PRINCIPLE INVESTIGATOR

Prof. Dr. med. Sascha David

 

EXPERIMENTAL STAFF

  • Yvonne Nicolai (RA)

Lab manager that supervises all experiments and teaches students

  • Temitayo O Idowu (Msc)

PhD student (Mechanisms of Tie2 cleavage) – experiments ongoing

  • Valerie Etzrodt (cand. med.)

Struc Med thesis (Role of MIR155 in endothelial permeability) – experiments ongoing

  • Philipp Gronski (cand. med.)

Doctoral thesis (Endothelial pericyte interaction) – experiments ongoing

  • Thorben Pape (cand. med.)

Struc Med Thesis (Pharmaceutical off-target effects on Ang-2) – experiments ongoing

  • Janine Hauschild

Doctoral thesis (Dual Ang2 VEGF inhibition in murine sepsis) – manuscript published

  • Eva Hachmeister (cand. med.)

Doctoral thesis (Role of statins on Ang2 (ARDSnet trial)) – thesis writing

  • Hannah Knaup (cand. med.)

Doctoral thesis (Plasmaexchange in sepsis) – reviews completed / summa cum laude

  • Jennifer Retzlaff

Struc Med Thesis (Flunarizine - Ang2) – reviews completes / summa cum laude

  • Ramin Rokhzan

Struc Med thesis / Biomedical Exchange Program (Boston, Harvard Medical School) - 

reviews completes / summa cum laude

Alumni

Dr. rer nat. Kristina Thamm PhD      – summa cum laude

Dr. med. Thomas Stiehl                     – summa cum laude

PD Dr. med. Alexander Lukasz          – summa cum laude

CLINICAL STAFF

  • Dilek Cansiz

Medizinische Dokumentationsassistentin – Spare14 ARDS/Sepsis Register (LOGO) Koordination und Datenmanagement

Debuty Principle Investigator – REPERFUSE, EXCHANGE, CytoreleaseEx

Principle Investigator - SPARE14

  • Dr. med. Julius J Schmidt (Nephrologie)

Investigator – EXCHANGE, SPARE14

  • Nina Rittgerodt (cand. med.)

Doctoral thesis (local prostaglandin infusion in NOMI) -  recruiting

  • Philipp Wand (cand. med.)

Doctoral thesis (plasmaexchange in sepsis, RCT) - recruiting

  • Robert Friedrich (cand. med.)

Student co-worker / Project: antikoagulation in VV-ECMO – manuscript in preparation

  • Jan Fuge MPH, Datamanagment (Pneumologie)

continuous generous IT and statistical support

 

EXPERIMENTAL LAB FOCUS

 

Our group is interested in molecular mechanisms regulating endothelial barrier function in response to inflammation. We have been focusing on the Angiopoietin (Angpt) / Tie ligand receptor system over the last ten years. Tie2 is a transmembrane receptor tyrosinekinase that is essential for embryonic vessel development. In mature organisms its function shifts toward maintenance of endothelial homeostasis and reaction to insults. Angpt-1 is the major circulating Tie2 agonist that promotes protective anti-permeability signals, whereas Angpt-2 has antagonistic properties. Our group was the first to proof in a murine knockout model that Angpt-2 directly contributes to sepsis morbidity and mortality.

 

Based on this finding we have conducted a series of experiments exploring potential therapeutic strategies (antibody, siRNA etc.) to eliminate or block the injuries Angpt-2 protein in sepsis models. We are also conducting drug repurposing screens to identify potential off-target Angpt-2 regulators (T. Pape).

Recently, we have gained much attention in the regulation of the Tie2 receptor expression per se and are currently working on the underlying mechanisms of posttranslational Tie2 modifications (T. Idowu).

MicroRNAs might be involved in Tie2 processing in disease as well so that we are studying the potential of MIRs in inflammatory diseases (V. Etzrodt).

We are also interested in the interaction between endothelial cells and pericytes – both with regard to Angiopoietin signaling and bioactive adrenomedullin (bioADM) (P. Gronski).

 

 

CLINICAL LAB FOCUS

 

The major interest of our clinical subgroup is focused on questions regarding medical critical care mostly in the context of sepsis and septic shock. We are currently conducting a randomized controlled trial together with the Uniklinik Bonn (Dr. Bode/Putensen) to analyse the role of plasmaexchange in early septic shock on hemodynamic stability (NCT04231994). Funding for a German multicenter RCT with a clinically meaningful endpoint is under review at the DFG (EXCHANGE trial). Dr. Stahl is the responsible researcher for this project.

 

In order to better understand sepsis and ARDS we are collecting human biosamples (BALF and serum) and clinical characteristics of sepsis +/- ARDS patients. This register (SPARE14) will help to directly translate experimental findings of our basic research group from bench to bedside. Dr. Seeliger is the responsible researcher for this project.

 

We are also conducting research on extracorporeal cytokine removal in patients treated with CAR-T cells suffering from severe cytokine release syndrome (CytoreleaseEx, NCT04048434). This project is financially supported by Cytosorbents.

 

We are currently running a prospective observational trial to analyze intra-arterial  prostaglandine infusion into the superior mesenteric artery in non-occlusive mesenteric ischemia (NOMI) patients. This project is conducted together with our Department of Interventional Radiology (Hinrichs).

SUPPORT

 

Our experiments are currently supported by the „Deutsche Forschungsgemeinschaft“ (DFG), the „Deutsche Lungenzentrum“ (DZL) and others.

 

COLLABORATIONS

  • Prof. Samir Parikh, MD, BIDMC and Harvard Medical School, Boston, MA, USA
  • Paul van Slyke, PhD, Vasomune Therapeutics, Toronto, Canada
  • PD Dr. med. Christian Bode, Operative Intensivmedizin, Uniklinik Bonn
  • Prof. Dr. med. Christian Könecke, MHH Hämatologie
  • Prof. Dr. rer. nat. Ulrich Maus PhD, MHH Experimentelle Pneumologie
  • PD Dr. med. Jan Hinrichs, MHH Radiologie
  • WHERE TO MEET US

    Members of our group are actively contributing to annual meeting of the following societies:

  • European Society of Intensive Care Medicine (ESICM)
  • Deutsche Gesellschaft für Internistische Intensiv- und Notfallmedizin (DGIIN)
  • Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI)
  • SepsisUpdate