Surgery, Craniofacial Molecular Biology
Childrens Hospital Los Angeles
School of Dentistry
Ostrow School of Dentistry
- Signal Transduction
- Developmental Biology
- Gene Regulation/Transcription
Research OverviewMolecular mechanisms of lung development and injury repair.
My laboratory focuses on the molecular mechanisms of TGF-ß/BMP signaling in regulating lung development and lung injury repair.
TGF-ß/BMP are a group of peptide growth factors that play essential roles in regulating cell proliferation, differentiation, migration, and apoptosis. Our previous studies found that early mouse embryonic lung development was stimulated by BMP4, and inhibited by TGF-ß in a lung explant culture system. Abrogation of BMP signaling in vivo during mouse embryonic lung development results in neonatal respiratory failure. However, blockade of TGF-ß/Smad3 signaling causes abnormal postnatal lung growth and maturation, which further contributes to the susceptibility to emphysema in adult mice. Therefore, TGF-ß/BMP signaling related regulation plays essential roles in normal lung development and lung injury repair. Deficiency of these pathways may be related to several respiratory diseases.
Current research projects in the laboratory are: (1) To determine BMP signal pathway and its significance during mouse lung development, including BMP receptor Alk3 and downstream Smads (Smad1 and Smad5); (2) To identify the molecular mechanisms of BMP antagonist Gremlin in neutralizing BMP ligand activity; (3) To determine the role of deficient TGF-ß signaling (including TGF-ß type II receptor and Smad3) in abnormal lung alveolarization and subsequent emphysema pathogenesis; (4) To determine the roles of lung resident mesenchymal stem cells in development and pulmonary diseases.