CAG Center for Endotheliomics
The CAG Center for Endotheliomics (ENDO-MODS CAG) focusses on the endothelium’s function and role in acute critical illness and seeks to lower mortality rates among patients with multi-organ failure. Multi-organ failure in critically ill patients follows shock caused by trauma, blood poisoning or resuscitation after cardiac arrest. Multi-organ failure is caused by damage to the endothelium with failing blood flow and thus failing oxygen supply to vital organs.
In Europe, more than 1 million critically ill patients die of multi-organ failure each year, and in Denmark alone more than 7,500 out of 31,000 intensive-care patients die each year. Improved diagnosis and treatment of the most critically ill patients in Danish hospitals will have a significant positive effect on survival rates.
The CAG seeks to improve survival rates of critically ill patients via precision diagnostics and treatment of multi-organ failure by uncovering how the endothelium function of the individual patient can lead to multi-organ failure or, at worst, death.
The CAG brings clinical experts in trauma, blood poisoning and cardiac arrest treatment together with experts in systems biology, bioengineering and bioinformatics. Together they will – using omics technologies and mathematical modelling of the metabolism of the endothelial cell – provide new knowledge of its role in critical illness and multi-organ failure, identify diagnostic markers of the individual patient’s endothelial phenotype and thus open up new possibilities for targeted precision treatment.
The new knowledge will be based on both genome-scale metabolic models enabling mathematical modelling of the function of the endothelial cell in critical illness and bioinformatics analysis, which together will offer new knowledge and tools for use in clinical practice.
Training and Competency Development
The CAG Center for Endotheliomics draws on a series of medical specialties within acute critical illness and cooperates closely with systems biologists and bioinformaticians. Training and knowledge sharing will take the form of PhD courses for students at the PhD schools at the Technical University of Denmark and the University of Copenhagen as well as courses and seminars for clinicians and healthcare personnel within the involved specialties.
The ENDO-MODS CAG aim to improve our understanding of how the patients ENDOPHENOTYPE affects development of multiorgan dysfunction syndrome (MODS) when challenged with acute critical illness and to translate this novel knowledge in to improved diagnostic and therapeutic capabilities.
The ENDO-MODS CAG introduces a novel research field focusing on the microvascular endothelium at the systemic level and that the individual patient’s cellular response (ENDOPHENOTYPES) to critical illness is pre-determined and differ between patients also with the same disease explaining the observed differences in outcome.
The ENDO-MODS CAG introduce genome scale metabolic models as the scaffold for multi-omics data integration and computational modeling as tools to decipher the pathophysiology responsible for MODS development and progression clinically. Additionally, supervised machine learning algorithms will be applied to data from electronic patient records, Danish registries and clinical databases of these critically ill patients to characterize the clinical disease trajectories resulting from the individual patients ENDOPHENOTYPE, thereby, laying the foundation for novel patient stratifications and therapeutic interventions.
Our research projects
ENDO-OMICS
The ENDO-OMICS is a multicenter, prospective observational exploratory study in 1.000 patients admitted to the intensive care unit (ICU) 4131 at Rigshospitalet, Bispebjerg Hospital, Hvidovre Hospital, Køge Hospital and at the ICU at Nordsjællands Hospital.
Blood samples will be analyzed by genomic, transcriptomic, proteomic and metabolomic techniques with the overall aim to develop computational modeling of the endothelial cell to deepen the biological understanding/ paving the way for more precise diagnostics and new treatments.
ENDO-OMICS is currently recruiting.
COMBAT-SHINE
COMBAT-SHINE is a randomized, double-blind, clinical trial investigating the effect of continuous infusion of prostacyclin (1 ng/kg/min) vs. placebo (saline) for 72 hours in 384 patients with septic shock and SHINE (Shock induced Endotheliopathy), defined by a plasma concentration of soluble thrombomodulin (sTM) > 10 ng/ml.
The primary endpoint is mean daily SOFA score within 90 days of ICU admission.
The study is coordinated by the CAG Trial Unit in collaboration with the intensive care units at Rigshospitalet 4131, North Zealand Hospital, Bispebjerg Hospital, Hvidovre Hospital and Herlev Hospital together with Center for Health Economics and Policy (CHEP) at Copenhagen University. Primary investigator is Assoc. Prof. M. Bestle, ICU, North Zealand Hospital.
COMBAT-SHINE is currently recuiting.
COMBAT-SHINE is funded by Innovation Fund Denmark and Independent Research Fund Denmark
SHINE-TRAUMA
SHINE-TRAUMA is a randomized, double-blind, clinical trial investigating the effect of continuous infusion of prostacyclin (1 ng/kg/min) vs. placebo (saline) for 72 hours on number of ICU free days in 220 trauma patients with haemorrhagic shock.
The study is coordinated by the CAG Trial Unit at Rigshospitalet and clinical partners are the trauma centers at the Rigshospitalet and the University Hospitals in Odense, Århus and Oslo.
SHINE-TRAUMA is currently recruiting.
SHINE-TRAUMA is funded by Novo Nordisk Foundation and Danske Regioners Medicinpulje.
Hillerød Metabolomics
Hillerød Metabolomics is a prospective clinical study investigating metabolic changes in whole blood in patients with acute critical illness.
