Menu

Lung Aging and Regeneration

Prof. Dr. Mareike Lehmann

Prof Lehmann studied molecular biomedicine at the University of Bonn and Yale University before moving to Switzerland for her PhD. She joined the Comprehensive Pneumology Center in Munich for a Postdoc where she got interested in lung aging. She then started her own group in Munich focusing on cellular senescence in chronic lung diseases and has recently been appointed professor of translational inflammation research at the Philipps University Marburg. She was awarded with a prestigious Emmy Noether award that will further allow her to explore cellular senescence and inflammaging in the development of COPD and IPF with a special focus on  extracellular vesicles (EVs). Prof Lehmann was awarded the rising star of research award of the American Thoracic Society and the Early Career Member Award of the European Respiratory Society.

Lung diseases and respiratory infections are leading causes of death world-wide. The elderly population is at increased risk of developing age-related chronic and acute lung diseases and the ongoing COVID-19 pandemic illustrates the need to better understand and target age-related predisposition of the lung to disease development.

We want to understand how cellular aging affects stem cell capacities and cell-cell crosstalk, especially between immune cells and stem cells. In order to allow the aging lung to efficiently repair, we aim to develop biomarkers as well as therapeutic strategies targeting cellular aging phenotypes, thereby opening novel avenues for the diagnosis and treatment of chronic lung diseases.

We use state of the art technologies including single cell/ single nuclei RNA sequencing and multiplex staining and imaging approaches to investigate lung aging. We focus on developing clinically relevant human models. To this end we employ alveolar organoids that can be supplemented with immune cells. To be able to test potential anti-senescent therapies in the human system, we are developing a human aging model based on human precision cut lung slices (PCLS) that displays relevant hallmarks of aging such as cellular senescence. This model will be used to verify target engagement of anti-senescent therapies in the human system and will help to screen for relevant biomarkers for companion diagnostics development.

Cellular Senescence in chronic lung diseases

Different hallmarks of aging, such as cellular senescence, have been identified as pathogenic drivers of chronic lung diseases (CLDs) such as Chronic Obstructive Pulmonary Disease (COPD) or Idiopathic Pulmonary Fibrosis (IPF). Cellular senescence describes a cell cycle arrest of cells with a simultaneous upregulation of various secreted inflammatory factors that are collectively termed the senescence associated secretory phenotype (SASP). The SASP has various functional consequences including detrimental effects on repair and regeneration. We aim to define cell- and disease-specific cellular senescence to develop novel approaches to pharmacologically target cellular senescence in chronic lung diseases. To this end we develop novel clinically relevant human models of lung aging and senescence to build platforms for the identification of novel targets.

Extracellular vesicles as mediators of age-associated chronic lung diseases

Extracellular vesicles (EVs) are small vesicles secreted by all cells that play an important role in (long range) cellular communication and tissue homeostasis and alterations of their production have been described and contribute to chronic lung diseases. Indeed, evidence is accumulating that aging cells secrete parts of their secretome via EVs, thereby acquiring the potential to travel long distances and potentially contribute to aging-associated comorbidities of patients. However, how EVs from senescent cells influence other cells is currently unknown. We isolate, identify and characterize EVs from aging-associated chronic lung diseases to assess their effect on pathomechanisms of disease.

Immunoregulation of stem cell function

Evidence is accumulating that dysregulation of the immune system plays a crucial role in CLDs. Immune cells do not only orchestrate inflammatory reactions but can influence non-immune cells including stem cells. Senescence of the immune system (immunosenescence) contributes to aging of solid organs. How immunosenescence affects stem cell function of the lung is not understood yet and we set out to characterize this.

Cooperative Projects in the ILH

  • Bernd Schmeck: Crosstalk of lung aging and inflammation
  • Miguel Alejandre-Alcazar: Early life obesity drives lung stem cell aging and predisposes to IPF development
  • Herbert Schiller: Multiomic characterization of lung inflammaging and cell senescence

 

Contact

Prof. Dr. Mareike Lehmann

Institute for Lung Research
AG Translational Inflammation Research
Philipps-University Marburg

Hans-Meerwein-Straße 2
35043 Marburg

Tel.: +49 (0) 6421 28 65043
Fax: +49 (0) 6421 28 21993

Email: mareike.lehmann@uni-marburg.de

Dr. Sabrina von Einem
Research Coordinator

Tel: +49 (0) 6421 28 65713
Fax: +49 (0) 6421 28 21993

Email: sabrina.voneinem@uni-marburg.de

 

