schaffung weiterer Clusters im kom-
Matching Funds. menden Jahr wird diskutiert. Prof. Dr. Hugues Abriel, MD PhD
Das DKF Zytometrie Labor hat Jährlich verleiht das DKF einen For-
ebenfalls einen SNF R’Equip Förder schungspreis von CHF 30’000 zur Un-
ungsb eitrag zugesprochen erhalten. terstützung eines vielversprechenden
Dieser ermöglichte den Kauf eines Projektes einer jungen Forscherin/eines
6 DCR Annual Report 2012 / DKF Jahresbericht 2012
Organisation
Organisation
The role of the DCR is to provide
optimal infrastructure and scientific
support to its research groups, of
which there were 51 at the end of
2012. The vast majority (43) of these
groups are from departments of the
Inselspital, Bern University Hospital.
The remainder (8) are internal DCR
groups, involved in the scientific sup-
port and coordination of equipment
and infrastructure on a daily basis.
The 51 groups are divided into 6 Re-
search Divisions. Equally important,
the DCR is responsible for operating
technology and animal core facilities.
Furthermore, the groups of the de-
partment are supported by central ser-
vices responsible for administration,
informatics and technical support.
7 DCR Annual Report 2012 / DKF Jahresbericht 2012
Organigram
Organigram
DCR External Advisory Board University of Bern
Faculty of Medicine
DCR Board of Trustees
Directorate Administration and Central Services
Prof. H. Abriel, Director Administrator
Prof. W. Hofstetter, Deputy Director Finances and DCR Secretaries
Management and Support Secretary of Director
DCR Human Resources
Facility Manager
IT-Support
Technical Services
House Staff
51 Research Groups in Animal Core Facilities
6 Research Divisions
Central Animal Facility
Kinderklinik Mu50 Animal Facility
(Coordinator: PD Dr. M. Heller)
M.E. Müller-Haus CMF, Clean Mouse Facility
(Coordinator: Prof. W. Hofstetter)
Murtenstrasse 50, Augenklinik ESI, Experimental Surgery Unit
(Coordinator: Prof. R. Rieben)
Pathologie, Sahli-Haus 1+2 Technology Core Facilities
(Coordinator: Prof. R. Jaggi)
Pavillon 52 Confocal Microscopy
(Coordinator: Prof. C. Boesch) (Head: Prof. S. Yousefi)
Tiefenau
(Coordinator: Prof. A.-C. Andres) Cytometry Laboratory
(Head: Dr. S. Müller)
Core Activities
Genomics
(Head: Prof. R. Jaggi)
Live Cell Imaging (LCI)
(Head: Dr. F. Blank)
Mass Spectrometry and Proteomics
Laboratory (Head: PD Dr. M. Heller)
8 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Sites
123
M.E. Müller-Haus Murtenstrasse 50 Pathologie
Murtenstrasse 35 Murtenstrasse 31
5
4 6
Pavillon 52 Kinderklinik Sahli-Haus 1
Freiburgstrasse 3 Freiburgstrasse 15 Freiburgstrasse 14a
7 8 9
Sahli-Haus 2 Augenklinik Tiefenau
Freiburgstrasse 14 Freiburgstrasse 8 Tiefenaustrasse 120c
9
Friedbühlstrasse
2
Mu50
Murtenstrasse
BIentsteelnshpoitcahl haus
M.E. 1
Müller-Haus
3
INO Pathologie
Sahli-Haus 1 6
Haller-Haus
Sahli-Haus 2 7
Poliklinik Trakt 2 Poliklinik Trakt 1
Augenklinik8
Frauenklinik Kinderklinik Freiburgstrasse
5 Pavillon52
4
9 DCR Annual Report 2012 / DKF Jahresbericht 2012
Key People
Key People
DCR Board of Trustees Members Ex Officio
Prof. Dr. Claudio Bassetti (since Feb.) Prof. Dr. Hugues Abriel
Prof. Dr. Hans-Uwe Simon Prof. Dr. Daniel Candinas Prof. Dr. Marcel Egger
Chair (since Sep.) Prof. Dr. Sabina Gallati Prof. Dr. Peter Eggli
Prof. Dr. Peter Jüni Prof. Dr. Matthias Gugger
Prof. Dr. Christoph Müller Prof. Dr. Anton Sculean
(Chair: until Aug.) Prof. Dr. Andreas Stuck
Prof. Dr. Lutz-Peter Nolte Regula Käch
Marianne Thormann (until Feb.)
Directorate External Advisory Board
Prof. Dr. Hugues Abriel Prof. Dr. Willy Hofstetter Prof. Dr. Gisou van der Goot
Director Deputy Director EPF Lausanne, Switzerland
Prof. Dr. Paul Klenerman
Administration and Central Services University of Oxford, UK
Prof. Dr. Karl Schaller
Administrator, Finances and Secretary of Director University of Geneva, Switzerland
DCR Secretaries Verena Frazao Prof. Dr. Radek Skoda
Gaby Bloem University of Basel, Switzerland
Administrator (Mar.–Sep.) DCR Human Resources
Basak Ginsbourger Silvia Rösselet IT-Support
Administrator (since Nov.) Michelle Cibien
Ruth Scheuter Facility Manager Thomas Späti
Secretary Bernhard Grossniklaus (since July)
José Schranz
Secretary Technical Services
Otto Aeby
Head DCR Maintenance
10 DCR Annual Report 2012 / DKF Jahresbericht 2012
Key People
Coordinators of Research Divisions
Prof. Dr. Anne-Catherine Prof. Dr. Chris Boesch PD Dr. Manfred Heller
Kinderklinik
Andres, Tiefenau Pavillon 52
Prof. Dr. Willy Hofstetter Prof. Dr. Rolf Jaggi Prof. Dr. Robert Rieben
Murtenstrasse 50,
M.E. Müller-Haus Pathologie, Sahli-Haus 1+2 Augenklinik
Heads of Technology Core Facilities
Dr. Fabian Blank PD Dr. Manfred Heller Prof. Dr. Rolf Jaggi
Live Cell Imaging (LCI) Mass Spectrometry and Genomics
Proteomics Laboratory
Dr. Stefan Müller Prof. Dr. Shida Yousefi
Cytometry Laboratory Confocal Microscopy
11 DCR Annual Report 2012 / DKF Jahresbericht 2012
Technology Core Facilities
Confocal Microscopy
www.pki.unibe.ch/content/confocal_microscopy
Achievements 2012 Finances 2012 Prof. Dr. Shida Yousefi
The service team of the Institute of The Confocal Microscopy Core Facility shida.yousefi@pki.unibe.ch
Pharmacology trained more than collected CHF 10,525 in user fees. PhD at University of Zurich (1996). Postdocs at
50 scientists from the University of Disbursements included CHF 5,000 University of Toronto General Hospital (CA)
Bern in confocal microscopy and im- for consumables, CHF 1,500 for and Novartis Research Centre, Horsham (UK).
aging techniques. Training was spe course expenses and CHF 16,994 for Since 2000, Principal Investigator, Institute
cifically performed using ongoing Imaris maintenance, plus CHF 4,320 of Pharmacology, University of Bern. Since 2002,
research projects of the users. At least for an upgrade to Imaris Suite. Many Head, DCR Confocal Microscopy Core Facility,
five original articles have been pub- faculties of the University of Bern located at Institute of Pharmacology, University
lished in which the authors used our used the Imaris software. In addition, of Bern.
facility to produce state-of-the-art the DCR paid CHF 6,366 (mainte-
results. As in previous years, all the nance flat fee), as well as CHF 28,036 Staff Members
activities and services of the facility (replacement of UV laser), CHF 1,471 Prof. Dr. Shida Yousefi, Head
were coordinated with the Microscopy (repair of 100X objective lens) and Dr. Zhaoyue He, Postdoctoral Fellow
Imaging Center, University of Bern. CHF 1,050 (replacement of lamp) in Evelyne Kozlowski, Laboratory
repairs for the LSM 510 Exciter confo- Technician
Performance Report 2012 cal microscope.
Thirty-one different research groups
from the DCR and/or Inselspital Outlook 2013
departments used the LSM 5 Exciter In March 2012, the new Live Cell Im-
confocal microscope for a total of aging (LCI) Core Facility, headed by
1,373 hours. As in previous years, we Dr. Fabian Blank, was opened at
organised a biannual two-day prac Murtenstrasse 50. Prof. Yousefi will
tical course for PhD and MD students, continue to coordinate the Confocal
and technicians. These courses pro- Microscopy and Image Analysis Fa
cility within the Institute of Pharma-
vided beginners with a basic know cology until March 2013, by which
time the LCI Facility will be fully func-
ledge of fluorescent staining tech- tional. Dr Blank will then also be in
niques and subsequent confocal charge of the training courses.
microscopy analysis, including imag-
ing software. Overall, we trained
more than 35 scientists. Twenty-four
different laboratories received sup-
port and licences for Imaris software.
Prof. Yousefi was responsible for up-
dating and maintaining the floating
licences, as well as providing technical
support to users. In terms of person-
nel resources, Prof. Yousefi was the
main person responsible for intro
ducing the confocal microscope and
the imaging analysis software (Imaris
and Huygens) to new users. Two
members of Prof. Hans-Uwe Simon’s
research group, Dr. Zhaoyue He and
Ms. Evelyne Kozlowski, were addition-
ally responsible for training.
12 DCR Annual Report 2012 / DKF Jahresbericht 2012
Technology Core Facilities
Cytometry Laboratory
www.facslab.unibe.ch
Achievements 2012 Finances Dr. Stefan Müller
By the end of the year, we were able to In contrast to 2011, we had to order stefan.mueller@dkf.unibe.ch
buy and install an automated, robotic important service work for our instru-
96-well/384-well sampling device—the ments and expenses were CHF 6,200 Studies in microbiology at University of Bern;
HyperCyt-HyperView system. It is now higher than the revenues. Since 2011 PhD (1996). Postdoc in intestinal mucosal
being thoroughly tested. This system rather than 2012 was the exceptional immunology at University of Bristol (UK)
allows massively reduced sample vol- year with regard to service and repair (2000-2001); Head, Flow Cytometry Laboratory,
umes and high-throughput, walk-away costs, we have implemented user School of Cellular and Molecular Medicine
measurements of extensive screening fee adjustments starting from 2013. (2001). Since 2004, Senior Scientist in Gastro-
experiments at a fraction of the time enterology at DCR; since 2010, Head, Flow
and cost of manual sample acquisition. Outlook 2013 Cytometry Core Facility.
In addition, our SNF R’Equip application –– To increase capacity for state-of-
for the ImageStreamX imaging flow Staff Members
cytometer was successful. This instru- the-art 5 lasers/up to 18 colour Dr. Stefan Müller, Head
ment will be installed in early 2013. measurements, we are applying for Dr. Claudio Vallan, Scientific and
The availability of an imaging flow cyto financial support to upgrade the Educational Support
meter will allow our users to take their older BD LSR II cytometer to the Sabine Schneider, Laboratory
flow cytometry experiments a step “SORP”-level. Technician (until Mar.)
further: in addition to the traditional –– The server login system has been Bernadette Wider, Laboratory
FACS analyses with plots and histo- running since 1 January 2013, Technician
grams, fluorescent microscopic images allowing billing and statistics based
are taken of each and every cell, allow- on the log files.
ing morphometry, signalling, (co-)loca –– We plan to offer at least two FACS
lisation and many more aspects to be courses. Dates and programme will
assessed in statistically powerful ways be posted on our webpage. Course
and out of complex mixtures of cells. participants from the Graduate School
The server login system is now work- for Cellular and Biomedical Sciences
ing. From the beginning of 2013, billing will be entitled to 2 ECTS points.
processing and statistical evaluations will –– The ImageStreamX cytometer will
be easier to handle and more reliable. be installed and thoroughly tested.
In 2012, we offered two FACS Users will be trained to use the new
courses and organised a workshop and equipment.
a seminar, held by company represent-
atives, on topics of wide interest to
our FACS users.
Performance Report
We had a very busy year with the
state-of-the-art BD LSR II SORP cytom-
eter being almost constantly booked
during regular office hours, and often
until very late. Altogether, measure-
ments on our analysis instruments
increased by 6% compared to 2011.
However, sorting decreased by 10.5%
compared to 2011, mainly due to an
unusually quiet last quarter in 2012.
13 DCR Annual Report 2012 / DKF Jahresbericht 2012
Technology Core Facilities / DCR Internal Research Groups
Genomics (Core Facility)
www.gcf.dkf.unibe.ch
Molecular Biology (Research Group)
www.molbiol.dkf.unibe.ch
Achievements 2012 Prof. Dr. Rolf Jaggi
Steroid hormones are essential regulators of proliferation in oestrogen-de- rolf.jaggi@dkf.unibe.ch
pendent breast cancer. Oestrogen binds to the oestrogen receptor (ER) and
the complex translocates into the nucleus. There it acts as a transcription factor Studies in cell biology, PhD (1982). Postdoc
stimulating or repressing specific genes, some of which regulate or stimulate (1984-1986) and Group Leader (1986-1988) in
cell proliferation. It has been known for decades that these tumour cells can Ludwig Institute for Cancer Research, Bern.
be inhibited efficiently by anti-oestrogens like tamoxifen (Tam). Another drug, Research in Institute of Clinical and Experimen-
letrozole (Let), has a similar effect but acts through different mechanisms. tal Cancer Research, Bern (1988-1996), several
Despite extensive research, many aspects of the underlying processes are still research periods in Ireland with Prof. Finian
not understood. While a majority of ER-positive cancers respond similarly to Martin, at University College, Dublin (1989-
both drugs, some tumours can only be inhibited by either Tam or Let, and an- 1992). Habilitation (1990), Professor (1996) at
other group are resistant to both drugs or become resistant during treatment. University of Bern. Since 2010, Coordinator in
Many patients who develop resistance have a poor prognosis, dying within five DCR; since 2011, Head of Genomics Core Facility.
years. Moreover, most ER-positive cancers express the ER in only a fraction of
tumour cells, while the remaining cells have no ER and cannot respond directly
to anti-oestrogens. The mechanism by which these tumours are inhibited is
unknown but anti-ER drugs have a significant effect in tumours that contain
only a few percent of ER-positive cells.
Our group worked with material from a global trial of more than 8,000
ER-positive breast cancer patients, run by the International Breast Cancer Study
Group. They showed that Let for five years or Let for two years followed by
Tam for 3 years was superior to any treatment starting with Tam. Although the
difference was only about 3%, it was statistically significant. We obtained mate-
rial from about 300 patients representing two groups (Tam or Let for five years).
About half of each group had a recurrence within five years. Gene expression
was measured using a NanoString nCounter. We are searching for genes or
groups of genes (profiles) whose expression correlates with disease-free survival.
Performance Report
Genomics
In May 2012, we obtained an Ion Torrent PGM instrument (financed by the
Faculty of Medicine). After a short introduction, we could run our own experi-
ments using both 314 or 316 chips. Overall, we were very happy with the per-
formance of the machine. We tested DNA from cancer cell lines and partially
fragmented DNA isolated from FFPE material for the presence of mutations
and deletions using a commercially available cancer panel. Some of the results
were directly compared to the results of standard analyses by pyrosequencing.
In collaboration with Erik Vassella, we found very good agreements between
the two techniques. As a consequence, the Institute of Pathology plans to use
the Ion Torrent again in 2013. In December 2012, an independent study from
the Vetsuisse Faculty was performed with primers designed in-house and several
genomic DNAs derived from horse blood. These results were evaluated by the
Bioinformatics Unit and were very valuable. In addition, the Molecular Biology
technician made several hundred libraries and started many runs for the Illumina
HiSeq 2000 sequencer of the University of Bern Next Generation Sequencing
(NGS) Platform.
