Main Content
Lehmann Lab
Our group studies how aging changes the lung and predisposes to the development of multiple chronic lung diseases.
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.
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 built 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.
Tools
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.
