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News from the Institute for Lung Research
2024
New Insights into COPD: Two Biomarkers Allow Risk Assessment at Early Stages of the Disease
Hendrik Pott from Bernd Schmeck’s research group together with colleagues from within and from outside the Philipps-Universität have made progress in the treatment of chronic obstructive pulmonary disease (COPD): A large-scale study, funded by the research platform PerMed-COPD, shows that two specific lung markers - the permeability for carbon monoxide and the so-called hyperinflation of the lung - can reliably predict the risk for exacerbation of the disease and for premature death.
The researchers found that a decrease of the diffusion capacity for carbon monoxide or a hyperinflation of the lung within the study's observation period of 18 months indicate an increased risk of death in the following years. They looked at three different data sets in the patient cohort of around 1,300 people: the development of the disease pattern, the quality of life recorded via questionnaires, and the results of pulmonary function tests. Correlating these attributes with various inflammatory proteins, they found the relevance of the biomarkers.
“These markers aid in identifying particularly vulnerable patients at an early stage and in providing them a better treatment,” explains Dr. Hendrik Pott. COPD, which is often triggered by smoking and air pollution, causes permanent damage to the lungs. With new findings like these, physicians will in the future be able to respond to patients' needs in a better, personalized manner.
The researchers, led by Dr. Hendrik Pott, report their results in the journal “Respirology”.
Take a deep breath with Mareike Lehmann
On the occasion of World COPD Day on September 20, Mareike Lehmann gave a very interesting interview explaining how COPD affects the life of patients and what it does to their lungs. She explicitly pointed out the responsibility of politicians to improve the air quality in Germany and to take measures that reduce smoking among the German population.
In addition, international, e. g., COPD-iNEt, and national, Deutsches Zentrum für Lungenforschung (DZL), networks to strengthen and accelerate innovative research are of uttermost significance in the chase for therapies or drugs.
Mareike Lehman and her lab take a new, alternative approach to help patients by searching ways to activate the lung’s self-healing powers, which are lost in COPD. To pursue this goal, they want to reverse changes in the lung stem cells in order to promote lung regeneration. The Institute for Lung Research here at Philipps-Universität Marburg offers an excellent environment for COPD research, as the university with its School of Medicine and the intertwined renowned hospital UKGM combines strong basic with strong clinical research. These excellent conditions allow to conduct genuine translational research, as clinicians and basic scientists sit down at the same table to help patients.
The complete interview can be found here.
Innovative Tools for Lung Research: Workshop on Precision-Cut Lung Slices
Mareike Lehmann is the lead author of a publication summarizing the findings of an American Thoracic Society (ATS) Workshop on precision-cut lung slices.
As effective treatments for acute and chronic lung diseases remain urgently needed, innovative research tools that enable new insights and facilitate the translation to clinical application play a central role in this process. Precision-cut lung slices (PCLS) have gained significant importance in recent years in supporting this process.
The American Thoracic Society (ATS) recently hosted a workshop with 35 experts on the topic of precision-cut lung slices (PCLS) to discuss the role of PCLS derived from human tissue in lung research and to establish consensus on methods, metrics, and technologies. This workshop was led by Mareike Lehmann in collaboration with Melanie Königshoff (University of Pittsburgh, USA). The workshop results are summarized in a publication intended to serve as a guide for lung researchers interested in PCLS. For further information, please consult the DZL homepage.
Exciting New Therapeutic Approach for Pulmonary Fibrosis
The ability of the lung to regenerate after minor injuries, such as those caused by viruses or pollutants, is impaired in patients with pulmonary fibrosis. Mareike Lehman and her team, in collaboration with researchers from the University of Pittsburgh, the University of Burgundy and the Helmholtz Zentrum München, have now discovered that in pulmonary fibrosis, extracellular vesicles transport the protein SFRP1 (secreted frizzled related protein 1), which is responsible for the impaired regenerative capacity of the lung. This protein represents a potential target for new therapies and could serve as a biomarker to better recognize pulmonary fibrosis.
The research team was able to validate these results on several levels, e. g., in organoid models and in lung and connective tissue cells from patients, which underlines the medical significance of these exciting findings. The results were published in the journal JCI insight.
In addition to specifically influencing the protein, the scientists next want to find out at what stage of the disease the protein occurs and how it reacts to the drugs currently available. We wish them success!
Further information can be found on the homepage of Philipps University.
Best-Poster Award for Amine Chahin
At the 20th annual retreat of the international graduate program Molecular Biology and Medicine of the Lung (MBML), June 26th to 28th, 2024 at Rauischholzhausen, graduate Student Amine Chahin won the award for the best poster. Congratulations to Amine!! Amine, who started to work in Mareike Lehmann’s group last year, presented his exciting results on Lung aging in COPD and IPF.
The retreat addressed the research areas pulmonary hypertension and right heart failure, hypoxia and oxygen sensing, lung fibrosis, lung progenitor cells and regeneration, acute respiratory distress syndrome, lung development and bronchopulmonary dysplasia, lung cancer, and Chronic Obstructive Pulmonary Disease (COPD). Talks from international experts in the field of lung research, e. g. by Steven Corcello (Stanford University, USA), Larissa A. Shimoda (John Hopkins School of Medicine, USA), or Darcy Wagner (Lund, Sweden), were followed by poster sessions from the graduate students of the international program.
