Translational Research - Université de Genève
Translational Research - Université de Genève
Translational Research - Université de Genève
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FACULTÉ DE MÉDECINE<br />
<strong>Translational</strong> <strong>Research</strong><br />
Host-Pathogen Interactions
HUG – Geneva University Hospitals<br />
FMH – Swiss Medical Association<br />
SNSF – Swiss National Science Foundation<br />
Microbiology at the Medical Faculty of the University of Geneva<br />
Microbes have always accompanied human beings either by positively influencing our health<br />
through stimulation of the immune system and providing essential nutrients, such as certain<br />
vitamins, or by causing various diseases. Although several diseases can now be treated<br />
effectively or are even on the point of being eradicated, some infectious pathogens persist or<br />
reappear in the headlines and new emergent diseases threaten our health. The rapid<br />
<strong>de</strong>velopment of medicine has increased our life expectancy and quality of life consi<strong>de</strong>rably.<br />
However, some of the treatments themselves, together with an aging population, constitute<br />
new challenges as patients become more susceptible to infections. Global trends such as rapid,<br />
mass long-distance travel and climate change greatly influence the steadily changing picture<br />
of infectious diseases. Moreover, the appearance of multi- and fully-resistant pathogens poses<br />
serious challenges to treatment and is of particular concern in long-lasting persistent infections<br />
which represent a heavy bur<strong>de</strong>n to the individual and society.<br />
It is for these reasons that research in microbiology at the Faculty of Medicine of the University<br />
of Geneva is very broad, ranging from basic to clinical research and diagnostics. The<br />
microorganisms studied in the different contexts are very diverse; several different bacteria,<br />
eight classes of viruses, two apicomplexa parasites and yeast, are actively studied from<br />
different perspectives. Inherent to this diversity is a wi<strong>de</strong> range of approaches from classical<br />
genetics to molecular techniques including state-of-the-art nucleic acid analysis, proteomics,<br />
and imaging. Taking advantage of the medical environment, research in microbiology with a<br />
strong translational component is intrinsically linked to immunology and pathology, other<br />
strong research directions at our Faculty.<br />
Prof. Patrick Lin<strong>de</strong>r<br />
Vice-Presi<strong>de</strong>nt of the Fundamental Medicine Section<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
3
The structure of the Faculty favours translational research<br />
The Medical Faculty is composed of three different sections: fundamental (SMF), clinical (SMC)<br />
and <strong>de</strong>ntal medicine (SMD). <strong>Research</strong> in microbiology is carried out in all of them as well as in<br />
many different <strong>de</strong>partments. Host-pathogen interactions are thus approached through a<br />
variety of techniques and from very different angles providing an excellent environment for<br />
fundamental, applied and translational research. The mutually beneficial contacts are<br />
supplemented by an array of different platforms that provi<strong>de</strong> expertise and equipment in stateof-the-art<br />
techniques (genomic analyses, imaging, proteomics, etc.).<br />
4 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Teaching at the Medical Faculty<br />
We train medical stu<strong>de</strong>nts in microbiology, immunology and infectious diseases, important<br />
areas in all medical disciplines.<br />
Aspects of microbiology and immunology appear throughout the teaching modules but are<br />
mainly concentrated in the first and third years of the medical <strong>de</strong>gree. In the third year, an<br />
entire module is <strong>de</strong>voted to immunity and infection. Within this module, the stu<strong>de</strong>nts learn<br />
the basics about infectious diseases through lectures and problem-oriented teaching before<br />
starting hospital training in the fourth year of their studies. Throughout the Bachelor<br />
programme stu<strong>de</strong>nts are also trained in clinical skills.<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
5
Host-Pathogen <strong>Research</strong> at the Faculty<br />
6 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Fundamental Medicine<br />
• Department of Microbiology and Molecular Medicine<br />
• Department of Pathology and Immunology<br />
• Department of Physiology and Cellular Metabolism<br />
Clinical Medicine<br />
• Department of Internal Medicine Specialties<br />
Division of Infectious Diseases (HUG)<br />
Infection Control Programme (HUG)<br />
• Department of Internal Medicine, Rehabilitation<br />
and Geriatrics<br />
• Department of Pediatrics<br />
• Department of Anaesthesiology, Pharmacology<br />
and Intensive Care (APSI)<br />
• Department of Health and Community Medicine<br />
Division of International and Humanitarian<br />
Medicine (HUG)<br />
Dental Medicine<br />
• Division of Periodontology and Oral Pathophysiology<br />
• Division of Cariology and Endodontics<br />
Host-Pathogen Interactions<br />
at the Medical Faculty of the University of Geneva<br />
Bacteriology<br />
Dominique Belin<br />
Department of Pathology and Immunology 10<br />
Patrick Lin<strong>de</strong>r<br />
Department of Microbiology and Molecular Medicine 12<br />
Patrick Viollier<br />
Department of Microbiology and Molecular Medicine 14<br />
Daniel Lew<br />
Department of Internal Medicine Specialties<br />
Division of Infectious Diseases (HUG) 16<br />
Jacques Schrenzel / Patrice François<br />
Department of Internal Medicine Specialties<br />
Division of Infectious Diseases (HUG) 18<br />
William Kelley<br />
Department of Internal Medicine Specialties<br />
Infectious Diseases Service (HUG) 24<br />
Christian van Del<strong>de</strong>n<br />
Department of Internal Medicine Specialties,<br />
Department of Microbiology and Molecular Medicine 26<br />
Virology<br />
Dominique Garcin<br />
Department of Microbiology and Molecular Medicine 28<br />
Oliver Hartley<br />
Department of Pathology and Immunology 30<br />
Daniel Pinschewer<br />
Department of Pathology and Immunology 32<br />
Laurent Roux<br />
Department of Microbiology and Molecular Medicine 34<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
7
Michel Strubin<br />
Department of Microbiology and Molecular Medicine 36<br />
Laurent Kaiser / Caroline Tapparel Vu<br />
Department of Internal Medicine Specialties 38<br />
Francesco Negro<br />
Department of Internal Medicine Specialties<br />
Department of Pathology and Immunology 42<br />
Parasitology<br />
Dominique Soldati-Favre<br />
Department of Microbiology and Molecular Medicine 44<br />
François Chappuis<br />
Department of Health and Community Medicine<br />
Division of International and Humanitarian Medicine (HUG)<br />
Mé<strong>de</strong>cins sans Frontières 46<br />
Louis Loutan<br />
Department of Health and Community Medicine,<br />
Division of International and Humanitarian Medicine (HUG) 48<br />
Mycology<br />
Martine Collart<br />
Department of Microbiology and Molecular Medicine 50<br />
Host Response<br />
Alain Gervaix<br />
Department of Pediatrics 52<br />
Klara Posfay-Barbe<br />
Department of Pediatrics 54<br />
Marc Chanson<br />
Department of Pediatrics 56<br />
8 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Irène Garcia-Gabay<br />
Department of Pathology and Immunology 58<br />
Pierre Cosson<br />
Department of Cell Physiology and Metabolism 60<br />
Jérôme Pugin<br />
Department of Anaesthesiology, Pharmacology and Intensive Care<br />
Department of Microbiology and Molecular Medicine 62<br />
Karl-Heinz Krause<br />
Department of Pathology and Immunology 64<br />
Vaccinology<br />
Claire-Anne Siegrist<br />
Department of Pathology and Immunology<br />
Department of Pediatrics<br />
WHO Collaborative Center for Vaccine Immunology 66<br />
Dental Bacteriology<br />
Serge Bouillaguet<br />
Division of Cariology and Endodontics 68<br />
Andrea Mombelli<br />
Division of Periodontology and Oral Pathophysiology 70<br />
Hygiene and Infection control<br />
Didier Pittet<br />
Infection Control Programme, HUG 72<br />
Stephan Harbarth<br />
Infection Control Programme, HUG 74<br />
Bene<strong>de</strong>tta Allegranzi<br />
Infection Control Programme, HUG<br />
WHO “Clean Care is Safer Care” Programme 76<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
9
Bacteriology<br />
Dominique Belin<br />
Department of Pathology and Immunology<br />
Dominique Belin obtained his PhD in 1979 at the University of Geneva. He atten<strong>de</strong>d Rockefeller<br />
University in New York for three years as a postdoctoral Fellow, and then became visiting<br />
Associate Professor at Harvard Medical School, Boston (1990-1994). He was appointed Associate<br />
Professor (2002) and then full Professor (2009) of the Department of Pathology and<br />
Immunology.<br />
Genetic analysis of the translocation machinery in E. coli and of unknown genes of<br />
bacteriophages T4<br />
Our studies of the interaction of signal sequences with the translocation machinery in E. coli,<br />
has led to the i<strong>de</strong>ntification of a new class of mutations that selectively <strong>de</strong>crease export<br />
mediated by mutant or foreign signal sequences. We have also <strong>de</strong>veloped a gain-of-function<br />
bioinformatic and biochemical system to <strong>de</strong>fine the parameters of signal sequences.<br />
We are currently investigating the potential functions of phage T4 unknown genes. We have<br />
i<strong>de</strong>ntified inserts that are toxic when expressed and are concentrating our efforts on gene 55.1.<br />
High expression of 55.1 prevents growth while low expression confers a high sensitivity to UV<br />
irradiation caused by a <strong>de</strong>ficient repair. We have isolated phage and bacterial suppressors of<br />
these phenotypes. This approach will be exten<strong>de</strong>d to the other toxic unknown genes of T4.<br />
10 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Mattenberger Y, Mattson S, Métrailler J, Silva F, Belin D (2011) 55.1, a gene of unknown function<br />
of phage T4, impacts on Escherichia coli folate metabolism and blocks DNA repair by the<br />
NER. Mol Microbiol. 82:1406-21<br />
Van Stelten J, Silva F, Belin D & Silhavy T (2009) Effects of Antibiotics and a Proto-Oncogene<br />
Homolog on Destruction of Protein Translocator SecY. Science 325: 753-6.<br />
Biéler S, Silva F, Soto C & Belin D (2006) Bactericidal Activity of both Secreted and Non-secreted<br />
Microcin E492 Requires the Mannose Permease. J. Bact. 188, 7049-61.<br />
Belin D, Guzman LM, Bost S, Konakova M, Silva F & Beckwith J (2004) Functional activity of<br />
eucaryotic signal sequences in Escherichia coli: the ovalbumin family of serine protease<br />
inhibitors. J. Mol. Biol. 335, 437-53.<br />
Guzman LM, Belin D, Carson MJ and Beckwith J (1995) Tight regulation, modulation, and high<br />
level expression by vectors containing the arabinose P BAD promoter. J. Bact. 177, 4121-4130.<br />
Bost S and Belin D (1995). A new genetic selection i<strong>de</strong>ntifies essential residues in SecG, a<br />
component of the Escherichia coli protein export machinery, The EMBO Journal 14,<br />
4412-4421.<br />
Contact: Dominique.Belin@unige.ch<br />
Bacteriology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
11
Bacteriology<br />
Patrick Lin<strong>de</strong>r<br />
Department of Microbiology and Molecular Medicine<br />
Patrick Lin<strong>de</strong>r obtained his un<strong>de</strong>rgraduate training in Basel and his PhD on replication in<br />
Escherichia coli at the University of Geneva in 1984. He spent three years in Gif-sur-Yvette in<br />
France as a postdoctoral Fellow, before he came back to Switzerland as Junior Group Lea<strong>de</strong>r at<br />
the Biozentrum, University of Basel. He was appointed Lecturer at the University of Geneva in<br />
1994, Associate Professor in 2000 and full Professor in 2007 of the Department of Microbiology<br />
and Molecular Medicine.<br />
RNA metabolism and horizontal gene transfer in Staphylococcus aureus<br />
Our group has a long-standing interest in the biological role of DEAD-box RNA helicase family<br />
proteins. These RNA helicases unwind short RNA duplexes, displace proteins from RNA, or<br />
function as regulated clamps on RNA. They are therefore i<strong>de</strong>al key players in gene expression.<br />
After studying DEAD-box proteins in yeast for many years, our group switched gradually to the<br />
analysis of RNA helicases in the opportunistic pathogen S. aureus. Our main focus is the analysis<br />
of two RNA helicases and their role in virulence expression and adaptation to different growth<br />
conditions.<br />
One of the helicases is required for efficient biofilm formation in a clinical S. aureus strain.<br />
Recent data indicate that it is part of the <strong>de</strong>gradosome and thereby regulates the abundance<br />
of a central regulatory RNA, the mRNA of the agr quorum sensing system, thus regulating<br />
adhesion versus dispersal.<br />
The second RNA helicase seems to confer increased resistance to acid stress and may influence<br />
survival in neutrophils.<br />
12 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Bacterial DEAD-box RNA helicases, characterised by their<br />
conserved motifs, are involved in ribosome biogenesis, translation<br />
initiation and RNA <strong>de</strong>cay and thereby contribute to the versatility<br />
of these microorganisms.<br />
Red<strong>de</strong>r P & Lin<strong>de</strong>r P (2012) New Range of Vectors with a Stringent 5-Fluoroorotic Acid-Based<br />
Counterselection System for Generating Mutants by Allelic Replacement in Staphylococcus<br />
aureus. Appl Environ Microbiol 78:3846-3854.<br />
Lin<strong>de</strong>r P and Jankowsky E (2011) From unwinding to clamping - the DEAD box RNA helicase<br />
family. Nat Rev Mol Cell Biol 12, 505-516. [review]<br />
Xu SY, Corvaglia AR, Chan SH, Zheng Y, Lin<strong>de</strong>r P (2011) A type IV modification-<strong>de</strong>pen<strong>de</strong>nt<br />
restriction enzyme SauUSI from Staphylococcus aureus subsp. aureus USA300. Nucleic Acids<br />
Res. 39, 5597-610<br />
Corvaglia AR, François P, Hernan<strong>de</strong>z D, Perron K, Lin<strong>de</strong>r P*, Schrenzel J (2010) A type III-like<br />
restriction endonuclease functions as a major barrier to horizontal gene transfer in clinical<br />
Staphylococcus aureus strains. Proc Natl Acad Sci U S A. 107:11954-8.<br />
* corresponding author; “Editors choice” in Science, selected by the Faculty of 1000 Biology.<br />
Banroques J, Doère M, Dreyfus M, Lin<strong>de</strong>r P, Tanner NK (2010) Motif III in the superfamily 2<br />
”helicases” helps convert the binding energy of ATP into a high affinity RNA binding site in<br />
the yeast DEAD-box protein Ded1. J. Mol. Biol. 396:949-96<br />
Contact: Patrick.Lin<strong>de</strong>r@unige.ch<br />
Bacteriology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
13
Bacteriology<br />
Patrick Viollier<br />
Department of Microbiology and Molecular Medicine<br />
Patrick Viollier graduated in 1999 with a PhD in Microbiology from the Biozentrum, University<br />
of Basel. After a four-year postdoctoral course at the Stanford University School of Medicine<br />
he joined the Case Western Reserve University School of Medicine as Assistant Professor in<br />