14 DCR Annual Report 2012 / DKF Jahresbericht 2012
Technology Core Facilities / DCR Internal Research Groups
Finances techniques may also be of interest for cancer cells in ER-positive breast
Genomics other studies on gene expression from cancer (R. Jaggi) CHF 6,800
The Genomics Core Facility had a single cells or small groups of cells –– Foundation biobank-suisse: Ver-
working credit of CHF 15,000 from that are surrounded by other cells. gleich von Gewebeproben aus ver-
the DCR for 2012. Part of the money schiedenen Biobanken der Schweiz:
was used to set up the Ion Torrent Staff Members Analyse der Genexpression mit RNA
instrument and perform initial test Prof. Dr. Rolf Jaggi, Group Leader aus gefrorenen und aus fixierten
runs. We provide reagents and chips Dr. Stefan Wyder, Mammakarzinom-Gewebeproben
for single libraries and single chips so Bioinformatician (until Oct.) (R. Jaggi, D. Simeon-Dubach)
that research groups do not have to Muriel Fragnière, Laboratory CHF 12,800
build up their own stocks. In addition, Technician
we bought a server that can be used Véronique Vocat, PhD Student Teaching Activities
for data analysis. It was integrated –– Matthias Schindler: MSc
into the existing infrastructure in the Collaborators –– Véronique Vocat: PhD Student
server room of the Bioinformatics Unit. Molecular Biology –– 1st-year medical students: Problem
Currently, it is being used for data Aebi S, Lucerne Cantonal Hospital,
analysis using the CLC Genomics Switzerland Based Learning
workbench (license provided by the Bubendorf L, University of Basel, –– Omics: Lecture on disease profiling
Bioinformatics Unit). Switzerland –– Selected topics in molecular
Cathomas R, Graubünden Cantonal
Outlook 2013 Hospital, Switzerland pathology: Lecture on molecular
Genomics Gautschi O, Lucerne Cantonal processes of disease
In December 2012, the Inselspital Hospital, Switzerland –– Tumour biology: Lecture on
decided to support clinical research Kammler R, International Breast genomics
groups who plan NGS studies. A sec- Cancer Study Group, Switzerland
ond laboratory technician could be Kristiansen G, University of Publications
hired and she will share the work relat- Bonn, Germany Molecular Biology
ed to high throughput sequencing on Krupp G, AmpTech, Germany MicroRNA-29b is involved in the
the Illumina instrument and the low Pestalozzi B, Zurich, Switzerland Src-ID1 signaling pathway and is dys-
throughput Ion Torrent instrument. Perren A, University of Bern, regulated in human lung adenocarci-
The two technicians will be responsible Switzerland noma. Rothschild, SI; Tschan, MP;
for the maintenance of the two sys- Regan M, Dana-Farber Cancer Federzoni, EA; Jaggi, R; Fey, MF;
tems and will provide support and Institute, USA Gugger, M; Gautschi, O (2012) in:
service to clinical groups who want to Rothschild S, Basel Cantonal Oncogene, 31(38), p. 4221-4232.
use the equipment. In addition, we Hospital, Switzerland MicroRNA-381 represses ID1
will install new protocols, e.g., for long Vassella E, University of Bern, and is deregulated in lung adenocarci
reads (400 bp) and we will develop Switzerland noma. Rothschild, SI; Tschan, MP;
novel applications on the Ion Torrent. Viale G, European Institute of Jaggi, R; Fey, MF; Gugger, M;
Oncology, Italy Gautschi, O (2012) in: J Thorac Oncol,
Molecular Biology Zlobec I, University of Bern, 7(7), p. 1069-1077.
We will extend our studies on gene Switzerland Efficacy of Cetuximab in Metastatic
expression with ER-positive and Castration-Resistant Prostate Cancer
ER-negative cells by isolating single Grants Might Depend on EGFR and PTEN Ex-
cells or small clusters of cells (e.g., by Amounts allocated for 2012: pression: Results from a Phase II Trial
FACS) and analysing gene expression Molecular Biology (SAKK 08/07). Cathomas, R; Rother-
in their RNA. The procedure is cur- –– Swiss Cancer League: Molecular pro- mundt, C; Klingbiel, D; Bubendorf, L;
rently being tested with cells from cell Jaggi, R; Betticher, DC; Brauchli, P;
lines, the RNA is reverse transcribed filing from archival human breast Cotting, D; Droege, C; Winterhalder,
and amplified by PCR. The PCR prod- cancer samples (R. Jaggi) CHF 43,500 R; Siciliano, D; Berthold, DR; Pless, M;
ucts will again be analysed using –– Swiss Cancer League: Identification Schiess, R; von, MR; Gillessen, S
nCounter. The protocol will then be of a clinically applicable prognostic (2012) in: Clin Cancer Res, 18(21),
applied to cells derived from breast RNA signature of prostate cancer p. 6049-6057.
cancers stored in the Biobank Bern. (R. Jaggi, G. Kristiansen) CHF 137,700
The procedure will allow us to charac- –– W.+H. Berger-Janser Foundation:
terise ER-positive and ER-negative Characterization of ER-negative
cells in breast cancer. These and similar
15 DCR Annual Report 2012 / DKF Jahresbericht 2012
Technology Core Facilities / DCR Internal Research Groups
Mass Spectrometry and
Proteomics Laboratory (Core Facility)
Protein and Cell Biology
(Research Group) www.pmscf.dkf.unibe.ch
Achievements 2012 PD Dr. Manfred Heller
As in the past year, our single instrument LC-MS platform was continuously manfred.heller@dkf.unibe.ch
analysing protein samples, with a few exceptions (breakdowns, maintenance and
a lull at the end of summer/beginning of autumn). The steady increase of ana- PhD in Chemistry/Biochemistry from the Uni-
lytical runs forced us to install a new data interpretation server (6 quad core, versity of Bern (1994). Postdoc positions at
2.7 MHz, 50 GB RAM). We could secure a total of CHF 460,000 from the Fac- University of Auckland (NZ) and Washington
ulties of Medicine, Science and Vetsuisse in matching funds for the SNF R’Equip (USA). Return to Switzerland in 1999 to Uni
grant. We tested mass spectrometers from two vendors and purchased two versity of Geneva, followed by three years
new LC-MS systems following WTO guidelines. as Senior Scientist at GeneProt Inc., Geneva,
We were successful in the spring round of the CRUS SCIEX-NMSch pro- working on large-scale proteomics projects
gramme, which fosters training placements in Switzerland for young scientists using LC-MS, MALDI-MS and robotics. Since
from new EU states. Marian Petrovic has joined us for one year, after which 2003, Head of Proteomics and Mass Spec
he will finish his PhD at the Pavol Jozef Šafárik University (SK). He has already trometry Laboratory (PMSCF), a DCR Core Fa-
run a series of experiments with the goal to improve the algorithm for the cility since 2008. Fifteen years experience
theoretical prediction of the isoelectric point of polypeptides (in collaboration in the use of mass spectrometry for protein
with the Proteome Informatics Group at the Swiss Institute of Bioinformatics, analytics, proteomics and bioinformatics.
Geneva) and define characteristic traits in the proteome of primary endothelial
cells of different origins.
Niurka Meneses developed new strategies to characterise the interactome
of plasma membrane proteins. Our target was transient receptor potential
cation channel subfamily M member 4 protein (TRPM4). Formaldehyde and
photoactivable amino acids were employed to cross-link TRPM4 with its nearest
interaction partners. The cross-linked complexes were separated by SDS-PAGE
and proteins identified by LC-MS/MS. Necessitated by non-specific background,
we are developing bioinformatics approaches to distinguish true from false
positive interactors.
We tested cell culture conditions that enable the in-vivo labelling of primary
endothelial cells with stable-isotope marked amino acids (SILAC). We intend to
perform quantitative proteome studies of these delicate cells using this method.
Furthermore, we have improved our protocol for microparticle isolation and
proteomic analysis.
Performance Report
Mass Spectrometry and Proteomics
The lab had to be moved to a temporary facility within the Children’s Hospital
in April. We took the chance to do some preventive maintenance on all instru-
ments. This caused some problems on one of the HPLCs that took several
weeks to fix. Furthermore, a malfunction in a power supply board on the mass
spectrometer caused unexpected shutdowns of the system. Despite the down
times, we will break last year’s sample throughput record anew (666 in 2011,
>>1000 in 2012).
16 DCR Annual Report 2012 / DKF Jahresbericht 2012
Technology Core Facilities / DCR Internal Research Groups
Finances Grants
Mass Spectrometry and Proteomics Amounts allocated for 2012:
In April, we changed our billing struc- Protein and Cell Biology
ture from a charge based on type of –– SNF: NCCR TransCure sub-project:
analysis to one based on actual ma-
chine time and other resources used. Physiology, pharmacology and
The Faculty of Medicine Resources pathophysiology of the calcium-ac-
Committee granted CHF 8,000 to cover tivated non-selective cation TRPM4
some of the running costs. The Core channel (M. Hediger, H. Abriel,
Facility budget covered seven months’ M. Heller) CHF 111,300
salary for Sophie Braga-Lagache. –– Sciex-NMSch: Quantification of new
Thanks to the accumulation of funds protein synthesis by endothelial
in the last years and this year’s revenue, cells under shear stress using SILAC
we were able to roughly break even. method (M. Petrovic, M. Heller)
CHF 15,500
Outlook 2013 Teaching Activities
The year 2013 will be a milestone for –– 1 st-year medical students: Problem
our facility. In calendar week 7, we
can move back to the refurbished Based Learning, Tutor block 1
laboratories, which can hold up to four –– P roteomics lectures: Tumour bio
LC-MS instruments, featuring uninter-
rupted power supply and air condi- logy (Faculty of Medicine, Biomedi-
tioning. Two new LC-MS instruments cal Engineering), Omics (Faculty
will be installed, giving us more free- of Science)
dom in working on more complicated
proteomics projects and developing Publications
new methods, such as an in-depth Cause or Effect of Arteriogenesis: Com-
discovery proteome analysis within positional Alterations of Microparticles
24 hours, targeted quantification for from CAD Patients Undergoing Exter-
clinical samples, and lipidomics. We nal Counterpulsation Therapy. Al, KA;
will receive professional bioinformatics Traupe, T; Stutz, M; Buchs, N; Heller, M
support thanks to new bioinformatics (2012) in: PLoS One, 7(10), p. e46822.
positions funded by the Faculty of Eukaryotic translation elongation
Science and Inselspital funds. This factor 1A (eEF1A) domain I from S.
support is essential for our ambitious cerevisiae is required but not sufficient
goals. for inter-species complementation.
Eltschinger, S; Greganova, E; Heller, M;
Staff Members Butikofer, P; Altmann, M (2012) in:
PD Dr. Manfred Heller, Head PLoS One, 7(7), p. e42338.
Dr. Niurka Meneses Moreno, Proteome remodelling during de-
Postdoctoral Fellow (Research Group) velopment from blood to insect-form
Sophie Braga-Lagache, Laboratory Trypanosoma brucei quantified by
Technician (Core Facility) SILAC and mass spectrometry.
Natasha Buchs Tetkovic, Gunasekera, K; Wuthrich, D; Braga-La-
Laboratory Technician (Core Facility gache, S; Heller, M; Ochsenreiter, T
& Research Group) (2012) in: BMC Genomics, 13(1), p. 556.
Marian Petrovic, visiting PhD Student
(SCIEX program, Research Group
& Core Facility)
Collaborators
Müller M, Swiss Institute of
Bioinformatics, Switzerland
Wittwer M, Labor Spiez, Switzerland
17 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Bone Biology &
Orthopaedic Research
www.bonebiology.dkf.unibe.ch
Research Highlights 2012 / Outlook 2013 Prof. Dr. Willy Hofstetter
Bone Biology & Orthopaedic Research Group hofstetter@dkf.unibe.ch
Highlights of our research on bone cell biology, inflammatory diseases and
molecular transport systems include: MSc in Biochemistry at ETH Zurich; PhD in Bio-
–– During Prof. Hofstetter’s sabbatical at the Matsumoto Dental University, chemistry (supervisor Prof. N. Herschkowitz) at
the Children’s Hospital of the Inselspital. Post-
Japan, a new osteoclast resorption assay was developed, which will be modi- doc at the University of Georgia (US). Joined
fied to be used as a medium-throughput assay. the Institute of Pathophysiology, University of
–– The transporter repertoire of osteoblast and osteoclast lineage cells was ana- Bern. Since 1997, Head, Bone Biology & Ortho-
lysed using low-density arrays. Functional tests will be performed to assess paedic Research Group, DCR.
the roles of specific molecular transporters in bone metabolism. Glutamate
was found to be an osteogenic compound. Inhibition of glutamate transport-
ers in osteoblasts caused an increase in extracellular glutamate and a stimu-
lation of osteoblast differentiation (W. Xie).
–– The bone phenotypes of TRPV6, NCX1 and MK2 knockout mice were char-
acterised on cell and tissue levels.
–– IL17 was found to inhibit osteoclast development by inducing the release of
GM-CSF by osteoblast lineage cells. Since the effect was dependent on the
presence of monocyte/macrophage lineage cells, the respective mechanisms
need to be further investigated (D. Balani).
–– A ntagonists of osteogenic signalling pathways were found to be upregulated
in delayed fracture healing in mice. This suggests that an excess of inhibitors
rather than a lack of growth factors is responsible for the delay in healing.
–– A genetically engineered inhibitor of BMP antagonists was found to increase
the efficacy of BMP2 in vivo. A critical size defect model in rats was used to
investigate bone healing and biomaterial turnover.
–– T he first experiments were performed using a bioreactor that allows the ap-
plication of complex mechanical loading protocols on osteochondral grafts.
Dedifferentiation and redifferentiation of chondrocyte lineage cells of bovine
origin were investigated in vitro (R. Egli, A. Tekari).
Osteo-Articular Research Group
Highlights of our research on cartilage biology and degeneration, and imaging
techniques to assess osteoarthritic changes include:
–– The regulated expression of S100A1 and S100B proteins in primary human
articular chondrocytes in culture was demonstrated by combining FACS,
Western blot, cellular ELISA and qRT-PCR.
–– The precise measurements of cartilage thickness within the intact joint (nor-
mal versus arthritic) were performed by combining contrasting agents
with microCT. A strong correlation with histology was shown in rat, rabbit
and goat animal models.
–– A study of growth factor release between leukocyte- and platelet-rich fibrin
(L-PRF), plasma and blood clot showed the superiority of L-PRF for potential
use in clinical treatments of tears in the red-white zone of the meniscus
(M. Schär).
–– T esting collagen-derived sponges for neochondrogenesis was performed
with human chondrocytes in vitro (D. Herz).
18 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Group Members Grants 2012 Teaching Activities
Bone Biology & Orthopaedic Amounts allocated for 2012: –– M asters course in Biomedical Engi-
Research Group Bone Biology & Orthopaedic Research
Prof. Dr. Willy Hofstetter, –– SNF: NCCR TransCure sub-project neering: Tissue Engineering (Nesic)
Group Leader –– Masters course in Biomedical Engi-
Dr. Rainer Egli, Senior Scientist – Role of ion transporter TRPV6 and
Dr. Antoinette Wetterwald, other transporters in bone homeo- neering: Osteology (Hofstetter)
Senior Scientist stasis (M. Hediger, W. Hofstetter) –– 3rd-year dentistry students: Patho-
Silvia Dolder, Laboratory Technician CHF 70,000
Mark Siegrist, Laboratory Technician –– S NF: NFP64 – Nanofibres rein- physiology – Skeleton (Hofstetter)
Deepak Balani, PhD Student forced bone substitute materials: –– 1st-year medical students: Molecu-
(until May) Effect of delayed fibre degradation
John Choy, PhD Student on cells and tissues (R. Luginbuehl, lar biology practical courses
Adel Tekari, PhD Student K. Maniura, W. Hofstetter) (Hofstetter)
Wenjie Xie, PhD Student –– SNF: Biofunctionalization of ß-Tri- –– 2nd-year medical students: Kidney
calcium Phosphate Ceramics for the block – calcium and phosphate
Osteo-Articular Research Group Repair of Osseous Defects (F. Klenke, metabolism (Hofstetter)
PD Dr. Dobrila Nesic, Group Leader W. Hofstetter) CHF 80,000
Dr. Jose Diaz Romero, Senior Scientist –– S NF: Osteoclastogenesis and chronic Publications
Dr. Aurélie Quintin, Research inflammatory rheumatic disorders, L51P – a BMP2 variant with osteoin-
Assistant (M. Seitz, D. Aeberli, B. Engelhardt, ductive activity via inhibition of
JV Stein, W. Hofstetter) Noggin. Albers, CE et al. (2012) in:
Clinicians with projects in the group –– ITI Foundation: Functionalization of Bone, 51(3), p. 401-406.
Dr. Frank Klenke, Consultant, CaP bone substitutes with growth IL-17A stimulates GM-CSF release
Department of Orthopaedic Surgery, factors (F. Klenke, W. Hofstetter) in the presence of 1,25(OH)(2) D(3)
Inselspital –– RMS: Cartilage Tissue Formation of by osteoblasts and inhibits osteoclast
Cells Seeded on Structured Scaf- development in vitro. Balani, D et al.
Collaborators folds in Physiological Conditions (2012) in: Arthritis Rheum.
Aeberli D, Inselspital, Switzerland (W. Hofstetter) CHF 70,000 Mitogen-activated protein kinase
Fuster D, Inselspital, Switzerland 2 (MK2) regulates physiological and
Kohl, S, Inselspital, Switzerland Osteo-Articular Research pathological bone turnover. Braun, T
Koller B, Scanco Medical AG, –– A O Foundation: Start-up grant et al. (2012) in: J Bone Miner Res.
Switzerland Comparison of cartilage histopa-
Loughlin J, University of Newcastle, UK S-11-96N – S100 as a cellular marker thology assessment systems on hu-
Luginbuehl R, RMS Foundation, for chondrogenicity of human man knee joints at all stages of osteo-
Switzerland aritcular chondrocytes (D. Nesic, arthritis development. Pauli, C et al.
Müller R, ETH Zurich, Switzerland M. Zumstein) CHF 60,000 (2012) in: Osteoarthritis Cartilage,
Schäfer B, Geistlich Pharma AG, –– Geistlich Pharma: Testing collagen 20(6), p. 476-485.
Switzerland derived matrices in vitro (D. Nesic) Blockade of the hedgehog path-
Sebald W, University of CHF 50,000 way inhibits osteophyte formation in
Würzburg, Germany –– KTI 9853.1 PFLS-LS: Comprehen- arthritis. Ruiz-Heiland, G et al. (2012)
Seitz M, Inselspital, Switzerland sive morphological characterization in: Ann Rheum Dis, 71(3), p. 400-407.
