Molecular mechanisms of lung development
Injury repair and regeneration
Growth factor signaling
Mesenchymal stem cells in lung development and pulmonary diseases
Neonatal respiratory distress (RDS) is the leading cause of death among premature infants in the US, and even when cured, it often has lifelong complications. Wei Shi, MD, PhD, of the Developmental Biology and Regenerative Medicine research program is working to develop new therapies for preventing and treating neonatal respiratory distress that avoid these debilitating side effects.
Premature babies are at higher risk for RDS because their lungs cannot yet produce surfactant, a soap-like substance that reduces surface tension in the alveoli so the lungs can expand. RDS affects 10 percent of all premature babies in the US and the risk rises with increasing prematurity. Infants born prior to 29 weeks have a 60 percent chance of developing the condition.
Treatments for RDS – such as surfactant replacement, oxygen therapy, steroids and mechanical ventilation – have drastically reduced premature morbidity due to RDS, from 100 % to just 10 %. However, RDS can still have lasting side effects. Affected infants are more likely to develop chronic lung disease or neurological disorders, and some therapies that initially save lives can add to that risk.
Dr. Shi is interested in identifying the molecular pathways responsible for fetal lung transition from the amniotic fluid environment to postnatal air breathing, and to use these basic biological findings to develop better treatment options for infant respiratory distress. He is currently investigating bone morphogenic protein (BMP) and its role in the process of neonatal respiratory adaptation with the aim of finding a target for clinical translation.
BMP functions in the development of many organs, including the early branching stages of lung formation. Dr. Shi has found that an increase in BMP activity is required for neonatal lung adaptation and he is working to discover why BMP is so crucial to this process.
He is also studying lung mesenchymal (embryonic connective tissue) stem cell function in lung development and repair. His lab is working to develop innovative molecular tools that will allow continued advancement in this area.
- Dissecting TGF-beta and BMP signaling mechanisms in regulating lung development and neonatal respiratory distress, as well as in adult lung fibrosis.
- Defining the roles of TGF-beta and BMP signaling in maintaining adult lung. homeostasis and the relationship to COPD/emphysema.
- Determining that abnormal lung development is a predisposing factor to adult chronic lung diseases.
- Determining the roles of APC/Wnt signaling in regulating lung development, lung injury repair and regeneration.
- Constructing a rich multiscale atlas of lung alveolar development.
- Defining lung resident mesenchymal stem cell origins and functions, as well as their roles in maintenance of lung homeostasis and in pathogenesis of lung diseases.
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