2004. In 2009 he was appointed Associate Professor in the Department of Microbiology and<br />
Molecular Medicine at the Faculty of Medicine.<br />
Bacterial cell cycle control<br />
We study the molecular mechanisms that coordinate events during the bacterial cell division<br />
and <strong>de</strong>velopmental cycle using a powerful genetic and synchronisable mo<strong>de</strong>l system: the<br />
dimorphic alpha-proteobacterium Caulobacter crescentus. In the past we relied on<br />
comprehensive forward genetic and cell biological approaches to uncover polarity factors that<br />
couple polar differentiation with the cell division cycle in Caulobacter. We also i<strong>de</strong>ntified an<br />
oxido-reductase-like cytokinetic regulator that coordinates cell division with the differentiation<br />
programme in response to NAD(H) and found that diffusion barrirers can exist within bacterial<br />
subcellular compartment (stalk, green) cells that have a volume in the femtoliter range.<br />
We now also use Caulobacter to explore how bacteriophages (black arrow) seize the cell cycle<br />
machinery, to illuminate how viral-host replication cycles are coordinated at the most<br />
fundamental level.<br />
14 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Hughes HV, Huitema E, Pritchard S, Keiler K, Brun YV and Viollier PH (2010) Protein localization<br />
and dynamics within a bacterial organelle. PNAS 107:5599-604.<br />
Radhakrishnan SK, Pritchard S and Viollier PH (2010) Coupling prokaryotic cell fate cell fate and<br />
division control by a bifunctional and oscillating oxido-reductase homolog.<br />
Dev Cell 18:90-101.<br />
Radhakrishnan SK, Thanbichler M and Viollier PH (2008) The dynamic interplay between a cell<br />
fate <strong>de</strong>terminant and a lysozyme homolog drives the asymmetric division cycle of<br />
Caulobacter crescentus. Genes Dev. 22: 212-25.<br />
Huitema E, Matteson D, Pritchard S, Kumar Radhakrishnan S and Viollier PH (2006) Bacterial<br />
birth scar proteins mark future flagellum assembly site. Cell 124:1025-37.<br />
Holtzendorff J, Hung D, Bren<strong>de</strong> P, Reisenauer A, Viollier PH, McAdams HH and L. Shapiro (2004)<br />
Oscillating Global Regulators Control the Genetic Circuit Driving a Bacterial Cell Cycle.<br />
Science 304(5673):983-7.<br />
Contact: Patrick.Viollier@unige.ch<br />
Bacteriology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
15
Bacteriology<br />
Daniel Lew<br />
Department of Internal Medicine Specialties<br />
Division of Infectious Diseases (HUG)<br />
Daniel Lew obtained his Doctorate of Medicine in 1976 from the University of Geneva. He holds<br />
FMH-certified specialised qualifications in internal medicine and in infectious disease. He was<br />
Clinical and <strong>Research</strong> Fellow at Harvard Medical School before coming back to Geneva. In 1989<br />
he was appointed full Professor, Head of Infectious Diseases Division, at the Department of<br />
Internal Medicine.<br />
<strong>Research</strong> activity<br />
Between 1980 and 2003 we studied signal transduction (in particular intracellular calcium)<br />
and activation mechanisms in neutrophils.<br />
As a secondary subject, we established a group interested in the physiopathology of foreign<br />
body infection and osteomyelitis (in particular the pathogenic role of S.aureus).<br />
Since 2003 a new group interested in signaling and glycopepti<strong>de</strong> resistance in S.aureus has<br />
been formed and participates in the creation of a large thematic area involving several groups<br />
with SNSF funding in S.aureus research in the Infectious Diseases Service.<br />
<strong>Translational</strong> activities<br />
One of the main aims of the Infectious Diseases Service was to achieve a high level of<br />
integration containing <strong>Research</strong> Laboratories, Clinical Microbiology Laboratories (Bacteriology<br />
and Virology) and a Clinical Service with consultations in all the services of our hospital as well<br />
as the <strong>de</strong>velopment of Infection Control (now a fully in<strong>de</strong>pen<strong>de</strong>nt service in the hospital but<br />
integrated into our service at the aca<strong>de</strong>mic level). This has led to several training programmes<br />
at various levels and clinical research groups with multiple interactions.<br />
16 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Galbusera E*, Renzoni A*, Andrey DO, Monod A, Barras C, Tortora P, Polissi A, and Kelley WL (2011)<br />
Site-specific mutation of Staphylococcus aureus VraS reveals a crucial role for the VraR-VraS<br />
sensor in the emergence of glycopepti<strong>de</strong> resistance. Submitted Antimicrob Agents<br />
Chemother 55:1008-20<br />
*Both authors contributed equally to this work.<br />
Ferry T, Uçkay I, Vaudaux P, François P, Schrenzel J, Harbarth S, Laurent F, Bernard L, Van<strong>de</strong>nesch<br />
F, Etienne J, Hoffmeyer P, Lew D (2010) Risk factors for treatment failure in orthopedic <strong>de</strong>vicerelated<br />
methicillin-resistant Staphylococcus aureus infection. Eur J Clin Microbiol Infect Dis.<br />
29:171-80.<br />
Vaudaux P, Huggler E, Bernard L, Ferry T, Renzoni A, Lew DP (2010) Un<strong>de</strong>restimation of<br />
vancomycin and teicoplanin MICs by broth microdilution leads to un<strong>de</strong>r<strong>de</strong>tection of<br />
glycopepti<strong>de</strong>-intermediate isolates of Staphylococcus aureus. Antimicrob Agents Chemother<br />
Sep 54:3861-70.<br />
Renzoni A, Kelley WL, Barras C, Monod A, Huggler E, François P, Schrenzel J, Stu<strong>de</strong>r R, Vaudaux<br />
P and Lew DP (2009) I<strong>de</strong>ntification by genomic and genetic analysis of two new genes<br />
playing a key role in glycopepti<strong>de</strong> intermediate resistance in Staphylococcus aureus.<br />
Antimicrob Agents Chemother 53: 903-911.<br />
Renzoni A, Barras C, François P, Charbonnier Y, Huggler E, Garzoni C, Kelley WL, Majcherczyk P,<br />
Schrenzel J, Lew DP and Vaudaux P (2006). Transcriptomic and functional analysis of an<br />
autolytic-<strong>de</strong>ficient teicoplanin-resistant <strong>de</strong>rivative of methicillin-resistant Staphylococcus<br />
aureus. Antimicrobial Agents and Chemotherapy 50: 3048-61.<br />
Contact: Daniel.Lew@hcuge.ch<br />
Bacteriology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
17
Bacteriology<br />
Jacques Schrenzel<br />
Department of Internal Medicine Specialties<br />
Division of Infectious Diseases (HUG)<br />
Jacques Schrenzel obtained his medical <strong>de</strong>gree in 1989 at the University of Geneva. After clinical<br />
training at the Geneva University Hospitals (HUG) he carried out research on neutrophils in<br />
infectious diseases. He was postdoctoral Fellow at the Mayo Clinic in Rochester, Minnesota<br />
from 1997 to 2000. On his return to Geneva he was awar<strong>de</strong>d an Assistant Professorship by the<br />
Swiss National Science Foundation and became a pioneer in the genomic analysis of pathogens<br />
(www.genomic.ch). Since 2004 he has been responsible for the Central Bacteriology Laboratory<br />
of the HUG and was appointed Associate Professor in 2010.<br />
Persistence and virulence in Staphylococcus aureus infections<br />
Metagenomics of infectious diseases<br />
We study the pathogenesis of S. aureus infections with a special focus on its ability to persist<br />
as well as to survive host <strong>de</strong>fences. This more specifically concerns the mechanisms of biofilm<br />
formation and the capacity of the bacteria to survive within eukaryotic cells by regulating the<br />
gene expression of numerous bacterial metabolic and virulence-related targets. These<br />
approaches used bacterial genetics, home-brew high-<strong>de</strong>nsity microarrays and, more recently,<br />
next generation sequencing. This explains the creation of our own bioinformatics group and<br />
the more recent <strong>de</strong>velopment of research topics using metagenomics to address clinically<br />
relevant questions, within local and international consortia.<br />
18 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Corvaglia AR, François P, Hernan<strong>de</strong>z D, Perron K, Lin<strong>de</strong>r P and Schrenzel J (2010) A novel<br />
restriction endonuclease functions as a major barrier to horizontal gene transfer in clinical<br />
Staphylococcus aureus strains. PNAS 107:11954-11958. Editor’s choice, Science 329:121.<br />
Lazarevic V, Whiteson K, Hernan<strong>de</strong>z D, François P, Schrenzel J (2010) Study of inter- and intraindividual<br />
variations in the salivary microbiota. BMC Genomics 11:523.<br />
François P, Harbarth S, Huyghe A, Renzi G, Bento M, Gervaix A, Pittet D and Schrenzel J (2008)<br />
Methicillin-Resistant Staphylococcus aureus, Geneva, Switzerland 1993-2005. Emerg Infect<br />
Dis 14:304-307.<br />
Hernan<strong>de</strong>z D, François P, Farinelli L, Osteras M, and Schrenzel J (2008) De novo Bacterial Genome<br />
Sequencing: Millions of Very Short Reads Assembled on a Desktop Computer. Genome<br />
<strong>Research</strong> 18:802-809.<br />
Garzoni C, François P, Huygue A, Tapparel C, Charbonnier Y, Renzoni A, Couzinet S, Lucchini S,<br />
Lew D, Vaudaux P, Kelly WI and Schrenzel J (2007) A Global View of Staphylococcus aureus<br />
Whole Genome Expression Upon Internalization in Human Epithelial Cells. BMC Genomics<br />
8:171.<br />
Contact: Jacques.Schrenzel@genomic.ch<br />
Bacteriology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
19
Bacteriology<br />
Patrice François / Jacques Schrenzel<br />
(Genomic <strong>Research</strong> Lab)<br />
Patrice François obtained his PhD <strong>de</strong>gree at the University of Paris XIII in 1996. In 2000 he was<br />
involved in the creation of the Genomic <strong>Research</strong> Laboratory at Geneva University Hospitals.<br />
His primary research interests are mechanisms of S. aureus adhesion to foreign body and roles<br />
of small RNAs on bacterial pathogenicity. He obtained his Privat Docent in 2011.<br />
Deciphering the virulence of S. aureus infections<br />
Using the capacity of massively parallel methods such as microarrays or high-throughput<br />
sequencing, we aim to explore all genomic elements potentially involved in epi<strong>de</strong>miological<br />
or virulence traits of MRSA. We study at the genome scale those genetic events that potentially<br />
trigger bacterial adaptation as evi<strong>de</strong>nced by modifications in spreading, virulence and<br />
pathogenicity. Our main efforts involve genomic regions that remain poorly explored to date,<br />
namely the segments consi<strong>de</strong>red so far as intergenic regions, in or<strong>de</strong>r to unravel genomic<br />
elements responsible for “the success of S. aureus” in clinical or epi<strong>de</strong>miological settings. We<br />
are now characterising small RNA molecules that we have discovered in S. aureus for their<br />
potential roles as regulatory RNA during infection.<br />
This work is un<strong>de</strong>r the direct supervision of Patrice François as part of the research structure<br />
established by J. Schrenzel.<br />
20 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Bacteriology<br />
Fischer A, Yang SJ, Bayer AS, Vaezza<strong>de</strong>h AR, Herzig S, Stenz L, Girard M, Sakoulas G, Scherl A,<br />
Yeaman MR, Proctor RA, Schrenzel J, François P (2011) Daptomycin-Resistance mechanisms<br />
in clinically-<strong>de</strong>rived S. aureus strains assessed by a combined transcriptomics and<br />
proteomics approach. Journal of Antimicrobial Chemotherapy 66:1696-711.<br />
Nair D, Memmi G, Hernan<strong>de</strong>z D, Bard J, Beaume M, Gill S, Francois P, Cheung AL (2011) Whole<br />
genome sequencing of Staphylococcus aureus strain RN4220, a key laboratory strain used<br />
in virulence research, i<strong>de</strong>ntifies mutations that affect not only virulence factors but also<br />
the fitness of the strain. Journal of Bacteriology 193:2332-5.<br />
Beaume MD, Hernan<strong>de</strong>z L, Farinelli M, Osteras J, Schrenzel J, François P (2010) Cartography of<br />
Methicillin-Resistant Staphylococcus aureus Transcripts: Detection, Orientation and<br />
Temporal Expression during Growth Phase and Stress Conditions. Plos One 20;5:e10725.<br />
Megevand C, Gervaix A, Heininger U, Berger C, Aebi C, Vaudaux B, Kind C, Gnehm HP, Hitzler<br />
M, Renzi G, Schrenzel J, François P (2010) Molecular epi<strong>de</strong>miology of the nasal colonization<br />
by methicillin-susceptible Staphylococcus aureus in Swiss children. Clin.Microbiol.Infect.<br />
16:1414-1420.52.<br />
François P, Scherl A, Hochstrasser D and Schrenzel J (2010) Proteomic approaches to study<br />
Staphylococcus aureus pathogenesis. J. Proteomics 73:701-708.<br />
Lazarevic V, Whiteson K, Huse S, Hernan<strong>de</strong>z D, Farinelli L, Osteras M, Schrenzel J and François P<br />
(2009) Metagenomic study of the oral microbiota by Illumina high-throughput sequencing.<br />
J.Microbiol.Methods 79:266-271.<br />
François P, Uckay I, Iten A, Renzi G, Dahran S, Camus V, Sax H and Schrenzel J (2008) In vivo<br />
<strong>de</strong>tection of clonally <strong>de</strong>rived methicillin-resistant/methicillin-susceptible Staphylococcus<br />
aureus strains is not a rare event. J.Clin.Microbiol. 46:1890-1891.<br />
Contact: Patrice.Francois@genomic.ch<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
21
Bacteriology<br />
Jacques Schrenzel<br />
(Clinical Bacteriology Lab)<br />
Clinically relevant and efficient microbiological diagnosis<br />
The bacteriology lab is a production-oriented laboratory that aims to provi<strong>de</strong> rapid and clinically<br />
relevant bacterial diagnosis for patients at the Geneva University Hospitals (HUG). We host the<br />
National Reference Center for Meningococci. Efforts are concentrated on reducing turn-around<br />
times by implementing state-of-the art methods such as MALDI-TOF, PCR-ESI-MS or other<br />
molecular methods before they are commercially available. We also have a track record of assay<br />
<strong>de</strong>velopment in the research lab followed by successful technology transfer to the routine lab,<br />
mostly for infection control purposes (<strong>de</strong>tection and genotyping of MRSA, Clostridium difficile,<br />
ESBL, etc.). We always pay particular attention to building upon local competences (infection<br />
control service, etc.) and expanding them by creating international consortia whenever nee<strong>de</strong>d.<br />
22 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Bacteriology<br />
Afshari A, Schrenzel J, Ieven M, Harbarth S (2012) Bench-to-bedsi<strong>de</strong> review: Rapid molecular<br />
diagnostics for bloodstream infection - a new frontier? Crit Care 29 :16-222<br />
Poirel L, Schrenzel J, Cherkaoui A, Bernabeu S, Renzi G, Nordmann P (2011) Molecular analysis<br />
of NDM-1-producing enterobacterial isolates from Geneva, Switzerland. J Antimicrob<br />
Chemother 66:1730-3.<br />
Kaleta EJ, Clark AE, Cherkaoui A, Wysocki VH, Ingram EL, Schrenzel J, Wolk DM (2011)<br />
Comparative Analysis of PCR-Electrospray Ionization/Mass Spectrometry (MS) and MALDI-<br />
TOF/MS for the I<strong>de</strong>ntification of Bacteria and Yeast from Positive Blood Culture Bottles. Clin<br />
Chem. 57:1057-67.<br />
Focke M, Stumpf F, Faltin B, Reith P, Bamarni D, Wadle S, Mueller C, Reinecke H, Schrenzel J,<br />
François P, Mark D, Roth G, Zengerle R and Von Stetten F (2010) Microstructuring of polymer<br />
films for highly sensitive genotyping by real-time PCR on a centrifugal microfluidic platform.<br />
Lab-on-Chip 10:2519-2526.<br />
