Dr. Whitsett's laboratory discovered surfactant proteins B and C, cloned the genes encoding the surfactant proteins A, B, C, and D, Scgb1a1, TTF-1 and others and utilized transgenic mouse models to delete and mutate these genes in transgenic mice. They identified transcriptional networks regulating lung morphogenesis and perinatal lung maturation contributing to the understanding of the roles of TTF-1, CEBPα, SOX2, SOX17, FOXA1, FOXA2, FOXA3, SPDEF, KLF5, CDC42 and others using both in vitro and in vivo methods. They identified multiple transcription factors regulating goblet cell differentiation airway epithelial cells including critical role of SPDEF, FOXA3 and airway goblet cells controlling innate immunity. They produced transgenic mouse models for conditional deletion and expression of genes involved in lung development, disease, and repair. They have generated transgenic models of pulmonary adenocarcinoma and explored the role of transcription factors mediating pulmonary adenocarcinoma in vivo and in vitro. They utilized RNA-Seq, microarray, Chip-Seq in the application of Nex-Gen sequencing and bioinformatics to identify and understand networks involved in the regulation of lung development and disease using clinical sample, as well as in vitro and in vivo models.
Dr. Whitsett has a long interest in training both in the clinical setting in “Neonatology” and in “Pulmonary Biology” and has contributed to the direct training of more than 80 graduate or post-graduate students in his laboratory. The scope of his work is represented in several recent reviews. Initial discoveries from his laboratory provided early insights into the genes and proteins critical for surfactant function including ABCA3, SFTPC, SFTPB, SFTPA, SFTPD.
MD: Columbia University, New York, NY, 1973.
Residency: Pediatrics, Mt. Sinai Hospital, New York City, 1974 to 1976.
Fellowship: Neonatology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, 1976 to 1977.
Rare Lung Diseases
Neonatology, Perinatal Biology, Pulmonary Biology, Developmental Biology, Fibrosis
Single cell RNA analysis identifies cellular heterogeneity and adaptive responses of the lung at birth. Nature Communications. 2019; 10:37.
Bronchopulmonary dysplasia. Nature Reviews. Disease Primers. 2019; 5:78.
Postnatal Alveologenesis Depends on FOXF1 Signaling in c-KIT+ Endothelial Progenitor Cells. American Journal of Respiratory and Critical Care Medicine. 2019; 200:1164-1176.
The S52F FOXF1 Mutation Inhibits STAT3 Signaling and Causes Alveolar Capillary Dysplasia. American Journal of Respiratory and Critical Care Medicine. 2019; 200:1045-1056.
Integration of transcriptomic and proteomic data identifies biological functions in cell populations from human infant lung. American Journal of Physiology: Lung Cellular and Molecular Physiology. 2019; 317:L347-L360.
Building and Regenerating the Lung Cell by Cell. Physiological Reviews. 2019; 99:513-554.
MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell differentiation. JCI insight. 2018; 3:e122490.
EMC3 coordinates surfactant protein and lipid homeostasis required for respiration. The Journal of Clinical Investigation. 2017; 127:4314-4325.
Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection. Science Translational Medicine. 2017; 9:eaaf9412.
INFLAMMATION. Modulating pulmonary inflammation. Science. 2016; 351:662-663.