Siebenrock KA, Inselspital, of arthritis in animal models by Inhibition of endogenous antago-
Switzerland microCT – innovative biomarkers nists with an engineered BMP-2
Stok K, ETH Zurich, Switzerland for assessment of arthritic cartilage variant increases BMP-2 efficacy in
Zulliger M, Scanco Medical AG, and bone (D. Nesic, R. Mueller, rat femoral defect healing. Sebald, HJ
Switzerland B. Koller) CHF 45,828 et al. (2012) in: Acta Biomater, 8(10),
Zumstein M, Inselspital, Switzerland –– RMS and Biomet International: p. 3816-3820.
Zwerina J, Technical University, The effect of Leukocyte- and Plate- Modulation of human osteoblasts
Dresden, Germany let-Rich Fibrin, Leukocyte- and by metal surface chemistry. Hofstetter,
Platelet-Rich Plasma and blood clot W et al. (2012) in J Biomed Mat Res
on the migration of fibroblast and (in press).
endothelial cells: an in vitro study Expression of antagonists of WNT
(M. Zumstein, M. Schär, D. Nesic) and BMP signaling after non-rigid
CHF 24,600 fixation of osteotomies. Montjovent;
MO et al. (2012) in Bone (in press).
19 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Cardiovascular Research
www.cvrc.dkf.unibe.ch
Research Highlights 2012 / Outlook 2013 Prof. Dr. Robert Rieben
Vascular endothelial cells and their role in ischemia/reperfusion (I/R) injury as robert.rieben@dkf.unibe.ch
well as in transplant rejection were the focus of our research in 2012.
We continued a project on the use of plasma products to attenuate I/R injury Studies in biology at the University of Bern;
in a rat hind limb ischemia model. For our experiments, we used C1-inhibitor PhD in Immunology (1992). SNF postdoc
(C1-INH), an enzyme isolated from human plasma known to block the comple- in Leiden (NL) working on xenotransplantation
ment-, coagulation- and kallikrein/kinin-pathways. The rats were treated sys- (1994-1997). Involved in several EU research
temically by C1-INH shortly before induction of ischemia in a hind limb. This ex- projects since then. Return to Bern in 1997
perimental setup was chosen in order to mimic the clinical situation of elective to establish a research group. Habilitation
surgery on extremities. We observed a significant reduction of the tissue oedema (2002); Associate Professor (2007). Since 2005,
that occurs after reperfusion of the hind limb, by the use of C1-INH. This find- Group Leader, Cardiovascular Research, DCR.
ing may have a rather immediate impact on clinical practice because C1-INH
is already registered for clinical use and there is as yet no other treatment avail-
able to prevent I/R injury in skeletal muscle. Currently, we are analysing tissue
and plasma samples from these experiments in order to describe the mecha-
nism by which C1-INH prevents I/R injury in this model. All of the cascade sys-
tems seem indeed to be involved but the sequence of events by which the
innate immune system causes the inflammatory reaction leading to reperfusion
injury remains to be elucidated in detail.
Similar to I/R injury, vascular endothelial cells are also activated in models
of xenotransplantation. We use both in vitro and ex vivo perfusion models of
pig-to-human xenotransplantation in order to study mechanisms of endothelial
cell activation/vascular rejection and therapeutic strategies to prevent them.
An in vitro model in which whole, non-anticoagulated human blood is incu
bated with porcine endothelial cells grown on microspheres was used to study
the effect of human transgenes on xenorejection mechanisms. As a simple
readout, time to coagulation can be used in this system, which is dependent on
activation of the porcine endothelial cells and thus loss of their natural antico-
agulation properties. We found that human thrombomodulin, a membrane
protein regulating the coagulation cascade, significantly prolonged time to co-
agulation in our model, suggesting that this gene should indeed be included
in multi-transgenic pigs to be bred as organ donors for human patients. In addi-
tion, the role of the lectin pathway of complement was demonstrated for the
first time in a pig-to-human xenotransplantation model. In 2013, ex vivo per
fusions of pig legs with whole human blood will be performed, using donor pigs
expressing different human transgenes. These experiments are being carried
out in collaboration with the Department of Plastic and Hand Surgery, Inselspital
and the Ludwig-Maximilian University of Munich (DE).
20 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Group Members –– SNF: Composite tissue preservation Kamat, P; Juon, B; Jossen, B;
Prof. Dr. Robert Rieben, by extracorporeal blood perfusion Gajanayake, T; Rieben, R; Vogelin, E
Group Leader and vascular cytoprotection to (2012) in: J Inflamm (Lond), 9(1), p. 18.
Dr. Yara Banz, Research Associate extend the time limit to replanta- Ischemia/reperfusion injury of
(Pathology) tion or transplantation (E. Vögelin, porcine limbs after extracorporeal
Dr. Jana Ortmann, Research M.A. Constantinescu, R. Rieben) perfusion. Muller, S; Constantinescu,
Associate (Tiefenau Hospital) CHF 75,000 MA; Kiermeir, DM; Gajanayake, T;
Dr. Pranitha Kamat, Postdoctoral Bongoni, AK; Vollbach, FH; Meoli, M;
Fellow (until Nov.) –– CSL Behring: Effects and mecha- Plock, J; Jenni, H; Banic, A; Rieben, R;
Julie Denoyelle, Laboratory nisms of anti-inflammatory Vogelin, E (2012) in: J Surg Res.
Technician treatment by plasma products to Pancuronium dose refinement
Anjan Bongoni, PhD Student attenuate ischemia/reperfusion in experimental pigs used in cardio-
Claudia Dührkop, PhD Student injury (R. Rieben) CHF 85,000 vascular research. Veres-Nyéki, O;
Shengye Zhang, PhD Student Rieben, R; Spadavecchia, C;
Uyen Schmutz, Web Designer, –– American Society for the Surgery Bergadano, A (2012) in: Vet Anaesth
BNF Program (Sep.-Nov.) of the Hand: A Novel Therapeutic Analg, e-pub ahead of print,
Franziska Wiedmer, Webmaster, Method Targeting Local Immuno- doi:10.1111/j.1467-2995.2012.00732.x.
BNF Program (since Oct.) suppression in Composite Tissue
Allotransplantation (E. Vögelin,
R. Rieben, T. Gajanayake)
USD 20,000
Collaborators Teaching Activities
Bovin N, Institute of Bioorganic –– Elective module in the Master
Chemistry, Russia
Constantinescu MA, Inselspital, of Biomedical Sciences curriculum:
Switzerland Induction of transplantation
Gorantla V, University of Pittsburgh tolerance in composite tissue allo
Medical Center, USA transplantation
Hani R, EMPA Dübendorf, Switzerland –– Elective course 5034 for medical
Heier J, EMPA Dübendorf, Switzerland students: Ihr Partner im Labor –
Jenni HJ, Inselspital, Switzerland Forschung auf den Gebieten
Khattab A, Inselspital, Switzerland Organtransplantation, Chirurgie
Klymiuk N, University of Munich, und Herzinfarkt
Germany –– 3rd-year medical students: Problem
Korchagina E, Institute of Based Learning tutorial – Störungen
Bioorganic Chemistry, Russia der Auseinandersetzung zwischen
Ruder T, University of Zurich, körpereigen und fremd
Switzerland –– Graduate School for Cellular and
Seebach J, Geneva University Biomedical Sciences PhD students:
Hospital, Switzerland Immunology tutorial
Spirig R, CSL Behring AG, Switzerland –– Four high-school students:
Stringer S, University of Patenschaften für Maturaarbeiten
Manchester, UK (2-week lab stay each)
Vemula P, Massachusetts Institute
of Technology, USA Publications
Vögelin E, Inselspital, Switzerland Evaluation of multimeric tyros-
Wolf E, University of Munich, ine-O-sulfate as a cytoprotectant in
Germany an in vivo model of acute myocardial
infarction in pigs. Banz, Y; Hess, OM;
Grants Meier, P; Korchagina, EY; Gordeeva,
Amounts allocated for 2012: EA; Robson, SC; Gajanayake, T;
–– SNF: Endothelial cell protection – Csizmadia, E; Mettler, D; Haeberli, A;
Bovin, NV; Rieben, R (2012) in:
The role of heparan sulfate Cardiology, 121(1), p. 59-70.
proteoglycans and complement Assessment of endothelium and
in pathophysiology and prevention inflammatory response at the onset
of ischemia / reperfusion injury of reperfusion injury in hand surgery.
(R. Rieben) CHF 130,000
21 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Ion Channels
and Channelopathies
www.ionchannels.dkf.unibe.ch
Research Highlights 2012 / Outlook 2013 Prof. Dr. Hugues Abriel
Our group’s research focuses on the role of ion channels in human diseases, hugues.abriel@dkf.unibe.ch
so-called channelopathies. In the past years, we have been mainly investigating
voltage-gated channels involved in the generation of the cardiac action poten- Training both as a biologist at ETH Zurich and
tial and their roles in cardiac arrhythmias. physician at University of Lausanne. After two
In 2012, several members of the group studied the cardiac sodium channel years at Lausanne University Hospital, post-doc
Nav1.5. Diana Shy and Ludovic Gillet investigated a new genetically modified at Columbia University (US). In 2002, Swiss
mouse model in which the Nav1.5 channel is truncated and, as a consequence, National Science Foundation Professor and start
cannot interact with important regulatory proteins. A manuscript is ready for of independent research studying the role of
submission. Valentin Sottas studied several genetic variants of Nav1.5 found in ion channels in human disorders. Since 2009,
patients with cardiac arrhythmias. This study was carried out within the frame of Professor of Pathophysiology, University of Bern
the SNF-funded SCOPES collaboration with Russian and Ukrainian scientists. and DCR Director. Since 2012 member of the
In parallel, we continued our work on another cardiac channel called TRPM4. research council of the SNF.
Ninda Syam, Valentin Sottas and Yassine Amarouch performed biochemical
and functional investigations of genetic variants of the TRPM4 gene found in
patients with cardiac arrhythmias. A first article on patients with Brugada
syndrome was accepted in 2012, and we will submit another one on patients
with cardiac conduction defect during 2013.
In these different projects, both Jean-Sébastien Rougier, Senior Teaching
and Research Assistant since July 2012, and Maria Essers, Laboratory Manager,
have played an essential role in coaching the younger scientists of the group.
In collaboration with Isabelle Decosterd’s group (Pain Center, University
Hospital of Lausanne), we also demonstrated the role of the drug rufinamide
in blocking the voltage-gated sodium channel Nav1.7 and its effect in a mouse
model of neuropathic pain. Using the same model but in rats, we could also
show that the ubiquitin ligase Nedd4-2, which is known to regulate sodium
channels, is decreased in dorsal root ganglion cells.
On another note, we had the great fortune to organise the general assem-
bly of the EUTrigTreat consortium, of which we are part. This meeting entitled
“Identification and therapeutic targeting of common arrhythmia trigger me
chanisms” was organised in Beatenberg (CH) in June 2012.
As for the main perspectives for 2013, we will continue our investigations
on the molecular determinants underlying the distribution of the different
pools of Nav1.5 in cardiac cells, and will also pursue our research on the roles
of TRPM4 in physiology and disease. In addition, in the framework of the NCCR
TransCure, and in collaboration with the groups of Jean-Louis Reymond and
Matthias Hediger (University of Bern), we will focus on screening pharmaco-
logical compounds targeting TRPM4. This study will be performed by Yassine
Amarouch, who was awarded a TransCure International Fellowship from
January 2013.
22 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Group Members –– SNF: NCCR TransCure subproject – Mapping genetic variants associated
Prof. Dr. Hugues Abriel, Physiology, pharmacology and with beta-adrenergic responses
Group Leader pathophysiology of the calcium-ac- in inbred mice. Hersch, M; Peter, B;
Dr. M. Yassine Amarouch, tivated non-selective cation TRPM4 Kang, HM; Schupfer, F; Abriel, H;
Postdoctoral Fellow channel (M. Hediger, H. Abriel, Pedrazzini, T; Eskin, E; Beckmann, JS;
Dr. Ludovic Gillet, Postdoctoral Fellow M. Heller) CHF 185,200 Bergmann, S; Maurer, F (2012) in:
Dr. Jean-Sébastien Rougier, Research PLoS One, 7(7), p. e41032.
Assistant, Senior Teaching Assistant –– SNF: Force-controlled patch clamp Deubiquitylating enzyme USP2
Maria Essers, Laboratory Technician (pc-FluidFM) (T. Zambelli, H. Abriel) counteracts Nedd4-2-mediated down-
Louis Amport, Secretary (since Aug.) CHF 111,400 regulation of KCNQ1 potassium chan-
Verena Frazao, Secretary nels. Krzystanek, K; Rasmussen, HB;
Cédric Laedermann, PhD Student –– European Commission: EUTrigTreat Grunnet, M; Staub, O; Olesen, SP;
Markus Mühlemann, PhD Student – Identification and therapeutic Abriel, H; Jespersen, T (2012) in: Heart
(since Aug.) targeting of common arrhythmia Rhythm, 9(3), p. 440-448.
Diana A. Shy, PhD Student trigger mechanisms (S. Lehnart, Role of “non-cardiac” voltage-gat-
Valentin Sottas, PhD Student H. Abriel) CHF 114,000 ed sodium channels in cardiac cells.
Ninda Syam, PhD Student Rougier, JS and Abriel, H (2012) in:
Teaching Activities J Mol Cell Cardiol, 53(5), p. 589-590.
Collaborators –– Coordination of pathophysiology Unexpected dominance: Brugada
Barò I, French National Research syndrome SCN5A variants exert nega-
Agency, CNRS, France lectures for dentistry students tive dominance via alpha-subunit
Bezzina C, University of Amsterdam –– Dentistry students: Kidney and interaction. Rougier, JS and Abriel, H
Academic Medical Centre, (2012) in: Cardiovasc Res, 96(1), p. 1-3.
The Netherlands electrolytes pathophysiology Cardiac sodium channel Na(V)1.5
Decosterd I, University of Lausanne, –– MSc Biomedical Sciences: Ion chan- distribution in myocytes via interact-
Switzerland ing proteins: The multiple pool model.
Hatem SN, French National nels in cardiac diseases Shy, D; Gillet, L; Abriel, H (2012) in:
Research Agency, INSERM, France –– BSc Life Sciences: Cardiac ion chan- Biochim Biophys Acta.
Hediger M, NCCR TransCure, Rufinamide Attenuates Mechanical
Switzerland nels in health and disease Allodynia in a Model of Neuropathic
Lehnart SE, FP7 EUTrigTreat Pain in the Mouse and Stabilizes Volt-
Consortium, University of Göttingen, Publications age-gated Sodium Channel Inactivat-
Germany Cardiac sodium channel Na(v)1.5 ed State. Suter, MR; Kirschmann, G;
Remme CA, University of Amsterdam mechanosensitivity is inhibited by Laedermann, CJ; Abriel, H; Decosterd,
Academic Medical Center, ranolazine. Abriel, H (2012) in: I (2012) in: Anesthesiology.
The Netherlands Circulation, 125(22), p. 2681-2683. Prevalence of Significant Genetic
Staub O, University of Lausanne, TRPM4 channels in the cardiov ascu Variants in Congenital Long QT Syn-
Switzerland lar system: physiology, pathophysiolo- drome is Largely Underestimated.
Sychov O, SNF SCOPES Project, gy, and pharmacology. Abriel, H; Zaklyazminskaya, EV and Abriel, H
Ukraine Syam, N; Sottas, V; Amarouch, MY; (2012) in: Front Pharmacol, 3, p. 72.
Zaklyazminskaya EV, SNF SCOPES Rougier, JS (2012) in: Biochem Pharma-
Project, Russia col, 84(7), p. 873-881.
Zambelli T, ETH Zurich, A modern approach to classify
Switzerland missense mutations in cardiac
channelopathy genes. Abriel, H and
Grants Zaklyazminskaya, EV (2012) in: Circ
Amounts allocated for 2012: Cardiovasc Genet, 5(5), p. 487-489.
–– SNF: In vivo relevance of the PY and Dynamic of ion channel expression
at the plasma membrane of cardio
PDZ-domain binding motifs of myocytes. Balse, E; Steele, DF; Abriel,
the cardiac sodium channel Nav1.5 H; Coulombe, A; Fedida, D; Hatem,
(H. Abriel) CHF 230,000 SN (2012) in: Physiol Rev, 92(3),
–– SNF: Roles of ion channel-interacting p. 1317-1358.
proteins in cardiac channelopathies Neuronal expression of the ubiqui-
(H. Abriel, E.V. Zaklyazminskaya, tin ligase Nedd4-2 in rat dorsal root
O.S. Sychov) CHF 27,500 ganglia: Modulation in the spared
nerve injury model of neuropathic
pain. Cachemaille, M; Laedermann, CJ;
Pertin, M; Abriel, H; Gosselin, RD;
Decosterd, I (2012) in: Neuroscience,
227, p. 370-380.
