From Flicker to Flame: How Ischemia-Reperfusion Injury and CMV Reactivation Induce Chronic Lung Allograft Dysfunction

• Applicant: Dr. Annika Schmidt
• Subject Area: Pneumology, Thoracic Surgery ; Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 566593497

Lung transplantation provides a life-saving option for patients with end-stage pulmonary diseases, yet post-transplant outcomes remain limited by complications such as primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD). PGD, triggered by ischemia-reperfusion injury (IRI), is the leading cause of early post-transplant mortality, while CLAD represents the primary barrier to long-term graft survival. Cytomegalovirus (CMV) reactivation further amplifies immune dysregulation, driving both acute and chronic allograft injury. This project investigates the interplay between IRI, CMV reactivation, and immune cell dynamics in lung transplantation, with a focus on adaptive-like NK cells and macrophage subtypes. Employing mouse models and clinical samples, the study aims to delineate how these immune mechanisms exacerbate graft injury and identify potential therapeutic targets to mitigate immune-mediated damage and improve long-term outcomes. The project integrates a comprehensive training and mentorship framework tailored to the development of an independent surgeon-scientist. The applicant will receive hands-on experience with advanced immunological methods, including high-dimensional flow cytometry, single-cell RNA sequencing, and spatial transcriptomics. These technical skills are complemented by formal coursework in bioinformatics, statistical computing, and translational research design. Mentorship from leading experts in lung transplantation immunology provides guidance on both experimental design and career development. Structured opportunities, such as biweekly lab meetings, journal clubs, and international conferences, including the International Society for Heart and Lung Transplantation (ISHLT), ensure continuous skill-building and networking, paving the way for establishong an independent academic career. The research is conducted in the UCSF Lung Transplant Research Laboratory, a state-of-the-art facility renowned for its multidisciplinary approach and robust translational science programs. The laboratory benefits from the resources of UCSF’s Bakar ImmunoX initiative, providing cutting-edge technologies and fostering collaborative research across diverse scientific disciplines. This dynamic and supportive environment includes access to a diverse patient population, a rich biorepository of clinical samples, and an extensive network of collaborators. Together, this unique combination of resources, mentorship, and collaboration enables the successful execution of the project’s goals while establishing a strong foundation for the applicant’s long-term contributions to transplantation science.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Hosts: Professor Daniel R. Calabrese; Professor John R. Greenland