Kapellos Lab
Immunoregulation in obstructive airway diseasesThe Kapellos Lab investigates the heterogeneity in structure and functions of human lung immune cells, primarily myeloid cells, to better understand the inflammatory mechanisms that drive the initiation and development of obstructive airway diseases.
The Kapellos Lab investigates the heterogeneity and functions of human immune cells, particularly myeloid cells, in order to better understand the inflammatory mechanisms that drive the initiation and progression of obstructive lung diseases.
The immune system plays a pivotal role in obstructive airway diseases, which are characterized by chronic inflammation and structural changes in the airways, including chronic obstructive pulmonary disease (COPD), non-cystic fibrosis bronchiectasis and allergic asthma. Immune cells mediate and modulate pathophysiological mechanisms by responding to various environmental triggers, such as inhaled pollutants and allergens, ultimately promoting irreversible inflammation and lung tissue damage. Understanding the interactions between immune cells and the respiratory system is essential for uncovering the mechanisms driving disease progression, from the initial stages to more advanced manifestations. Insights into immune responses are crucial for identifying therapeutic targets and developing novel drugs.
Our laboratory is dedicated to exploring obstructive airway diseases, with the primary objective of unraveling the immune system's contributions to disease progression. We aim to identify cellular pathways that can be targeted to mitigate disease manifestations and improve clinical outcomes and patient quality of life. By meticulously assessing the molecular heterogeneity of clinical cohorts affected by obstructive airway diseases, we strive to accelerate the development of personalized therapeutics.
We employ a dual-pronged strategy in our research. First, we leverage cutting-edge omics technologies and computational analyses to define immune molecular phenotypes relevant to disease. To gain deeper insights into host-pathogen interactions, we integrate the genomic profiling of clinical samples with microbiome analysis through 16S rRNA sequencing and metagenomics. Second, to validate our findings, we utilize ex vivo lung models, including in vitro functional assays from human lung fluids, fresh explanted lung tissue and blood specimens from patients with COPD, bronchiectasis and allergic asthma. Precision-cut lung slices strengthen our mechanistic investigations, while highly multiplexed imaging technologies allow us to determine the spatial distribution and cell-cell interactions of innate and adaptive immune cells. Lastly, through established local and international collaborations with experts in animal models of disease, we assess the translatability of proposed mechanisms and candidate drugs from our human models in vivo.
We currently focus on three major scientific avenues:
- Molecular heterogeneity of the immune system in obstructive airway diseases: We are actively working on immunophenotyping COPD and bronchiectasis patients in collaboration with the Ludwig-Maximilian-University clinics. We hypothesize that immune composition in the lung and circulation undergoes significant alterations over the course of obstructive airway diseases. Our goal is to identify clinical biomarkers for early detection that distinguish severity stages and endotypes. Additionally, we investigate how immune responses are shaped by microbiome changes and how immune cells respond to microbial dysbiosis.
- Immune cell metabolism in obstructive airway diseases: We aim to understand how immune cell metabolism drives disease progression.Specifically, we investigate the role of macromolecules, particularly secreted proteins and lipid mediators, in shaping immune cell trajectories from early to advanced disease stages. By identifying key cellular players undergoing metabolic reprogramming, we explore how these changes influence immune function and assess the potential to repurpose therapeutics to reverse disease-associated gene expression profiles.
- Deep imaging analysis in obstructive airway diseases: We employ advanced iterative immunofluorescence to investigate immune cell localization and spatial interactions in COPD and bronchiectasis. Through in silico analysis, we examine sex-related immune responses, focusing on the interplay between immune and non-immune alveolar populations. We integrate these imaging approaches with in-house transcriptomics and proteomics datasets to provide crucial mechanistic insights into disease progression.
If you are interested in joining our interdisciplinary team, feel free to reach out to Dr. Kapellos to discuss your scientific interests and project ideas.