23 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Mammary Gland Biology
and Carcinogenesis
www.dkf.unibe.ch/research-group/2/
Research Highlights 2012 / Outlook 2013 Prof. Dr. Anne-Catherine Andres
Eph receptor tyrosine kinases and their membrane-bound ephrin ligands play anne-catherine.andres@dkf.unibe.ch
key roles during morphogenesis and adult tissue homeostasis. Receptor-ligand
interactions result in forward and reverse signalling from the receptor and Graduated from the Department of Cell Biology,
ligand respectively. We have previously shown that EphB4 and ephrin-B2 are University of Bern. Entered into the field of
differentially expressed in the mammary gland and that their deregulated ex- breast cancer research at the Ludwig Institute,
pression in the mammary epithelium of transgenic mice leads to perturbations Bern. Established the first oncogene-bearing
of the mammary parenchyma and vasculature. In addition, over-expression of transgenic mouse strain. Continued the project
EphB4 and expression of a truncated ephrin-B2 mutant, capable of receptor after 1988 at the Friedrich Miescher-Institute,
stimulation but incapable of reverse signalling, confers a metastasising pheno- Basel and subsequently at the CNRS in
type on NeuT-initiated mouse mammary tumours. Strasbourg (FR). Since 1991, Group Leader,
This transgenic model serves as a tool to investigate the role of EphB4/ Mammary Gland Biology Group, DCR; Associate
ephrin-B2 signalling in the control of the mammary stem cell niche. We have Professor 2002.
shown that over-expression of the native ephrin-B2 gene leads to an augmen-
tation of the luminal and bi-potent precursor cell fractions. Overexpression
of EphB4 resulted in a comparable phenotype. In contrast, mammary glands of
truncated ephrin-B2 transgenic mice contained significantly more stem cells
and alveolar ER-positive progenitor cells. Thus, ephrin-B2-derived signalling is
involved in the control of the stem cell niche and in the regulation of cell fate
decisions.
We intend to characterise signal transduction pathways involved in the
ephrin-B2-induced phenotypes by microarray analyses on RNA from different
transgenic mammary epithelial subpopulations. In these analyses, we will
concentrate on the expression of genes involved in either the TGF-beta or the
wnt signalling pathway, since preliminary results have indicated that these
pathways might be the primary targets of the attenuated ephrin-B2 expression.
In addition, we have joined a collaborative project with the Department
of Gynaecology and Obstetrics, Inselspital and the Institute of Pathology, Uni-
versity of Bern aiming at the comparative analysis of the epithelial cell hierarchy
in distinct groups of human breast cancers.
24 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Group Members –– S chweizerische Stiftung für Klinisch- Publications
Prof. Dr. Anne-Catherine Andres, Experimentelle Tumorforschung: Deregulated ephrin-B2 signaling in
Group Leader Transgenic mouse models to study mammary epithelial cells alters the stem
Dr. Philip Känel, Postdoctoral Fellow the molecular mechanisms leading cell compartment and interferes with
Dr. Robert Strange, Consultant to the invasive phenotype of the epithelial differentiation pathway.
François Achermann, Laboratory mammary tumors (A.-C. Andres) Kaenel, P; Antonijevic, M; Richter, S;
Technician CHF 40,000 Kuchler, S; Sutter, N; Wotzkow, C;
Carlos Wotzkow, Laboratory Strange, R; Andres, AC (2012) in: Int J
Technician Teaching Activities Oncol, 40(2), p. 357-369.
–– Member, Graduate School The multifaceted roles of Eph/
Collaborators ephrin signaling in breast cancer.
Djonov V, University of Bern, Commission Biological Systems Kaenel, P; Mosimann, M; Andres, AC
Switzerland –– Member, Commission for the (2012) in: Cell Adh Migr, 6(2),
Günthert A, Inselspital, Switzerland p. 138-147.
Stute P, University of Bern, Master Studies Curriculum in
Switzerland Biomedical Sciences
Tapia C, University of Bern, –– B achelor and Master studies in
Switzerland biomedical sciences: Organiser
and teacher, Tumour biology
Grants programme
Amounts allocated for 2012: –– 1st-year medical students:
–– S NF: The role of EphB4 and Organiser and teacher, Develop-
mental biology programme; Trans-
ephrin-B2 in the control of the genic seminar: Lecture on cell
mammary gland stem/progenitor death of multicellular organisms
cell population (A.-C. Andres) –– 1st-year veterinary medicine students:
CHF 64,000 Lecture on transgenic animals
–– S wiss Cancer League: The molecular –– Graduate School: Molecular bio
mechanisms provoking the ephrin-B2 logical methods in clinical diagnosis
induced deregulation of the mam- practical course
mary stem cell niche and leading to –– Master in Bioengineering:
metastatic tumour growth.
(A.-C. Andres) CHF 100,000 Molecular biology practical course
–– 1 st-year medical students elective
module: Genetic mutations –
cyto- and molecular genetics
25 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Phytopharmacology, Bioanalytics
and Pharmacokinetics
www.phytopharm.dkf.unibe.ch
Research Highlights 2012 / Outlook 2013
Highlights of our research include:
–– A ll the constituents of a Bryophyllum pinnatum leaf extract, its press juice Prof. Dr. Rudolf Brenneisen
used to prevent premature delivery, could be identified. Flavonoids were rudolf.brenneisen@dkf.unibe.ch
shown to be the main active compounds. Using in vitro and clinical studies,
we could also demonstrate the inhibiting effects of the leaf press juice on Fed. dipl. in Pharmaceutical Sciences and PhD
the overactive bladder. A pilot study on children with Attention Deficit at the University of Bern. Head, Department
Hyperactivity Disorder has been started, showing positive preliminary effects. of Phytochemistry & Pharmacognosy, Institute
of Pharmacy, University of Bern (1981). Habili-
–– A study of the plasma of patients with alcoholic liver fibrosis or hepatitis C tation and Privatdozent (1988). Vice-Director,
vs. healthy volunteers showed increased anandamide levels. This confirms Institute of Pharmacy (1990-91); Associate
the impact of liver diseases on the endocannabinoid system. Professor (1993). Since 1997, Group Leader,
Phytopharmacology, Bioanalytics and Pharma-
–– In vitro validation studies with vaporiser devices showed that non-pyrolytic cokinetics Group, DCR. President, Swiss Acade-
inhalation is an efficient and significantly less harmful application mode my of Pharmaceutical Sciences; President,
for cannabinoids. Swiss Committee for Drugs of Abuse Testing
since 2008.
In 2013, we will continue the endocannabinoid profiling on plasma samples
collected from patients suffering from non-alcoholic fatty liver disease.
26 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Group Members –– W eleda AG Arlesheim: Clinical a new treatment option of overactive
Prof. Dr. Rudolf Brenneisen, efficacy, pharmacology and analytics bladder. Schuler, V; Suter, K; Furer, K;
Group Leader of Bryophyllum (U. von Mandach) Eberli, D; Horst, M; Betschart, C;
Dr. Christian Lanz, Laboratory CHF 50,000 Brenneisen, R; Hamburger, M; Mennet,
Supervisor, Research Assistant M; Schnelle, M; Simoes-Wust, AP;
Karin Fürer, PhD Student –– Additional funding: Neuropharma von, MU (2012) in: Phytomedicine,
Dr. Johan Mattsson, Postdoctoral cology of iv THC (D. Freeman, 19(10), p. 947-951.
Fellow, BNF Program (Mar-Sep) P. Morrison) CHF 10,000 Communication breakdown:
delta-9 tetrahydrocannabinol effects
Collaborators Teaching Activities on pre-speech neural coherence.
Doblin R, Multidisciplinary Associa- –– 1 st-year pharmacy students: Stone, JM; Morrison, PD; Brugger, S;
tion of Psychedelic Studies, USA Nottage, J; Bhattacharyya, S; Sumich,
Dufour J-F, Inselspital, Switzerland Introduction to pharmaceutical A; Wilson, D; Tunstall, N; Feilding, A;
Freeman D, University of Oxford, UK sciences Brenneisen, R; McGuire, P; Murray,
Gasser P, Solothurn, Switzerland RM; Ffytche, DH (2012) in: Mol Psychi-
Hamburger M, University of Basel, Publications atry, 17(6), p. 568-569.
Switzerland Cannabidiol inhibits THC-elicited para- Acute effects of intravenous heroin
Morrison P, King’s College London, UK noid symptoms and hippocamp al- on the hypothalamic-pituitary-adrenal
Schnelle M, Weleda AG, Switzerland dependent memory impairment. axis response: A controlled trial. Walter,
Skendaj R, University Hospital Englund, A; Morrison, PD; Nottage, J; M; Gerber, H; Kuhl, HC; Schmid, O;
Basel, Switzerland Hague, D; Kane, F; Bonaccorso, S; Joechle, W; Lanz, C; Brenneisen, R;
Stickel F, Inselspital, Switzerland Stone, JM; Reichenberg, A; Brenneisen, Schächinger, H; Riecher-Rössler, A;
Von Mandach U, University Hospital R; Holt, D; Feilding, A; Walker, L; Wiesbeck, GA; Borgwardt, SJ in: J Clin
Zurich, Switzerland Murray, RM; Kapur, S (2012) in: Psychopharmacol (in press).
Wüest A, Paracelsus Hospital J Psychopharmacol.
Richterswil, Switzerland Single-dose Pharmacokinetics and
Tolerability of Oral Delta-9-Tetrahydro-
Grants cannabinol in Patients with Amyo-
Amounts allocated for 2012: trophic Lateral Sclerosis. Joerger, M;
–– Department of Visceral Surgery and Wilkins, J; Fagagnini, S; Baldinger, R;
Brenneisen, R; Schneider, U; Goldman,
Medicine, Hepatology Insels pital, B; Weber, M (2012) in: Drug Metab Lett.
Prof. J.-F. Dufour (R. Brenneisen) Bryophyllum pinnatum inhibits
CHF 30,000 detrusor contractility in porcine bladder
strips–a pharmacological study towards
27 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Vasoactive Peptide
www.dkf.unibe.ch/research-group/22/
Research Highlights 2012 / Outlook 2013 Dr. Sidney G. Shaw
Our primary research focus is the physiology and pathology of peptides in shaw@dkf.unibe.ch
cardiovascular disease and secondary complications of diabetes. Contributory
factors include a complex interplay between toll-like receptors, vasoactive MA (Hons) in Biochemistry and PhD in Neuro
peptides and the nitric oxide system. Activation or blockade of key elements pharmacology at Oxford University (UK).
regulating these pathways offers new therapeutic options for modifying dam- Wellcome Trust Fellow and Lecturer in Pharma-
age progression. Modulation can also prevent the loss of insulin-producing cology, Trinity College Oxford (1978-1983).
beta-cells in the pancreas. Studies of molecular mechanisms regulating vascular Research Associate, Department of Hyper
cell apoptosis, the innate immune system, dendritic cell activation, cytokine tension, University of Bern (1984-1996). Since
expression and toll-like receptor function are currently in progress. Techniques 1996, Group Leader, Vasoactive Peptide Group,
include proteomics, micro arrays and biochemical analysis, as well as trans DCR. Member, Editorial Board of Cardiovasc
genic animal models and cell culture. Med, Vasc Pharmacol and Cardiol Res Pract.
Our second research area involves the role of brain glucocorticoids in chronic Member, Swiss Soc Nephrol, Am Soc Hyperten-
alcohol abuse. We have on-going clinical trials and experimental studies of sion, European Soc Cardiol and European
glucocorticoid antagonists as therapeutics in the management of withdrawal, Assoc Study Diabetes.
funded by the UK Medical Research Council.
This year, Dr. Shaw was Executive Guest Editor of a Cardiology Research &
Practice special issue on “Cell Signalling Pathways Leading to Novel Therapeu-
tic Strategies in Cardiovascular Disease”. In terms of events, Dr. Shaw was
Co-organiser and Chairman of the 4th UCL-Royal Free International Cardiovas-
cular Diseases Workshop, which took place on 12 September. This workshop is
held each year at the Royal Free Hospital campus of University College London,
UK. He was also a member of the organizing committee and Co-chairman
of the International Society for Applied Cardiovascular Biology meeting, held
from 12-15 September at University College London, UK.
28 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Internal Research Groups
Group Members Teaching activities Cell signaling pathways leading to
Dr. Sidney G. Shaw, Group Leader –– 3rd-year dental medicine students: novel therapeutic strategies in cardio-
Jane Shaw, Laboratory Technician vascular disease. Shaw, S; Baker, D;
Pathology and internal medicine – Abraham, D; Tsui J (2012) in: Cardio
Collaborators endocrinology pathophysiology logy Research and Practice (in press).
Dashwood M, Royal Free Hospital, UK
Jakob S, Insels pital, Switzerland Publications
Little H, Kings College London, UK Toll-like receptors in ischaemia and
Patel H, Royal Free Hospital, UK its potential role in the pathophysio
Reichen J, University of Bern, logy of muscle damage in critical limb
Switzerland ischaemia. Patel, H; Shaw, SG;
Rieben R, University of Bern, Shi-Wen, X; Abraham, D; Baker, DM;
Switzerland Tsui, JC (2012) in: Cardiol Res Pract,
Ruschitzka F, University Hospital 2012, p. 121237.
Zurich, Switzerland Torcetrapib impairs endothelial
Tsui J, University College London, UK function in hypertension. Simic, B;
Hermann, M; Shaw, SG; Bigler, L;
Grants Stalder, U; Dorries, C; Besler, C;
Amounts allocated for 2012: Luscher, TF; Ruschitzka, F (2012) in:
–– Royal Society Joint International Eur Heart J, 33(13), p. 1615-1624.
Additive effect of homocysteine-
Research Grant: The role of Toll like and cholesterol-lowering therapy on
receptor signalling in Peripheral endothelium-dependent vasodilation
Arterial Disease (J. Tsui, S. Shaw) in patients with cardiovascular disease.
CHF 30,000 Wustmann, K; Klaey, M; Burow, A;
–– UK Medical Research Council: Shaw, SG; Hess, OM; Allemann,
Importance of 11-beta-hydroxyster- Y (2012) in: Cardiovasc Ther, 30(5),
oid dehydrogenase (HSD-1) in p. 277-286.
the consequences of chronic alcohol Therapeutic role of toll-like recep-
consumption (H. Little, S. Shaw) tor modification in cardiovascular
CHF 50,000 dysfunction. Navi, A; Patel, H; Shaw, S;
–– European Foundation for the Study Baker, D; Tsui, J (2012) in: Vascul
of Diabetes: The role of toll like re- Pharmacol.
ceptor signalling in diabetes related The Emerging Role of TLR and
cardiovascular disease (S. Shaw) Innate Immunity in Cardiovascular Dis-
CHF 50,000 ease. Spirig, R; Tsui, J; Shaw, S (2012)
in: Cardiol Res Pract, 2012, p. 181394.