The purpose is to measure the concentrations of neurotransmitters (metabolites) in plasma from patients with acute critical illness and in healthy controls, and to use the results to provide a better understanding of the significance of these neurotransmitters for endothelial cell damage.
The partners are Intensive Care Unit (ITA), Hillerød Hospital and Rigshospitalet.
CAG Center for Endotheliomics has collaborators nationally and around the world.
National collaborators
COMBAT-SHINE
- Peter Søe-Jensen, MD, PhD, EDIC, Dept. of Intensive Care, Herlev Hospital
- Klaus Tjelle Kristiansen, MD, Dept. of Intensive Care, Hvidovre Hospital
SHINE-TRAUMA – Danish Trauma Consortium (DANTRAK)
- Prof. Hagen Schmal, Dept. of Orthopeadic Surgery, Odense University Hospital
- Pernille Bovbjerg, MD, Dept. of Orthopeadic Surgery, Odense University Hospital
- Malene Pall, MD, Dept. of Anaesthesiologyand Intensive Care V, Odense University Hospital
- Christian Fenger-Eriksen, MD, PhD, Department of Anaesthesiology, Aarhus University Hospital
- Christian Nielsen, MD, PhD, Department of Anaesthesiology, Aarhus University Hospital
- Prof. Hans Kirkegaard, MD, DMSc, PhD, Research Center for Emergency Medicine, Aarhus University
- Christina Gaarder, MD, PhD, Department of Traumatology, Oslo University Hospital, Norway
- Prof. Paul Naess, MD, PhD, Department of Traumatology, Oslo University Hospital, Norway
University of Copenhagen
- Theis Lange, Section of Biostatistics, University of Copenhagen
- Prof. Karsten Vrangbæk, Department of Political Science and Public Health, University of Copenhagen
International collaborators
TACTIC/INTRN
- Prof. Karim Brohi,Centre for Trauma Sciences, Queen Mary University of London, UK
- Prof. Simon Stanworth, Radcliff Department of Medicine, University of Oxford, UK
- Prof. Nicole Juffermans, Department of Intensive Care Medicine, Academic MedicalCenter, Amsterdam, The Netherlands
- Prof. Marc Maegele, Department of Traumatology and Orthopedic SurgeryCologne-Merheim Medical Center (CMMC), Germany
- Christina Gaarder, MD, PhD, Department of Traumatology, Oslo University Hospital, Norway
Center for Translational Injury Research (CeTIR)
- Prof. Charles E. Wade PhD, Department of Surgery, McGovern Medical School, UTHealth, Houston, USA
- Assistant Prof. Jessica C. Cardenas, Ph.D, Department of Surgery, McGovern Medical School, UTHealth, Houston, USA
Center for Systems Biology, Iceland University
- Prof. Ottar Rolfsson, MSc, PhD, Center for Systems Biology, University of Iceland, Iceland
- Adrian Lopez Garcia de Lomana, PhD, Center for Systems Biology, University of Iceland, Iceland
Harvard Medical School, Boston, USA
- Prof. Joseph Loscalzo, MD, PhD, MA, Head of Department of Medicine, Brigham and Women´s Hospital, Harvard Medical School, Boston, USA
- Sarah McGarrity, MSc, PhD, postdoc, Department of Medicine, Brigham and Women´s Hospital, Harvard Medical School, Boston, USA
CAG chairmanship
CAG key-members
CAG Staff Members
Science
-
Igor Marín de Mas PhD, Principle InvestigatorPI, development of quantitative modeling of endothelial cell metabolism, Technical University of Denmark
-
Hanne Hee Henriksen MD, PhD student
Investigating the influence of endo-phenotypes on trauma patient outcome.
-
Peter Bruun Rasmussen MSc, PhD student
Improving the compatibility match between blood donors and recipients though a data driven machine learning and systems biology approach.
Funding and strategy
Research infrastructure
Laboratory Technologists
-
Randa Zo el-Ghina B.Sc. Head of Clinical laboratory in Transfusion Medicine.
In our laboratory, bleeding patients are monitored by hemostasis analyzes and by blood components.
We are in close cooperation with ER and OP and we constantly try to implement research in the routine. -
Line Grønkjær Hansen B.Sc., Biomedical Laboratory Technologist
Responsibility for handling and adding samples into different Biobanks.
Perform and coordinate laboratory experiments, writing SOP and working according to GLP.
Conduct laboratory assays using different techniques such as: Elisa, Flowcytometry, TEG and Multiplate. -
Rola Zohair Ghadban B.Sc. Bioanalytiker
Responsible for handling biological samples for the biobank. Performs assay analyzes based on various techniques, such as ELISA, TEG and Multiplate.
Clinical trials
-
Kristine Holst Pedersen M.Sc. Pharm. Senior Clinical Trial Coordinator
Responsible for administrative project coordinator for clinical trials e.g. SHINE-TRAUMA and COMBAT-SHINE’. Advisor on GCP and regulatory issues.
-
Mikkel Gybel-Brask MD Staff specialist
Data quality assurance and patient inclusion in clinical trials.
-
-
Tanja Igland BScN, Research coordinator on the ENDO-OMICS clinical trial
If your inquiry concerns your symptoms, medical history and treatment, please contact your private doctor.
