SUMMARY
Mooney Mori, M.D., Ph.D., is a physician-scientist specializing in organ generative medicine who is dedicated to overcoming the limitations of current treatments for end-stage lung diseases. His laboratory develops pioneering strategies to generate functional human lungs using pluripotent stem cells through conditional blastocyst complementation — a transformative technology that enables in vivo whole-organ generation.
By integrating developmental biology, genome editing and advanced stem cell engineering, Dr. Mori's team is redefining the possibilities of regenerative lung therapy for patients awaiting transplant. His group was the first to successfully generate structurally and functionally complete lungs in mice, establishing a robust preclinical proof of concept. His research also investigates the temporal regulation of lung progenitor niches, organ size determination and interspecies barriers to enable scalable and translational applications.
Focus areas
- Transplantable lung generation using pluripotent stem cells and interspecies blastocyst complementation. Dr. Mori's lab established the first successful model of generating structurally and functionally complete lungs in mice, using donor pluripotent stem cells to reconstitute both epithelial and mesenchymal lineages, including vasculature. This groundbreaking platform now serves as the foundation for ongoing efforts to translate lung generation into large animal models using patient-specific induced pluripotent stem cells with the goal of future autologous transplantation.
- Humanized lung models for cystic fibrosis and genetic lung diseases. Dr. Mori and his team engineer human lung tissue in small animal hosts using induced pluripotent stem cells derived from patients with cystic fibrosis and other monogenic lung disorders. These in vivo humanized models provide a powerful platform to dissect disease mechanisms and test therapeutic interventions in a physiologically relevant setting.
- Models of bronchopulmonary dysplasia and preterm lung development. By integrating pluripotent stem cell-derived alveolar and airway organoids with in vivo explant cultures, Dr. Mori investigates the developmental arrest and molecular dysregulation underlying neonatal lung diseases such as bronchopulmonary dysplasia. This work seeks to identify vulnerable developmental windows and therapeutic targets to improve outcomes in premature infants with impaired lung maturation.
- Stem cell niche regulation across developmental time and species. Dr. Mori's group explores the dynamic regulation of stem and progenitor cell niches during lung development, from early lung precursors to lineage-committed cells. Their work has identified conserved mechanisms of progenitor interaction and tissue compartmentalization across species, with a focus on translating these principles from rodents to swine and ultimately to human biology.
- Organ size control and evolutionary scaling of the lung. Through comparative single-cell transcriptomics, genome editing and artificial intelligence-based modeling, Dr. Mori has uncovered evolutionarily conserved regulators of lung organ size. These findings address a central challenge in regenerative medicine — how to bioengineer lungs at the correct anatomical and physiological scale for human use, in both in silico and ex vivo systems.
Significance to patient care
Dr. Mori's research focuses on helping people with incurable end-stage lung diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary hypertension, severe asthma and lung conditions present from birth. For these individuals, current treatments only help manage symptoms — they don't cure the disease. Lung transplants are the only real cure, but they are limited by a shortage of donor organs. Even when someone gets a transplant, the need for lifelong medicines introduces big risks, including infection, cancer and other health conditions.
Dr. Mori's work offers a life-changing solution: creating healthy, working lungs from a patient's own cells. This could remove the need for donor lungs and the strong medicines used to prevent rejection. This solution also may lower the risk of complications after surgery. His approach has the potential to dramatically expand access to next-generation transplantation therapies for lungs or other organs generated from patients' own cells. With continued support, his research is building a future where no one has to die while waiting for a lung.
Professional highlights
- Mayo Clinic:
- Chair, Lung Innovation Collaborative Initiative, Mayo Clinic, 2024-present.
- DOM35 Ignite Award, Department of Medicine, Mayo Clinic in Rochester, Minnesota, 2025.
- Mayo Clinic Advanced Innovation Research (MC-AIR) Genesis Program, Mayo Clinic Research Innovation Office, 2025.
- Principal investigator, "Development of Humanized Lungs in Mice for Modeling Cystic Fibrosis Diseases," funded by the Cystic Fibrosis Foundation, 2024-present.
- Research Award, Sharp Corporation, 2021-present.
- National Institutes of Health:
- Committee member, NIH ORIP S10 High-End Instrumentation Grant Review Panel, for the Leica Stellaris Confocal Microscope, Columbia University Center for Human Development, 2022-2024.
- Principal investigator, NIH R01HL148223 Award, National Heart, Lung, and Blood Institute, 2019-2023.
- Principal investigator, Peer Reviewed Medical Research Program, Discovery, Expansion, and Investigator-Initiated Awards, U.S. Department of Defense, 2017-2024.
- Study section reviewer, Research Funding Program, United Kingdom National Centre for the Replacement, Refinement & Reduction of Animals in Research, 2023.
- RX1 Bioprinter Technology Innovation Award, Aspect Biosystems, 2021.