Susan H. Guttentag, MD

Lung surfactant plays an important role in managing both premature and term newborns with lung disease. Surfactant is a soap-like material made by cells in the small airspaces of the lung, the alveolar type 2 cells.  Surfactant is released into the airspaces where it spreads across the surface of the airspace to to maintain inflation during the breathing cycle. Diseases of surfactant fall into 3 categories: developmental, genetic, and acquired. The immature lungs of premature infants are often not yet able to make sufficient amounts of surfactant, and these infants develop Respiratory Distress Syndrome (RDS). Surfactant protein B, SP-B, is an important component of surfactant. Infants with a genetic defect in the SP-B gene have normal lung development but poor quality surfactant that gives rise to an RDS-like disease at term that is often fatal. Full term newborns are born with a full complement of surfactant, but diseases like pneumonia can inactivate normal surfactant, resulting in lung disease.

My research focuses on the formation of alveolar type 2 cells in the developing and injured lung. Using in vitro models of alveolar type 2 cell differentiation, we examine the biosynthesis of surfactant components and the cell biology of surfactant assembly into lysosome-like structures known as lamellar bodies.  Hermansky-Pudlak Syndrome, a rare form of albinism associated with lung fibrosis, is a family of diseases that affect post-Golgi trafficking in all cells, and affects the trafficking of a subset of proteins to lamellar bodies.  It remains unclear how the HPS proteins contribute to the abnormal lamellar bodies seen in HPS and whether this is important to lung fibrosis in HPS patients. We use mouse models of HPS that recapitulate the development of lung disease in patients with HPS, and together with in vitro cell culture models we are investigating how trafficking to lamellar bodies is disrupted in HPS. In addition to examining the basis for abnormal lamellar body development in HPS, we are using this mouse model to understand the pathobiology of lung disease in HPS with an eye toward developing pre-clinical data for novel therapies. In short, the focus of my research program is 1) to understand alveolar type 2 cell differentiation in developing lung, 2) to expand our knowledge of alveolar type 2 cell functions, and 3) to examine the contribution of alveolar type 2 cells to pulmonary physiology and pathophysiology, in both neonates and adults.