29 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from
the Inselspital
DCR Research Groups from the Inselspital
Forty-three research groups from depart- Endometrium & Ovary: Prof. Dr. Michael Dr. Urban Novak, Prof. Dr. Thomas Pabst,
ments of the Inselspital were affiliated von Wolff Prof. Dr. Andreas Tobler, PD Dr. Mario
with the DCR at the end of 2012. Below is Tschan
a list of the groups and the names of the Experimental Haematology (Adults):
Chairs of Departments and/or Group Prof. Dr. Gabriela Baerlocher, Dr. Elisabeth Ophthalmology: Prof. Dr. Sebastian Wolf,
Leaders. Fifteen of the groups are featured Oppliger Leibundgut PD Dr. Volker Enzmann, PD Dr. Ute
on the following pages. Other groups Wolf-Schnurbusch
will be featured in future annual reports. Gastroenterology / Mucosal Immuno
logy: Prof. Dr. Andrew Macpherson, Prof. Orthopaedic Surgery: Prof. Dr. Klaus-Arno
Anaesthesiology: Prof. Dr. Frank Stüber, Dr. Kathy McCoy, Dr. Markus Geuking, Siebenrock, Prof. Dr. Ernst B. Hunziker
Dr. Rolf Lauber, PD Dr. Martin Luginbühl Prof. Dr. Frank Seibold
Perception and Eye Movement:
Angiology: Prof. Dr. Iris Baumgartner, Geriatrics / Medicine of Ageing: Prof. Dr. Claudio L. Bassetti, PD Dr. Stephan
Prof. Dr. Nicolas Diehm Prof. Dr. Andreas Stuck, PD Dr. Andreas Bohlhalter, Prof. Dr. René Müri,
Schoenenberger PD Dr. Thomas Nyffeler
Audiology: Prof. Dr. Marco Caversaccio,
Prof. Dr. Martin Kompis, PD Dr. Pascal Senn Haematology / Oncology (Paediatrics): Plastic Surgery: Prof. Dr. Andrej Banic,
Prof. Dr. Kurt Leibundgut, PD Dr. Alexandre PD Dr. Mihai Constantinescu,
Cardiology: Prof. Dr. Bernhard Meier, Arcaro Prof. Dr. Dominique Erni, Prof. Dr. Robert
Prof. Dr. Yves Allemann, Prof. Dr. Etienne Rieben, Dr. Maziar Shafighi
Delacrétaz, Prof. Dr. Paul Mohacsi, PD Dr. Hand Surgery: Prof. Dr. Esther Vögelin,
Claudio Sartori, Prof. Dr. Urs Scherrer, Prof. Dr. Robert Rieben Prenatal Medicine: Prof. Dr. Daniel Surbek
Prof. Dr. Christian Seiler, Prof. Dr. Thomas
Suter, Prof. Dr. Stephan Windecker Hepatology: Prof. Dr. Jean-François Psychosomatic Medicine: Prof. Dr. Roland
Dufour, PD Dr. Andrea de Gottardi, von Känel
Cardiovascular Surgery: Prof. Dr. Thierry Prof. Dr. Jeff Idle, PD Dr. Nasser Semmo,
Carrel, Prof. Dr. Hendrik Tevaearai, Prof. Dr. Marc Solioz, Prof. Dr. Felix Stickel Pulmonary Medicine (Adults):
Dr. Henriette Brinks, Prof. Dr. Martin Czerny, Prof. Dr. Thomas Geiser, PD Dr. Christophe
PD Dr. Florian Dick, Dr. Sarah Longnus Human Genetics: Prof. Dr. Sabina Gallati, von Garnier, PD Dr. Barbara Rothen
Dr. Johannes Lemke, Dr. André Schaller
Cranio-Maxillofacial Surgery: Pulmonary Medicine (Paediatrics):
Prof. Dr. Tateyuki Iizuka, Dr. Nikola Saulacic Intensive Medicine: Prof. Dr. Jukka Takala, Prof. Dr. Nicolas Regamey
Prof. Dr. Stephan Jakob
Dental Research: Prof. Dr. Anton Sculean, Radiation Oncology: Prof. Dr. Daniel
Prof. Dr. Adrian Lussi, PD Dr. Dieter Internal Medicine: Prof. Dr. Karin Aebersold, Dr. Yitzhak Zimmer
Bosshardt, Prof. Dr. Matthias Chiquet, Fattinger, Prof. Dr. Beatrice U. Müller
Prof. Dr. Reinhard Gruber, PD Dr. Sigrun Eick Rheumatology: Prof. Dr. Peter M. Villiger,
Magnetic Resonance Spectroscopy and Dr. Frauke Förger, Dr. Stefan Kuchen,
Dermatology: Prof. Dr. Luca Borradori, Methodology, AMSM: Prof. Dr. Chris Prof. Dr. Michael Seitz, Prof. Dr. Beat Trueb
Dr. Bertrand Favre, PD Dr. Robert Hunger, Boesch, Prof. Dr. Roland Kreis, PD Dr. Peter
Prof. Dr. Dagmar Simon, Prof. Dr. Nikhil Vermathen Thoracic Surgery: Prof. Dr. Ralph A.
Yawalkar Schmid, PD Dr. Steffen Frese, Dr. Thomas
Nephrology and Hypertension: Marti, Dr. Renwang Peng
Endocrinology of the Breast: Prof. Dr. Bruno Vogt, Prof. Dr. Brigitte Frey
PD Dr. Petra Stute Triadic Family Functioning:
Neurology: Prof. Dr. Claudio L. Bassetti, Prof. Dr. Daniel Surbek, Dr. Werner Stadlmayr
Endocrinology / Diabetology (Adults): Prof. Dr. Alain Kaelin, Prof. Dr. Heinrich
Prof. Dr. Peter Diem Mattle, Prof. Dr. René Müri Tumor-Immunology: Prof. Dr. Adrian
Ochsenbein
Endocrinology / Diabetology / Meta Neurosurgery: Prof. Dr. Andreas Raabe,
bolism (Paediatrics): Prof. Dr. Primus Prof. Dr. Michael Reinert Urology: Prof. Dr. George Thalmann,
Mullis, Prof. Dr. Christa Flück, Dr. Marco Cecchini, PD Dr. Katia
PD Dr. Jean-Marc Nuoffer Nuclear Medicine: Prof. Dr. Thomas Monastyrskaya
Krause, PD Dr. Martin A. Walter
Endometriosis and Gynaecological Visceral and Transplantation Surgery:
Oncology: Prof Dr. Michel D. Müller, Oncology / Haematology (Adults): Prof. Dr. Daniel Candinas, Dr. Deborah
Prof. Dr. Nick A. Bersinger Prof. Dr. Martin Fey, PD Dr. Oliver Gautschi, Stroka
31 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Audiology
www.artorg.unibe.ch/content/research_units/artificial_hearing_research
Research Highlights 2012 / Outlook 2013 Prof. Dr. Marco Caversaccio
2012 was a year of transition for the Audiology group: Prof. Stieger joined marco.caversaccio@insel.ch
Harvard Medical School (US) as a Research Fellow, a number of projects were MD from University of Geneva. Research
successfully finished and the results published in high-ranking journals, and new fellowship at Imperial College London (UK).
projects, along with an additional PhD-thesis, were started. Broad research focus with special interest
Two new, large-scale EU-projects, HEAR-EU (www.hear-eu.org) and NAONOCI in technical assistance systems (NCCR CO-ME).
(www.nanoci.org) started this year. Both investigate novel methods to improve Since 2009, Chair, Department of Ear, Nose
hearing and speech understanding in deaf patients. and Throat Diseases, Head and Neck Surgery,
Members of our group received several awards for their work, including Inselspital. Since 2010, also Vice-Director,
best scientific paper for “Development of an auditory implant manipulator” ARTORG Center for Biomedical Engineering,
by Stieger et al. in the Journal of Laryngology and Otology, and best poster University of Bern.
award for “Novel Body Access for Hemodialysis” by Guignard et al. at the KTI
Medtech Event. Prof. Dr. Martin Kompis
Among the successfully finalised projects in 2012 was a multi-centre Swiss martin.kompis@insel.ch
study on tinnitus in cochlear implant patients, which was received with consider- MD from University of Zurich. PhD in electrical
able interest at several international conferences. Another long-term project engineering from ETH Zurich. Postdoc at Pur-
on acoustic trauma in the Swiss army was finalised and published. Anja Kurz, due University (US). Since 1997, Head of Audi-
a PhD student who started in 2011, finished her first sub-project, a comparison ology, Department of Ear, Nose and Throat
of two bone-anchored hearing aids in different acoustic settings. Diseases, Head and Neck Surgery, Inselspital.
In 2013, work on the EU-projects will gain momentum and we expect Associate Professor of Biomedical Engineering
to see the very first results. Among other projects that will continue, is a new and Acoustics, University of Bern.
cooperation with Kosice University (SK). A first project involving adults with
single-sided sensorineural deafness has already started and the first measure-
ments have been performed. A project using a completely new bone conduction
hearing aid, the Bonebridge, was initiated in late 2012. First implantations
have already been performed successfully in Bern by Prof. Caversaccio. Wilhelm
Wimmer, a new PhD student, joined our team in August to work on this project.
Furthermore, we expect Jéremie Guigniard to successfully finish his PhD work
next year.
Prof. Dr. Christof Stieger
christof.stieger@artorg.unibe.ch
Studies in electrical engineering and medical
physics at EPF Lausanne and ETH Zurich, and at
University of Louvain la Neuve (BE). PhD from
University of Neuchâtel. Since 2008, Assistant
Professor of Artificial Hearing, Department
of Ear, Nose and Throat Diseases, Head and
Neck Surgery, Inselspital. Currently Research
Fellow at Eaton-Peabody Laboratory, Harvard
Medical School (US).
32 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
PD Dr. Pascal Senn
pascal.senn@insel.ch
MD from University of Bern. Board-certified
otolaryngologist, head and neck surgeon.
Research fellowship on inner ear stem cells at
Harvard and Stanford University Medical
Schools (US). Since 2008, Head Cochlear Im-
plant Division, Inselspital. Coordinator of
the EU-funded NANOCI project.
Group Members Grants Senn, P; Rostetter, C; Arnold, A;
Prof. Dr. Marco Caversaccio, Amounts allocated for 2012: Kompis, M; Vischer, M; Hausler, R;
Chair, Group Leader –– E uropean Commission: HEAR-EU Ozdoba, C; Mantokoudis, G;
Prof. Dr. Martin Kompis, Caversaccio, M (2012) in: Laryngo-
Group Leader (M.A. Gonzalez Ballester, scope, 122(9), p. 2043-2050.
PD Dr. Pascal Senn, Group Leader M. Caversaccio, S. Weber, in Laser Doppler vibrometric assess-
Prof. Dr. Christof Stieger, Group collaboration with ARTORG) ment of middle ear motion in Thiel-em-
Leader (until Nov.) CHF 280,000 balmed heads. Stieger, C; Candreia, C;
Dr. Marta Roccio, Postdoctoral –– E uropean Commission: NANOCI Kompis, M; Herrmann, G; Pfiffner, F;
Fellow (since Sep.) (P. Senn) CHF 120,000 Widmer, D; Arnold, A (2012) in: Otol
Simona Wiedmer, Research Assistant –– Cochlear Inc.: Optimized bone Neurotol, 33(3), p. 311-318.
Ruth Birrer, MD Student anchored stimulation (M. Kompis,
Nicolas Gerber, PhD Student M. Caversaccio) CHF 46,556
Jéremie Guignard, PhD Student –– Cochlear Inc.: Comparative study
Stefan Hahnewald, PhD Student Baha Intenso/BP110 (M. Kompis)
(since Sep.) CHF 29,160
Anja Kurz, PhD Student
Wilhelm Wimmer, PhD Student Five Selected Publications
(since Aug.) Extended frequency range hearing
thresholds and otoacoustic emissions
Collaborators in acute acoustic trauma. Buchler, M;
Koval J, Krempaska S, University Kompis, M; Hotz, MA (2012) in: Otol
of Kosice, Slovakia Neurotol, 33(8), p. 1315-1322.
Labadie R, Vanderbilt University, USA Tinnitus before and 6 months
Lenarz T, Hannover Medical School, after cochlear implantation. Kompis, M;
Germany Pelizzone, M; Dillier, N; Allum, J;
Merchant S, Rosowski J, DeMin, N; Senn, P (2012) in: Audiol
Mylanus E, Snik AD, Radboud Neurootol, 17(3), p. 161-168.
University, The Netherlands A multilingual audiometer simula-
Nakajima H, Harvard Medical School, tor software for training purposes.
Massachusetts Eye and Ear Infirmary, Kompis, M; Steffen, P; Caversaccio, M;
Boston, USA Brugger, U; Oesch, I (2012) in: Acta
Vetter R, University of Applied Otolaryngol, 132(4), p. 428-433.
Sciences, Burgdorf, Switzerland Retrograde cochlear implantation in
postmeningitic basal turn ossification.
33 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Cardiology
www.cvrc.dkf.unibe.ch
Research Highlights 2012 / Outlook 2013 Prof. Dr. Bernhard Meier
Allemann/Scherrer/Sartori Groups bernhard.meier@insel.ch
In 2012, we published the very first report demonstrating that assisted repro-
ductive technology (ART) induces vascular dysfunction in young, apparently Studied medicine at University of Zurich (1975);
healthy children. This vascular dysfunction is of similar magnitude to that which board certified: internal medicine (1980),
we recently reported in offspring of preeclampsia, a condition known to be cardiology (1983). Cardiology training at Emory
associated with a markedly increased risk of premature stroke. Our ongoing University (US). Head of invasive cardiology,
studies demonstrate that ART induces vascular dysfunction and arterial hyper- University Hospital, Geneva (1983-1992). Chair
tension in in vitro fertilised mice, and suggests that epigenetic mechanisms and Professor of Cardiology (1992), rotating
may play a role. Chair (2001), Inselspital. Involved in coronary
In a collaborative effort with a group in Bolivia, we provided evidence angioplasty since the first case in 1977. Cur-
that exaggerated chronic hypoxia in patients suffering from chronic mountain rently Chair of Cardiology, Inselspital.
disease not only induces pulmonary but also systemic vascular dysfunction.
This dysfunction appears to be related to exaggerated oxidative stress, causing
alveolar fluid accumulation in the pulmonary circulation during moderate
physical activity.
Delacrétaz Group Prof. Dr. Yves Allemann
One main objective of our group is to improve the detection of atrial fibrillation yves.allemann@insel.ch
(AF) and the prevention of AF-related stroke. The last decade has witnessed
intense developments in AF treatment, especially in ablative therapy, and man- Studied medicine at Universities of Neuchâtel
agement of AF will remain a key cardiology field in the coming years. A second and Lausanne; MD degree (1986). Swiss FMH
objective is to improve the management of patients with heart disease and certification: internal medicine (1994), cardio
complex arrhythmias, including patients who have grown-up with congenital logy (1998). Since 2002, Head, Outpatient Clinic,
heart disease and patients with scar-related ventricular arrhythmias. Preliminary Department of Cardiology, Inselspital. Since
data show that management with catheter ablation at an earlier stage of the 2008, Assistant Professor at University of Bern.
disease may improve the quality of life and long-term prognosis.
Mohacsi Group Prof. Dr. Etienne Delacrétaz
We aim to minimise the side effects of immunosuppression (increased susceptibili- etienne.delacretaz@insel.ch
ty to infections, cancer or nephro-/neurotoxicity) often observed in heart trans-
plant (HTx) patients by studying mechanisms for optimisation of tailored immuno- MD at University of Lausanne (1987), Resident
suppressive therapy. In collaboration with the Department of Clinical Chemistry, in internal medicine in Aigle, Morges, Geneva
we investigate whether genetic polymorphisms in drug metabolism, transport, (HUG); Chief Resident and Cardiovascular Re-
and targets of immunosuppressants affect the drug dose required to achieve ther- search Fellow in Lausanne (CHUV); Cardiology
apeutic blood trough drug levels in cardiac allograft recipients. In a second pro- Fellow in Bern (1994-1996), Fellow in electro-
ject, together with the Centre of Excellence for Prevention of Organ Failure (CA), physiology in USA at Brigham and Women’s
we study the clinical application of a novel blood test using genomic and pro- Hospital (1997-1999). Staff in electrophysiology:
teomic biomarkers to predict and detect graft rejection in HTx patients. Lausanne (1999-2000), Bern (2000). PD (2002),
Assistant Professor (2002), Associate Professor
Suter Group (2006) at University of Bern.
We seek to prevent cardiovascular side effects associated with cancer therapies,
as well as to improve clinical management strategies. It is a worrisome fact that
ischemia and cardiotoxic compounds can lead to cellular damage and irreversible
decline of cardiac function. Thus, it is critically important to understand these
complications in order to provide better diagnostics and therapy. We investigate
mechanisms of cardiotoxicity of old and new anti-cancer therapies and cardi-
ac-specific survival pathways that show potential as cardiovascular treatments.
