Ongoing research projects
Mechanisms of organ protection in sepsis.
Collaboration with the Department of Anesthesiology, University of Illinois Chicago, Prof. Dr. D. Schwartz, and the Department of Pharmacology, University of Illinois Chicago, Prof. Dr. R. Minshall, Prof. Dr. A. Malik. Funding: University of Zurich, Switzerland, Transfer Office. Beck Schimmer PI. A main goal of this project is to evaluate the effect of volatile anaesthetics in sepsis. In a model of acute (intravenous application of endotoxin) and subacute sepsis (cecal ligation puncture) volatile anesthetics are applied as preconditioning or postconditiong procedure and organ inflammation as well as survival are determined in general and with a special focus on liver, lung and kidneys.
Immunomodulatory effects of trifluorinated small molecules: new therapeutic opportunities for ischemia-reperfusion injury.
Collaboration with the Department of Anesthesiology, University of Illinois Chicago, Prof. Dr. D. Schwartz, and the Department of Pharmacology. Funding: Swiss National Research Foundation. Grant Nr. 320030_141216. Beck Schimmer PI. Numerous studies have shown that volatile anaesthetics such as sevoflurane, isoflurane or desflurane can efficiently protect liver, lung, heart and brain from tissue damage caused by ischemia-reperfusion injury. Most of these studies performed so far have focused on the characterization of inflammatory mediators and tissue damage markers. Scarce information is available about the clinical relevance of these surrogate markers of protective effects and the translation into clinical outcomes. This research program has been designed to address this question at a preclinical level. In a parallel work stream, this program will explore the potential benefits of intravenously administering a soluble experimental compound delivering on one side the active component of volatile anaesthetics that is hypothesized to be responsible for the protective effects and on the other side lacks the sedating effects of anaesthetics.
Anaesthesia and cancer.
Funding: Swiss National Research Foundation. Grant Nr. SNSF grant 316030_150803. Beck Schimmer PI. General anaesthetics have an immunosuppressive effect. As a consequence they may impair intravascular tumour cell fight during cancer surgery, when cancer cells detach and reach blood vessels (circulating tumour cells). Interaction of tumour cells with natural killer (NK) cells will be assessed after exposure to different general anaesthetics and NK cell activity will be determined.
Removal of blood cells.
Department of Chemistry and Applied Biosciences; Institute for Chemical and Bioengineering; Functional Materials Laboratory, Prof. Dr. W. Stark. Funding: Helmut Horten Foundation. Beck Schimmer PI. Magnetic nanoparticles are designed in order to specifically remove blood cells be it circulating tumour cells or leukocytes.
Impairment of the blood-brain barrier: Evaluation of the effect of pharmacological postconditioning. A study from in vitro to in vivo to the patient.
Collaboration within the University Research Priority Program Zurich Center for Integrative Human Physiology (ZIHP). Funding through ZIHP. Beck Schimmer PI.
Within this collaboration the effect of sevoflurane will be evaluated in an in vitro blood brain barrier model of hypoxia-reoxygenation. Sevoflurane will be applied in the reoxygenation phase and cell death will be determined, also elucidating intracellular pathways of protection. Similarly in a rat model of subarachnoidal haemorrhage the impact and possible therapeutic effect of sevoflurane will be elucidated.
Role of hypoxia and shear stress in endothelial cell proliferation.
Collaboration within thr Institute of Physiology (Prof. Dr. R. Wenger and Prof. Dr. V. Kurtcuoglu).
A cell model was established to modulate different scenarios to explore oxygen- and mechanosensing of different types of endothelial cells.