Otto Loewi Forschungszentrum

RESEARCH FOCUS Chronic respiratory and pulmonary diseases

PI: Akos Heinemann

Focus: Chemotactic factors, their receptors and adhesion molecules on both leukocytes and endothelial cells in blood vessels play a crucial role in the multistep process of leukocyte infiltration into tissues, and are therefore considered promising therapeutic targets in various inflammatory states. Platelets also play a role in this process and can activate blood clotting. We focus on deepening the understanding of leukocyte and endothelial function and their interaction with each other to develop new pharmacological targets and drugs. To do this, we use isolated cell systems, tissue cultures, patient samples and disease models.

Network: The Division of Pharmacology is characterized by cross-team collaborations with the research groups of Eva Sturm, Grazyna Kwapiszewska (disease models and patient samples), Rudolf Schicho (histology and fluorescence microscopy) and Gunther Marsche (lipid metabolism). Patient samples are provided in scientific collaboration by the clinical departments for pulmonology, cardiology, nephrology and obstetrics. Close cooperations also exist with the Ludwig Boltzmann Institute for Pulmonary Vascular Research and international partners.


Altered ER and mitochondrial responses in pulmonary fibrosís

  • Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis and unclear etiology. Previous reports proposed that endoplasmic reticulum (ER) stress and induction of unfolded protein response in alveolar epithelial cells fuel the progression of lung fibrosis. Similarly, a role of mitochondrial dysfunction in the pathogenesis of IPF has been described. The ER and mitochondria are connected through distinct sites, so called mitochondria-associated ER membranes (MAMs). Numerous processes such as Ca2+ signaling, lipid metabolism, stress signaling, mitochondrial fission/fusion, and autophagy are regulated via MAMs. How these interconnected molecular mechanisms of altered ER and mitochondrial responses contribute to IPF onset and progression are not clear. Therefore, we aim to identify early mechanistic triggers in the ER and/or mitochondria which might play a role in the onset of IPF.
  • Project duration: 2024-2028
  • Funded by: PhD Program Molecular Medicine, Medical University of Graz
  • Project team: Thomas Bärnthaler, Katharina Jandl; Grazyna Kwapizsewska (Otto Loewi Research Center, Division of Physiology and Ludwig Boltzmann Institute for Lung Vascular Research), Wolfgang Graier (Gottfried Schatz Research Center).

Succinate as a new therapeutic target in idiopathic pulmonary fibrosis

  • Idiopathic pulmonary fibrosis is a chronic progressive pulmonary disease, with short median survival. During the last decade, metabolic processes have been recognised as playing a crucial role in this disease. Most research has focused on the Krebs cycle, a metabolic pathway that is crucial in providing energy as well as metabolites for further metabolic processes. This project aims to elucidate the role of succinate, an intermediate in the Krebs cycle. By using in vivo, in vitro and ex vivo approaches, we will illuminate whether this metabolite might represent a potential target in fibrotic disease.
  • Duration: 2021-2025
  • Funded by: Docfund RespImmun, FWF
  • Project partners: Rishi Rajesh, Reham Atallah, Grazyna Kwapizsewska und Leigh Marsh (Otto Loewi Research Center, Division of Physiology und Ludwig Boltzmann Insitut für Lungengefäßforschung), Stefano Angiari (Otto Loewi Research Center, Division of Immunology), Corina Madreiter-Sokolowski (Division of Molecular Biology and Biochemistry)


Phenotypic Changes of Eosinophil Granulocytes in Aging

  • It is well-established that aging is associated with impaired immune cell function and hence, increased susceptibility to disease, a phenomenon known as immunosenescence. This effect has long been described in cells of the adaptive immune system (especially in B- and T-cells). However, there is much less data in innate immunity. Eosinophilic granulocytes are cells of the innate immune system and traditionally associated with allergic disease and defense against parasites. Their role in aging in human subjects is unclear, although there are promising data from animal experiments. This project aims to elucidate possible therapeutic targets for the treatment of immunosenescence using RNASeq, as well as functional methods in comparing eosinophils from young and aged individuals.
  • Duration: 2022-2026
  • Funded by: PhD Program Molecular Medicine, Medical University of Graz
  • Project partners: Svetlana Pahernik, Reham Atallah, Johannes Fessler (Otto Loewi Research Center, Division of Immunology), Wolfgang Schwinger (Department of Pediatric Hemato-Oncology), Dominique Thomas (Goethe University Frankfurt).

The involvement of 15-prostaglandindehydrogenase in acute kidney injury

  • Acute kidney injury (AKI) is a very common condition with poor long-term outcomes defined as a rapid decline of kidney function. Up to now, there are no pharmacologic treatment options. Among the most frequent etiologies are nephrotoxic agents, such as non-steroidal anti-inflammatory drugs (NSAID), which act by inhibiting prostaglandin (PG) synthesis. Of note, some PGs, especially PGE2 have been shown to exert beneficial effects on kidney function. In vivo, PGE2 is rapidly metabolized via 15- prostaglandin dehydrogenase (PGDH), which is also responsible for the degradation of lipoxin A4, another nephroprotective mediator. The aim of this project is to elucidate the contribution of 15-PGDH to AKI and to establish its inhibition as a potential therapeutic strategy.
  • Duration: 2022-2023
  • Funding: Apart-Mint (ÖAW)
  • Project partners: Agnes Mooslechner, Kathrin Eller (Deparment of Nephrology), Marion Pollheimer (Pathology), Dominique Thomas (Goethe University Frankfurt).

Basement membrane fragments as novel mediators of leukocyte activation

  • The basement membrane is pivotal in ensuring the barrier function of the endothelium. In various acute or chronic lung diseases, the basement membrane is attacked by proteases, which can lead to fragmentation and simultaneous release of bioactive fragments, so-called matrikines. This project investigates the impact of basement membrane matrikines on leukocyte function and its contribution to acute lung diseases. Through detailed pharmacological characterization, we aim to identify novel targets to modulate the function of matrikines on leukocytes.
  • Project duration: 2022-2024
  • Funded by: Start-up grant, Medical University of Graz
  • Project team: Katherina Jandl, Grazyna Kwapizsewska and Ceren Ayse Mutgan (Otto Loewi Research Center, Division of Physiology and Ludwig Boltzmann Institute for Lung Vascular Research), Malgorzata Wygrecka (Center for Infection and Genomics of the Lung (CIGL), Faculty of Medicine, Justus Liebig University).

Division of Pharmacology

Univ.-Prof. Dr.
Akos Heinemann  
T: +43 316 385 74112