This new investigator proposal describes a 5 year training program for the development of a career as a Physician scientist in pulmonary medicine. The principal investigator has completed a fellowship in pulmonary and critical care medicine at Boston University and a one year research fellowship in the Department of Biochemistry at Stanford University, where he now continues as an Instructor in the Pulmonary and Critical Care division of the Department of Medicine. In carrying out the proposed research, the Principal Investigator will acquire expertise in lung histology, mouse genetics, molecular biology, and genomic approaches. Dr. Mark A. Krasnow will mentor the Principal Investigator's scientific development. He is Professor and Chairman of Biochemistry at Stanford and an Investigator in the Howard Hughes Medical Institute who has trained numerous individuals who have gone on to establish their own laboratories and successfully compete for independent funding. The Principal Investigator has also enlisted three internationally recognized authorities in the fields of lung epithelial cell biology, alveolar development and mouse genetics, respectively, as consultants. He will work closely with the mentor and consultants to ensure fulfillment of the specific aims. An advisory committee of senior investigators at Stanford has also been assembled and will provide scientific and career advice. Research will focus on development and maintenance of the alveolar type 1 (AT 1) cell.
Specific aims i nclude: 1) Identify and characterize using molecular markers the putative bi-potential progenitor of AT 1 cells in mouse lung and determine when and where it arises, and how it changes during lung development, 2) Use mouse transgenic techniques to label and trace the fate of mature AT 2 cells to determine whether the AT 2 cell is an obligate progenitor to the AT 1 cell, 3) To identify potential regulators of AT 1 fate by using RNA in situ hybridization to screen for transcription factor genes that are selectively expressed in terminal airspace epithelium at the time of AT 1 morphogenesis. By bringing together unique resources from multiple departments, this program integrates specialized areas of expertise that will ensure fulfillment of the specific aims. This work will be relevant for understanding and ultimately treating lung diseases like emphysema, lung cancer, and pulmonary fibrosis.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZHL1-CSR-X (O1))
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Colombini-Hatch, Sandra
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Stanford University
Schools of Medicine
United States
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Desai, Tushar J; Brownfield, Douglas G; Krasnow, Mark A (2014) Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature 507:190-4
Treutlein, Barbara; Brownfield, Doug G; Wu, Angela R et al. (2014) Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature 509:371-5