Cherkaoui A, Emonet S, Hibbs J, Tangomo M, Girard M, François P , and Schrenzel J (2010)<br />
Comparison of two Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass<br />
Spectrometry Methods with Conventional Phenotypic I<strong>de</strong>ntification for Routine Bacterial<br />
Speciation. J Clin Microb 48:1169-1175.<br />
Ceroni D, Cherkaoui A, Ferey S, Kaelin A and J. Schrenzel (2010) Kingella kingae osteoarticular<br />
infections in young children: clinical features and contribution of a new specific real-time<br />
PCR assay to the diagnosis. J Pediatr Orthop 30:301-304.<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
23
Bacteriology<br />
William L. Kelley<br />
Department of Internal Medical Specialties<br />
Division of Infectious Diseases (HUG)<br />
William L. Kelley graduated in 1981 from Williams College (USA), with a BA in Biology. In 1991<br />
he obtained a PhD in microbiology-immunology with supplemental specialisation from the<br />
University Programme in Genetics, Duke University Medical Center. Following postdoctoral<br />
studies with molecular chaperones and protein folding, he focused his reseach on<br />
Staphylococci. In 2007 he became Privat-Docent of the HUG in the Department of Internal<br />
Medicine, Infectious Diseases Service.<br />
Staphylococcus aureus environmental sensing systems<br />
Our laboratory studies the range of mechanisms Staphylococcus aureus possesses that link<br />
extracellular signals to changes in gene expression. We are particularly interested in the family<br />
of histidine kinase two-component systems which are wi<strong>de</strong>ly found in the microbial world.<br />
Our work focuses on two of these systems: VraRS, which responds to cell wall active antibiotics<br />
such as penicillins and glycopepti<strong>de</strong>s, and SrrAB, which responds to aerobic/anaerobic shift<br />
and orchestrates adaptations in energy production and redox balance. Curiously, SrrAB is also<br />
intimately involved in the transcriptional regulation of toxins, such as toxic shock superantigen,<br />
as well as S. aureus’ <strong>de</strong>fence against nitrogen monoxi<strong>de</strong> (NO), a key effector of the innate<br />
immune response. We recently discovered that Spx, a global regulator of thiol and oxidative<br />
stress <strong>de</strong>fence, is essential in S. aureus. Using <strong>de</strong>ep sequencing and genetic methods we have<br />
uncovered novel genes that are Spx-regulated and suggest an important link between sensory<br />
pathways governing redox homeostasis and the general stress response. Collectively, our work<br />
<strong>de</strong>lves into drug resistance mechanisms including MRSA, virulence factor regulation, secretion,<br />
transmembrane signalling, and the discovery of essential genes or processes that constitute<br />
promising targets for therapeutic intervention.<br />
24 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Jousselin A, Renzoni A, Andrey DO, Monod A, Lew DP and Kelley WL (2012) The<br />
posttranslocational chaperone lipoprotein PrsA is involved in both glycopepti<strong>de</strong> and<br />
oxacillin resistance in Stpahlyococcus aureus. Antimicrobial Agents Chemother. 56: In press.<br />
Renzoni A, Andrey DO, Jousselin A, Barras C, Monod A, Vaudaux P, Lew D and Kelley WL (2011)<br />
Whole genome sequencing and complete genetic analysis reveal novel pathways to<br />
glycopepti<strong>de</strong>s resistance in Staphylococcus aureus. PloS One e21577.<br />
Galbusera E, Renzoni A, Andrey DO, Monod A, Barras C, Tortora P, Polissi A and Kelley WL (2011)<br />
Site-specific mutation of Staphylococcus aureus VraS reveals a crucial role for the VraR-VraS<br />
sensor in the emergence of glycopepti<strong>de</strong>s resistance. Antimicrobial Agents Chemother<br />
55:1008-1020.<br />
Andrey DO, Renzoni A, Monod A, Lew DP, Cheung, AL and Kelley WL (2010) Control of the<br />
Staphylococcus aureus toxic shock tst promoter by the global regulator SarA. J. Bacteriol.<br />
192:6077-6085.<br />
Garzoni C and Kelley WL (2009) Staphylococcus aureus: new evi<strong>de</strong>nce for intracellular<br />
persistence. Trends Microbiol. 17:59-65.<br />
Contact: William.Kelley@hcuge.ch<br />
Bacteriology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
25
Bacteriology<br />
Christian van Del<strong>de</strong>n<br />
Department of Internal Medical Specialties<br />
Department of Microbiology and Molecular Medicine<br />
Christian van Del<strong>de</strong>n obtained his Medical Degree in 1988 at the University of Geneva, then<br />
FMH-certified qualifications in Internal Medicine in 1995 and in Infectious Diseases in 1999.<br />
He held a three-year Postdoctoral <strong>Research</strong> Fellowship at the University of Rochester, New York<br />
working on virulence regulation in Pseudomonas aeruginosa and returned to Geneva with a<br />
Score A grant from the SNSF. Since 1998 he has led a research laboratory in the Department of<br />
Microbiology and Molecular Medicine, and has been Head of the Immunocompromised Host<br />
Programme at HUG since 2003. He is a co-foun<strong>de</strong>r and member of the Executive Office of the<br />
Swiss Transplant Cohort Study and Presi<strong>de</strong>nt of the Swiss Transplant Infectious Diseases<br />
Working Group. He was appointed Associate Professor in 2011.<br />
Role of Quorum-Sensing and Socio-Microbiological Behavior in the Pathogenesis of<br />
Pseudomonas aeruginosa infections<br />
Since 1998 we have studied resistance and virulence in P. aeruginosa. Our approach is<br />
translational; we bring clinical hypothesis and strains into the laboratory, use genetics and<br />
molecular microbiology for both “in patient” and “in vitro” studies, and try to implement our<br />
findings at the bedsi<strong>de</strong>. With this approach we have characterised the <strong>de</strong>velopment of<br />
resistance on therapy and have i<strong>de</strong>ntified novel virulence regulators. Recently we i<strong>de</strong>ntified<br />
Quorum-Sensing (QS) as a major risk factor for the progression from colonisation to infection<br />
in intubated patients. We also investigated this progression from a socio-microbiological angle<br />
with the <strong>de</strong>velopment of QS-cheating and microbiological intra-species warfare based on<br />
pyocin production. We further studied the efficacy of inhibiting QS to prevent infection in these<br />
patients. Our clinical research activity involves infections in transplant recipients and their<br />
prevention.<br />
26 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
van Del<strong>de</strong>n C, Köhler T, Brunner-Ferber F, Francois B, Carlet J and Pechère JC<br />
(2012) Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated-pneumonia<br />
by inhibition of quorum-sensing: a randomized controlled trial. Intensive Care Med 38:1118-<br />
1125.<br />
Köhler T, Guanella R, Carlet J and van Del<strong>de</strong>n C (2010) Quorum-sensing-<strong>de</strong>pen<strong>de</strong>nt virulence<br />
during Pseudomonas aeruginosa colonisation and pneumonia in mechanically ventilated<br />
patients. Thorax 65:703-710.<br />
Köhler T, Perron GG, Buckling A and van Del<strong>de</strong>n C (2010) Quorum sensing inhibition selects for<br />
virulence and cooperation in Pseudomonas aeruginosa PLos Pathogen 6;6:e1000883<br />
Köhler T, Donner V and van Del<strong>de</strong>n C (2010) Lipopolysacchari<strong>de</strong> as shield and receptor for Rpyocin<br />
mediated killing in Pseudomonas aeruginosa. Journal of Bacteriology 192:1921-1928.<br />
Köhler T, Buckling A and van Del<strong>de</strong>n C (2009) Cooperation and virulence of clinical<br />
Pseudomonas aeruginosa populations. Proc Natl Acad Sci USA 106:6339-6344<br />
Contact: Christian.vanDel<strong>de</strong>n@hcuge.ch<br />
Bacteriology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
27
Virology<br />
Dominique Garcin<br />
Department of Microbiology and Molecular Medicine<br />
Dominique Garcin obtained his PhD at the Ecole Normale Supérieure in Lyon in 1989. Thereafter<br />
he joined the Department of Microbiology and Genetics, HUG where he was appointed Lecturer<br />
(Maître d’Enseignement et <strong>de</strong> Recherche) in 2010.<br />
The molecular basis of ligand recognition by RIG-I and viral escape strategies<br />
Viral infections are responsible for extensive human and animal suffering and <strong>de</strong>ath. Very few<br />
antiviral molecules are available and, more importantly, escape mutants resistant to existing<br />
antiviral agents generally emerge rapidly for RNA viruses, due to their high mutation rate. On<br />
the other hand, one of the first lines of <strong>de</strong>fence against viral infection is innate immunity.<br />
Detailed knowledge of how this is established and how viruses escape these antiviral <strong>de</strong>fenses,<br />
is critical for un<strong>de</strong>rstanding how to prevent viral infection. Our laboratory has long experience<br />
in studying negative strand virus (NSV) RNA synthesis, replication and their interactions with<br />
their host, in particular the IFN antagonists that the virus expresses to counteract the innate<br />
immune response.<br />
28 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Marq JB, Hausmann S, Veillard N, Kolakofsky D, Garcin D (2011) Short double-stran<strong>de</strong>d RNAs<br />
with an overhanging 5’ ppp-nucleoti<strong>de</strong>, as found in arenavirus genomes, act as RIG-I <strong>de</strong>coys.<br />
J Biol Chem. 286:6108-16<br />
Marq JB, Kolakofsky D and Garcin D (2010) Unpaired 5’ ppp-nucleoti<strong>de</strong>s, as found in arenavirus<br />
dsRNA panhandles, are not recognized by RIG-I. J. Biol. Chem. 285: 18208-16.<br />
Marq JB, Hausmann S, Luban J, Kolakofsky D and Garcin D (2009) The dsRNA binding domain<br />
of the vaccinia virus E3L protein inhibits both RNA and DNA-induced activation of , IFNβ.<br />
J.Biol. Chem. 284:25471-8<br />
Hausmann S., Marq JB, TapparelC, Kolakofsky D, Garcin D (2008) RIG-I and dsRNA-Induced IFNβ<br />
Activation. PLoS ONE 3: e3965<br />
Strahle L, Marq JB, Brini A, Hausmann S, Kolakofsky D, Garcin D (2007) Activation of the beta<br />
interferon promoter by unnatural Sendai virus infection requires RIG-I and is inhibited by<br />
viral C proteins. J. Virol. 81: 12227-37<br />
Marq JB, Brini A, Kolakofsky D, Garcin D (2007) Targeting of the Sendai virus C protein to the<br />
plasma membrane via a pepti<strong>de</strong>-only membrane anchor. J. Virol. 81:3187-97<br />
Contact: Dominique.Garcin@unige.ch<br />
Virology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
29
Virology<br />
Oliver Hartley<br />
Department of Pathology and Immunology<br />
Oliver Hartley completed his PhD in protein engineering at the University of Cambridge, UK in<br />
1997. Following a brief Fellowship at the Glaxo Institute for Molecular Biology in Geneva, he<br />
joined Robin Offord’s lab as a postdoctoral Fellow at the University of Geneva. He became a<br />
group lea<strong>de</strong>r in the Department of Structural Biology and Bioinformatics in 2005, where he<br />
has been an Assistant Professor since 2008.<br />
Macromolecular engineering to prevent infectious diseases<br />
With a focus on the prevention of infectious diseases, our work is based on the engineering of<br />
proteins and pepti<strong>de</strong>s to i<strong>de</strong>ntify new macromolecules with potential use as medicines. Our<br />
main work has involved the engineering of chemokines to produce highly potent HIV entry<br />
inhibitors for use as medicines in prevention. A first clinical study of our best molecule is<br />
scheduled to take place at the HUG in 2012. In addition to continuing fundamental studies of<br />
the unusual inhibitory mechanisms of these molecules, we have recently begun work on the<br />
<strong>de</strong>velopment of a macromolecular vaccine <strong>de</strong>livery platform. Our approach, which enables<br />
‘plug-and-play’ incorporation of antigens and immune modulators into multivalent<br />
nanoparticles, is being evaluated in collaboration with colleagues in the Faculty.<br />
30 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Gaertner HF, Cerini F, Kamath A, Rochat A-F, Siegrist C-A, Menin L & Hartley O (2011) Efficient<br />
orthogonal bioconjugation of <strong>de</strong>ndrimers for synthesis of bioactive nanoparticles.<br />
Bioconjugate chemistry 20: 1103-1114.<br />
Escola JM, Kuenzi G, Gaertner H, Foti M, & Hartley O (2010) CC chemokine receptor 5 (CCR5)<br />
<strong>de</strong>sensitization: cycling receptors accumulate in the trans-Golgi network J Biol Chem<br />
285:41772-80<br />
Gaertner H, Cerini F, Escola JM, Kuenzi G, Melotti A, Offord R, Rossitto-Borlat I, Ne<strong>de</strong>llec R,<br />
Salkowitz J, Gorochov G, Mosier D, & Hartley O (2008) Highly potent, fully recombinant<br />
anti-HIV chemokines: reengineering a low-cost microbici<strong>de</strong> Proc Natl Acad Sci USA<br />
105:17706-17711<br />
Hartley O, Gaertner H, Wilken J, Thompson D, Fish R, Ramos A, Pastore C, Dufour B, Cerini F,<br />
Melotti A, Heveker N, Picard L, Alizon M, Mosier D, Kent S & Offord R (2004) Medicinal<br />
chemistry applied to a synthetic protein: <strong>de</strong>velopment of highly potent HIV entry inhibitors<br />
Proc Natl Acad Sci USA 101:16460-16465<br />
Le<strong>de</strong>rman MM, Veazey RS, Offord R, Mosier DE, Dufour J, Mefford M, Piatak M Jr, Lifson JD,<br />
Salkowitz JR, Rodriguez B, Blauvelt A & Hartley O (2004) Prevention of vaginal SHIV<br />
transmission in rhesus macaques through inhibition of CCR5 Science 306: 485-487<br />
Contact: Oliver.Hartley@unige.ch<br />
Virology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
31
Virology<br />
Daniel Pinschewer<br />
Department of Pathology and Immunology<br />
Daniel Pinschewer obtained his medical Doctorate in 2001. He was awar<strong>de</strong>d a stipendiary<br />
Professorship by the SNSF in 2007 and was appointed full Professor in 2011.<br />
Virus-host balance, pathogenesis and vaccination against persistent infection<br />
Our laboratory has a general interest in antiviral immunity and viral pathogenesis, with three<br />
main foci: i) immune control of persistent viral infections, ii) viral pathogenesis of<br />
”autoimmune” diseases, and iii) virally vectored vaccines against persistent infection. We<br />
approach these topics by exploiting a reverse genetics system for lymphocytic choriomeningitis<br />
virus we have <strong>de</strong>veloped. This molecular virological approach is combined with animal mo<strong>de</strong>ls<br />
to investigate virus-host interaction in the systemic organismic context. Our mainly basic rather<br />
than applied research nevertheless aims at addressing questions of medical relevance.<br />
32 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Bonilla WV, Fröhlich A, Senn K, Kallert S, Fernan<strong>de</strong>z M, Johnson S, Kreutzfeldt M, Hegazy AN,<br />
Schrick C, Fallon PG, Klemenz R, Nakae S, Adler H, Merkler D, Löhning M, Pinschewer DD<br />
(2012) The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses. Science<br />
335:984-9.<br />
Bergthaler A, Flatz L, Hegazy AN, Johnson S, Horvath E, Löhning M and DD Pinschewer (2010)<br />
Viral replicative capacity is the primary <strong>de</strong>terminant of lymphocytic choriomeningitis virus<br />
persistence and immunosuppression. Proc Natl Acad Sci USA 107:21641-6.<br />
Flatz L, Hegazy AN, Bergthaler A, Verschoor A, Claus C, Fernan<strong>de</strong>z M, Gattinoni L, Johnson S,<br />
Kreppel F, Kochanek S, van <strong>de</strong>n Broek M, Radbruch A, Lévy F, Lambert PH, Siegrist CA, Restifo<br />
