Selective targeting of myofibroblasts during lung regrowth and alveolar regeneration

• Applicant: Professor Elie El Agha, Ph.D.
• Subject Area: Pneumology, Thoracic Surgery ; Developmental Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458065839

Alveolar regeneration requires coordinated engagement of epithelial stem cells and mesenchymal niche cells to restore the intricate alveolar architecture of the lung. The current paradigm is that certain aspects of lung organogenesis are mimicked during injury repair in the adult stage. During lung development, alveolar myofibroblasts (AMFs) play a critical role in the subdivision of primitive alveolar sacs into mature alveoli. In the previous funding period, we showed that AMF-like cells emerge during lung regrowth following pneumonectomy or alveolar regeneration following influenza virus-induced lung injury in the adult stage. For the renewal of the proposal, we plan to carry out intersectional genetics to target AMF-like cells allowing both lineage tracing and genetic ablation with high precision compared to conventional genetic approaches. To complement our in vivo approach, we also plan to use state-of-the-art ex vivo tools such as lung organoids to pursue mechanistic studies and assess the therapeutic potential of selected candidates. We will also use human biobanked lung material to translate our findings to the human context. This porposal will serve as a building block towards achieving regenerative therapies in the diseased human lung.

• DFG Programme: Research Grants