The Krasnow Lab uses genetic and genomic approaches to elucidate, at single-cell resolution, the genetic programs that control development, renewal, and regeneration of the lung and explore how they go awry in lung cancer and other serious lung diseases that have no effective and durable therapies. We are especially interested in lung stem cells and how they are activated by injury and controlled in three dimensions to generate functional tissue, and how oncogenic mutations activate some parts of the stem cell program to generate continuously growing, non-functional tissue (tumors) that is ultimately deadly. We have recently purified and characterized human alveolar stem cells and shown that introduction of oncogenic mutations transforms them, initiating early-stage lung adenocarninoma, the leading cancer killer. We can now study the initiation of human lung adenocarcinoma ex vivo. We hope this leads to a deep molecular understanding of the process and new approaches to early detection of lung cancer and rational, targeted therapies that can eliminate the tumors before they become deadly. We are also using purified alveolar stem cells to reconstruct native human alveoli (“alveolar organlets”) to study additional aspects of alveolar biology and cancer, including tumor immunology. We want to extend this approach to other parts of the lung and other forms of lung cancer, and ultimately to regenerate an entire human lung. We use similar approaches to map the breathing pacemaker and neural circuit of breathing and to identify breathing arrhythmias.

We have also established an international consortium including Stanford, Bay Area, French, and Malagasy students and scientists and a laboratory in Madagascar, and have created cellular, molecular, and genomic resources and genetic tools that establish mouse lemur as a tractable genetic model organism for the study of primate-specific physiology, behavior, diseases, and ecology. These include mouse lemur stem cells and cancers that are absent or poorly modeled in mice.