NP, Löhning M, Ochsenbein AF, Nabel GJ and DD Pinschewer (2010) Development of<br />
replication-<strong>de</strong>fective lymphocytic choriomeningitis virus vectors for induction of potent<br />
CD8 + T cell immunity. Nat. Med. 16:339-45<br />
Flatz L., Rieger T., Merkler D., Bergthaler A., Regen T., Sche<strong>de</strong>nsack M., Bestmann L., Verschoor A.,<br />
Kreutzfeldt M., Brück W., Hanisch U.K., Günther S. and DD Pinschewer (2010). T cell<strong>de</strong>pen<strong>de</strong>nce<br />
of Lassa fever pathogenesis. PLoS Pathog. 26;6(3):e1000836<br />
Bergthaler A, Flatz L, Verschoor A, Hegazy AN, Hol<strong>de</strong>ner M, Fink K, Eschli B, Merkler D,<br />
SommersteinR, HorvathE, Fernan<strong>de</strong>zM, FitscheA, SennBM, VerbeekJS, O<strong>de</strong>rmattB, Siegrist<br />
CA and DD Pinschewer (2009) Impaired antibody response causes persistence of prototypic<br />
T cell-contained virus. PLoS Biol 7:e1000080<br />
Contact: Daniel.Pinschewer@unige.ch<br />
Virology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
33
Virology<br />
Laurent Roux<br />
Department of Microbiology and Molecular Medicine<br />
Laurent Roux obtained his PhD in 1976 at the Molecular Biology Department of Geneva<br />
University. After three years as a postdoctoral Fellow in the Biology Department at the<br />
University of California San Diego, he became <strong>Research</strong> Assistant at the Department of Internal<br />
Medicine. He was then appointed as <strong>Research</strong> Associate in the Department of Genetics and<br />
Microbiology, where he was appointed Associate Professor in 2000 and full Professor in 2009.<br />
Paramyxovirus multiplication cycle: virion morphogenesis and production<br />
Using Sendai virus as a prototype for members of the Paramyxoviridae family, we aim to <strong>de</strong>fine:<br />
i) which viral constituent(s) is (are) required for formation of virus particles, and ii) which<br />
mechanisms prevail in the incorporation of the viral constituents into the virus particles. We<br />
have <strong>de</strong>veloped an integrated suppression complementation (ISCS) system that allows a<br />
structure-function analysis of the viral proteins in the context of an infection. The aim of this<br />
study is twofold: i) acquisition of fundamental information about the mechanisms that prevail<br />
in the formation of Paramyxovirus virus particles, and ii) the ability to produce virus particles<br />
that express on their envelope <strong>de</strong>fined surface antigens and that could serve as vaccine vectors.<br />
34 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Miazza V, Mottet-Osman G, Startchick S, Chaponnier C and Roux L (2011) Sendai virus induced<br />
cytoplasmic actin remo<strong>de</strong>ling correlates with efficient virus particle production. Virology,<br />
410:7-16.<br />
Gosselin-Grenet AS, Mottet-Osman G, Roux L (2010). Sendai virus particle production: Basic<br />
requirements and role of the SYWST motif present in HN cytoplasmic tail. Virology, 405:<br />
439-447.<br />
Gosselin-Grenet AS, Marq, JB, Garcin D and Roux L (2007). Sendai virus budding in the course<br />
of an infection does not require Alix and VPS4A host factors. Virology 365: 101-112.<br />
Mottet-Osman G, Iséni F, Pelet T, Wiznerowicz M, Garcin D and Roux L (2007). Suppression of<br />
the Sendai virus M protein through a novel siRNA approach inhibits viral particle production<br />
but does not affect viral RNA synthesis. J. Virol. 81: 2861-2868.<br />
Gosselin-Grenet AS, Mottet-Osman G and Roux L (2006). From assembly to virus particle<br />
budding: pertinence of the <strong>de</strong>tergent resistant membranes. Virology 344: 296-303<br />
Contact: Laurent.Roux@unige.ch<br />
Virology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
35
Virology<br />
Michel Strubin<br />
Department of Microbiology and Molecular Medicine<br />
Michel Strubin received his PhD from the University of Geneva in 1987. After initial post-doctoral<br />
training at the ISREC in Lausanne, he left for a two-year stay at Harvard Medical School in<br />
Boston, USA. In 1992 he joined the Department of Microbiology and Molecular Medicine with<br />
a START Fellowship from the SNSF. In 2001 he was appointed Associate Professor in the same<br />
Department.<br />
The HBx protein of Hepatitis B Virus and Regulation of Gene Expression<br />
The HBx protein of hepatitis B virus<br />
Chronic infection by hepatitis B virus (HBV) is a leading cause of liver cancer. HBV enco<strong>de</strong>s a<br />
small protein, known as HBx, which is essential for viral infection and has been implicated in<br />
HBV-associated liver cancer. We found that HBx promotes HBV gene expression by an unusual<br />
mechanism that affects only extrachromosomal DNA templates and that requires HBx to<br />
function as a substrate receptor for a cellular E3 ubiquitin ligase. We now wish to i<strong>de</strong>ntify the<br />
substrate(s) recruited by HBx to the E3 ligase and further explore the mechanisms whereby<br />
HBx promotes viral gene expression un<strong>de</strong>r experimental conditions closer to natural HBV<br />
infection. Because of its uncommon property and key role in viral transcription, HBx may<br />
represent an attractive target for new antiviral therapies.<br />
Regulation of gene expression<br />
We are using yeast as a mo<strong>de</strong>l system to address fundamental questions about the<br />
mechanisms by which gene transcription is regulated. We are particularly interested in<br />
un<strong>de</strong>rstanding how the transcription machinery, a large complex that contains many proteins<br />
in addition to the RNA polymerase, assembles at the beginning of genes and how cells control<br />
this event. We also study the dynamics and epigenetic modifications of chromatin and their<br />
importance in transcriptional regulation.<br />
36 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Van Breugel PC, Robert EI, Mueller H, Decorsière A, Zoulim F, Hantz O and Strubin M (2012)<br />
Hepatitis B virus X protein stimulates gene expression selectively from extrachromosomal<br />
DNA templates. Hepatology doi: 10.1002/hep.25928. [Epub ahead of print]<br />
Li, T, Robert EI, van Breugel PC, Strubin M* and Zheng N* (2010) A promiscuous alpha-helical<br />
motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase<br />
machinery. Nat. Struct. Mol. Biol. 17: 105-11<br />
(* corresponding authors)<br />
Jamai A, Puglisi A and Strubin M (2009) Histone chaperone Spt16 promotes re<strong>de</strong>position of<br />
the original H3-H4 histones evicted by elongating RNA polymerase. Mol. Cell 35: 377-83<br />
Martin-Lluesma S, Schaeffer C, Robert EI, van Breugel PC, Leupin O, Hantz O and Strubin M<br />
(2008) Hepatitis B virus X protein affects S phase progression leading to chromosome<br />
segregation <strong>de</strong>fects by binding to damaged DNA binding protein 1. Hepatology 48: 1467-<br />
76.<br />
Jamai A, Imoberdorf, RM and Strubin, M (2007) Continuous histone H2B and transcription<strong>de</strong>pen<strong>de</strong>nt<br />
histone H3 exchange in yeast cells outsi<strong>de</strong> of replication. Mol. Cell 25, 345-55.<br />
Contact: Michel.Strubin@unige.ch<br />
Virology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
37
Virology<br />
Laurent Kaiser<br />
Department of Internal Medicine Specialties<br />
Laurent Kaiser obtained his Medical Degree in Geneva in 1987 and a medical<br />
thesis in 1996. He completed a full training in Internal Medicine and a board<br />
certification in Infectious Diseases in 1999 and in clinical microbiology in<br />
2006. He spent two years as a research associate at the University of Virginia<br />
in Charlottesville, USA. He has been appointed associate professor at the<br />
Faculty of Medicine in 2006 and is Director of the Laboratory of Virology at the Geneva<br />
University Hospitals.<br />
Clinical virology<br />
Based within the HUG, the laboratory performs more than 140,000 diagnostic procedures<br />
annually. It runs a complete panel of virological tests adapted to a large university centre caring<br />
for immunocompromised patients and transplant recipients, including serology, antigen<br />
<strong>de</strong>tection, automated and non-automated molecular assays, viral sequencing and virus culture.<br />
The goal of the team is to integrate the activities of a routine laboratory with clinical<br />
<strong>de</strong>velopments, new diagnostic assays, and basic research in the field of virology.<br />
Reference centers: influenza and emerging viral diseases<br />
The laboratory integrates and supports two National Reference Centres fun<strong>de</strong>d by the Swiss<br />
Fe<strong>de</strong>ral Office of Public Health. This team conducts influenza surveillance in Switzerland and<br />
provi<strong>de</strong>s basic diagnostic capabilities for unusual and rare viral diseases. This inclu<strong>de</strong>s<br />
potentially dangerous agents as well as more common viruses that are not part of routine<br />
diagnostic procedures in most laboratories.<br />
Clinical research: respiratory viruses<br />
The clinical research conducted by the group aims to investigate the clinical impact and<br />
epi<strong>de</strong>miology of respiratory viruses by using appropriate molecular assays. In particular,<br />
investigations have focused on the impact of respiratory viruses in immunocompromised hosts<br />
and European or African children. Close collaboration with the basic research group allows the<br />
investigation of unusual clinical observations in the field of clinical virology and promotes<br />
translational projects.<br />
Acute HIV infection and resistance<br />
This group (Sabine Yerly) has built recognised expertise in the field of HIV diagnostics, acute<br />
HIV infection and molecular epi<strong>de</strong>miology of HIV transmission. The group acts also as a<br />
reference centre for the study of HIV resistance-associated mutations and the interpretation<br />
of new resistance patterns. This activity has the advantage of being immediately beneficial to<br />
the clinician in charge of managing complex antiretroviral regimens.<br />
38 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Cor<strong>de</strong>y S, Petty TJ, Schibler M, Martinez Y, Gerlach D, Van Belle S, Turin L, Zdobnov E, Kaiser L,<br />
Tapparel C (2012) i<strong>de</strong>ntification of site-specific adaptations conferring increased neural cell<br />
tropism during human enterovirus 71 infection. PloS Pathogens. [Epub ahead of print]<br />
Tapparel C, Cor<strong>de</strong>y S, Junier Th, Farinelli L, Van Belle S, Soccal PM, Aubert JD, Zdobnov E, Kaiser<br />
L (2011). Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract<br />
Infections. PLoS ONE 6: e21163.<br />
Soccal PM, Aubert JD, Bri<strong>de</strong>vaux PO, Garbino J, Thomas Y, Rochat T, Rochat TS, Meylan P, Tapparel<br />
C, Kaiser L (2010) Upper and lower respiratory viral infections and acute graft rejection in<br />
lung transplant recipients. Clin Infect Dis 51: 163-170.<br />
Cor<strong>de</strong>y S, Junier T, Gerlach D, Gobbini F, Farinelli L, Zdobnov E, Winther B, Tapparel C, Kaiser L<br />
(2010) Rhinovirus Genome Evolution during Experimental Human Infection. PloS One<br />
5 :e10588- e10588.<br />
Yerly S, Junier T, Gayet-Ageron A, Amari EB, von Wyl V, Günthard HV, Hirschel B, Zdobnov E, Kaiser<br />
L (2009) The impact of transmission clusters on primary drug resistance in newly diagnosed<br />
HIV-1 infection. Swiss HIV Cohort Study, AIDS 23 : 1415-23.<br />
Tapparel C, Junier T, Gerlach D, Van Belle S, Turin L, Cor<strong>de</strong>y S, Mühlemann K, Regamey N, Aubert<br />
JD, Soccal PM, Eigenmann P, Zdobnov E and Kaiser L (2009) New respiratory enterovirus and<br />
recombinant rhinoviruses among circulating picornaviruses. Emerg Infect Dis. 15: 719-26.<br />
Garbino J, Soccal PM, Aubert JD, Rochat T, Meylan P, Thomas Y, Tapparel C, Bri<strong>de</strong>vaux PO, Kaiser<br />
L (2009) Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in<br />
adults. Thorax, vol 64: 399-404.<br />
Contact: Laurent.Kaiser@hcuge.ch<br />
Virology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
39
Virology<br />
Caroline Tapparel Vu<br />
Department of Internal Medicine Specialties<br />
Caroline Tapparel Vu obtained her PhD in Molecular Virology in 1998 at the Faculty of Medicine<br />
in Geneva. After postdoctoral training in human genetics and bacteriology, she set up basic<br />
research on rhinoviruses and enteroviruses in the Department of Internal Medicine in 2005.<br />
Insights into rhino/enterovirus diversity and evolution<br />
Rhinoviruses and enteroviruses are small non-enveloped positive strand RNA viruses within<br />
the Enterovirus genus of the Picornaviridae family. Human rhinoviruses (HRV) are frequently<br />
associated with upper respiratory tract diseases and exacerbations of pre-existing disor<strong>de</strong>rs<br />
such as asthma. Human enteroviruses (HEV) contain important neurotropic pathogens such<br />
as Poliovirus or Enterovirus 71 (EV71). HRV and HEV are characterised by high genetic variability<br />
which complicates the <strong>de</strong>velopment of antivirals or vaccines. Our research group aims to<br />
improve the un<strong>de</strong>rstanding of the large phenotypic diversity observed among these closely<br />
related viruses. Thanks to reverse genetic assays the group investigates the correlation between<br />
genomic features and specific viral phenotypes.<br />
In addition, two of the major mechanisms of picornavirus evolution, recombination and<br />
mutations, are studied in vitro and during natural human infections, with the help of nextgeneration<br />
sequencing approaches. Furthermore, we continue to <strong>de</strong>velop novel generic<br />
molecular tools to <strong>de</strong>tect and quantify divergent viral strains with greater sensitivity.<br />
40 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Cor<strong>de</strong>y S, Petty TJ, Schibler M, Martinez Y, Gerlach D, Van Belle S, Turin L, Zdobnov E, Kaiser L,<br />
Tapparel C (2012) I<strong>de</strong>ntification of site-specific adaptations conferring increased neural cell<br />
tropism during human enterovirus 71 infection. PloS Pathogens Epub ahead of print<br />
Schibler M, Yerly S, Vieille G, Docquier M, Turin L, Kaiser L, Tapparel C (2012) A Critical Analysis<br />
of Rhinovirus RNA Load Quantification by Real-TIme RT-PCR. J Clin Microbiol Epub ahead<br />
of print .<br />
Schibler M, Gerlach D, Martinez Y, Van Belle S, Turin L, Kaiser L, Tapparel C (2011) Experimental<br />
Human Rhinovirus and Enterovirus Interspecies Recombination. J Gen Virol 93: 93-101.<br />
Tapparel C, Cor<strong>de</strong>y S, Junier T, Farinelli L, Van Belle S, Soccal PM, Aubert JD, Zdobnov E, Kaiser L<br />
(2011) Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract<br />
Infections. PLoS One 6:e21163.<br />
Cor<strong>de</strong>y S, Junier T, Gerlach D, Gobbini F, Farinelli L, Zdobnov E, Winther B, Tapparel C, Kaiser L<br />
(2010) Rhinovirus genome evolution during experimental human infection PLoS One<br />
5:e10588.<br />
Tapparel C, Cor<strong>de</strong>y S, Van Belle S, Turin L, Lee WM, Regamey N, Meylan P, Mühlemann K, Gobbini<br />
F, Kaiser L (2009) New molecular <strong>de</strong>tection tools adapted to emerging rhinoviruses and<br />
enteroviruses. J Clin Microbiol 47:1742-9<br />
Tapparel C, Junier T, Gerlach D, Van Belle S, Turin L, Cor<strong>de</strong>y S, Mühlemann K, Regamey N, Aubert<br />
JD, Soccal PM, Eigenmann P, Zdobnov E, Kaiser L (2009) New respiratory enterovirus and<br />
recombinant rhinoviruses among circulating picornaviruses. Emerg Infect Dis 15:719-26.<br />
