Thursday, 27th October 2016
08.30 - 9.00 REGISTRATION
9.00 - 11.00 Industry Session
Please click this Link for further details about the Industry session.
11.00 – 11.30 Coffee break & Exhibition
Tackling inflammation across multiple diseases via Systems Medicine
Chairs: Walter Kolch, MD & Edda Klipp, PhD
Edda Klipp is full professor for Theoretical Biophysics at Humboldt-Universität zu Berlin since 2008. She has a doctoral degree in theoretical biophysics and held a position as research scientist at Humboldt-Universität following a postdoctoral period in Berlin. From 2001 to 2006, she was junior research group leader in “Kinetic modeling” before taking over the head of the research group “Computational Systems Biology” at Max-Planck Institute for Molecular Genetics until 2008. In 2009 she was awarded an honorary doctor of Göteborg University. 2015 she was awarded the Caroline-von-Humboldt professorship at Humboldt-Universität zu Berlin. Klipp carries out multi-disciplinary research projects to understand cellular organization, dynamics of cellular processes and stress response. Her group has long-standing experience in computational systems biology with focus on dynamic modeling of regulatory processes including signaling, cell cycle, metabolism, transcriptional regulation and growth control. Methods comprise dynamic modeling with ODE systems, dynamic systems theory, parameter estimation, sensitivity analysis, and SBML models as well as spatial modeling and discrete network modeling. There is long tradition in close interaction with experimental biologists and scientists of diverse fields. Prof. Klipp is a founding member of the International Society of Systems Biology, member of several scientific advisory boards for systems biology consortia and institutions and she is principal investigator in several European and national research consortia for systems biology. She organizes a graduate program in Computational Systems Biology in Berlin.
Professor Douglas James Veale
Centre for Arthritis and Rheumatic Disease, University College Dublin, Ireland
Douglas J. Veale is a Professor of Medicine, Director of Translational Research and The Centre for Arthritis and Rheumatic Diseases (CARD). He is a Consultant Rheumatologist at St Vincent’s University Hospital and Fellow/Principal Investigator at The Conway Institute for Biomedical and Biomolecular Research, University College Dublin (UCD).
He is a Fellow of The Royal College of Physicians in Ireland (1997) and The Royal College of Physicians, London (1999). Professor Veale graduated from the Royal College of Surgeons in Ireland in 1984 and obtained his MD by thesis from UCD in 1992.
Professor Veale has established an international reputation in translational research in the areas of Psoriatic Arthritis, biopharmaceutical therapy and biomarkers. He has established CARD in Dublin receiving a EULAR Centre of Excellence Award in 2014. CARD has received funding from The American Federation for Ageing Research, USA, The European Union FP6 programme and FP7 Innovative Medicines Initiative (IMI), The Health Research Board of Ireland, Science Foundation Ireland, the Programme for Research in Third Level Institutions, Ireland and several of academia-industry partnership programmes.
Rheumatoid arthritis – Can Systems Biology improve the diagnosis and treatment?
Douglas J Veale
Systems Biology Ireland, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, and Department of Rheumatology, Centre for Arthritis and Rheumatic Diseases, St Vincent's University Hospital, Dublin Academic Medical Centre, Dublin, Ireland.
Rheumatoid Arthritis (RA) is a progressive autoimmune disease characterised by synovial inflammation with damage to the adjacent articular cartilage and bone. New therapeutic strategies represent an significant advance in treatment over the last 15 years, however many patients do not respond, have sub-optimal responses or suffer adverse effects. Identification of biomarkers for early diagnosis and specific treatment may enable precision medicine for RA patients.
We have developed a systems biology approach to the study ofsubjects who are risk of developing RA, in addition to patients with established disease. Furthermore, we have examined Patients before and after current treatments who were categorised after followup into responders and nonresponders based on clinical disease outcome. mRNA was isolated from cells derived from peripheral blood, synovial fluid and synovial tissue for RNAseq. Reads were aligned to the UCSC hg19 genome assembly using the STAR aligner and differentially expressed genes were identified using the DeSeq2 R package. Ingenuity® Pathway Analysis (IPA) software was used to examine gene enrichment within differentially expressed genes. Interaction network analysis and identification of key hub nodes was performed using InnateDB and Cytoscape.
Initial analysis identified differential expression of 155 genes between responders vs non responders. IPA pathway and Gene Ontology analysis demonstrated these were associated with several relevant pathways e.g. antigen presentation, with top GO functions related to RA. Differential gene expression was associated with leukocyte trafficking and alterations in extracellular matrix components, which was further confirmed by additional IPA network analysis of the RA dataset, identifying a key Inflammatory response/cell movement network. Finally an interaction network analysis identifed candidates as key hub genes preferentially connected to the 155 differentially expressed genes.
