Otto Loewi Forschungszentrum

Research focus: Metabolism and the gut

PI: Gunther Marsche

Focus: The main research interest of my research team is to understand the role of high-density lipoproteins (HDL) in inflammatory and allergic diseases. HDL are complex endogenous nanoparticles that play a vital role in maintaining metabolic homeostasis and vascular health. HDL is involved in crucial functions such as reverse cholesterol transport and immunomodulatory activities, and its ability to interact with various immune cells and structural cells places it at the forefront of numerous disease pathophysiologies. However, when there is inflammatory dysregulation, HDL can undergo pathogenic remodeling and post-translational modifications that render it dysfunctional or even pro-inflammatory. We seek to understand why HDL may lose its protective effects in inflammatory diseases. To this end, we are studying the complex composition of HDL and measuring its diverse functionalities.

Network: We have collaborations with the Division of Physiological Chemistry (Gerhard Cvirn), the Division of Physiology (Nandu Goswami), the Division of Immunology and Pathophysiology (Sandra Holasek), the Division of Molecular Biology and Biochemistry (Sasa Frank), the Division of Gastroenterology and Hepatology (Rudolf Stauber und Vanessa Stadlbauer-Köllner), the Department of Internal Medicine (Philipp Eller), the Department of Dermatology and Venereology (Peter Wolf) and the Department of Obstetrics and Gynaecology (Christian Wadsack).

Projects

Apolipoprotein AI mimetic peptide lipid assemblies

  • HDLs are complex particles whose composition and function are significantly impacted in inflammatory diseases. As a result, there is a need to replace or even enhance the diminished function of HDL in such conditions. Apolipoprotein A-1 (apoA-I), the most abundant protein in HDL, is responsible for its well-established anti-inflammatory effects. In this project, we investigate the structure and function of artificially synthesized peptides, ranging from 18-37 amino acids in length, that differentially mimic the activity of full-length apoA-I while being lipidated.
  • Duration: 2022-2025
  • Funded by: FWF
  • Project partners: Ruth Prassl (Medical University of Graz), Mounir Tarek (Laboratory of Theoretical Physics and Chemistry, University of Lorraine in France)

 

Synthetic high-density lipoproteins in allergic lung inflammation

  • Eosinophils play a crucial role in allergic inflammation, making them versatile and important effector cells. HDL mimetic nanoparticles show promise as a potential therapy for hyper-eosinophilic conditions, like asthma, where eosinophil migration from the bloodstream to the affected tissues is a key factor in disease exacerbation. This project tests the pro-resolving effects of reconstituted HDL (rHDL) on eosinophil and neutrophil effector responses and endothelial function. Additionally, rHDL is applied to models of allergic lung inflammation to assess its potential therapeutic benefits.
  • Duration: 2021-2025
  • Funded by: FWF
  • Project partners: Katharina Jandl, Ruth Prassl (Medical University of Graz)

Influence of preeclampsia on lipid metabolism

  • HDL represents the major lipoprotein class in human umbilical cord blood, whereas in maternal serum cholesterol is mainly carried by low-density lipoproteins. HDL promotes numerous beneficial effects on the vasculature, including attenuation of the inflammatory response in vascular endothelium and immune cells and stimulation of endothelial nitric oxide production. In this project we investigate the effects of obesity and hypertension in pregnancy on HDL composition and function.
  • Duration: 2018-2022
  • Funded by: FWF
  • Project partners: Christina Christoffersen, Department of Biomedical Sciences, Faculty of Health and Science, University of Copenhagen, Denmark; Mireille van Poppel (University of Graz); Christian Wadsack (Medical University of Graz)

 

Division of Pharmacology

Assoz.-Prof. Priv.-Doz. Mag. Dr.
Gunther Marsche 
T: +43 316 385 74128

Team