Darrell N. Kotton, MD
Dr. Kotton’s research program focuses on developing novel cell and gene based therapies for reconstitution of injured lung epithelia. His laboratory has engineered lentiviral technology for mouse and human somatic cell reprogramming and has utilized this new technology to derive the first lung disease-specific induced pluripotent stem (iPS) cells from humans with cystic fibrosis and alpha-1 antitrypsin deficiency. Dr. Kotton’s approach to directed differentiation of pluripotent stem cells, such iPS or ES cells, utilizes embryonic development as a roadmap, whereby the sequential milestones of early lung development are recapitulated in vitro in order to direct ES and iPS cells efficiently into definitive endoderm precursors of lung epithelium. This model system allows easy access to cells at early developmental timepoints, thereby allowing the study of basic mechanisms controlling cell fate decisions and lung lineage specification. Dr. Kotton’s laboratory applies this system in order advance our understanding of basic lung developmental biology, stem cell biology, and ultimately to bioengineer novel cell reconstitution strategies for degenerative or inherited lung diseases. One outcome of this work has been the generation of transplantable bioartificial lungs by re-seeding decellularized mammalian lung scaffolds with candidate lung progenitor populations.