Professor Dr. Ursula Klingmüller has completed her PhD at the age of 28 years from Heidelberg University, Germany and performed postdoctoral studies at Harvard Medical School in Boston and the Whitehead Institute for Biomedical Research in Cambridge, MA, USA. She is head of the division "Systems Biology of Signal Transduction" at the German Cancer Research Center (DKFZ) in Heidelberg, Germany and full professor at the University of Heidelberg. She has published more than 90 papers in reputed journals and has been serving as an editorial board member of many international journals.
Eleni Chouri is a PhD candidate in the Laboratory of Translational Immunology
at the University Medical Center of Utrecht in the research group of Professor
Timothy Radstake. The aim of her research is to identify epigenetic alterations in
Systemic sclerosis in order to unravel pathogenic pathways and possible
Jasper Koehorst is a PhD candidate at Wageningen University and Research in The Netherlands and working in the EU Systems medicine Infect project to understand severe soft tissue infections. He uses semantic web technologies for the integration of large scale ~omics dat sets with the aim to increase the molecular understanding of host pathogen interactions in necrotizing fasciitis and other necrotizing soft tissue infections.
13.30 – 14.30 Lunch & Exhibition
Clinical Implementation of Systems Medicine
Chairs: Damjana Rozman, PhD & Werner Müller, PhD
Prof. Dr. Natal van Riel (1973) is Associate Professor of Systems Biology and Metabolic Diseases at the Department of Biomedical Engineering of the Eindhoven University of Technology (TU/e) and Professor of Computational Modelling at the Academic Medical Center - University of Amsterdam (AMC - UvA). He was trained in system identification and control engineering at the Department of Electrical Engineering, TU/e (MSc degree in 1995). In 2000 he obtained a PhD degree in Molecular Cell Biology from Utrecht University (Prof. Verrips; Netherlands) for research on integrating computational modelling and experiments to study cell metabolism ( PhD thesis ). The research was carried out in the Biotechnology group of Unilever Research Vlaardingen. From 2000 to 2003 he worked in the Department of Electrical Engineering of TU/e investigating the application of system and control theory to understand biological processes. In 2003 he was appointed as Assistant Professor in the Department of Biomedical Engineering at the same university and initiated Systems Biology research in Eindhoven. This research was expanded when he joined the group of Prof. Hilbers in 2006 to lead the Computational Systems Biology research program, investigating complex, multi-factorial diseases. In 2014 he was appointed as Associate Professor. In 2014 he was a visiting scholar of the Department of Bioengineering at the University of California San Diego (UCSD) in the group of Prof. Palsson. His current research focuses on metabolic network modelling, methods for model parametrization and analysis of dynamic models, and applications in Metabolic Syndrome and associated diseases such as Type 2 Diabetes.
A systems approach of bile acid metabolism to explain effects of bariatric surgery in Metabolic Syndrome (RESOLVE Diabetes)
by Prof. Dr. Natal Van Riel, Eindhoven University of Technology, The Netherlands
Metabolic Syndrome (MetSyn) is characterized by obesity in combination with several metabolic derangements. MetSyn is a risk factor for cardiovascular diseases, non-alcoholic fatty liver disease and type 2 diabetes. The Systems Medicine project RESOLVE studies the molecular pathology of two hallmarks of MetSyn: hypertriglyceridemia and low HDL-cholesterol.
Bariatric surgery is currently the most effective treatment of morbid obesity, but also of the co-morbidities associated with MetSyn. The metabolic benefits of bariatric surgery reach further than the long term reduction in body weight by reduced food intake. In Roux-en-Y gastric bypass the rewiring of the intestinal track impacts digestion, absorption and metabolism. Through combining basic pre-clinical and clinical research, network analysis and computational modelling, we try to unravel the underlying dynamics and mechanisms. Changes in gut hormone dynamics, microbiota composition and bile acids composition and dynamics have been observed. Here we report on the role of bile acids as contributors to the health benefits associated with metabolic surgery.
Frank Lammert is Professor of Internal Medicine and Head of the Department of Medicine at Saarland University Hospital Homburg, Germany. Between 2002 and 2007 he was Associate Professor of Gastroenterology and Assistant Professor for Molecular and Clinical Hepatology at the University of Bonn and Aachen University (RWTH), respectively.
Prof. Lammert studied medicine and economics at the Universities of Düsseldorf, Hagen and Aachen supported by a scholarship of the German National Academic Foundation and obtained his PhD summa cum laude at Aachen University in 1995.
Frank Lammert held a number of academic faculty appointments, including Research Fellow at Harvard Medical School, Department of Medicine, Boston, where he worked in the laboratory of Prof. Martin C. Carey, funded by the German Research Foundation (DFG). Frank Lammert has served as member of the Governing Board of the German Association for the Study of the Liver (GASL), the German Gastroenterological Association (DGVS), the European Association for the Study of the Liver (EASL) and Associate Editor of the Journal of Hepatology.
His research interest include the genetics of complex liver diseases, hepatic fibrogenesis and hepatobiliary transport. Prof. Lammert received the Theodor Frerichs Award of the German Society for Internal Medicine in 2002 and the Siegfried Thannhauser Award of the German Gastroenterological Association in 2005.
