Medical student and BREATH junior scientist Lena M. Leiber has won the poster prize in the Regeneration and Organ Replacement disease area at the DZL Annual Meeting 2024 in Bad Nauheim.

Since 2019, Lena M. Leiber has been a medical student at Hannover Medical School (MHH). She developed an early interest in pulmonary medicine through personal activities such as playing the trombone and singing, diverse internships, and her voluntary engagement as a (board) member of Hannover’s local group of Education against Tobacco (AgT Hannover), a medical students’ initiative. In 2022, as part of her one-year structured doctoral scholarship, she became an MD student and founding member of Prof. Dr. med. Jonas C. Schupp's DZL research group at the DZL site BREATH at MHH, where she continues her research as an assistant scientist. The main focus of her doctoral thesis is to decipher the transcriptomic and histopathophysiologic characteristics of restrictive allograft syndrome (RAS), a fatal lung disease that can occur after lung transplantation.

Chronic lung allograft dysfunction (CLAD) after lung transplantation (LuTx) is a progressive remodeling process that manifests as restrictive and/or obstructive phenotypes. Due to the lack of effective therapeutic options, CLAD remains a major cause of post-LuTx morbidity, the need for re-transplantation (ReTx), and mortality after LuTx. Up to 30% of CLAD patients are diagnosed with the restrictive phenotype, known as restrictive allograft syndrome (RAS), which is associated with an even more limited prognosis compared to the more common obstructive phenotype (survival rate after diagnosis: 6–18 months for RAS vs. 3–5 years for BOS). The pathogenesis of RAS remains enigmatic, although some potential risk factors have been identified.

Lena M. Leiber and her colleagues from the BREATH working group of Prof. Dr. med. Jonas C. Schupp at MHH strive to decipher the cellular mechanisms of chronic lung diseases using cutting-edge technologies such as single-cell transcriptomics and spatial transcriptomics. In their work, Lena M. Leiber and her colleagues performed the first single-cell transcriptomic analysis of human RAS lungs to elucidate the transcriptomic characteristics of RAS in relation to the histopathological features of the pulmonary injury patterns present. Generating single-nucleus RNA sequencing (snRNA-seq) data from RAS and control tissue enabled her to identify aberrant epithelial, ectopic COL15A1+ endothelial, and CTHRC1+ fibrotic fibroblast populations which were previously undiscovered in RAS but associated with other fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). Various immunohistological techniques, in situ RNA hybridization, and micro-CT scans revealed specific distribution patterns of these in RAS newly discovered cell populations and facilitated a complementary 3D structural analysis of their snRNA-seq-based findings.

Despite the clinical, histologic, and etiologic differences between RAS and IPF, their snRNAseq study uncovered a surprising overarching principle in the cellular and molecular pathogenesis of the fibrosing lung. This principle involves a shared composition of the fibrotic niche, characterized by aberrant basaloid cells, ectopic COL15A1+ vascular endothelial cells, and CTHRC1+ fibrotic fibroblasts. This finding supports the rationale for potentially transferable therapeutic approaches across progressive fibrotic lung diseases.

In collaboration with DZL PIs Prof. Dr. med. Jens Gottlieb, Prof. Dr. med. Danny Jonigk, and Prof. Dr. rer. nat. Christine Falk, they will continue to conduct further research on RAS and CLAD at MHH, Germany’s largest lung transplant center.

Text: Lena Leiber / BREATH/AZ
Photo: Lena Leiber