Contact: Caroline.Tapparel@hcuge.ch<br />
Virology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
41
Virology<br />
Francesco Negro<br />
Department of Internal Medicine<br />
Department of Pathology and Immunology<br />
Francesco Negro obtained his Medical Degree in 1982 at the University of Turin, Italy. He was<br />
postdoctoral Fellow in Georgetown, University School of Medicine, Rockville, Maryland, USA<br />
from 1986 to 1989, and guest researcher at the Laboratory of Infectious Diseases at the National<br />
Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA in 1989. After having<br />
spent some time back in Turin, he joined the HUG in 1994. He was appointed Associate<br />
Professor in 2006.<br />
Pathogenesis of chronic hepatitis C<br />
Our laboratory studies the pathogenesis of chronic hepatitis C, including both hepatic and<br />
extrahepatic manifestations, with particular regard to: HCV-induced fatty liver; HCV-induced<br />
insulin resistance; interactions between HCV and the metabolic syndrome;<br />
factors/mechanisms of liver disease progression and resistance to interferon alpha-based<br />
antiviral therapy (particularly host genetic and metabolic factors). This research is carried out<br />
through the following approaches: in vitro, using (i) different expression mo<strong>de</strong>ls of single HCV<br />
proteins (including lentivectors), (ii) subgenomic-length or full-length (infectious) HCV replicon<br />
systems, and (iii) co-cultures of HCV-expressing hepatoma cells with other cell types of major<br />
relevance in the pathogenesis of the metabolic syndrome as well as in vivo, using human<br />
tissues (liver and peripheral blood mononuclear cells), taken in the setting of various<br />
observational and interventional clinical trials<br />
42 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Bochud PY, Bibert S, Kutalik Z, Patin E, Guergnon J, Nalpas B, Goossens N, Kuske L, Müllhaupt B,<br />
Gerlach T, Heim M, Moradpour D, Cerny A, Malinverni R, Regenass S, Dollenmaier G, Hirsch<br />
H, Martinetti G, Gorgiewski M, Bourlière M, Poynard T, Theodorou I, Abel L, Pol S, Dufour JF,<br />
Negro F (2012) IL28B alleles associated with poor HCV clearance are protective against liver<br />
necroinflammatory activity and fibrosis progression in patients infected with non-1 HCV<br />
genotypes. Hepatology 55:384-394<br />
Clément S, Peyrou M, Sanchez-Pareja A, Bourgoin L, Ramadori P, Suter DM, Vinciguerra M,<br />
Guilloux K, Pascarella S, Rubbia-Brandt L, Negro F, Foti M (2011) Downregulation of PTEN<br />
and IRS1 by HCV 3a core protein triggers steatosis in hepatocytes. Hepatology 54:38-49<br />
Bochud PY, Cai T, Overbeck K, Bochud M, Rickenbach M, Dufour JF, Muellhaupt B, Borovicka J,<br />
Heim M, Moradpour D, Cerny A, Malinverni R, Francioli P, Negro F (2009) Genotype 3 is<br />
associated with accelerated fibrosis progression in chronic hepatitis C. J Hepatol 51:655-666<br />
Clement S, Juge-Aubry C, Conzelmann S, Pazienza V, Pittet-Cuenod B, Meier C, Negro F (2008)<br />
Monocyte chemoattractant protein-1 secreted by adipose tissue induce lipid accumulation<br />
in hepatocytes. Hepatology 48:799-807<br />
Leandro G, Mangia A, Hui J, Fabris P, Rubbia-Brandt L, Colloredo G, Adinolfi LE, Asselah T, Jonsson<br />
JR, Smedile A, Terrault N, Pazienza V, De Lalla F, Giostra E, Sonzogni A, Ruggiero G, Marcellin<br />
P, Powell EE, George J, Negro F (2006) The relationship between hepatic steatosis,<br />
inflammation and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data.<br />
Gastroenterology 130: 1636-1642<br />
Contact: Francesco.Negro@unige.ch<br />
Virology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
43
Parasitology<br />
Dominique Soldati-Favre<br />
Department of Microbiology and Molecular Medicine<br />
Dominique Soldati-Favre obtained her PhD <strong>de</strong>gree at the University of Zürich in 1990. She was<br />
then a postdoctoral Fellow at Stanford University, Assistant Professor at the University of<br />
Hei<strong>de</strong>lberg and Rea<strong>de</strong>r at Imperial College London. She was appointed Associate Professor in<br />
2004 at the Department of Microbiology and Molecular Medicine and then full Professor in<br />
2010. Dominique Soldati-Favre has been Vice-Dean of the Faculty since 2011.<br />
Study of factors governing invasion and replication in Apicomplexan parasites<br />
Gliding motility is a unique attribute of the phylum Apicomplexa, which is crucial for parasite<br />
migration across biological barriers, host cell invasion and egress from infected cells. Timing<br />
and orientation of gliding motility are tightly regulated by formins that spatially control actin<br />
filaments polymerisation by assembly of a functional motor complex, which is governed by<br />
posttranslational modifications and by the action of a rhomboid protease, which disengages<br />
parasite adhesins and host receptors complexes and trigger the switch from an invasive to a<br />
replicative mo<strong>de</strong>. Our research focuses on regulators of actin dynamics, myosin motors,<br />
adhesins and proteases. Our aim is to elucidate how these proteins act in concert to control<br />
the lytic cycle of the parasite and assure infection.<br />
44 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Active host cell entry Intracellular replication<br />
Santos JM, Ferguson DJP, Blackman MJ and Soldati-Favre D (2011) Intramembrane Cleavage of<br />
AMA1 Triggers Toxoplasma to Switch from an Invasive to a Replicative Mo<strong>de</strong>. Science 331:473 -7.<br />
Frénal K, Polonais V, Marq, JB, Stratmann R, Limenitakis J, and Soldati-Favre D (2010) Functional<br />
Dissection of the Apicomplexan Gli<strong>de</strong>osome Molecular Architecture. Cell Host & Microbe<br />
8:343-57.<br />
Daher W., Plattner F, Carlier MF, and Soldati-Favre D (2010) Concerted action of two formins in<br />
gliding motility and host cell invasion by Toxoplasma gondii. PloS Pathogens. 76: e1001132<br />
Sheiner L, Santos JM, Klages N, Parussini F, Jemmely N, Friedrich N, Ward GE, Soldati-Favre D<br />
(2010) Toxoplasma gondii transmembrane microneme proteins and their modular <strong>de</strong>sign.<br />
Mol Microbio 77:912-29.<br />
Pino P, Aeby E, Foth BJ, Sheiner L, Soldati T, Schnei<strong>de</strong>r A, Soldati-Favre D (2010) Mitochondrial<br />
translation in absence of local tRNA aminoacylation and methionyl tRNA Met formylation<br />
in Apicomplexa. Mol. Microbiol. 76:706-18.<br />
Friedrich N, Santos J, Liu Y, Palma AS, Leon E, Saouros S, Kiso M, Blackman MJ, Matthews S, Feizi<br />
T and Soldati-Favre D (2010) Members of a novel protein family containing microneme<br />
adhesive repeat domains act as sialic acid-binding lectins during host cell invasion by<br />
apicomplexan parasites. J. Biol. Chem. 285: 2064-2076.<br />
Contact: Dominique.Soldati-Favre@unige.ch<br />
Parasitology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
45
Parasitology<br />
François Chappuis<br />
Department of Community Medicine and Primary Care<br />
Division of International and Humanitarian Medicine (HUG)<br />
Mé<strong>de</strong>cins sans Frontières<br />
François Chappuis obtained his Medical Degree in 1997 at the University of Geneva and a PhD<br />
in Medical Sciences in 2008 at the University of Antwerp, Belgium. He obtained the Privat-<br />
Docent in 2008 and was nominated as Associate Professor in Humanitarian Medicine in 2012.<br />
He is responsible for a travel and tropical medicine consultation at the HUG and is a medical<br />
adviser for leishmaniasis and trypanosomiasis programmes at Mé<strong>de</strong>cins Sans Frontières (MSF).<br />
Improved diagnosis, treatment and control of leishmaniasis and trypanosomiasis<br />
We are focusing our research efforts on improving case-management and control of some of<br />
the most neglected tropical diseases (NTDs) that affect poor communities in Asia, Africa, South<br />
America and Geneva (Latin American migrants). We have validated rapid diagnostic tests (RDT)<br />
for use at point-of-care for visceral leishmaniasis and Chagas disease. On the treatment si<strong>de</strong>,<br />
we have <strong>de</strong>monstrated the superiority of eflornithine over melarsoprol for the treatment of<br />
advanced African trypanosomiasis, partially clarified the causes of antimonials treatment<br />
failure in patients with cutaneous (Peru) and visceral leishmaniasis (Nepal), and revealed the<br />
high toxicity of nifurtimox in adult patients with Chagas disease. On the control si<strong>de</strong>, we have<br />
shown the lack of efficacy of impregnated bednets on the transmission of visceral<br />
leishmaniasis in Asia.<br />
46 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Jackson Y, Alirol E, Getaz L, Wolff H, Combescure C, Chappuis F (2010) Tolerance and safety of<br />
nifurtimox in patients with chronic Chagas disease. Clin Infect Dis 51: e69-75.<br />
Chappuis F, Mauris A, Holst M, Albajar-Vinas P, Jannin J, Luquetti AO, Jackson Y (2010) Validation<br />
of a rapid immunochromatographic assay for the diagnosis of chronic Chagas disease<br />
among Latin American immigrants in Geneva, Switzerland. J Clin Microbiol 48: 2948-52.<br />
Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, Boelaert M (2007) Visceral<br />
leishmaniasis: what are the needs for diagnosis, treatment and control? Nature Reviews<br />
Microbiol 5: 873-82 and S7-S16.<br />
Chappuis F, Rijal S, Soto A, Menten J, Boelaert M (2006). A meta-analysis of the diagnostic<br />
performance of the direct agglutination test and rK39 dipstick for visceral leishmaniasis,<br />
BMJ 333: 723-7.<br />
Chappuis F, Udayraj N, Stietenroth K, Meussen A, Bovier PA (2005). Eflornithine is safer than<br />
melarsoprol for the treatment of second stage Trypanosoma brucei gambiense human<br />
African trypanosomiasis. Clin Infect Dis 41: 748-51.<br />
Contact: Francois.Chappuis@hcuge.ch<br />
Parasitology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
47
Parasitology<br />
Louis Loutan<br />
Department of Community Medicine and Primary Care<br />
Division of International and Humanitarian Medicine (HUG)<br />
Louis Loutan obtained his medical qualification in 1978. He was appointed Associate Professor<br />
in 2007.<br />
Travel and migration of humans and pathogens<br />
We have explored various aspects of travel and migration medicine ranging from hepatitis A<br />
vaccine (immunogenicity and tolerance), to antimalarial drugs and the epi<strong>de</strong>miology of<br />
imported infectious diseases by migrants and travelers. We are currently moving into issues<br />
related to globalisation (access to health care, changing epi<strong>de</strong>miology of infectious diseases<br />
ID in the urban environment, refugee health). Future research directions will strengthen the<br />
links between fundamental parasitology and the clinical context.<br />
48 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Socioeconomic disparities have a great impact on infectious diseases<br />
Alirol E, Getaz L, Stoll B, Chappuis F, Loutan L (2011). Urbanisation and infectious diseases in a<br />
globalised world. Lancet Infect Dis.11:131-41.<br />
Bovier P, Bock J, Farinelli T, Frösner G, Glaus J, Herzog C, Loutan L (2010). Predicted 30-year<br />
protection after vaccination with an aluminium-free virosomal hepatitis A vaccine. J Med<br />
Virol 82:1629-34.<br />
Dahlgren A, DeRoo L, Avril J, Bise G, Loutan L (2009). Health risks ans risk-taking behaviours<br />
among international committee of the red cross (ICRC) expatriate returning from<br />
humanitarian missions. J Trav Med 16:382-390.<br />
Jackson Y, Getaz L, Wolff H, Holst M, Mauris A, Tardin A, Sztajzel J, Besse V, Loutan L, Gaspoz JM<br />
et al. (2010) Prevalence, clinical staging and risk for blood-borne transmission of chagas<br />
disease among latin american migrants in Geneva, Switzerland. PLoS NeglTrop Dis 4:e592.<br />
Chen L, Wilson M, Davis W, Loutan L et al. (2009) Illness in long-term travelers visiting<br />
geosentinel clinics. Emerg Infect Dis 15;1773-1782.<br />
Hatz C, Soto J, Nothdurft HD, Zoller T, Weitzel T, Loutan L, Bricaire F et al. (2008) Treatment of<br />
acute uncomplicated falciparum malaria with artemether-lumefantrine in non-immune<br />
populations : a safety, efficacy, and pharmacokinetic study. Am J Trop Med Hyg 78: 241-247.<br />
Contact: Louis.Loutan@unige.ch<br />
Parasitology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
49
Mycology<br />
Martine A. Collart<br />
Department of Microbiology and Molecular Medicine<br />
Martine Collart obtained her PhD in 1990 at the University of Geneva. She continued her<br />
research at Harvard Medical School in Boston with Kevin Struhl, where she i<strong>de</strong>ntified the NOT<br />
genes using a genetic selection in yeast. In 1993 she started her own in<strong>de</strong>pen<strong>de</strong>nt group to<br />
pursue the characterisation of the Not genes, in the Department of Medical Biochemistry of<br />
the Faculty of Medicine at the University of Geneva. She was appointed Associate Professor in<br />
the Department of Microbiology and Molecular Medicine in 2004 and full Professor in 2011.<br />
Genetic and Biochemical characterisation of the conserved Ccr4-Not complex in yeast<br />
We work on characterising, in the yeast S. cerevisiae, the function of an essential multisubunit<br />
protein complex that is conserved across the eukaryotic kingdom, the Ccr4-Not complex. This<br />
complex has two known enzymatic activities, ubiquitination provi<strong>de</strong>d by the RING finger Not4<br />
E3 ligase, and <strong>de</strong>a<strong>de</strong>nylation provi<strong>de</strong>d by the Caf1 and Ccr4 subunits. Despite growing<br />
knowledge on these enzymatic functions, the role of the other subunits, the relationship<br />
between the different subunits and their activities, and the reason for the association of these<br />
different subunits in a complex is unknown. Our more recent experiments suggest that this<br />
complex may serve as a chaperone allowing the assembly of multicomponent complexes in<br />
cells. The tremendous complexity of this system in which a multisubunit complex regulates<br />
assembly of other multisubunit complexes in eukaryotic cells, makes the yeast S. cerevisiae a<br />
perfect mo<strong>de</strong>l organism for study because of its powerful genetics that can be combined with<br />
biochemistry.<br />
50 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Panasenko OO and Collart MA (2012) Presence of Not5 and ubiquitinated Rps7A in polysome<br />
fractions <strong>de</strong>pends upon the Not4 E3 ligase. Mol. Microbiol. 83: 640-632.<br />
Collart MA and Panasenko OO (2012) The Ccr4-Not complex. Gene 492: 42-53.<br />
Olesya O. Panasenko and Martine A. Collart (2011) Not4 E3 ligase contributes to proteasome<br />
assembly and functional integrity via the Ecm29 chaperone. Mol. Cell. Biol. 31: 1610-1623.<br />
Azzouz N, Panasenko OO, Colau G and Collart MA (2009) The Ccr4-Not complex physically and<br />
functionally interacts with TRAMP and the nuclear exosome. PLoS One 4:e6760.<br />
Panasenko OO, David F and Collart MA (2009) Ribosome association and stability of the nascent<br />
polypepti<strong>de</strong>-associated complex is <strong>de</strong>pen<strong>de</strong>nt upon its own ubiquitination. Genetics 181:<br />
447-460.<br />
Contact: Martine.Collart@unige.ch<br />
Mycology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
51
Host Response<br />
Alain Gervaix<br />
Department of Pediatrics<br />
Alain Gervaix obtained his medical <strong>de</strong>gree at the University of Geneva in 1986, then specialty<br />
