Project Details
Description
Chronic rejection of transplanted lung is a serious complication in up to 50% of all transplanted lungs. Here, we aim to understand the contributing cells and microenvironmental prerequisities during lung remodeling affecting the development of bronchiolitis obliterans syndrome (BOS). This project uses human material and correlates to patient parameters, thus has a high translational potential. Each participating patient material is well-characterized, and all analyses will be linked to severity of disease, the rapidity of the formation of the BOS plaques and lung function deteriouration at the time of tissue retrieval. Built on our previous research, we here aim to delineate subsets of mesenchymal and epithelial cells and the ECM context and turnover that promote propagation of inflammation and pathological changes, using spatial transcriptomics, immunohistology and mass spectrometry. In this way we will unravel specific disease related cell-cell interactions and cell-microenvironment cues that propagate the formation of BOS. By analysing plasma from patients with BOS and the mass spectrometral fingerprint in the lung, we aim to identify novel biomarkers that mirror ongoing remodeling. In this way, we can identify patients early, at risk of developing BOS, and intervene with pharmaceuticals. BOS plaques can occur in vessels, small airways or in the alveoli. Using spatial transcriptomics and histological tools we will be able to find what in the lung architecture triggers the onset of BOS, and consequently novel molecular pathways that may be therapeutically targetable will be unraveled. Taken together, the project; a collaboration between Academia and hospitals in Lund, Groningen, and Gothenburg to obtain critical numbers of patients, will be able to generate novel targets (within 2 years) and biomarkers (within 2-3 years) that follow development of BOS. Biomarker screening in clinical settings will be doable within 4-6 years.
Status | Active |
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Effective start/end date | 2024/01/01 → 2025/12/31 |
Funding
- The Swedish Heart Lung Foundation