34 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Prof. Dr. Paul Mohacsi Group Members Collaborators
paul.mohacsi@insel.ch Prof. Dr. Bernhard Meier, Chair Bailey D, University of Glamorgan, UK
Prof. Dr. Stephan Windecker, Head de Groot NM, Leiden University
MD at University of Zurich. Postdoc in USA at of Research Medical Center, The Netherlands
Stanford University Medical Center (1991-1993). Germond M, Centre of Medically
Since 1993, Medical Director, Heart Failure and Prof. Dr. Yves Allemann, Group Leader Assisted Procreation, Switzerland
Cardiac Transplantation, and Head of Research, PD Dr. Claudio Sartori, Group Leader Largiadèr C, Inselspital, Switzerland
Department of Cardiology, Inselspital. Konsiliarus Prof. Dr. Urs Scherrer, Group Leader McManus B, Wilson-McManus J,
in Transplantation Immunology, University of Dr. Emrush Rexhaj, Clinical Research University of British Columbia, Canada
Freiburg (DE) (2008-2012). Visiting Professor in Associate Pratalli L, Picano E, National
Canada at University of British Columbia (2008, Dr. Stefano Rimoldi, Clinical Research Council, Italy
2011). eMBA from University of Zurich (2009). Research Associate Raio L, Inselspital, Switzerland
Elisa Bouillet, Laboratory Technician Salinas Salmon C, Villena M,
Agim Pireva, MD Student Bolivian Institute of High-Altitude
Biology, Bolivia
Prof. Dr. Etienne Delacrétaz, Sapp J, QEII Health Sciences Centre,
Group Leader Canada
Dr. Laurent Roten, Research Associate Sawyer, DB, Vanderbilt University
Dr. Jens Seiler, Research Associate Medical Center, USA
PD Dr. Hildegard Tanner, Research Solà J, Chételat O, CSEM SA,
Associate Switzerland
PD Dr. Claudio Sartori Prof. Dr. Paul Mohacsi, Group Leader Grants
Claudio.Sartori@chuv.ch Dr. Raschid Setoud, Postdoctoral Amounts allocated for 2012:
MD at University of Lausanne (1991). FMH cer- Fellow –– SNF: Coronary Collateral Circulation
tification in internal medicine (2000). Postdoc Alexia Roschi, Laboratory Technician
at University of California, San Francisco (US). of the Human Heart (C. Seiler)
Since 2003, Assistant Professor at University Prof. Dr. Christian Seiler, Group CHF 237,000
Hospital Lausanne (CHUV). Visiting Professor Leader, Deputy Chair –– SNF: Systemic vascular function
at Department of Cardiology, Inselspital. Dr. Nicolas Brugger, Research in young healthy offspring of
Associate preeclampsia (Y. Allemann, Y. Vial,
Prof. Dr. Urs Scherrer Dr. Stefano de Marchi, Research S. Rimoldi, D. Hutter, L. Raio)
urs.scherrer2@insel.ch Associate CHF 103,000
MD, University of Zurich (1975). Postdoc at UT Dr. Steffen Glökler, Research –– SNF: Insulin-resistance in offspring
Southwestern Medical School, Dallas (US). Di- Associate of assisted reproductive tech
rector of research laboratory, CHUV, Lausanne Dr. Michael Stoller, Research nologies (C. Sartori, S. Rimoldi,
(1990-2011). Honorary Professor of Medicine, Associate Y. Allemann) CHF 140,000
University of Lausanne. Currently, Visiting Pro- PD Dr. Tobias Traupe, Research –– Swiss Society of Hypertension As-
fessor, Department of Cardiology, Inselspital. Associate tra-Zeneca Scholarship: Vascular
Published the first report demonstrating foetal dysfunction in offspring of assisted
programming of vascular dysfunction in humans. Prof. Dr. Thomas M. Suter, reproductive technologies: role of
Group Leader epigenetic mechanisms (E. Rexhaj,
Dr. Christian Zuppinger, Research U. Scherrer, Y. Allemann)
Associate CHF 40,000
Dr. Philippe Beauchamp, –– CTI: Body-on-the-Plate – An Inte-
Postdoctoral Fellow (since Aug.) grated Ready-To-Use Platform For
Investigating Multi Organ Toxicity
(C. Zuppinger) CHF 110,000
–– Swiss Heart Foundation: The Effect
of Acute Afterload Reduction
on Coronary Collateral Function
(S. Glökler, C. Seiler) CHF 44,000
–– Swiss Transplant Cohort Study: Eval-
uation of genomic and proteomic
blood biomarkers for diagnosis
of heart/kidney allograft rejection
(P. Mohacsi) CHF 30,000
35 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Prof. Dr. Christian Seiler Five Selected Publications
christian.seiler@insel.ch Cancer therapy modulates VEGF sign-
aling and viability in adult rat cardiac
Studied medicine at Bern University (1979-1985); microvascular endothelial cells and
Postdoc in USA at University of Texas Health cardiomyocytes. Chiusa, M; Hool, SL;
Science Center (1990-1992). Since 1997, Direc- Truetsch, P; Djafarzadeh, S; Jakob,
tor of Echocardiography; since 1998, Staff SM; Seifriz, F; Scherer, SJ; Suter, TM;
Physician Interventional Cardiology at Depart- Zuppinger, C; Zbinden, S (2012) in:
ment of Cardiology, Inselspital. PD (1997); As- J Mol Cell Cardiol, 52(5), p. 1164-1175.
sociated Professor (2000); Full Professor (2010). Long-term outcome of ablative
Vice President, Bern Cantonal Ethics Com therapy of post-operative atrial
mittee. Co-Head, Masters curriculum, Faculty tachyarrhythmias in patients with te-
of Medicine, University of Bern. tralogy of Fallot: a European multi-cen-
tre study. de Groot, NM; Lukac, P;
Prof. Dr. Thomas M. Suter Schalij, MJ; Makowski, K; Szili-Torok,
Thomas.Suter@insel.ch T; Jordaens, L; Nielsen, JC; Jensen,
HK; Gerdes, JC; Delacretaz, E (2012)
MD at University of Zurich (1986), Cardiology in: Europace, 14(4), p. 522-527.
and CCU/ICU Fellowship in internal medicine at Editorial Comment: The clinical re
Zurich University School of Medicine. In USA, levance of antibody-mediated rejection:
Research Fellowship in Cardiovascular Physiology a new era of heart transplantation.
at Boston University School of Medicine; Cardio Mohacsi, P; Martinelli, M; Banz, Y;
logy Fellowship at Boston University (1992-1998); Boesch, C (2012) in: Eur J Cardiothorac
Internship at Brigham and Women’s Hospital Surg, 42(6), p. 1047-1049.
(1998). Since 2005, Associate Professor, Univer- Systemic vascular dysfunction in
sity of Bern. patients with chronic mountain sick-
ness. Rimoldi, SF; Rexhaj, E; Pratali, L;
Bailey, DM; Hutter, D; Faita, F; Salmon,
CS; Villena, M; Nicod, P; Allemann, Y;
Scherrer, U; Sartori, C (2012) in: Chest,
141(1), p. 139-146.
Systemic and pulmonary vascular
dysfunction in children conceived
by assisted reproductive technologies.
Scherrer, U; Rimoldi, SF; Rexhaj, E;
Stuber, T; Duplain, H; Garcin, S;
de Marchi, SF; Nicod, P; Germond, M;
Allemann, Y; Sartori, C (2012) in:
Circulation, 125(15), p. 1890-1896.
Prof. Dr. Stephan Windecker
stephan.windecker@insel.ch
MD Degree at University of Heidelberg (DE)
(1992). FMH certification in cardiology. Currently,
Professor of Invasive Cardiology at University
of Bern and Chief of Cardiology, Inselspital.
President-Elect, European Association of Percu-
taneous Cardiovascular Interventions.
36 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
DCR Research Groups from the Inselspital
Cardiovascular Surgery
www.herzundgefaesse.insel.ch/de/forschung
Research Highlights 2012 / Outlook 2013 Prof. Dr. Thierry Carrel
Our research focuses on the following projects: t hi e r r y.c a r re l @ ins e l.ch
Myocardial Tissue Engineering Studied medicine at University of Bern; clinical
Engineering of contractile bio-artificial tissues for myocardial repair. This training in general surgery, FMH (1990); cardio-
SNF-funded project was initiated in 2003 and expanded to include collabora- vascular surgery FMH (1993) in Basel and Bern.
tions with EMPA, St. Gallen and the Department of Cardiology, University Habilitation in Zurich (1993), followed by fellow-
of Fribourg. ships at clinics in Paris (FR), Hannover (DE) and
Helsinki (FI). Joined Clinic for Thoracic and Car-
Non-Heart Beating Donors diovascular Surgery, Inselspital as Senior Attend-
Since its formation in 2009, this group aims to evaluate reperfusion strategies ing (1995). Since 1999, Chair, Department of
to promote the use of hearts obtained from donors after cardiac death. Cardiovascular Surgery, Inselspital.
2012 has seen further consolidation and expansion, making this a central re-
search group of the Department of Cardiovascular Surgery.
Myocardial Recovery Prof. Dr. Hendrik Tevaearai Stahel
This project focusing on evaluation of mechanisms leading to reverse remodel- hendrik.tevaearai@insel.ch
ling of failing hearts has progressed from incubation to a fully operational re-
search group in 2012. Thanks to the generous support of both the Swiss Heart Studied medicine at University of Lausanne,
Foundation and the DCR, the outlook for this group in 2013 is strong. followed by clinical training in general surgery,
FMH (1995) and cardiovascular surgery FMH
Limb Ischemia/Reperfusion (2002). Research fellowship at Duke University
This project evaluates the molecular pathways underpinning muscle cell death (US) (1999-2001). Since 2003, Senior Attend-
of skeletal muscle and future pathways to protect ischemic muscle against ing and since 2005, Head of Research and
reperfusion injury. The gathered data bolster the strategic value of the approach Development, Department of Cardiovascular
to develop new translational approaches. Surgery, Inselspital.
Clinical Research: Cardiac
Clinical research in cardiac surgery continued to focus on aortic projects, in-
cluding the elucidation of a new mechanism of propagation in type B aortic
dissection. Several clinical papers were published in this field of research.
2013 will start with the publication of a very promising project on a new bio-
marker in patients with asymptomatic thoracic aortic disease.
Clinical Research: Vascular Dr. Henriette Brinks
Research focused on optimised management strategies for ruptured abdominal henriette.brinks@insel.ch
aortic aneurysm and on the general improvement of follow-up surveys in the
context of observational research. In an award-winning (USGG 2012) randomised Studied medicine at Charité Medical School,
experiment, a strategy was identified that allowed achievement of close to Berlin (DE). Joined Department of Cardiovascular
100% follow-up information of retrospective series. This method will be used Surgery, Inselspital as a Resident (2005). Postdoc
to follow a larger vascular patient sample in 2013, to validate a novel scoring in USA at Thomas Jefferson University (2008-
system for postoperative complications. 2009). Returned to Inselspital (2010) to continue
training in cardiovascular surgery. Clinical com-
mitments as well as Group Leader, Cardiovas-
cular Surgery, DCR.
38 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Prof. Dr. Martin Czerny Group Members and molecular interventions for lim-
martin.czerny@insel.ch Prof. Dr. Thierry Carrel, Chair iting reperfusion injury to the heart
Studied medicine in Vienna (AT); worked at Prof. Dr. Hendrik Tevaearai Stahel, (S. Longnus, H. Brinks, H. Tevaearai)
Clinic for Cardiothoracic Surgery, Medical Uni- Head of Research and Development CHF 40,000
versity of Vienna (1998-2009). General Surgery Dr. Henriette Brinks, Senior –– R esearch Prize 2012: Ventricular
(2004) and Vascular Surgery (2005) qualifica- Attending, Group Leader unloading combined with inotropic
tions, as well as MBA (2008). In 2009, joined Prof. Dr. Martin Czerny, Senior gene therapy in the failing heart
Department of Cardiovascular Surgery, Insel- Attending, Group Leader (H. Brinks) CHF 30,000
spital as an Attending, becoming Head of Car- PD Dr. Florian Dick, Senior –– U niversity of Bern, Faculty of Medi-
diac Surgery Research in 2010. Attending, Group Leader cine Resource Committee: Blood
Dr. Sarah Longnus, Group Leader Gas Analyzer for Ischemia/Reperfu-
PD Dr. Florian Dick Dr. Regula von Allmen, Research sion Injury (T. Carrel, H. Tevaearai,
florian.dick@insel.ch Associate S. Longnus) CHF 17,780
Studied medicine at University of Basel; FMH Dr. Stéphanie Lecaudé, Postdoctoral –– University of Bern, Faculty of
(2005) including a vascular surgery specialisa- Fellow (since Aug.) Medicine Resource Committee:
tion. Joined Department of Cardiovascular Sur- Brigitta Gahl, Statistician Isolated, perfused rat heart system
gery, Inselspital as a Resident (2004); Attend- Bettina Kohler, Data Manager for Ischemia/Reperfusion Injury
ing (2006). Spent a year in Vascular Surgery Monika Sperisen, Data Manager (T. Carrel, H. Tevaearai, S. Longnus)
Research Group, Imperial College London (GB). Sorin Ciocan, Laboratory CHF 41,518
Since returning, Head of Vascular Surgery Technician (since Nov.) –– S wiss Heart Foundation: Towards
Research (2010) and Senior Attending (2012). Céline Fouassier, Laboratory myocardial recovery: Enhanced
Technician (until Nov.) adrenergic response via ßARKTct
Dr. Sarah Longnus Céline Giroud, Laboratory Technician gene therapy in the unloaded heart
sarah.longnus@insel.ch Veronika Mathys, Laboratory (H. Brinks) CHF 68,000
Studied biology at University of Western Technician (since Dec.)
Ontario (CA); PhD at Department of Pathology Adrian Segiser, Laboratory Five Selected Publications
and Laboratory Medicine, James Hogg Re- Technician (since May) Endovascular suitability and outcome
search Centre, University of British Columbia Joevin Sourdon, Laboratory after open surgery for ruptured ab-
(CA). Postdocs in Boston (US) and Nice (FR). Technician (until Aug.) dominal aortic aneurysm. Dick, F et al.
Since 2009, Group Leader, Cardiovascular Barbara Schweizer, Secretary (2012) in: Br J Surg, 99(7), p. 940-947.
Surgery, DCR. (Apr.-Sep.), Data Manager (Oct.-Dec.) Early reperfusion hemodynamics
Laura Seidel, Secretary predict recovery in rat hearts: a poten-
Monika Dornbierer, MD-PhD Student tial approach towards evaluating
Géraldine Guex, PhD Student cardiac grafts from non-heart-beating
donors. Dornbierer, M et al. (2012) in:
Collaborators PLoS One, 7(8), p. e43642.
Banfi A, Melly L, University Fine-tuning of substrate architec-
Hospital Basel, Switzerland ture and surface chemistry promotes
Brugger J, Grossenbacher J, Gullo M, muscle tissue development. Guex, AG
EPF Lausanne, Switzerland et al. (2012) in: Acta Biomater, 8(4),
Cook S, Frobert A, Giraud M-N, p. 1481-1489.
University of Fribourg, Switzerland Controlled angiogenesis in the
Flück M, Manchester Metropolitan heart by cell-based expression of spe-
University, UK cific vascular endothelial growth
Fortunato G, EMPA St. Gallen, factor levels. Melly, LF et al. (2012) in:
Switzerland Hum Gene Ther Methods, 23(5),
Guzzela L, Schmid M, ETH Zurich, p. 346-356.
Switzerland Mild hypothermia during global
Ullrich N, University of Bern, cardiac ischemia opens a window of
Switzerland opportunity to develop heart donation
after cardiac death (DCD). Stadelmann,
Grants M et al. in: Transplant International
Amounts allocated for 2012: (in press).
–– R uth und Arthur Scherbarth Foun-
dation: Cardioprotection: Physical
39 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Cranio-Maxillofacial Surgery
www.dkf.unibe.ch/research-group/57/
Research Highlights 2012 / Outlook 2013 Prof. Dr. Tateyuki Iizuka
Clinical Studies tateyuki.iizuka@insel.ch
Paediatric patients with fractures of the anterior skull base frequently present
with associated injuries, many with multiple associated injuries, including MD and DDS in Germany; PhD in Medicine
polytrauma. The analysis of occurrence, sites, and types of associated injuries (1992). Since 1996, Associate Professor at
indicated the need for multidisciplinary trauma units. Helsinki University (FI). Since 2000, Professor
We studied whether a daily course of antibiotics affects the incidence of of Cranio-Maxillofacial Surgery, University of
postoperative infection after displaced fractures. Patients with orbital blow-out Bern; Chair of Department since 2006. Lecturer
fractures were randomly assigned to two groups, both of which were given at Helsinki University, External Professor at
amoxicillin/clavulanic acid intravenously from the time of admission to 24h Osaka Dental University (JP) and National Uni-
postoperatively. The 5-day group were then given amoxicillin/clavulanic acid versity of Singapore. Director of postgrad uate
orally for 4 further days and the 1-day group a placebo orally at the same time programmes in oral and maxillofacial surgery
intervals. Results showed that a postoperative 1-day course of antibiotics in Switzerland, Germany, Finland and European
may be as effective in preventing infective complications in patients with dis- Association for Cranio-Maxillofacial Surgery.
placed orbital fractures as a 5-day regimen.
Assessment of peri-implant bone changes is considered one of the critical Dr. Nikola Saulacic
components for long-term success of dental implants. Peri-implant bone changes, nikola.saulacic@insel.ch
frequently assessed by reporting on bone height, might actually neglect the
process of bone remodelling. Hard and soft tissue parameters around implants Studies in dental medicine and MSc from
supporting fixed prostheses were analysed over a period of 5 years. An increase University of Belgrade (RS). European PhD
in bone density indicated a regain of the crestal bone level after initial bone (2005) at University of Santiago de Compostela
loss around implants. (ES). Research and Teaching Associate at
University of Geneva (2006-2007). Since 2007,
Preclinical Studies Research Associate, University of Bern. Since
We previously demonstrated in vivo that the application of a collagen barrier 2012, Group Leader, Cranio-Maxillofacial
membrane in periosteal distraction osteogenesis was beneficial to bone forma- Surgery, DCR.
tion. An in vitro study performed at the School of Dental Medicine, University
of Bern demonstrated that bone morphogenic protein-2 and transforming growth
factor 1 soak-loaded membranes increased osteoblast proliferation when com-
pared to control collagen membranes. Administration of bone morphogenic
protein-2 increased osteoblast differentiation markers such as osterix, collagen I,
and osteocalcin, as well as mineralisation of primary osteoblasts. The ongoing
in vivo study evaluates the contribution of the barrier membrane soaked with
growth factors to bone formation in periosteal distraction osteogenesis in rats
and assessment of new bone formation using two rates of periosteal distrac-
tion in rabbits.
The collaboration with the School of Dental Medicine includes in vivo studies
performed at the Clinic for Oral Surgery. These evaluated impact of harvesting
techniques on cell viability and release of molecules affecting bone formation
and the use of new materials (TiZr) on osseointegration of dental implants.
40 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Group Members Pohl, Y; Wahl, G (2012) in: Implant
Prof. Dr. Tateyuki Iizuka, Chair Dent, 21(4), p. 323-329.
Dr. Nikola Saulacic, Head of Occurrence, types and severity
Research, Group Leader of associated injuries of paediatric pa-
Dr. Eliane Brolese, Research tients with fractures of the frontal
Assistant skull base. Schaller, B; Hosokawa, S;
Dr. Maiko Haga, Research Buttner, M; Iizuka, T; Thoren, H (2012)
Assistant (since Nov.) in: J Craniomaxillofac Surg, 40(7), p.