qualifications in Paediatrics in 1994 and in Infectiology in 1999. He spent two years at the<br />
University of San Diego, California, USA as a Postdoctoral <strong>Research</strong> Fellow and came back to<br />
the HUG as the Head of the Paediatric Infectious Disease and Emergency Division. He was<br />
appointed Associate Professor in 2006 and full Professor in 2012. Since 2011 he has been Vice-<br />
Dean of the Faculty.<br />
Inflammatory markers in bacterial infection<br />
Our group works mainly on the value of inflammatory markers such as procalcitonin and<br />
C-reactive protein in the prediction of serious bacterial infection in young children with fever<br />
without source.<br />
Procalcitonin is a 116 amino acid protein produced by multiple organs in response to bacterial<br />
challenge. Investigations performed in fever without source, pyelonephritis, meningitis and<br />
pneumonia have shown that this protein is superior to other blood markers in predicting a<br />
bacterial infection. We recently validated and published a biological score based on the results<br />
of procalcitonin, C-reactive protein and urine dispstick to help physicians in the diagnosis of<br />
severe infections in children less than 3 years of age.<br />
52 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Galetto-Lacour A, Zamora SA, Andreola B, Bressan S, Lacroix L, Da Dalt L, Gervaix A (2010).<br />
Validation of a laboratory risk in<strong>de</strong>x score for the i<strong>de</strong>ntification of severe bacterial infection<br />
in children with fever without source. Arch Dis Child. 95:968-73.<br />
Lacour AG, Zamora SA, Gervaix A (2008). A score i<strong>de</strong>ntifying serious bacterial infections in<br />
children with fever without source. Pediatr Infect Dis J. 27:654-6.<br />
Leroy S, Romanello C, Galetto-Lacour A, et al. (2007) Procalcitonin to reduce the number of<br />
unnecessary cystographies in children with a urinary tract infection: a European validation<br />
study. J Pediatr. 150:89-95.<br />
Galetto-Lacour A, Zamora SA, Gervaix A (2003). Bedsi<strong>de</strong> procalcitonin and C-reactive protein<br />
tests in children with fever without localizing signs of infection seen in a referral center.<br />
Pediatrics. 112:1054-60.<br />
Gervaix A, Galetto-Lacour A, Gueron T, et al. (2001) Usefulness of procalcitonin and C-reactive<br />
protein rapid tests for the management of children with urinary tract infection. Pediatr<br />
Infect Dis J. 20:507-11.<br />
Contact: Alain.Gervaix@hcuge.ch<br />
Host Response<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
53
Host Response<br />
Klara Posfay-Barbe<br />
Department of Pediatrics<br />
Klara Posfay Barbe obtained her MD in 1994 at the University of Geneva. After intensive training<br />
in pediatrics at the HUG, she followed from 2001 to 2004 a postdoctoral training in paediatric<br />
infectious diseases and clinical research at the University of Pittsburgh Medical Center, USA.<br />
In 2004 she returned to the Department of Paediatrics in Geneva where she was appointed<br />
Cheffe <strong>de</strong> Clinique Scientifique in 2004 and Mé<strong>de</strong>cin Adjoint in 2009. In 2011, she obtained her<br />
Privat-Docent. She is currently Head of the Department of Paediatric Infectious Diseases.<br />
Immune responses to infection in children<br />
Our group mostly studies antibody responses against well known antigens such as varicella or<br />
Haemophilus influenzae in different settings (immunocompromised children, very young<br />
infants), or against “new” bacteria (such as Parachlamydiae spp.). We are also interested in new<br />
antigens present on Streptococcus pneumoniae, such as pneumococcal surface proteins (PcpA,<br />
PhtD, PrtA, LytB), which elicit antibody responses after disease or carriage. These antigens,<br />
which are conserved across all pneumococcal serotypes, could be used in the future to <strong>de</strong>velop<br />
new vaccines. Finally, we also study innate immunity by measuring the effect of pneumococcal<br />
infection on the cellular expression of Toll-like receptors in children with recurrent lower<br />
respiratory tract infections.<br />
.<br />
54 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Schäppi MG, Meier S, Bel M, Siegrist CA, Posfay-Barbe KM (2012), the H1N1 Study Group.<br />
Protective Antibody Responses to Influenza A/H1N1/09 Vaccination in Children with Celiac<br />
Disease. J Pediatr Gastroenterol Nutr. 54:817-819<br />
L’Huillier AG, Wildhaber BE, Belli DC, Diana A, Rodriguez M, Siegrist CA, Posfay-Barbe KM (2012).<br />
Successful serology-based intervention to increase protection against vaccine-preventable<br />
diseases in liver-transplanted children: A 19-yr review of the Swiss national reference center.<br />
Pediatr Transplant. 16:50-7<br />
Hagerman A, Posfay-Barbe KM, Grillet S, Ochs MM, Brookes RH, Greenberg D, Givon-Lavi N,<br />
Dagan R, Siegrist CA (2011). Failure to elicit seroresponses to pneumococcal surface proteins<br />
18:756-62<br />
Lienard J, Croxatto A, Aeby S, Jaton K, Posfay-Barbe K, Gervaix A, Greub G (2011). Development<br />
of a new Chlamydiales-specific real-time PCR and its application to respiratory clinical<br />
samples. J Clin Microbiol. 49:2637-42.<br />
Posfay-Barbe KM, Kobela M, Sottas C, Grillet S, Taguebue J, Ekoe T, Lambert PH, Lecoultre C,<br />
Siegrist CA (2010). Frequent failure of adolescent booster responses to tetanus toxoid<br />
<strong>de</strong>spite infant immunization: waning of infancy-induced immune memory? Vaccine<br />
28:4356-61<br />
Contact: Klara.PosfayBarbe@hcuge.ch<br />
Host Response<br />
Fold-increase of anti-pneumococcal surface protein (PSP) antibody concentrations<br />
in bacteraemic children. The ratio of convalescent to acute anti-PSP antibody geometric<br />
mean concentration (GMC) is illustrated for each PSP and age group. PcpA,<br />
pneumococcal choline-binding protein A; PhtD, pneumococcal histidine triad D; PrtA,<br />
serine proteinase precursor A. (Hagerman et al., 2011)<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
55
Host Response<br />
Marc Chanson<br />
Department of Pediatrics<br />
Marc Chanson obtained his PhD in 1991 at the University of Geneva. From 1991 to 1993 he was<br />
Post Doctoral Fellow at the Albert Einstein College of Medicine, Department of Neurosciences,<br />
in New York. Before his return to Geneva in 1995 he was postdoctoral Fellow at the Department<br />
of Physiology at the University of Utrecht. He was nominated Lecturer in 2002 and Associate<br />
Professor in 2012.<br />
Gap junctional intercellular communication in cystic fibrosis airway disease<br />
We are studying the regulation and function of gap junction channels in normal and inflamed<br />
lungs. Gap junctions interconnect ciliated airway epithelial cells that constitute the physical<br />
barrier between the host and the environment. In cystic fibrosis (CF), mutations of the cystic<br />
fibrosis transmembrane conductance regulator (CFTR), which is expressed in ciliated cells, alters<br />
the airway epithelium barrier. This impaired <strong>de</strong>fence is associated with chronic infection and<br />
inflammation of the lung, leading to progressive loss of respiratory function. However, the links<br />
between the genetic <strong>de</strong>fect in CF and initiation of the chronic infection of the airways are poorly<br />
known. We have found that CFTR regulates the activity of gap junction channels and that gap<br />
junctional intercellular communication contributes to the <strong>de</strong>fence mechanisms of airway<br />
epithelial cells to infection. More recently, we have observed that quorum sensing molecules<br />
produced by opportunistic pathogens in CF (Pseudomonas aeruginosa, Staphylococcus aureus)<br />
interfere with the function of gap junctions in airway epithelial cells. Further studies aim at<br />
the analysis of the un<strong>de</strong>rlying mechanisms and at un<strong>de</strong>rstanding the consequence of gap<br />
junction channel <strong>de</strong>regulation in the pathogenesis of CF.<br />
56 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Losa D, Chanson M, Crespin S (2011). Connexins as therapeutic targets in lung disease. Expert<br />
Opinion on Therapeutic Targets 15:989-1002<br />
Scheckenbach KEL, Losa D, Crespin S, Du<strong>de</strong>z T, Bacchetta M, O’Grady S, Chanson M (2011). PGE2<br />
regulation of CFTR activity and airway surface liquid volume requires gap junctional<br />
communication. Am J Respir Cell Mol Biol 44:74-82.<br />
Sarieddine MZ, Garcia I, Foglia B, Kwak BR, Chanson M (2009). Targeting Connexin43 protects<br />
against acute lung inflammation. J Cell Mol Med 13: 4560-4570.<br />
Huang S, Du<strong>de</strong>z T, Scerri I, Thomas MA, Giepmans BNG, Suter S, Chanson M (2003). Defective<br />
activation of c-Src in CF airway epithelial cells results in loss of TNF-α-induced gap junction<br />
regulation. J Biol Chem 278: 8326-8832.<br />
Chanson M, Scerri I, Suter S (1999). Defective regulation of gap junctional coupling in cystic<br />
fibrosis pancreatic duct cells. J Clin Invest 103: 1677-1684.<br />
Contact: Marc.Chanson@hcuge.ch<br />
A human airway epithelial cell surroun<strong>de</strong>d<br />
by Pseudomonas aeruginosa (in red) and expressing<br />
the apoptotic marker AnnexinV (in green).<br />
Host Response<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
57
Host Response<br />
Irene Garcia-Gabay<br />
Department of Pathology and Immunology<br />
Irene Garcia-Gabay obtained her PhD in immunology at the University of Geneva (1982). After<br />
a Fellowship at the Pasteur Institute, Paris, France, she did postdoctoral work at the Swiss<br />
Institute for Experimental Cancer <strong>Research</strong> (ISREC), Department of Molecular Biology. In 1994,<br />
she was a recipient of funds from the Marie Heim-Vögtlin programme from the SNSF and<br />
established her laboratory. She is Lecturer and <strong>Research</strong> Associate at the Department of<br />
Pathology and Immunology.<br />
Host <strong>de</strong>fence mechanisms against mycobacterial infections<br />
Our laboratory is interested in host resistance to Mycobacterium tuberculosis and M. bovis BCG<br />
infections. We are working on cellular mediators such as cytokines involved in innate and<br />
adaptive immunity to control these intracellular pathogens. We have long experience of Tumor<br />
Necrosis Factor (TNF), a pro-inflammatory cytokine activated by mycobacteria in macrophages<br />
and T cells, which plays a critical role in granuloma formation and protection against<br />
mycobacteria. On the other hand, TNF is a main target for the treatment of inflammatory<br />
diseases and its inhibition may reactivate latent tuberculosis. We are evaluating the activity of<br />
the different TNF molecules and interactions with soluble and membrane-bound TNF receptors,<br />
to <strong>de</strong>fine the regulatory mechanisms involved in both host protection and inflammatory<br />
disor<strong>de</strong>rs in or<strong>de</strong>r to dissociate these two activities and propose new strategies of intervention<br />
in inflammation and infection.<br />
58 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Olleros ML, Vesin D, Bisig R, Santiago-Raber ML, Schuepbach-Mallepell S, Kollias G, Gai<strong>de</strong> O and<br />
Garcia I (2012) Membrane-bound TNF induces protective immune responses to M. bovis BCG<br />
infection: regulation of memTNF and TNF receptors comparing two memTNF molecules.<br />
PLoS ONE 7:e31469<br />
Garcia I, Olleros ML, Quesniaux VF, Jacobs M, Allie N, Nedospasov SA, Szymkowski DE, Ryffel B<br />
(2011) Roles of soluble and membrane TNF and related ligands in mycobacterial infections :<br />
effects of selective and non-selective TNF inhibitors during infection. Adv Exp Med Biol<br />
691:187-201.<br />
Olleros ML, Vesin D, Fotio AL, Santiago-Raber ML, Tauzin S, Szymkowski DE, Garcia I (2010)<br />
Soluble TNF, but not membrane TNF, is critical in LPS-induced hepatitis. J. Hepatol. 53:1059-<br />
1068.<br />
Allie N, Keeton R,Court N, Abel B, Fick L, Vasseur V, Vacher R, Olleros ML, Drutskaya MS, Guler G,<br />
Nedospasov SA, Garcia I, Ryffel B, Quesniaux VF, Jacobs M (2010) Limited role for<br />
lymphotoxin a in the host immune response to Mycobacterium tuberculosis. J. Immunol.<br />
185:4292-301.<br />
Olleros ML, Vesin D, Lambou AF, Janssens JP, Ryffel B, Rose S, Frémond C, Quesniaux VF,<br />
Szymkowski DE and GarciaI (2009) Dominant-Negative TNF Protects from Mycobacterium<br />
bovis BCG and Endotoxin-Induced Liver Injury Without Compromising Host Immunity to<br />
BCG and M. tuberculosis. J. Infectious Diseases, 199:1053-63.<br />
Contact: Irene.Garcia-Gabay@unige.ch<br />
Host Response<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
59
Host Response<br />
Pierre Cosson<br />
Department of Cell Physiology and Metabolism<br />
Pierre Cosson obtained his PhD in Immunology at the University of Marseille (1990). He spent<br />
two years as a Postdoctoral Fellow at the National Institutes of Health, Bethesda, USA, and<br />
then joined the Basel Institute of Immunology (Basel, CH) as an in<strong>de</strong>pen<strong>de</strong>nt researcher. He<br />
was awar<strong>de</strong>d an Swiss National Science Foundation START Fellowship in 1997 and joined the<br />
Geneva Faculty of Medicine, where he was later appointed Associate Professor (2002) and full<br />
Professor (2009) at the Departement of Cell Physiology and Metabolism. Since 2009, Pierre<br />
Cosson has held the Doerenkamp- Naef-Zbin<strong>de</strong>n Chair for the <strong>de</strong>velopment of alternatives to<br />
animal experiments.<br />
Dictyostelium amoebae: a mo<strong>de</strong>l to study host-pathogen interactions<br />
Our group makes use of Dictyostelium amoebae as a mo<strong>de</strong>l to study interactions between<br />
phagocytic cells and bacteria. This genetically tractable mo<strong>de</strong>l allows us to study cellular<br />
mechanisms such as cell adhesion, phagocytosis and intracellular killing. Bacterial<br />
pathogenicity mechanisms can also be studied advantageously using this simple mo<strong>de</strong>l.<br />
60 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Le Coadic M, Simon M, Marchetti A, Ebert D, Cosson P (2012) Daphnia magna, a host to evaluate<br />
bacterial virulence. Appl. Environ. Microbiol. 78:593-5.<br />
Lelong E, Marchetti A, Simon M, Burns JL, van Del<strong>de</strong>n C, Köhler T, Cosson P (2011) Evolution of<br />
Pseudomonas aeruginosa virulence in infected patients revealed in a Dictyostelium<br />
discoi<strong>de</strong>um host mo<strong>de</strong>l. Clin. Microb. Infect. 17:1415-20.<br />
Lelong E, Marchetti A, Guého A, Lima WC, Sattler N, Molmeret M, Hagedorn M, Soldati T, Cosson<br />
P (2010) Role of magnesium and a phagosomal P-type ATPase in intracellular bacterial<br />
killing. Cell. Microb. 13:246-58.<br />
Froquet R, Lelong E, Marchetti A, Cosson P (2009) Dictyostelium discoi<strong>de</strong>um: a mo<strong>de</strong>l host to<br />
measure bacterial virulence. Nature Protocols. 4:25-30.<br />
Alibaud L, Köhler T, Coudray A, Prigent-Combaret C, Bergeret E, Perrin J, Benghezal M, Reimmann<br />
C, Gauthier Y, van Del<strong>de</strong>n C, Attree I, Fauvarque MO, Cosson P (2008) Pseudomonas<br />
aeruginosa virulence genes i<strong>de</strong>ntified in a Dictyostelium host mo<strong>de</strong>l. Cell. Microb. 10:729-40.<br />
BenghezalM, Fauvarque MO, Tournebize R, Froquet R, Marchetti A, Bergeret E, Lardy B, Klein G,<br />
Sansonetti P, Charette SJ, Cosson P (2006) Specific host genes required for the killing of<br />
Klebsiella bacteria by phagocytes. Cell. Microb. 8:139-48.<br />