Ten most important publications

  1. Lang,N.* Gote-Schniering, J.*, Porras-Gonzalez, D., Yang, L., De Sadeleer, L., Jentzsch, C.R., Shitov, V.A., Zhou, S., Ansari, M., Agami, A., Mayr, C., Kashani, B.H., Chen, Y., Heumos, L., Pestoni, J.C., Monar, E.S.Geeraerts, E., Anquetil, V., Saniere, L., Wögrath, M., Gerckens, M., Lehmann, M., Yildirim A.Ö., Hatz, R., Kneidinger, N., Behr, J., Wuyts, W.A., Stoleriu, G.M.,Luecken, M.D., Theis, F.J., Burgstaller, G*., Schiller,H*., Ex vivo tissue perturbations coupled to single cell RNA-seq reveal multi-lineage cell circuit dynamics in human lung fibrogenesis, Science Translational Medicine, 2023, *equal contribution, in press
  2. Heinzelmann, K., Hu, QJ., Dobrinskikh, E., Ulke, H., Ansari, M., Leavitt, C., Mirita, C., Trudeau., T., Saal, M., Rice, P., Gao, B., Janssen, W., Yang, I., Schiller, H., Vladar, E., Lehmann, M*., Königshoff, M.,*, Single cell RNA Sequencing Identifies G-protein Coupled Receptor 87 as a Novel Basal Cell Marker of Distal Honeycomb Cysts in Idiopathic Pulmonary Fibrosis, European Respiratory Journal, * equal contribution, co-corresponding authors, 2022: 59(6). 10.1183/13993003.02373-2021
  3. Strunz,M., Simon, L.M., Ansari, M., Mattner, L.F., Angelidis, I., Mayr, C.H., Kathiriya, J., Yee, M., Ogar, P., Sengupta, A., Kukhtevich, I., Schneider, R., Zhao, Z., Neumann, J.H.L, Behr, J., Voss, C., Stöger,T., Lehmann, M., Königshoff, M., Burgstaller, G., O’Reilly, M., Chapman, H.A., Theis, F J., Schiller, H.B. (2020) Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis, Nature Communications, 11 (1), 3559, 10.1038/s41467-020-17358-3
  4. Conlon, T.M.*, John-Schuster*, G , Heide, D., Pfister, D., Lehmann, M., Hu, Y., Ertüz Z., Lopez, M., Ansari, M., Strunz, M., Mayr, C., Ciminieri, C., Costa, R., Kohlhepp, M.S., Guillot, A., Günsel, G., Jeridi, A., Funk, M.C., Beroshvili, G., Prokosch, S., Hetzer, J., Verleden, S.E., Alsafadi, H., Lindner, M., Burgstaller , Lore Becker, G., Irmler, M., Dudek, M., Janzen, J., Goffin, E., Gosens, R., Knolle, P., Pirotte, B., Stöger, T., Beckers, J., Wagner, D.E., Singh, I., Theis, F.J., Hrabe de Angelis, M., O´Connor, T., Tacke, F., Boutros, M., Dejardin, E., Eickelberg, O., Schiller, H., Königshoff, M., Heikenwalder, M., Yildirim, AÖ. Inhibition of LTβR-signalling blocks epithelial apoptosis and activates endogenous Wnt-induced regeneration. (2020) Nature; 588(7836):151-156. *these authors contributed equally. 10.1038/s41586-020-2882-8
  5. Meiners, S. and Lehmann, M. (2020). Senescent cells in IPF: Locked in repair?, Frontiers in Medicine, 7, 1002. 10.3389/fmed.2020.606330
  6. Melo-Narvaez, C., Stegmayr, J., Wagner, D., Lehmann, M., (2020). Lung Regeneration: The effect of the diseases niche and ageingEuropean Respiratory Review, 29, 157. 10.1183/16000617.0222-2020
  7. Lehmann, M*., Hu, Q., Hafner, K., Costa, R., van den Berg, A., Königshoff, M*, (2020) WNT/β-catenin signaling induces cellular senescence in lung alveolar epithelial cells, Cellular Signaling, 70. 109588*co-corresponding author 10.1016/j.cellsig.2020.109588
  8. Lehmann M, Buhl L, Alsafadi HN, Klee S, Hermann S, Mutze K, Ota C, Lindner M, Behr J, Hilgendorff A, Wagner DE, Königshoff M. (2018) Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis. Respiratory Research 19:175. 10.1186/s12931-018-0876-y
  9. Martin-Medina, A., Lehmann, M., Burgy, O., Hermann, S., Baarsma, H.A., Wagner, D.E., De santis, M., Ciolek, F., Hofer, T.P., Frankenberger, M., Aichler, M., Lindner, M., Gesierich, W., Guentehr, A., Walch, A., Wolters, P., Lee, J.S., Behr, J., Königshoff, M. (2018). Increased extracellular vesicles mediate WNT-5A signaling in idiopathic pulmonary fibrosis. American journal of Respiratory and Critical Care Medicine. 198. 1527-1538. 10.1164/rccm.201708-1580OC 
  10. Lehmann, M., Korfei, M., Mutze, K., Klee, S., Skronska-Wasek, W., Alsafadi, H.N., Ota, C., Costa, R., Schiller, H.B., Lindner, M.Wagner, D.E:, Günther, A., Königshoff, M. (2017). Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo. The European Respiratory Journal 50: 1602367. 10.1183/13993003.02367-2016

Here you can find all ILH-publications

 

Funding

DFG Emmy Noether Junior Research Group “Targeting the heterogeneity of cellular aging in chronic lung diseases - A road to lung regeneration” (since 2023, 1.500.000 €); Philipps University Marburg W1 Tenure Track W2 Professorship “Translational Inflammation Research” (since 2022, 1.100.000€) “CD 73 blockade as a novel treatment for pulmonary fibrosis using single cell genomics in a human precision cut lung slice model”, Boehringer Ingelheim opnMe, PI (since 2022, 180.000€)

 

Group Members

Postdoc

Camila Melo-Narvaez

Doctoral Students

Efthymios Papakonstantinou Fousekis, Gowtham Kumar Boosarpu Gopinath, Amine Chahine

Medical students

Jakob Streckbein

Technical Assistants

Max Mikado Götz

 

chevron-down