In addition, two students from the Institute for Lung Research, Gowtham Boosarpu (Lehmann Lab & Schmeck Lab) and Efthymios Fousekis Papakonstantinou (Lehmann Lab), won the 2nd and 3rd prize, respectively, in this year’s MBML’s structured graduate program exam. Congratulations to Gowtham and Thym!
New Insights into the Mechanisms of Antibiotic Resistance in Lung Infections
The combat of the increasing health threat of multi-drug resistance in clinically relevant bacteria is of uttermost importance in clinical research. Marie Burt, who is pursuing her doctoral thesis in the young investigator group of Dr. Anna Lena Jung, together with colleagues from the research cluster Diffusible signals elucidated the role of outer membrane vesicles (OMVs) from Klebsiella pneumoniae in modulating bacterial stress responses, thereby shedding light on the interplay between OMVs and antibiotic resistance.
Through in vitro-, ex vivo- and in vivo-experiments, she showed that OMVs provide enhanced protection against polymyxins, a drug of last resort. These exciting findings have direct implications for the treatment of pneumonia and enable the development of novel therapeutic strategies against multidrug-resistant pathogens. They were published in the Journal of extracellular vesicles.
Carol Basbaum Award for Mareike Lehmann
The Assembly on Respiratory Cell and Molecular Biology (RCMB) of the American Thoracic Society (ATS) has honored Mareike Lehmann for her outstanding scientific achievements and her leadership potential. In particular, she receives the award for her research on the mechanisms of cellular aging in chronic lung diseases.
Congratulations!
The Carol Basbaum Award is aimed at young scientists with outstanding scientific achievements, mentorship and leadership potential in the field of cell and molecular biology of the respiratory tract. It was established in memory of Dr. Carol B. Basbaum, a brilliant scientist with an international reputation in the field of airway biology and inflammation. Dr. Basbaum died in 2005 at the height of her career. She was the first to describe the plasticity of airway epithelial cells and the role of several new molecules in the lung.
Congratulation! - Two Members of Our Lab Are Funded by the Von Behring-Roentgen-Stiftung
The Von Behring-Röntgen-Stiftung promotes research in the broad spectrum of medical sciences at the Philipps-Universität Marburg and the Justus-Liebig-Universität Gießen by financially supporting research projects and symposia and by grants and awards for outstanding researchers and projects. Starting in January 2024, six outstanding research projects from young researchers will be supported with 1 million Euro.
Two of these six researchers are members of the Institute for Lung Research! We congratulate Prof. Dr. Mareike Lehmann from the Lung Inflammaging Lab and Dr. Anna Lena Lung from the Young Researcher Group!
As part of the funded project, Mareike Lehmann will be focusing on the role of extracellular vesicles in the accompanying symptoms of idiopathic pulmonary fibrosis, an age-related, progressive lung disease with a fatal course. She is particularly interested in the influence of these vesicles on ageing processes in the heart.
Anna Lena Jung will decipher the antibiotic resistance of Klebsiella pneumoniae, a hospital germ that can cause severe pneumonia. Here, she is focusing on the role of outer membrane vesicles, small vesicles that are released under the influence of antibiotics. Her results will add to the development of new therapeutic approaches against the increasing antibiotic resistance of K. pneumoniae and to the improvement of our understanding of how the disease is triggered.
2023
How the Lung Fights against Bacterial Attack
Infections of the lower respiratory tract caused by Streptococcus pneumoniae (Spn) are a leading cause of death worldwide. Dr. Björn Klabunde, who pursued his doctoral thesis in the laboratory of Prof. Schmeck, discovered a new salvage pathway in Spn infections. Together with colleagues from the research cluster Diffusible signals, he investigated the bronchial epithelial cellular response to Spn infection on the transcriptomic, proteomic, and metabolic level.
He found the NAD+ salvage pathway to be dysregulated upon infection in a cell line model, in primary human lung tissue, and in vivo in rodents, leading to a reduced production of NAD+. Knockdown of NAD+ salvage enzymes (NAMPT, NMNAT1) increased bacterial replication. NAD+ treatment of Spn inhibited its growth while growth of other respiratory pathogens improved. Boosting NAD+ production increased NAD+ levels in immortalized and primary cells and decreased bacterial replication upon infection. NAD+ treatment of Spn dysregulated the bacterial metabolism and reduced intrabacterial ATP. Enhancing the bacterial ATP metabolism abolished the antibacterial effect of NAD+.
These exciting findings of the NAD+ salvage pathway acting as an antibacterial pathway in Spn infections and the prediction of NAD+ as an antibacterial mechanism were published in Nature Communications.
ECM Award for Mareike Lehmann
Prof. Dr. Mareike Lehmann, Professor for Translational Inflammation Research at the Institute for Lung Research, will be awarded the Early Career Member Award (ECM Award) of the European Respiratory Society (ERS). She was chosen for her pionieering work on cellular aging phenotypes in chronic lung diseases, including Idiopathic Pulmonary Fibrosis (IPF) and Chronic Obstractive Pulmonary Disease (COPD).
The ECM Award, which is intended to honour a promising early-career member of ERS based on potential for future scientific contribution as well as past and current engagement in the ERS, will be presented at the Annual International Congress 2023 of the ERS in Milan, Italy in September.
The ERS is one of the leading medical organisations in the respiratory field, with a growing membership spanning over 160 countries. The ERS prioritises science, education, and advocacy in order to promote lung health, alleviate suffering from disease, and drive standards for respiratory medicine globally. Further information can be found in die video about COPD at the ERS - RESPIRATORY channel and in the university's press release.