Dr. Peng Jiambo, Research e218-e221.
Assistant (since Oct.) The role of postoperative prophy-
Dr. Ken Nakahara, Postdoctoral lactic antibiotics in the treatment of
Fellow facial fractures: a randomised, dou-
Dr. Benoit Schaller, Research ble-blind, placebo-controlled pilot
Associate clinical study. Part 1: orbital fractures
Caroline-Dominique Zürcher, in 62 patients. Zix, J; Schaller, B;
Secretary Iizuka, T; Lieger, O (2012) in: Br J Oral
Maxillofac Surg.
Collaborators
Buser D, University of Bern,
Switzerland
Hofstetter W, University of Bern,
Switzerland
Lombardi T, University of Geneva,
Switzerland
Mataga I, University of Niigata, Japan
Scolozzi P, University of Geneva,
Switzerland
Sculean A, University of Bern,
Switzerland
Thoren H, University of Helsinki,
Finland
Wahl G, University of Bonn,
Germany
Grants
Amounts allocated for 2012:
None
Five Selected Publications
Low-profile titanium mesh in the use
of orbital reconstruction: A pilot
study. Lieger, O; Schaller, B; Kellner, F;
Messmer-Schai, B; Iizuka, T (2012) in:
Laryngoscope, 122(5), p. 982-991.
Osteoblast proliferation and differ-
entiation on a barrier membrane in
combination with BMP2 and TGFbeta1.
Miron, RJ; Saulacic, N; Buser, D;
Iizuka, T; Sculean, A (2012) in: Clin
Oral Investig.
Clinical and radiographic outcome
of dental implants supporting fixed
prostheses: the relevance of cortical
bone formation. Saulacic, N; Abboud, M;
41 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Dermatology
www.dkf.unibe.ch/research-group/72/dermatology
Research Highlights 2012 / Outlook 2013 Prof. Dr. Luca Borradori
Allergies luca.borradori@insel.ch
Thymic stromal lymphopoietin (TSLP) is a cytokine released by epithelial cells
upon stimulation by various environmental stresses (e.g., viruses, bacteria, aller- MD at University of Bern (1986). Resident in
gens) and one of the major culprits in the allergic inflammatory diseases asthma, Dermatology at University Hospitals of Paris (FR),
allergic rhinitis, and atopic dermatitis. In collaboration with the research groups Lausanne and Geneva (1989-1993). Postdoc in
of H.-U. Simon and S. Yousefi (Institute of Pharmacology), we demonstrated USA at National Cancer Institute (1993-1995)
that TSLP triggers the release by eosinophils of extracellular DNA in association and The Netherlands Cancer Institute (1995-
with eosinophilic cationic protein, termed eosinophil extracellular traps (EETs). 1997). Associate Professor, Chief of Unit, Re-
This release of EETs was dependent on integrin-mediated adhesion or produc- search Associate and Senior Resident, Dermatol-
tion of reactive oxygen species, and exhibited antimicrobial activity against ogy, University Hospital, Geneva (1997-2008).
Staphylococcus aureus and S. epidermidis. This mechanism provides a link between Since 2008, Chair, Department of Dermatology,
the injury to an epithelial barrier and increased TSLP expression, with subse- Inselspital.
quent pathogen defense response by eosinophils and eosinophilic inflammation.
Psoriasis Prof. Dr. Robert Hunger
Innate immune responses play a central role in psoriasis. Our investigations robert.hunger@insel.ch
showed that a new retinoid named alitretinion leads to clinical amelioration and
abrogates innate inflammation in palmoplantar pustular psoriasis. Heat shock Studied medicine at Universities of Fribourg
proteins may play an important part in plaque psoriasis. The expression of these and Bern (1984-1990); MD-PhD at University of
proteins in psoriasis and their regulation through proinflammatory cytokines is Bern (1996); board certified in Dermatology
currently been investigated. (2001). Postdoc in USA at University of Califor-
nia, Los Angeles (2001-2003). Since 2011, As-
Hidradenitis Suppurativa (HS) sociate Professor, Department of Dermatology,
Antimicrobial peptide cathelicidin expression was found to be significantly in- Inselspital.
creased in lesional HS skin at the mRNA and protein level. Using immunofluores-
cence double staining we could demonstrate that neutrophils and dendritic cells
expressing cathelicidin are present in the lesions. By analysing freshly isolated
cells from lesional skin by flow cytometry, we could further confirm the expression
of cathelicidine on CD15-positive neutrophils and CDD4+CD3-infiltrating cells.
Malignant Melanoma
We investigated the role of various immunohistochemical markers in predicting
disease progression and showed that high expression of the T cell marker FoxP3
is associated with bad prognosis in melanoma patients.
Plakins Prof. Dr. Dagmar Simon
Plectin is a cytolinker of the plakin family with intermediate filaments (IFs) that is dagmar.simon@insel.ch
important for cell cytoarchitecture, and for cell and tissue resilience to mechani-
cal stress, especially in the skin and skeletal muscle. Investigation of the inter Studied medicine at Friedrich-Schiller University
action of plectin with IFs revealed much more complex binding than previously Jena (DE); MD (1989); Research Fellowship in
published, thanks to a new method to test and quantify protein-protein inter- Canada at University of Toronto Women’s Col-
actions. Moreover, we found that phosphorylation of a serine residue in the lege Hospital (1991-1992); board certifications:
carboxyl tail of plectin inhibits its interaction with IFs, and identified two protein Dermatology (1993), Allergy and Clinical Im-
kinases catalysing this phosphorylation in vivo. Our data provide insights into munology (2003); PD (2006). Since 2010, Asso-
the molecular basis of plectin- and IF-related human diseases associated with ciate Professor, Department of Dermatology,
pathogenic mutations affecting functionally relevant sites within these molecules. Inselspital.
42 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Prof. Dr. Nikhil Yawalkar
nikhil.yawalkar@insel.ch
MD at University of Basel (1988). Board certifi-
cations: Dermatology (1995), Allergy and Clini-
cal Immunology (1998) at University of Bern.
Postdocs in USA at University of California, San
Francisco (1995) and Harvard Skin Disease Re-
search Center (2000-2002). Since 2006, Asso-
ciate Professor, Department of Dermatology,
Inselspital.
Group Members Collaborators Five Selected Publications
Prof. Dr. Luca Borradori, Chair, Green K, Northwestern University Endemic pemphigus foliaceus: to-
Group Leader Feinberg School of Medicine, USA wards understanding autoimmune
Prof. Dr. Robert Hunger, Herrmann H, German Cancer mechanisms of disease development.
Group Leader Research Center, Germany Di, ZG; Zambruno, G; Borradori, L
Prof. Dr. Dagmar Simon, Jaggi R, University of Bern, (2012) in: J Invest Dermatol, 132(11),
Group Leader Switzerland p. 2499-2502.
Prof. Dr. Nikhil Yawalkar, Shafighi M, Inselspital, Switzerland Alitretinoin abrogates innate in-
Group Leader Simon H-U, University of Bern, flammation in palmoplantar pustular
Dr. Bertrand Favre, Head of Switzerland psoriasis. Irla, N; Navarini, AA;
Laboratory Sonnenberg A, The Netherlands Yawalkar, N (2012) in: Br J Dermatol,
Dr. Masata Kakeda, Postdoctoral Cancer Institute, The Netherlands 167(5), p. 1170-1174.
Fellow Strelkov S, KU Leuven, Belgium Thymic stromal lymphopoietin
Dr. Isabelle Shepens, Postdoctoral Ugguccioni MG, Institute for stimulates the formation of eosinophil
Fellow (until Mar.) Research in Biomedicine, Switzerland extracellular traps. Morshed, M;
Nadja Begré, Laboratory Technician Yousefi S, University of Bern, Yousefi, S; Stockle, C; Simon, HU;
Ursula Läderach, Laboratory Switzerland Simon, D (2012) in: Allergy, 67(9),
Technician p. 1127-1137.
Evelyne Seger, Laboratory Technician Grants The role of androgens on hypox-
Prakash Lingasamy, Research Amounts allocated for 2012: ia-inducible factor (HIF)-1alpha-in-
Associate (until Aug.) –– SNF: Analysis of molecular and duced angiogenesis and on the survival
Jamal-Eddine Bouameur, of ischemically challenged skin flaps
PhD Student cellular mechanisms in immune-me- in a rat model. Shafighi, M; Olariu, R;
Elisabeth De Graauw, PhD Student diated tissue damage of the skin: Brun, C; Fathi, AR; Djafarzadeh, S;
(since Aug.) Hidradenitis suppurativa as a model Jakob, SM; Hunger, RE; Banic, A;
Mahbubul Morshed, PhD Student disease (R. Hunger, N. Yawalkar) Constantinescu, MA (2012) in: Micro-
Kseniia Poliakova, PhD Student CHF 70,000 surgery, 32(6), p. 475-481.
–– OPO Foundation, Zurich: The ef- Eosinophil extracellular DNA traps:
fects of thymic stromal lympho molecular mechanisms and potential
poietin (TSLP) on eosinophil extra- roles in disease. Yousefi, S; Simon, D;
cellular DNA release (D. Simon) Simon, HU (2012) in: Curr Opin Immu-
CHF 32,000 nol, 24(6), p. 736-739.
43 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Gastroenterology /
Mucosal Immunology
www.mucosalimmunology.ch
Research Highlights 2012 / Outlook 2013 Prof. Dr. Andrew Macpherson
Our research groups strive to understand the molecular and cellular immune Andrew.Macpherson@insel.ch
mechanisms involved in regulating host-microbial mutualism.
Studied biochemistry (PhD, 1983) and Medicine
Macpherson Group (MB, 1985) at University of Cambridge (UK).
IgA is the dominant antibody isotype secreted at mucus membranes, yet the Research Group Leader and senior medical
precise immunological functions of IgA are only partially understood. Using staff at University Hospital Zurich (1998-2004),
metabolic labelling of bacteria or plasmid-based systems to assess bacterial Professor of Medicine at McMaster University
proliferation, we are performing experiments to address whether mucosal anti- (CA) (2004-2008). Since 2008, Chief of Gastro-
bodies (and IgA in particular) have an impact on the dynamics of intestinal enterology and Co-Chair, Department of
commensal bacteria, such as bacterial proliferation, retention of bacteria in dif- Visceral Surgery and Medicine, Inselspital.
ferent niches, and shedding of bacteria. We are investigating the stratification
of bacteria within the gut and determining the dynamics of bacteria within Prof. Dr. Kathy McCoy
the different mucus layers lining the gut epithelium. Although under homeo- kathleen.mccoy@dkf.unibe.ch
static conditions live bacteria are compartmentalised to mucosal sites, bacterial
products can penetrate to systemic sites. We are actively studying the conse- Studied immunology (PhD, 1997) at Otago
quences of these products on the systemic immune system. In this context, we University and Malaghan Institute of Medical
also investigate the role of natural antibodies at systemic sites in handling these Research (NZ). Postdoctoral Fellow (1998-2000)
penetrating bacterial products. We are also investigating the impact of expo- and Senior Research Scientist /Group Leader
sure to intestinal microbes on the innate lymphoid system at intestinal and ex- (2000-2006) at Institute for Experimental Im-
tra-intestinal sites at different time points during immune development. munology, University Hospital Zurich. Assistant
Professor (2006-2010) and Director of Axenic/
McCoy Group Gnotobiotic Facilty (2008-2010) at McMaster
We have observed that the pathways that normally repress the production of IgE University (CA). Since 2010, DCR Group Leader,
antibodies are disrupted in the absence of microbes, resulting in extremely ele- Gastroenterology / Mucosal Immunology.
vated serum IgE levels in germ-free mice, which reflects immune dysregulation.
We have now elucidated that the complexity of the microbiota present early
in life is instrumental in instructing a normal immune regulatory status. A critical
threshold of microbial complexity has to be reached early during colonisation
to ensure proper induction of immune regulation. This is the first experimental
demonstration of a mechanism that could be an underlying cause of the obser-
vations described in the ‘hygiene hypothesis’. We are now investigating the role
of the innate immune system in sensing this microbial complexity and what signals
are involved in instructing regulation of the adaptive immune system.
Geuking Group Dr. Markus Geuking
In 2011, we published results showing that intestinal bacterial colonisation in- markus.geuking@dkf.unibe.ch
duces strong regulatory T cell and interleukin-10 responses to ensure immune
homeostasis following colonisation. Based on these findings, we are now in- Studied molecular biology and immunology
vestigating the antigen-specificity requirements for efficient regulatory T cell (PhD, 2006) at University of Zurich and ETH
induction using genetically modified E. coli strains expressing a particular T cell Zurich. Postdoctoral Fellow (2006-2010)
epitope that is recognised by a transgenic T cell receptor. In addition, we are at McMaster University (CA). Since 2010, DCR
investigating the cooperation between regulatory T cell and IgA responses in Group Leader, Gastroenterology / Mucosal
controlling mutualism with the intestinal microbiota. Immunology.
44 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Group Members Grants Five Selected Publications
Prof. Dr. Andrew Macpherson Amounts allocated for 2012: Microbial-immune cross-talk and reg-
Chief of Gastroenterology, Co-Chair –– SNF: Compartmentalisation of ulation of the immune system.
Prof. Dr. Kathy McCoy, Group Leader Cahenzli, J; Balmer, ML; McCoy, KD
Dr. Markus Geuking, Group Leader commensal intestinal microbes and (2012) in: Immunology.
Dr. Julia Cahenzli, Postdoctoral Fellow host IgA immunity in maintaining The function of secretory IgA
Dr. Mercedes Gomez de Aguero, host-microbial mutualism in the context of the intestinal contin-
Postdoctoral Fellow (A. Macpherson) CHF 335,000 uum of adaptive immune responses
Dr. Li Hai, Postdoctoral Fellow –– S NF: The role of antigen-specific and in host-microbial mutualism. Geuking,
Dr. Melissa Lawson, Postdoctoral Toll-like receptor-dependent de MB; McCoy, KD; Macpherson, AJ
Fellow novo generation of inducible regu- (2012) in: Semin Immunol, 24(1),
Dr. Yasuhiro Uchimura, Postdoctoral latory T cells in the induction p. 36-42.
Fellow (since Nov.) of intestinal immune homeostasis Homeland security: IgA immunity
Beatrice Flogerzi, Laboratory (M. Geuking) CHF 176,741 at the frontiers of the body.
Technician –– SNF: Shaping of the innate immune Macpherson, AJ; Geuking, MB; McCoy,
Madeleine Wyss, Laboratory system during neonatal exposure KD (2012) in: Trends Immunol, 33(4),
Technician to commensal intestinal microbes p. 160-167.
Yasmin Köller, PhD Student (since Feb.) (A. Macpherson) CHF 137,500 The habitat, double life, citizen-
William Kwong Chung, PhD Student –– S NF: Investigation into the impact ship, and forgetfulness of IgA.
Sandra Rupp, PhD Student (since Oct.) of environmental microbes on Macpherson, AJ; Geuking, MB; Slack,
regulation of IgE and allergic E; Hapfelmeier, S; McCoy, KD (2012)
Collaborators disease (K. McCoy) CHF 100,000 in: Immunol Rev, 245(1), p. 132-146.
Hardt WD, ETH Zurich, Switzerland –– E uropean Research Council: Interactions between the micro
Harris N, EPF Lausanne, Switzerland Mechanisms of hygiene-mediated biota and the immune system.
Heikenwalder M, Helmholtz Centre immune dysregulation and impact Hooper, LV; Littman, DR; Macpherson,
for Infection Research, Germany on the susceptibility to allergic and AJ (2012) in: Science, 336(6086),
Hooper L, University of Texas, USA autoimmune diseases (K. McCoy) p. 1268-1273.