Contact: Pierre.Cosson@unige.ch<br />
A Dictyostelium amoeba (white and green) ingesting<br />
a bacterium (red). The amoeba is trying to kill<br />
the bacteria, the bacteria is trying to kill the amoeba.<br />
Who is going to win?<br />
Host Response<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
61
Host Response<br />
Jérôme Pugin<br />
Department of Anaesthesiology, Pharmacology and Intensive Care<br />
Department of Microbiology and Molecular Medicine<br />
Jérôme Pugin obtained his MD <strong>de</strong>gree in 1984 in Geneva, and later specialised in both Internal<br />
and Intensive Care medicine. He shares his time between clinical work as a Deputy Head<br />
Physician of the Intensive Care Division at Geneva University Hospitals, and research in the<br />
Department of Microbiology and Molecular Medicine at the Faculty of Medicine of the<br />
University of Geneva. He spent three years between 1991 and 1994 in the Department of<br />
Immunology of the Scripps <strong>Research</strong> Institute in La Jolla, USA. Jérôme Pugin was appointed<br />
Associate Professor in 2007 and full Professor in 2012 at the Faculty of Medicine of Geneva.<br />
Since 2011 he has been Vice-Dean of the Faculty.<br />
Recognition of bacteria by innate immunity receptors<br />
Our research interests have focused over the last 20 years on the molecular and cellular<br />
pathogenesis of sepsis. In particular, we have worked on soluble proteins involved in the innate<br />
recognition of bacteria such as soluble CD14 and MD-2, as well as in the Toll-like receptors<br />
activated by Gram-negative and Gram-positive bacteria. Another area of study is the molecular<br />
pathogenesis and cell signaling of ventilator-induced lung injury, and lung inflammation in<br />
the context of acute respiratory distress syndrome. We have also i<strong>de</strong>ntified and tested<br />
biomarkers in the field of clinical sepsis.<br />
62 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Dunn-Siegrist I, Tissières P, Drifte G, Bauer J, Moutel S, Pugin J (2012) Toll-like Receptor Activation<br />
of Human Cells by Synthetic Triacylated Lipid A-like Molecules. J Biol Chem. 287: 16121-31<br />
Tissières P, Ochoda A, Dunn-Siegrist I, Drifte G, Morales M, Pfister R, Berner M, Pugin J (2012)<br />
Innate immune <strong>de</strong>ficiency of extremely premature neonates can be reversed by interferon-γ.<br />
PLoS One 7: e32863<br />
Tissières P, Araud T, Ochoda A, Drifte G, Dunn-Siegrist I, Pugin J (2009) The expression of the<br />
acute phase MD-2 gene <strong>de</strong>pends on the cooperation between PU.1 and C/EBP ß. J. Biol.<br />
Chem. 284: 26261-72<br />
Tissières P, Dunn-Siegrist I, Comte R, Nobre V, Pugin J (2008) Soluble MD-2 is an acute phase<br />
protein and an opsonin for Gram-negative bacteria. Blood 111: 2122-31<br />
Pugin J, Dunn-Siegrist I, Dufour J, Tissières P, Charles PE, Comte R (2008) Cyclic stretch of human<br />
lung cells induces an acidification and promotes bacterial growth. Am. J. Respir. Cell Mol.<br />
Biol. 38:362-70<br />
Elson G, Dunn-Siegrist I, Daubeuf B, Pugin J (2007) Contribution of Toll-like receptors to the<br />
innate immune response to Gram-negative and Gram-positive bacteria. Blood 109:1574-8<br />
Pugin J, Stern-Voeffray S, Daubeuf B, Matthay MA, Elson G, Dunn-Siegrist I (2004) Soluble MD-<br />
2 activity in plasma from patients with severe sepsis and septic shock. Blood 104: 4071-4079<br />
Contact: Jerome.Pugin@unige.ch<br />
LPS induced TLR4 clustering<br />
Host Response<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
63
Host Response<br />
Karl-Heinz Krause<br />
Department of Pathology and Immunology<br />
Karl-Heinz Krause obtained his medical <strong>de</strong>gree in 1984 at the University of Munich, where he<br />
also trained in internal medicine. After Fellowships at the Geneva University Hospitals (1984-<br />
87) and the University of Iowa Hospitals, USA (1987-89), he was recruited as a junior faculty<br />
member in Geneva. He was appointed Associate Professor in 1998 and full Professor in 2001 at<br />
the Department of Internal me<strong>de</strong>cine and Geriatrics. Since 2005 he has been affiliated to the<br />
Department of Pathology and Immunology, as well as the Department of Genetic and<br />
Laboratory Medicine , HUG.<br />
NADPH oxidases<br />
Reactive oxygen species (ROS) are a doubled-edged sword. They have crucial physiological<br />
functions, from host <strong>de</strong>fence to participation in biosynthetic processes and from intracellular<br />
signaling to regulation of gene expression. However, they can also be <strong>de</strong>structive and are linked<br />
to many disease processes. The NOX family of NADPH oxidases are one of the major sources<br />
of ROS and our laboratory is particularly interested in this enzyme family. ROS-generating NOX<br />
enzymes are a phylogenetically ancient system found in many unicellular organisms. They have<br />
a range of complex functions in multicellular organisms, notably a role in host <strong>de</strong>fence and<br />
inflammation. Much has been learned from patients with chronic granulomatous diseases<br />
(genetic NOX2 <strong>de</strong>ficiency), diseases characterised by the concommitant occurence of immune<br />
<strong>de</strong>ficiency and hyperinflammation.<br />
Neural differentiation of pluripotent stem cells<br />
A second focus of our laboratory is neuronal differentiation of pluripotent stem cells. Such<br />
differentiation protocols can be used to generate in vitro human neural cells and tissues. This<br />
is particularly relevant for the creation of human mo<strong>de</strong>l systems for diseases of the central<br />
nervous system. Among others, we are using the system to study viral infection of the human<br />
CNS. Also, we are working on the response to tumour invasion of human neural tissues, which<br />
in many respects can mimic antiviral responses.<br />
64 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Sorce S, Schiavone S, Tucci P, Colaianna M, Jaquet V, Cuomo V, Dubois-Dauphin M, Trabace L,<br />
and Krause KH (2010) The NADPH oxidase NOX2 controls glutamate release: a novel<br />
mechanism involved in psychosis-like ketamine responses. J Neurosci. 30:11317-25.<br />
Li B, Bedard K, Sorce S, Hinz B, Dubois-Dauphin M, Krause KH (2009) NOX4 expression in human<br />
microglia leads to constitutive generation of reactive oxygen species and to constitutive<br />
IL-6 expression. Journal of Innate Immunity 1:570-581.<br />
Bedard K, Attar H, Bonnefont J, Jaquet V, Borel C, Plastre O, Stasia MJ, Antonarakis SE, Krause<br />
KH (2009) Three common polymorphisms in the CYBA gene form a haplotype associated<br />
with <strong>de</strong>creased ROS generation. Hum Mutat 30:1123-33.<br />
Schäppi M, Deffert C, Fiette L, Gavazzi G, Herrmann F, Belli D, Krause KH (2008) Branched fungal<br />
beta-glucan causes hyperinflammation and necrosis in phagocyte NADPH oxidase<strong>de</strong>ficient<br />
mice. J Pathol. 214:434-44.<br />
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology<br />
and pathophysiology. Physiol Reviews 87(1):245-313.<br />
Contact: Karl-Heinz.Krause@unige.ch<br />
Host Response<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
65
Vaccinology<br />
Claire-Anne Siegrist<br />
Departments of Pathology and Immunology<br />
Department of Pediatrics<br />
WHO Collaborative Center for Vaccine Immunology<br />
Claire-Anne Siegrist graduated in 1983. She trained in paediatrics, infectious diseases and<br />
immunology prior to <strong>de</strong>dicating her professional life to all aspects of vaccinology. Associate<br />
Professor of Vaccinology (2000) and full Professor of Paediatrics (2006), she is Presi<strong>de</strong>nt of the<br />
Swiss National Advisory Committee on Immunization (2004), member of the UK National<br />
Committee (2008) and of the WHO Strategic Advisory Group of Experts on Immunization<br />
(2010). She leads the InfoVac expert network (www.infovac.ch), has <strong>de</strong>veloped vaccinology<br />
clinical <strong>de</strong>cision support software for health care professionals (www.viavac.ch), and is the<br />
foun<strong>de</strong>r of the Swiss Electronic Vaccination Record (www.myvaccines.ch)..<br />
Vaccine immunology from early life to vaccine safety<br />
Our research focusses on i) neonatal immunology in or<strong>de</strong>r to un<strong>de</strong>rstand the postnatal<br />
<strong>de</strong>velopment process of the immune system and how it is regulated to control early life<br />
immune responses to foreign antigens; ii) vaccine immunology through which we study the<br />
mo<strong>de</strong> of action of current and novel vaccines to i<strong>de</strong>ntify strategies capable of strengthening<br />
immune competence, especially in the very young and iii) clinical vaccinology to un<strong>de</strong>rstand<br />
the <strong>de</strong>terminants of vaccine responses in patients with varying levels of immune competence<br />
because of age, un<strong>de</strong>rlying disease or immunosuppression, and thus i<strong>de</strong>ntify optimal<br />
strategies.<br />
66 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Siegrist CA, van Del<strong>de</strong>n C, Bel M, Combescure C, Delhumeau C, Cavassini M, Clerc O, Meier S,<br />
Hadaya K, Soccal PM, Yerly S, Kaiser L, Hirschel B and A. Calmy (2012) Higher memory<br />
responses in HIV-infected and kidney transplanted patients than in healthy subjects<br />
following priming with the pan<strong>de</strong>mic vaccine. Plos One 7:e40428<br />
Kamath AT, Mastelic B, Christensen D, Rochat AF, Agger EM, Pinschewer DD, An<strong>de</strong>rsen P,<br />
Lambert PH and Siegrist CA (2012) Synchronization of DC activation and antigen exposure<br />
is required for the induction of Th1/Th17 responses. J Immunol. 188:4828-37<br />
Belnoue E, Tougne C, Rochat AF, Lambert PH, Pinschewer DD and Siegrist CA (2012) Homing and<br />
adhesion patterns <strong>de</strong>termine the cellular composition of the bone marrow plasma cell<br />
niche. J Immunol. 188:1283-91.<br />
Gabay C, Bel M, Combescure C, Ribi C, Meier S, Posfay-Barbe K, Grillet S, Seebach JD, Kaiser L,<br />
Wun<strong>de</strong>rli W, Guerne PA and Siegrist CA (2011) Impact of synthetic and biological disease<br />
modifying antirheumatic drugs on antibody responses to the ASO3-adjuvanted pan<strong>de</strong>mic<br />
influenza vaccine. Arthritis & Rheumatism 63:1486-96.<br />
Kamath AT, Rochat AF, Christensen D, Agger EM, An<strong>de</strong>rsen P, Lambert PH, Siegrist CA. A<br />
Liposome-based mycobacterial vaccine induces potent adult and neonatal multifunctional<br />
T cells through the exquisite targeting of <strong>de</strong>ndritic cells. PLoS One 4:e5771<br />
Kamath AT, Rochat AF, Valenti MP, Agger EM, Lingnau K, An<strong>de</strong>rsen P, Lambert PH, Siegrist CA<br />
(2008) Adult-like anti-mycobacterial T cell and in vivo <strong>de</strong>ndritic cell responses following<br />
neonatal immunization with Ag85B-ESAT-6 in the IC31 adjuvant. PLoS ONE 3:e3683.<br />
Belnoue E, Pihlgren M, McGaha TL, Tougne C, Rochat AF, Bossen C, Schnei<strong>de</strong>r P, Huard B, Lambert<br />
PH, Siegrist CA (2008) APRIL is critical for plasmablast survival in the bone marrow and<br />
poorly expressed by early life bone marrow stromal cells. Blood 111:2755-64.<br />
Contact: Claire-Anne.Siegrist@unige.ch<br />
Vaccinology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
67
Dental Bacteriology<br />
Serge Bouillaguet<br />
Division of Cariology and Endodontics<br />
Serge Bouillaguet obtained his <strong>de</strong>ntal <strong>de</strong>gree in 1983 and his Doctorate in Dental Surgery in<br />
Marseilles in 1984. He obtained a Doctorate in Medical Dentistry at the University of Geneva<br />
in 1989 and his Privat-Docent in 2003. He was appointed Lecturer in 2001 and appointed<br />
Associate Professor in 2011.<br />
Blue light-mediated inactivation of endodontic pathogens<br />
Our research interests focus on the evaluation of current antimicrobial strategies used in<br />
endodontics together with the <strong>de</strong>velopment of new approaches based on the photoinactivation<br />
of endodontic pathogens. We have i<strong>de</strong>ntified different photosensitisers which can<br />
be activated with conventional light curing units used in <strong>de</strong>ntal offices. We work on biofilm<br />
mo<strong>de</strong>ls using plastic or glass surfaces, membranes or <strong>de</strong>ntin disks. Biofilm formation and<br />
growth are monitored by LIVE/DEAD fluorescence microscopy to simultaneously <strong>de</strong>tect intact<br />
cells and <strong>de</strong>ad/injured ones. The expression virulence genes after treatment is also evaluated<br />
by PCR.<br />
In addition our group has routinely used cytotoxicity assays to evaluate the short or long term<br />
biological response of cultured cells (host cells) exposed to various disinfecting agents and<br />
endodontic biomaterials. We are assessing inflammatory reactions and oxidative stress induced<br />
by blue light-activated photosensitisers and the likelihood of lethal damage to resi<strong>de</strong>nt cells<br />
resulting from such stress.<br />
68 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Pileggi G, Wataha JC, Girard M, Grad I, Schrenzel J, LangeN, Bouillaguet S (2012) Blue lightmediated<br />
inactivation of Enterococcus faecalis in vitro. PhotoDiag PhotoTherapy (in press)<br />
Grad I, Hibaoui Y, Jaconi M, Chicha L, Bergström-Tengzelius R, Sailani MR, Pelte MF, Dahoun S,<br />
Mitsiadis TA, Töhönen V, Bouillaguet S, Antonarakis SE, Kere J, Zucchelli M, Hovatta O, Feki<br />
A (2011) NANOG priming before full reprogramming may generate germ cell tumours. Eur<br />
Cell Mater; 22:258-74<br />
Brackett MG, Messer RL, Lockwood PE, Bryan TE, Lewis JB, Bouillaguet S, Wataha JC (2010)<br />
Cytotoxic response of three cell lines exposed in vitro to <strong>de</strong>ntal endodontic sealers. J Biomed<br />
Mater Res B Appl Biomater. 95:380-6.<br />
Bouillaguet S, Wataha JC, Zapata O, Campo M, Lange N, Schrenzel J (2010) Production of reactive<br />
oxygen species from photosensitizers activated with visible light sources available in <strong>de</strong>ntal<br />
offices. Photomed Laser Surg. 28:519-25.<br />
Bronnec F, Bouillaguet S, Machtou P (2010) Ex vivo assessment of irrigant penetration and<br />
renewal during the final irrigation regimen. Int Endod J. 43:663-72.<br />
Bronnec F, Bouillaguet S, Machtou P (2010) Ex vivo assessment of irrigant penetration and<br />
renewal during the cleaning and shaping of root canals: a digital subtraction radiographic<br />
study. Int Endod J. 43:275-82.<br />
Bouillaguet S, Owen B, Wataha JC, Campo MA, Lange N, Schrenzel J (2008) Intracellular reactive<br />
oxygen species in monocytes generated by photosensitive chromophores activated with<br />
blue light. Dent Mater. 24:1070-6.<br />
Contact: Serge.Bouillaguet@unige.ch<br />
Dental Bacteriology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
69
Dental Bacteriology<br />
Andrea Mombelli<br />
Division of Periodontology and Oral Pathophysiology<br />
Andrea Mombelli graduated from the University of Bern School of Dental Medicine and<br />
completed his post-graduate studies reaching the status of Privat-Docent in 1992. He has a<br />
Swiss Fe<strong>de</strong>ral Diploma in Dentistry, a Doctorate in Dentistry (Dr. med. <strong>de</strong>nt.) and is a Swiss FMHcertified<br />
periodontist. Before being appointed as Professor and Head of the Division of Oral<br />
Physiopathology and Periodontology, School of Dental Medicine of the Medical Faculty, he held<br />
