Kapellos Lab

The immune system plays a pivotal role in obstructive airway diseases, such as chronic obstructive pulmonary disease (COPD), non-cystic fibrosis bronchiectasis and allergic asthma which are characterized by chronic inflammation and structural changes in the airways. Immune cells are involved in mediating and modulating these processes by responding to various environmental triggers, e.g. inhaled pollutants or allergens and promote irreversible inflammation and lung tissue damage. Understanding the intricate interactions between immune cells and the respiratory system is essential for revealing the underlying mechanisms of disease progression from the initial stages to more advanced manifestations and insights into immune responses are crucial for identifying therapeutic targets and designing novel drugs.

Our laboratory is dedicated to the exploration of obstructive airway diseases with a primary objective to unravel the contributions of the immune system to the progression of these diseases, spanning from early to advanced stages. Our goal is to identify cellular pathways that can be targeted to alleviate disease manifestations and to improve clinical outcome and patient quality of life. Central to our approach is a keen appreciation for patient diversity. Consequently, we meticulously assess the molecular heterogeneity of prospective clinical cohorts affected by obstructive airway diseases. This in-depth understanding aids us in expediting the design of novel personalized therapeutics.

In our research, we employ a dual-pronged strategy. We utilize cutting-edge single-cell transcriptomics technologies and computational analysis to define immune molecular phenotypes relevant to disease. Additionally, in 2024, we plan to incorporate microbiome analysis through 16S rRNA gene sequencing and metagenomics to complement the genomics profiling of human samples. To validate our findings, we employ ex vivo lung models, including in vitro functional assays from human lung fluid, fresh explanted lung tissue and blood specimens from patients suffering from COPD, bronchiectasis and allergic asthma. Precision cut lung slices (PCLS) further contribute to our mechanistic investigations. Moreover, we have established both local and international collaborations with experts in animal models of disease. This allows us to assess the translatability of proposed mechanisms and candidate drugs from our human models in vivo.

We currently focus on three major scientific avenues:

• Immune cell metabolism in COPD: We aim to elucidate how immune cell metabolism influences their functions in COPD. Our focus is on the role of lipids in the trajectory of myeloid cells from early to severe stages, with the goal of harnessing gene expression profiles for designing therapeutics, especially for tissue-resident macrophages.
• Sex-related immune responses in COPD: Our objective is to comprehensively characterize sex-related differences in the abundance and transcriptomic programs that are active in male and female COPD patients. Exploring the interplay between immune and non-immune alveolar populations is a priority to better understand the origins and mechanistic aspects of the observed differences in clinical manifestations.
• Heterogeneity of obstructive airway diseases: We are actively working on immunophenotyping bronchiectasis patients in collaboration with the LMU clinics. Our hypothesis is that the immune composition in the lung and periphery of bronchiectasis patients undergoes alterations over the course of the disease. We aim to identify clinical biomarkers distinguishing severity stages and endotypes. Additionally, we investigate how host responses are influenced by changes in the microbiome and how myeloid cells respond to the dysregulation of predominant microbial communities.

If you are interested in joining our interdisciplinary team, we welcome PhD and postdoctoral candidates to reach out to Dr. Kapellos to discuss their scientific interests and potential project ideas.