Palmer E, University of Basel, CHF 300,000
Switzerland –– Juvenile Diabetes Research Founda-
Powrie F, University of Oxford, UK tion: Type 1 diabetes protection
Santamaria P, University of through commensal intestinal bac-
Calgary, Canada terial exposure (A. Macpherson,
Sauer U, ETH Zurich, Switzerland K. McCoy) CHF 101,000
Stecher B, Ludwig Maximilian
University, Germany
45 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Haematology / Oncology
(Paediatrics)
www.dkf.unibe.ch/research-group/16/
Research Highlights 2012 / Outlook 2013 Prof. Dr. Kurt Leibundgut
We are involved in several projects aiming to identify molecular targets for the kurt.leibundgut@insel.ch
development of novel therapies for childhood cancer, with an emphasis on
embryonal tumours (medulloblastoma, neuroblastoma) and leukaemia (ALL and Medical Diploma (1981) and MD (1986) at
AML). We are also involved in several clinical studies in paediatric cancer patients. University of Zurich. PD (2000) and Associated
A summary of the main studies of 2012 is presented below. Professor (2009) at University of Bern. Since
2011, Head of Division of Paediatric Haemato
Laboratory Studies logy and Oncology, Department of Paediatrics,
We identified novel molecular targets for the development of targeted therapies Inselspital. Since 2003, Director of Paediatric
in neuroblastoma using RNA interference screening. Our studies revealed that and Adult Stem Cell Transplantation Program,
targeting the fibroblast growth factor receptor-2 (FGFR2) could sensitise neuro- Inselspital.
blastoma cells to cisplatin, a commonly used chemotherapeutic agent. In addi-
tion, an autocrine signalling loop involving fibroblast growth factor-2 (FGF-2) and PD Dr. Alexandre Arcaro
FGFR2 was described in primary neuroblastoma and neuroblastoma cell lines. alexandre.arcaro@dkf.unibe.ch
We evaluated R1507, a humanised neutralising antibody against the insu-
lin-like growth factor-1 receptor (IGF-1R), as an anti-proliferative agent in medul- Diploma in Biology at University of Lausanne
loblastoma and neuroblastoma. This study revealed that R1507 had single agent (1992). PhD at University of Fribourg (1995).
activity in only a limited number of medulloblastomas and neuroblastomas. Postdocs at Ludwig Institute for Cancer
However, R1507 could be combined with standard chemotherapeutic drugs such Research in London (UK) (1995-1996) and
as cisplatin. Lausanne (1998-2000). Lecturer, Imperial
We evaluated novel pharmacological inhibitors of the class II phosphoinositide College London (UK) (2000-2003). Oberassist-
3-kinase C2 (PI3KC2 ), as anti-proliferative agents in acute leukaemia, glioblas- ent, University Children’s Hospital Zurich
toma, medulloblastoma and neuroblastoma. Over-expression of PI3KC2 could (2004-2009); PD, University of Zurich (2008).
be documented in primary tumours at the mRNA and protein level. In addition, Since 2010, Group Leader/Oberassistent,
pharmacological inhibitors of PI3KC2 inhibited the proliferation and survival of Haematology / Oncology (Paediatrics), DCR
cell lines from the above-mentioned cancers. and PD, University of Bern.
We identified a novel role for PI3KC2 in the regulation of the actin cyto
skeleton and the activation of Rho family GTPases. A multi-protein complex
involving the guanine nucleotide exchange factor Dbl, Grb2 and PI3KC2 was
identified in various cell lines. This complex was shown to control several
Rho-dependent processes, including actin stress fibre formation and protection
from detachment-induced cell death (anoikis).
Clinical Studies
We prospectively investigate and monitor cognitive abilities in children with brain
tumours and in children with malignancies that do not involve the CNS. Neuro
psychological assessments are performed before and after medical interven-
tion, as well as yearly follow-up exams. The studies also include implementation
and evaluation of a cognitive training programme for affected children.
With the aim to improve supportive car in children with chemotherapy-in-
duced fever in neutropaenia, a variety of prospective and retrospective clinical
studies are being performed.
46 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Group Members synthetic lethal interaction partners chemotherapy-induced neutropenia:
Prof. Dr. Kurt Leibundgut, Head of of Myc genes in medulloblastoma results of the prospective multicenter
Division, Paediatric Haematology (A. Arcaro) CHF 60,000 SPOG 2003 FN study. Luthi, F; Leibund-
and Oncology –– S tiftung für klinisch-experimentelle gut, K; Niggli, FK; Nadal, D; Aebi, C;
PD Dr. Alexandre Arcaro, Tumorforschung: Identification and Bodmer, N; Ammann, RA (2012) in:
Group Leader characterization of leukemia stem Pediatr Blood Cancer, 59(1), p. 90-95.
Nohemi Benavides, Laboratory cells in pediatric acute lymphoblas-
Technician (since Aug.) tic leukemia using a novel in vivo
Ditte Guldager Christiansen, model (A. Arcaro, K. Leibundgut)
Laboratory Technician CHF 67,000
Julmy Friedgard, Laboratory –– Stiftung zur Krebsbekämpfung:
Technician Novel molecular targets for medul-
Anelia Schweri-Olac, Laboratory lo-blastoma in relation to c-Myc
Technician (A. Arcaro) CHF 10,000
Karolina Blajecka, PhD Student –– S wiss Paediatric Oncology Group:
(until June) Klinische Forschung, Multizenter-
Anna Borgström, PhD Student studien (K. Leibundgut) CHF 41,086
Paulina Cwiek, PhD Student
Valeriya Dimitrova, PhD Student Five Selected Publications
Katrin Höland, PhD Student Phosphoinositide 3-kinase C2beta
(until Mar.) regulates RhoA and the actin cytoske
Zaira Leni, PhD Student leton through an interaction with Dbl.
Geetha Parakkal, PhD Student Blajecka, K; Marinov, M; Leitner, L;
Fabiana Salm, PhD Student Uth, K; Posern, G; Arcaro, A (2012) in:
(until May) PLoS One, 7(9), p. e44945.
Anna Wojtalla, PhD Student Targeting PI3KC2beta impairs pro-
(until May) liferation and survival in acute leu-
kemia, brain tumours and neuroendo-
Collaborators crine tumours. Boller, D; Doepfner, KT;
Delattre O, Institut Curie, France De, LA; Guerreiro, AS; Marinov, M;
Frei K, University Hospital Shalaby, T; Depledge, P; Robson, A;
Zurich, Switzerland Saghir, N; Hayakawa, M; Kaizawa, H;
Gross N, CHUV Lausanne, Switzerland Koizumi, T; Ohishi, T; Fattet, S; Delattre,
Grotzer M, University Children’s O; Schweri-Olac, A; Holand, K; Grotzer,
Hospital Zurich, Switzerland MA; Frei, K; Spertini, O; Waterfield,
Haapa-Paananen S, VTT Turku, MD; Arcaro, A (2012) in: Anticancer
Finland Res, 32(8), p. 3015-3027.
Olsen J, University of Copenhagen, RNA interference screening identi-
Denmark fies a novel role for autocrine fibroblast
Westermann F, DKFZ Heidelberg, growth factor signaling in neuroblas-
Germany toma chemoresistance. Salm, F; Cwiek,
P; Ghosal, A; Lucia, BA; Largey, F;
Grants Wotzkow, C; Holand, K; Styp-Rekowska,
Amounts allocated for 2012: B; Djonov, V; Zlobec, I; Bodmer, N;
–– European Commission: ASSET Gross, N; Westermann, F; Schafer, SC;
Arcaro, A (2012) in: Oncogene.
(A. Arcaro) CHF 240,000 Novel Agents Targeting the IGF-1R/
–– Beatrice Borer-Stiftung: Neuropsy- PI3K Pathway Impair Cell Proliferation
and Survival in Subsets of Medulloblas-
chologische Evaluation von Kindern toma and Neuroblastoma. Wojtalla, A;
mit Malignomen (K. Leibundgut) Salm, F; Christiansen, DG; Cremona, T;
CHF 130,000 Cwiek, P; Shalaby, T; Gross, N;
–– Berner Stiftung für krebskranke Grotzer, MA; Arcaro, A (2012) in: PLoS
Kinder und Jugendliche: One, 7(10), p. e47109.
(K. Leibundgut) CHF 238,340 Serious medical complications
–– Novartis Foundation for medical- in children with cancer and fever in
biological research: Identification of
47 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Hand Surgery
www.handchirurgie.insel.ch
Research Highlights 2012 / Outlook 2013 Prof. Dr. Esther Vögelin
The highly promising use of composite tissue allotransplantation (CTA), for esther.voegelin@insel.ch
example hand transplantation, as a reconstructive treatment has become a clini-
cal reality. However, the major obstacle hindering the progress of CTA is the Studied medicine at University of Basel. Clinical
need for chronic immunosuppression. Thus, our current research focus is on training in plastic/reconstructive surgery at
discovery of novel strategies that can be used as a replacement for current im- Mount Vernon Hospital, Northwood (UK) and
munosuppressive protocols. We aim at developing a local immunosuppressive The Wellington Hospital, London (UK). Research
drug delivery system. This might reduce concomitant systemic exposure of Fellow in hand and microsurgery at University
drugs, which may eventually curb drug-specific adverse effects, as well as in- of California, Los Angeles, (US). Since 2007,
crease bioavailability of the drugs in the allograft. Physician-in-Chief and Co-Chair, Department
In collaboration with MIT in Boston (US), we have successfully developed of Plastic and Hand Surgery, Inselspital.
a novel, biocompatible hydrogel system that allows for encapsulation of the im-
munosuppressive drug FK506 in therapeutic concentrations. Enzymes that are
produced in the tissue during inflammatory conditions degrade the hydrogel
and release FK506 in an on-demand manner to prevent rejection. In 2012, rat
hind limb allotransplantations in a Brown Norway to Lewis model were per-
formed to evaluate the therapeutic potential of FK506-laden hydrogel. These
experiments showed that local, subcutaneous injection of the gel on day 1 post
transplantation alone is sufficient to prevent rejection for at least 100 days. In
2013, these experiments will be continued and analyses performed with respect
to drug release, immune responses, graft rejection and relevant molecular
mechanisms. Furthermore, we are investigating other potential drug delivery
systems/local immunosuppression that can be used in CTA.
Recently, an ex vivo system to perfuse amputated extremities with whole,
anticoagulated blood was set up in collaboration with the Plastic Surgery group
and the perfusionist’s team/Cardiovascular Surgery group. This system was
tested experimentally with pigs and is ready for clinical use to prolong the time
to replantation for traumatically amputated extremities. In 2012, the system
was used to perform experiments in the context of xenotransplantation, i.e.,
porcine limbs were perfused with human blood. This project is being carried
out in collaboration with the Ludwig-Maximilian University of Munich (DE),
Revivicor, Inc., Blacksburg (US), and the Department of Immunology and Aller-
gology, Geneva University Hospital. Limbs of alpha-gal knockout pigs, which
were further genetically modified by introduction of the human complement
regulator CD46 and human HLA-E, were ex vivo perfused with human blood in
order to test the effect of the different transgenes on xenorejection mediated
by human preformed anti-pig antibodies, the complement system, and natural
killer cells. So far, our data have revealed that, in contrast to solid organ per
fusions, no hyperacute rejection occurs during leg perfusion. This is quite sur-
prising and allows us to use this perfusion system to assess delayed rejection
mechanisms, which are still a major barrier for pig-to-human xenotransplanta-
tion. In 2013, the experiments will be continued and further transgenes will
be tested, with emphasis on the role of the coagulation system (human throm-
bomodulin transgene).
48 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Group Members –– American Foundation for Surgery of Ischemia/reperfusion injury of porcine
Prof. Dr. Esther Vögelin, Co-Chair, the Hand: A clinically relevant thera- limbs after extracorporeal perfusion.
Group Leader peutic approach to induce tolerance Muller, S; Constantinescu, MA;
Prof. Dr. Robert Rieben, Head in composite tissue allotransplan Kiermeir, DM; Gajanayake, T; Bongoni,
of Research tation (E. Vögelin, T. Gajanayake, AK; Vollbach, FH; Meoli, M; Plock, J;
Dr. Bettina Juon, Consultant R. Rieben) USD 20,000 Jenni, H; Banic, A; Rieben, R; Vogelin,
Dr. Franck Leclère, Consultant E (2012) in: J Surg Res.
Dr. Thusitha Gajanayake, –– Olga Mayenfisch Foundation: Impli- Early versus delayed surgical treat-
Postdoctoral Fellow cation of local immunosuppression ment in open hand injuries: a para-
in induction of donor-specific toler- digm revisited. Angly, B; Constan-
Collaborators ance in composite tissue allotrans- tinescu, MA; Kreutziger, J; Juon, BH;
Ayares D, Revivicor Inc., USA plantation (T. Gajanayake, E. Vögelin, Vogelin, E (2012) in: World J Surg,
Constantinescu MA, Olariu R, R. Rieben) CHF 20,000 36(4), p. 826-829.
Kiermeir DM, Inselspital, Switzerland
Gorantla V, University of Five Selected Publications
Pittsburgh, USA Assessment of endothelium and in-
Klymiuk N, Wolf E, flammatory response at the onset
Ludwig-Maximilian University of of reperfusion injury in hand surgery.
Munich, Germany Kamat, P; Juon, B; Jossen, B;
Seebach J, Geneva University Gajanayake, T; Rieben, R; Vogelin, E
Hospital, Switzerland (2012) in: J Inflamm (Lond), 9(1), p. 18.
Vemula P, Harvard University, USA Evaluation of a porcine whole-
limb heterotopic autotransplantation
Grants model. Kiermeir, DM; Meoli, M;
Amounts allocated for 2012: Muller, S; Abderhalden, S; Vogelin, E;
–– SNF: Composite tissue preservation Constantinescu, MA (2012) in:
Microsurgery.
by extracorporeal blood perfusion Nonanimal stabilized hyaluronic
and vascular cytoprotection to Acid for tissue augmentation of the
extend the time limit to replanta- dorsal hands: a prospective study on
tion or transplantation (E. Vögelin, 38 patients. Leclere, FM; Vogelin, E;
M. Constantinescu, R. Rieben) Mordon, S; Alcolea, J; Urdiales, F;
CHF 75,000 Unglaub, F; Trelles, M (2012) in: Aes-
thetic Plast Surg, 36(6), p. 1367-1375.
49 DCR Annual Report 2012 / DKF Jahresbericht 2012
DCR Research Groups from the Inselspital
Human Genetics
www.dkf.unibe.ch/research-group/12/human-genetics
Research Highlights 2012 / Outlook 2013 Prof. Dr. Sabina Gallati
Cystic Fibrosis (CF) sabina.gallati@insel.ch
One difficulty in diagnosis and therapy of CF, the most common lethal autoso-
mal-recessive hereditary disorder in Caucasians, is the huge phenotypic varia PhD in human genetics at University of Bern.
bility observed, even in patients carrying the same CF transmembrane conduct- Postdocs at Hammersmith Hospital and St. Mary’s
ance regulator (CFTR) genotype. We aim to elucidate mechanisms for this Hospital, London (UK), Boston Children’s Hospital
phenotypic heterogeneity at the genomic and proteomic level. We were able to and FBI-Academy, Quantico (US). Specialist in
identify six sequence variants (SNPs) in four genes of the CFTR interactome Medical and Genetic Analysis (FAMH). Since
that may modify disease severity. Moreover, generating proteome profiles from 1994, DCR Group Leader. Associate Professor
CF and non-CF primary nasal epithelial cell cultures, we detected differentially (1997). Since 2003, Head and Extraordinary
expressed proteins involved in oxidative stress, cytoskeletal organisation, polari- Professor of Human Genetics, Department of
sation, CFTR turnover and epithelial-to-mesenchymal transition. Thus, diverse Paediatrics, Inselspital.
pathways may modulate the phenotypic manifestation of CF. Future steps in-
clude investigation of influences of candidate gene variants on expression level,
as well as confirmation of our proteomics findings by Western blot analyses
and functional studies.
Epilepsy Dr. Johannes Lemke
Understanding the underlying molecular pathomechanisms of epilepsy, one of johannes.lemke@insel.ch
the most common disorders, affecting 2-4% of the general population, may
have an impact on the choice of pharmacologic therapies. We introduced a tar- Medical studies at University of Jena (DE); MD
geted next generation sequencing (NGS) approach for molecular genetic diag- (2005). Since 2010, Consultant in Human
nostics of epilepsy disorders and successfully applied this method in several Genetics Department of Paediatrics, Inselspital.
dozen cases. In so doing, we revealed various, apparently rare, genetic diseases,
which led to the suggestion that many orphan epilepsy entities might actually
not be as rare as suggested in the literature. As a result of a broad international
collaboration, we furthermore identified a main genetic predisposition factor
for focal childhood epilepsy (e.g., Rolandic epilepsy). As part of the Euro
EPINOMICS consortium, we collect and genotype patients with rare epilepsy
syndromes. Ideally, our results will give insight into the genetic bases of many
rare epilepsy disorders and even enable the development of novel therapeutic
approaches.
Mitochondrial Diseases Dr. André Schaller
A gene-panel for NGS was developed, allowing the simultaneous mutational andre.schaller@insel.ch
analysis of approx. 1450 nuclear-encoded mitochondrial genes in patients
with a mitochondrial disorder. After process optimisation and quality assurance, Studied biology at University of Bern; PhD
this analytical approach will be translated into routine diagnostics. In addition, (1999). Postdocs at Institute of Cell Biology,
we established a serial qPCR assay based on increasing amplicon size to meas- University of Bern, Infectious Disease and
ure degradation status of mtDNA samples. Using this approach, we can exclude Oncology, University of Zurich Children’s Hos-
erroneous mtDNA quantification due to degraded samples (e.g., long post-exci- pital. Assistant at Division of Human Genetics,
sion time, autolytic processes, freeze-thaw cycles) and ensure abnormal DNA Inselspital. Research Fellow at Institute for
content measurements (e.g., depletion) in non-degraded patient material. The Molecular and Cellular, CNRS (FR) (2006-2007).
third mitoNET Congress on Mitochondrial Medicine was successfully organised Since 2007, Senior Assistant, Division of
in Bern in July. Human Genetics, Department of Paediatrics,
Inselspital.
50 DCR Annual Report 2012 / DKF Jahresbericht 2012
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5 DCR Annual Report 2012 / DKF Jahresbericht 2012 Foreword – Director’s Report Dear readers and colleagues, Looking back at 2012, we can say that
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