the position of Head of the Laboratory for Oral Microbiology at the University of Bern School<br />
of Dental Medicine (1992-1999). Andrea Mombelli was associate Vice-Dean from 2005 to 2011.<br />
Antibiotic therapy as adjunct to periodontal treatment: effect of different timing on<br />
clinical, microbiological and systemic response<br />
A beneficial effect of adjunctive systemic antibiotics on the clinical outcome of periodontal<br />
therapy has been shown, but many questions remain with regard to their optimal use and the<br />
specific relationship of benefit and risk. In the context of this large RCT we study changes in<br />
the oral microbiota related to variation in the treatment protocol. Analyses focus on resistance<br />
<strong>de</strong>velopment and diagnostic and prognostic utility of microbiological parameters.<br />
70 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Mombelli, A., Cionca, N., Almaghlouth, A., Décaillet, F., Courvoisier, D.S. & Giannopoulou, C.<br />
(2012) Are there specific benefits of amoxicillin-metronidazole in Aggregatibacter<br />
actinomycetemcomitans-associated periodontitis? Double blind, randomized clinical trial<br />
of efficacy and safety. J. Periodontol DOI: 10.1902/jop.2012.120281<br />
Cionca N, Giannopoulou C, Ugolotti G & Mombelli A (2010) Microbiologic testing and outcomes<br />
of full-mouth scaling and root planing with or without Amoxicillin/Metronidazole in<br />
chronic periodontitis. J. Periodontol. 81: 15-23<br />
Mombelli A & Décaillet F (2011) The characteristics of biofilms in peri-implant disease. J. Clin.<br />
Periodontol. 38: 203-213<br />
Mombelli A, Cionca N & Almaglouth A (2011) Does adjunctive antimicrobial therapy reduce the<br />
perceived need for periodontal surgery? Periodontology 2000 55: 205-216<br />
Cappuyns I, Cionca N, Wick P, Giannopoulou C & Mombelli A (2012) Treatment of residual<br />
pockets with photodynamic therapy, dio<strong>de</strong> laser or <strong>de</strong>ep scaling. A randomized, split-mouth<br />
controlled clinical trial. Lasers Med. Sci. DOI: 10.1007/s10103-011-1027-6.<br />
Contact: Andrea.Mombelli@unige.ch<br />
Dental Bacteriology<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
71
Hygiene and Infection control<br />
Didier Pittet<br />
Infection Control Programme, HUG<br />
Didier Pittet obtained his medical <strong>de</strong>gree in 1983 on “Inositol phosphates and cellular<br />
activation” from the University of Geneva Faculty of Medicine, and is specialised in infectious<br />
diseases, hospital epi<strong>de</strong>miology and public health. In 1992 he became Head of the Infection<br />
Control and Prevention Programme at the HUG and Faculty of Medicine. In 2008, the<br />
Programme was <strong>de</strong>signated a WHO Collaborating Centre on Patient Safety. He was appointed<br />
Associate Professor at the Faculty of Medicine in 2000 and promoted to full Professor in 2010.<br />
He has received several <strong>de</strong>grees and awards for his work as External Lead of the WHO First<br />
Global Patient Safety Challenge “Clean Care Is Safer Care” initiative and is an international<br />
expert for the WHO.<br />
Prevention and control of healthcare-associated infection and antimicrobial<br />
resistance: local, national, and global perspectives<br />
MRSA and multidrug resistance. We are conducting various cohort studies to evaluate the value<br />
of screening and <strong>de</strong>colonisation to <strong>de</strong>crease MRSA transmission, including several<br />
epi<strong>de</strong>miological studies to address the emerging threat of community MRSA.<br />
Innovative strategies in infection control and prevention. Our group is <strong>de</strong>veloping and testing<br />
innovative multidisciplinary and multifaceted approaches to prevent or contain healthcareassociated<br />
infection, including microbiological aspects of transmission.<br />
“Clean Care is Safer Care”. As a WHO Collaborating Centre on Patient Safety and in association<br />
with WHO Patient Safety, we focus on the evaluation of the bur<strong>de</strong>n of healthcare-associated<br />
infection with the aim of i<strong>de</strong>ntifying and implementing the most feasible and effective<br />
solutions/measures for prevention worldwi<strong>de</strong>. The strategy is currently endorsed by two-thirds<br />
of the United Nations’ Member States.<br />
Infections in orthopaedic surgery and traumatology. Our research seeks to i<strong>de</strong>ntify novel<br />
strategies for the diagnosis, prevention and treatment of osteoarticular infections.<br />
Determinants and prevention of healthcare-associated infections in adult and paediatric<br />
critical care. We are investigating risk factors associated with <strong>de</strong>vice-associated infections in<br />
or<strong>de</strong>r to i<strong>de</strong>ntify novel prevention strategies.<br />
Epi<strong>de</strong>miology of noma in Niger. Our research focuses on the risk factors for noma and<br />
compares oral bacterial diversity of children with noma and controls from the same region.<br />
Prevention strategies will be tested following results of the current research.<br />
72 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Longtin Y, Sax H, Allegranzi B, Schnei<strong>de</strong>r F, Pittet D (2011) Vi<strong>de</strong>os in clinical medicine: hand<br />
hygiene. New Engl JMed 364:e24.<br />
Harbarth S, Fankauser C, Schrenzel J, Christenson J, Gervaz P, Bandiera-Clerc C, Renzi G, Vernaz<br />
N, Sax H, Pittet D (2008) Universal screening for methicillin-resistant Staphylococcus aureus<br />
at hospital admission and nosocomial infection in surgical patients. JAMA 299:1149-1157.<br />
Pittet D, Donaldson L (2005) Clean Care is Safer Care: a worldwi<strong>de</strong> priority. Lancet 366:1246-<br />
1247.<br />
Pittet D, Hugonnet S, Harbarth S, Mourouga P, Sauvan V, Touveaneau S, Perneger TV (2000)<br />
Effectiveness of a hospital-wi<strong>de</strong> programme to improve compliance with hand hygiene.<br />
Lancet 356:1307-1312.<br />
Eggimann P, Harbarth S, Constantin M-N, Touveneau S, Chevrolet JC, Pittet D (2000) Impact of<br />
a prevention strategy targeted at vascular-access care on inci<strong>de</strong>nce of infections in intensive<br />
care. Lancet 355:1864-1868.<br />
Contact: Didier.Pittet@hcuge.ch<br />
Hygiene and Infection control<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
73
Hygiene and Infection control<br />
Stephan Harbarth<br />
Infection Control Programme, HUG<br />
Stephan Harbarth earned his medical <strong>de</strong>gree from Ludwig-Maximilians-University in Munich<br />
in 1993, Germany, and completed his resi<strong>de</strong>ncy in internal medicine and tropical medicine at<br />
Munich University Hospitals. After serving as a Clinical Fellow in the Infectious Diseases<br />
Division and Infection Control Programme in the Department of Internal Medicine at Geneva<br />
University Hospitals, Dr Harbarth completed his Master <strong>de</strong>gree in epi<strong>de</strong>miology at Harvard<br />
University. He is board-certified (FMH) in infectious diseases and was appointed Associate<br />
Professor in 2010. Dr Harbarth’s work has garnered several awards, including the ICAAC Young<br />
Investigator Award from ASM (2003), the Young Investigator Award from ESCMID (2006), the<br />
Swiss Society for Infectious Diseases Award for epi<strong>de</strong>miological research (2008), and the SHEA<br />
Investigator Award in 2011.<br />
Control of MRSA and multidrug-resistance<br />
Over the last two <strong>de</strong>ca<strong>de</strong>s many institutions around the globe have experienced hyperen<strong>de</strong>mic<br />
multidrug-resistant microorganisms such as MRSA and ESBL-producing enterobacteriacae. Our<br />
group is currently conducting several clinical and epi<strong>de</strong>miological studies to evaluate key<br />
questions related to the control of acquisition, transmission and infection by multidrugresistant<br />
microorganisms. We participate in several large-scale European studies (MOSAR,<br />
SATURN, R-GNOSIS, Rapp-ID, AIDA) to address this important public health threat. We<br />
collaborate closely with the Genomics <strong>Research</strong> Laboratory at HUG, based on a productive<br />
translational research platform. The most notable examples of our research are the evaluation<br />
of a rapid molecular MRSA test evaluated in a large interventional cohort study (JAMA 2008),<br />
the advanced statistical analysis of epi<strong>de</strong>miologic trends in multiresistant microorganisms (JAC<br />
2008 and JAC 2011), the conduct of epi<strong>de</strong>miologic studies linking patient data with molecular<br />
investigations (J Clin Microbiol 2011; Clin Infect Dis 2011), the evaluation of antibiotic<br />
stewardship interventions (Lancet Infect Dis 2010, JAC 2011) and several currently ongoing<br />
placebo-controlled, randomised clinical trials to <strong>de</strong>colonise MRSA and ESBL carriers.<br />
74 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Chahwakilian P, Huttner B, Schlemmer B, Harbarth S (2011) Impact of the French campaign to<br />
reduce inappropriate ambulatory antibiotic use on the prescription and consultation rates<br />
for respiratory tract infections. J Antimicrob Chemother 66: 2872-9.<br />
Lee AS, Macedo M, François P, Renzi G, Schrenzel J, Vernaz N, Pittet D, Harbarth S (2011) Impact<br />
of Combined Low-Level Mupirocin and Chlorhexidine Resistance on Persistent MRSA<br />
Carriage after Decolonization Therapy: A Case-Control Study. Clin Infect Dis 52: 1422–1430.<br />
De Angelis G, François P, Lee A, Schrenzel J, Renzi G, Girard M, Pittet D, Harbarth S (2011)<br />
Molecular and Epi<strong>de</strong>miological Evaluation of Strain Replacement in Patients Previously<br />
Harboring Gentamicin-Resistant MRSA. J Clin Micro 49: 3880-84.<br />
Longtin Y, Sudre S, François P, Schrenzel J, Aramburu C, Pastore R, Gervaix A, Renzi G, Pittet D,<br />
Harbarth S (2009) Community-associated methicillin-resistant Staphylococcus aureus: Risk<br />
factors for infection and long-term follow-up. Clin Microbiol Infect 15: 552–559.<br />
Harbarth S, Fankhauser C, Schrenzel J, Christenson J, Gervaz P, Bandiera-Clerc C, Renzi G, Vernaz<br />
N, Sax H, Pittet D (2008) Universal screening for methicillin-resistant Staphylococcus aureus<br />
at hospital admission and nosocomial infection in surgical patients. JAMA 299: 1149-1157.<br />
Albrich WC, Harbarth S (2008) Healthcare personnel: Source, vector or victim of MRSA? LANCET<br />
Infectious Diseases 8: 289-311.<br />
Contact: Stephan.Harbarth@hcuge.ch<br />
Hygiene and Infection control<br />
Proportion of consultations at office-based doctors for a specific diagnosis resulting<br />
in antibiotic prescriptions in France, 1984-2009.<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
75
Hygiene and Infection control<br />
Bene<strong>de</strong>tta Allegranzi<br />
Infection Control Programme, HUG<br />
WHO “Clean Care is Safer Care” Programme<br />
Bene<strong>de</strong>tta Allegranzi obtained her medical <strong>de</strong>gree in 1994 in Verona, Italy, and her postgraduate<br />
<strong>de</strong>gree in infectious diseases and tropical medicine in 1998. She came to Geneva in<br />
2005 as a Consultant at the World Health Organization. She is currently Team Lea<strong>de</strong>r of the<br />
“Clean Care is Safer Care” programme at WHO HQ/PSP/IER. Dr Allegranzi spent the first twelve<br />
years of her career working as a general practioner and then became Assistant Professor in<br />
infectious diseases at the University of Verona, Italy, focusing on HIV, TB, treatment of critically<br />
ill patients, infection control and tropical medicine.<br />
A worldwi<strong>de</strong> perspective on infection control - prioritising settings with limited<br />
resources<br />
Prevention of healthcare-associated infection (HAI), the most frequent adverse event during<br />
health-care <strong>de</strong>livery affecting hundreds of millions of patients around the world, is the target<br />
of the Patient Safety Program “Clean Care is Safer Care”, launched by WHO in October 2005.<br />
Dr Allegranzi’s research activities, conducted in the context of the programme, have focused<br />
on hand hygiene, epi<strong>de</strong>miology of HAI worldwi<strong>de</strong>, and HAI surveillance and infection control<br />
implementation in <strong>de</strong>veloping countries. In particular, through her work Dr Allegranzi has<br />
highlighted the bur<strong>de</strong>n of HAI in low-resource settings and has studied interventions to reduce<br />
it. She leads a global campaign on hand hygiene, which currently inclu<strong>de</strong>s more than 15 000<br />
healthcare settings worldwi<strong>de</strong> and a network of 48 national campaigns.<br />
76 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
Allegranzi B, Bagheri Nejad S, Combescure C, Graafmans W, Attar H, Donaldson L, Pittet D (2011)<br />
Bur<strong>de</strong>n of en<strong>de</strong>mic healthcare-associated infection in <strong>de</strong>veloping countries: a systematic<br />
review and meta-analysis. The Lancet 377:228-41.<br />
Longtin Y, Sax H, Allegranzi B, Schnei<strong>de</strong>r F, Pittet D (2011) Hand Hygiene. Vi<strong>de</strong>o in Clinical<br />
Medicine. N Engl J Med 31;364.<br />
Allegranzi B, Sax H, Bengaly L, Richet H, Minta DK, Chraiti MN, Sokona FM, Gayet-Ageron A,<br />
Bonnabry P, Pittet D (2010) World Health Organization "Point G" Project Management<br />
Committee. Successful implementation of the world health organization hand hygiene<br />
improvement strategy in a referral hospital in Mali, Africa. Infect Control Hosp Epi<strong>de</strong>miol<br />
31:133-41.<br />
Pittet D, Allegranzi B (2008) Preventing infections acquired during health-care <strong>de</strong>livery. Lancet<br />
372:1719-20.<br />
Pittet D, Allegranzi B, Sax H, Dharan S, Pessoa-Silva CL, Donaldon L, Boyce JM (2006) WHO Global<br />
Patient Safety Challenge, World Alliance for Patient Safety. Evi<strong>de</strong>nce-based mo<strong>de</strong>l for hand<br />
transmission during patient care and the role of improved practices. Lancet Infect Dis 6:641-52.<br />
Contact: Bene<strong>de</strong>tta.Allegranzi@hcuge.ch , allegranzib@who.int<br />
Hygiene and Infection control<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine<br />
77
Faculté <strong>de</strong> Mé<strong>de</strong>cine<br />
<strong>Université</strong> <strong>de</strong> <strong>Genève</strong><br />
1, rue Michel Servet<br />
1211 <strong>Genève</strong> 4<br />
Faculty<br />
www.unige.ch/me<strong>de</strong>cine<br />
Center of Excellence in Bacteriology (CEBUG)<br />
www.cebug.ch<br />
Maladies infectieuses (HUG)<br />
maladiesinfectieuses.hug-ge.ch<br />
Institute of Genetics and Genomics of Geneva, iGE3<br />
www.ige3.unige.ch<br />
Centre for Clinical <strong>Research</strong><br />
crc.hug-ge.ch<br />
Genomic <strong>Research</strong> Laboratory<br />
www.genomic.ch<br />
Core Facilities<br />
www.unige.ch/me<strong>de</strong>cine/RECHERCHE/corefacilities_en.html<br />
For citation of information within this booklet,<br />
please contact the corresponding group lea<strong>de</strong>r,<br />
or Patrick Lin<strong>de</strong>r<br />
Thanks to all the contributors - including Cristiana Juge and Stéphane Couty<br />
Project Manager: Patrick Lin<strong>de</strong>r<br />
Graphic Design: René Aeberhard<br />
Editing: Liz Hopkins<br />
Coordination: Nicole Dana-Classen<br />
Geneva, September 2012<br />
78 <strong>Université</strong> <strong>de</strong> <strong>Genève</strong> • Faculté <strong>de</strong> mé<strong>de</strong>cine