Systems genetics of liver disease: from pathophysiology to clinical practice
Frank Lammert, Department of Medicine II, Saarland University, Homburg, Germany
During the past decades we have witnessed huge advances in our understanding of liver disease and physiology, and genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990s, developments in genomic technologies drove the identification of genes responsible for monogenic liver diseases. Recently genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders. Systems genetics analysis comprises quantitative measurements of hepatic phenotypes and mapping of quantitative traits in experimental crosses from inbred mouse strains and genetic reference populations. Extensive quantitative trait loci (QTL) mapping of liver phenotypes and expression profiling allows the identification of QTL genes that confer disease susceptibility also in humans. Moreover, the approach led to the identification of interacting QTL and gene networks in liver disease. Here we provide use cases for the integration of multiple datasets determined in BXD recombinant inbred lines to identify fibrosis susceptibility loci. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data.
Adapted from Karlsen TH, Lammert F*, Thompson RJ. J Hepatol 2015;62:S6-S14
Prof. Dr. Timothy R.D.J. Radstake, MD, Ph.D.
Director Utrecht Infection and Immunity FOCIS center of excellence.
Department of Rheumatology & Clinical Immunology
Laboratory of Translational Immunology
University Medical Center Utrecht
Heidelberglaan 100, 3485 CX Utrecht
Professor Radstake MD, Ph.D. attended medical school at the Radboud University in Nijmegen the Netherlands where he graduated in 2000. He next performed his PhD on the genetic factors that determine the susceptibility to Rheumatoid arthritis and the role of dendritic cells in this conditions that he finished in 2003 under the supervision of Professors van Riel and van den Berg.
Soon after that he started his own research line on translational rheumatology with the ultimate aim to translate clinical problems to novel therapeutic targets. Although starting his research in rheumatoid arthritis, over the years his group investigated a broader spectrum of rheumatic conditions including psoriatic arthritis and systemic sclerosis. From 2007–2008 prof. Radstake did a post-doctoral fellowship on the department of rheumatology at the Boston University School of Medicine (prof. R. Lafyatis) where he held a chair until 2014.
From March 2012 he holds the chair on translational immunology at the university medical Center Utrecht were his research team, comprising roughly 40 fte, focuses on a systems medicine approach with the ultimate goal to achieve personalized health care on the basis of molecular taxonomy rather that clinical diagnosis. A side to his clinical work and role as director of the Utrecht Infection & Immunity FOCIS center of excellence, he is current involved as a entrepreneur in multiple projects to bring potential therapeutic targets to the market, anti-CXCL4 as a novel therapeutic entry-point for scleroderma being the most progressed.
Audia S, et al. & Radstake TRDJ. Splenic TFH expansion participates in B cell differentiation and antiplatelet antibody production via CD40L and IL-21 during adult immune thrombocytopenia. Blood 2014.
L. van Bon, et al & Radstake TRDJ.Proteome-wide analysis identifies the chemokine CXCL4 as a clinical marker that drives critical pathological events in systemic sclerosis. New England Journal of Medicine 2014 Jan 30;370(5):433-43.
Radstake TRDJ et al. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nature Genetics 2010; May;42(5):426-9.
Anna Norrby-Teglund is Professor in medical microbial pathogenesis at Karolinska Institutet, Stockholm, Sweden. Her research focuses on host-pathogen interactions in severe acute infections, including sepsis, pneumonia and necrotizing soft tissue infections. She is coordinator of the FP7 INFECT-project.
Prof Markus Rehm is Director of the Institute of Cell Biology and Immunology within the faculty of Energy-, Process- and Biotechnology of the University of Stuttgart, one of the leading technical universities in Germany.
Prof Rehm also holds a visiting professorship at the Royal College of Surgeons in Ireland, where he previously was appointed as a research lecturer in the Department of Physiology and Medical Physics and where he served as member of the Executive Council of the RCSI Centre for Systems Medicine.
Prof Rehm is also the Coordinator of the MEL-PLEX Programme which aims to train researchers who can navigate confidently between clinical, academic and private sector research environments, and who have developed an innovative and creative mind-set to progress research findings towards applications.
His research team in Cell Biology and Experimental Systems Biology covers expertise in Biochemistry, Biophysics, Molecular Imaging, and Computational Modelling. His group develops and utilizes innovative experimental and mathematical approaches to monitor key processes controlling cell suicide and proliferation signaling. In combination with complex systems analyses this strategy provides functional insight into the intricate control of cell fate decisions between death and survival.
Specialties: Cell Biology, Biophotonics and Imaging, Systems Biology, Systems Medicine, Cell Death and Survival Signalling.
All members of EASyM are invited to take part in the General Assembly
0. Appointment of Chair and Secretary of the General Assembly,
Ascertainment that General Assembly is quorate
1. The annual report of the Executive Board
2. The financial report, including the statement of accounts
3. Exoneration of the Executive Board
4. Appointment of two financial auditors
5. Amendment of Internal Regulations article Article 18 (Duties of Support Staff)
6. EASyM future plans