CAG Center for Endotheliomics

About us

Center for Endotheliomics

The Center for Endotheliomics’ ambition is that research in Eastern Denmark lead to breakthroughs in the treatment of critically ill patients in need of intensive care patient who enter hospitals with either trauma, cardiac arrest or severe sepsis. For this patient group, survival is counted in hours, and up to half of the patients die within 72 hours – often as a result of organ failure.

Organ failure – or multi-organ failure – is when the organs stop functioning, which happens to the most critically ill patients in intensive care. However, whether the patient develops organ failure is largely determined by the endothelium, which is the cell layer that lines the inside of all blood vessels. How the individual patient’s endothelium reacts to shock, trauma, sepsis or cardiac arrest determines how severe organ failure the patient will develop – and thus the patient’s risk of death.

Mathematical model reconstructs the cell’s metabolism

The CAG brings together clinical experts in trauma, sepsis and cardiac arrest with experts in systems biology, biotechnology and bioinformatics. Together we will generate new knowledge about critical illness and multi-organ failure.

We have developed a method based on mathematical computer models that reconstructs the metabolism of the endothelial cell and thus its function (phenotype).

These models use metabolites in the patient’s blood plasma as well as genetic variations in the patient’s DNA to predict the condition of the endothelial cell. In this way, we can better understand how the individual patient’s endothelial cells respond to acute critical illness with shock.

The aim of the CAG is to exploit the new knowledge about the importance of endothelial cells for multi-organ failure and with mathematical modeling and systems biology understand the difference between the endothelial response in acute critical illness in surviving patients and in those who die. When we succeed, we can intervene and adjust the endothelium in time before the patient develops organ failure.

Center for Endotheliomics
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Research

Center for Endotheliomics introduces a novel research field focusing on the microvascular endothelium at the systemic level and that the individual patient’s cellular response (ENDOTYPES) to critical illness is pre-determined and differ between patients also with the same disease explaining the observed differences in outcome.

Center for Endotheliomics aim to improve our understanding of how the patients ENDOTYPE 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.

Center for Endotheliomics introduces 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 ENDOTYPE, 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

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.

COMBAT-COVID

COMBAT-COVID is a randomized, double-blind, clinical trial investigating the effect of continuous infusion of prostacyclin (1 ng/kg/min) vs. placebo (saline) in 80 patients with COVID-19 in mechanical ventilation. The primary endpoint is number of ventilator free days within 28 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.

Patient recruiting completed.

COMBAT-COVID is funded by Innovation Fund Denmark.

Hillerød Metabolomics

Hanne Hee Henriksen in the laboratory - Shine traumaHillerød 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.

Patient recruiting completed.

Collaborators

CAG Center for Endotheliomics has collaborators nationally and around the world.

National collaborators

 

COMBAT-SHINE

  • Niels Erikstrup Clausen, EDIC, Department of Anaesthesiology, Bispebjerg Hospital
  • Peter Søe-Jensen, MD, PhD, EDIC, Department of Intensive Care, Herlev Hospital
  • Klaus Tjelle Kristiansen, MD, Department of Intensive Care, Hvidovre Hospital

SHINE-TRAUMA – Danish Trauma Consortium (DANTRAK)

  • Prof. Hagen Schmal, Department of Orthopeadic Surgery, Odense University Hospital
  • Pernille Bovbjerg, MD, Department of Orthopeadic Surgery, Odense University Hospital
  • Malene Pall, MD, Department of Anaesthesiology and 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
Our team

CAG chairmanship

  • Pär Ingemar Johansson Professor, senior consultant, Department of Clinical Immunology, Rigshospitalet The Capital Region of Copenhagen

    CAG chairman, Center for Endotheliomics

  • Bernard O. Palsson Professor, CEO, Novo Nordisk Foundation Center for Biosustainability Technical University of Copenhagen

    CAG vice chairman, Center for Endotheliomics

CAG key-members

  • Lars K. Nielsen Professor, CSO, Novo Nordisk Foundation Center for Sustainability Technical University of Copenhagen
  • Christian Igel Professor, dr. habil., Department of Computer Science, Faculty of Science University of Copenhagen
  • Karina Banasik Associate professor, Novo Nordisk Foundation Center for Protein Research, The Faculty of Health and Medical Sciences University of Copenhagen
  • Anders Perner Professor, senior consultant, Intensive Care, Rigshospitalet The Capital Region of Denmark
  • Christian Hassager Professor, senior consultant, Department of Cardiology, rigshospitalet The Capital Region of Copenhagen
  • Ole Birger Pedersen Associate professor, senior consultant, Department of Clinical Immunology, Næstved Hospital Region Zealand
  • Morten Bestle Associate professor, senior consultant, Intensive Care, Nordsjaellands Hospital, Hilleroed The Capital Region of Denmark
  • Jesper Kjærgaard Senior consultant, Department of Cardiology, Rigshospitalet The Capital Region of Denmark
  • Jakob Stensballe Senior consultant, Trauma Anaesthesia, Rigshospitalet The Capital Region of Denmark
  • Lone M. Poulsen Senior consultant, Intensive Care, Zealand University Hospital, Køge Region Zealand

CAG Staff Members

Science

Funding and strategy

Research infrastructure

Laboratory Technologists

Clinical trials

Contact

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