Otto Loewi Forschungszentrum

Research Focus: Chronic respiratory and pulmonary diseases

PI: Leigh M. Marsh

Focus: Chronic lung diseases (CLD) such as COPD and IPF, are often complicated by the presence of pulmonary hypertension (PH), and are increasing cause of death in the aging population. Numerous immune cells potentially contribute to disease progression, leading to both parenchymal and vascular remodelling. Our workgroup within the Ludwig Boltzmann Institute for Lung Vascular Research, aims to understanding the deeper dynamics of these immune cells by going beyond individual populations and focusing on comprehensive inflammatory profiles. By combining computational flow cytometry, advanced data modelling and transcriptomic analysis, together with pre-clinical models, we aim to dissect the interaction and interdependence of these immune cells and determine their contribution to disease pathogenesis.

Networking: Our workgroup enjoys several close collaborations with the Ludwig Boltzmann Institute for Lung Vascular Research and other members of the OLRC. These include Grazyna Kwapiszewska (Vascular remodelling) and Slaven Crnkovic (multispectral imaging) and the research groups of Eva Sturm und Akos Heinemann (Division of Pharmacology) and Stefano Angiari / Herbert Strobl (Division of Immunology) . Outside the ORLC, we have long-term collaborations with Horst Olschewski / Gabor Kovacs (Division of Pulmonology, Med Uni Graz) and Luka Brcic / Gerald Hoefler (Diagnostic and Research Institute of Pathology, Med Uni Graz). External collaborations include Dagmar Gotthardt (University of Veterinary Medicine, Vienna), Gabriele Grunig (New York University School of Medicine), Francesca Polverino (Baylor College of Medicine, Houston, USA) and Bernd Schmeck (Phillips University Marburg, DE).


Inflammatory profiling in chronic lung disease

  • Inflammation plays an important role in mediating vascular remodelling in idiopathic form of pulmonary hypertension (PH). Where the accumulation of inflammatory cells in and around the vascular wall correlates with the degree of vascular remodelling. However, very little is known about the role of inflammation in PH associated with chronic lung disease. In this study, we will determine whether an underlying inflammatory cell profile exists in all forms of PH and how these cells regulate vascular remodelling processes.
  • Duration: 2021-2024
  • Funding body: FWF (KLI 844-B)
  • Project partners:Bernhard Reiter, Olaya Esparta Gonzalez (Otto Loewi Research Center, Med Uni Graz), Konrad Hötzenecker (Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna); Francesca Polverino (Baylor College of Medicine, Houston, USA), Horst Olschewski (Division of Pulmonology, Med Uni Graz); Jochen Wilhelm (Institute for Lung Health, Justus Liebig University Giessen, Germany).

Involvement of the pulmonary vasculature in the development of lung fibrosis

  • Pulmonary fibrosis is a central and serious problem in various diseases with pulmonary involvement. The pathogenesis of PF depends on the interaction of different pulmonary cell types, ultimately leading to destruction of lung architecture and respiratory deficits. Because the vascular compartment is severely affected, an important role of endothelial cells in disease pathogenesis is suggested. Therefore, we will systematically investigate the mechanisms of vascular maintenance and EC behaviour during fibrosis initiation and progression.
  • Duration: 2020-2024
  • Funding body: FFG-Österreichische Forschungsförderungsgesellschaft
  • Project partners: Anna Birnhuber / Grazyna Kwapiszewska (Ludwig Boltzmann Institute for Lung Vascular Research / Otto Loewi Research Center, Med Uni Graz)


Immune cell crosstalk as driver of vascular remodelling

  • Cardiovascular diseases are one of the leading causes of adult mortality worldwide and associated with poor quality of life. A common theme underlying these diseases is an altered immune response. In pulmonary hypertension (PH) immune cell infiltration is associated with degree of vascular remodelling. Here we are building on our European Journal publication and investigating the role of two previously uncharacterized immune populations potentially involved in disease pathogenesis, and how they may control the transition to a chronic inflammatory environment found in PH.
  • Duration: 2021-2025
  • Funding body: Med Uni Graz
  • Project partners: Olaya Esparta Gonzalez, Paul Vesely (Otto Loewi Research Center, Med Uni Graz), Grazyna Kwapiszewska (Ludwig Boltzmann Institute for Lung Vascular Research / Otto Loewi Research Center, Med Uni Graz), Simon Phipps (QIMR Berghofer Medical Research Institute, AUS), Mirjam Kool (Erasmus MC, Pulmonary Medicine Department, NL)

Compartment specific immunophenotyping in Chronic Obstructive Pulmonary Disease

  • Chronic obstructive pulmonary disease (COPD) is a highly heterologous disease with several know phenotypes, these can be distinguished by the pathology, degree of inflammation, or response to treatment. The presence of pulmonary hypertension (PH) in patients with COPD is associated with even worse survival. However, there is only limited knowledge how the compartment specific inflammatory profile overlaps in COPD and contributes to pathogenic remodelling. This project investigates whether the inflammatory cell profile exhibits a compartmental specific fingerprint and discriminates between different COPD phenotypes.
  • Duration: 2021-2025
  • Funding body: Docfund RespImmun, FWF
  • Project partners: Ayu Hutami Syarif, Bernhard Reiter, Slaven Crnkovic (Otto Loewi Research Center, Med Uni Graz), Alexander Avian (Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz), Konrad Hötzenecker (Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna); Francesca Polverino (Baylor College of Medicine, Houston, USA)

Division of Physiology & Pathophysiology

Leigh Marsh  
T: +43 316 385 72911
Forschungsgruppe Leigh Marsh