Alvira Lab in the department of pediatrics

Current Projects

Transcriptional Regulation of Alveolarization
Transcriptional Regulation of Alveolarization

Secondary septation, the process that marks the alveolar phase of lung development, is a finely tuned series of events, involving coordinated activities of multiple different cell types within the lung. Secretion of extracellular matrix components, proliferation and migration of myofibroblasts and epithelial cells, and pulmonary capillary angiogenesis, have been identified as key players in this process. However, in contrast to the identification of multiple transcription factors controlling branching morphogenesis during the early stages of lung development, the regulators that control and coordinate the individual components of alveolarization remain unknown. The nuclear factor kappa-B (NFκB) family of transcription factors plays a key role in regulating cell survival, differentiation, and inflammation, however, a role in lung development has not been previously identified. A main focus of the Alvira Lab is to define a novel unction for NFκB in regulating postnatal lung development using mouse models and primary cell lines.

Novel Mediators of Pulmonary Angiogenesis
Novel Mediators of Pulmonary Angiogenesis

Postnatal pulmonary angiogenesis is essential for alveolarization. We have recently demonstrated a high degree of constitutive NFκB signaling in primary pulmonary endothelial cells (PEC) isolated from neonatal mice as compared to those isolated from adult mice. Furthermore, inhibiting constitutive NFκB activity in the neonatal PEC with either pharmacologic inhibitors or RNA interference, blocked PEC survival, decreased proliferation, and impaired in vitro angiogenesis. In this project we are utilizing RNAi to block the individual components of the NFκB pathway, microarray analysis, and endothelial specific conditional knock-out mice in order to identify novel NFκB mediated targets that are essential for postnatal pulmonary angiogenesis.

Developmental Regulation of Lung Injury and Repair
Developmental Regulation of Lung Injury and Repair

Local and systemic infections can injury the lung. Clinical and experimental evidence suggests that unique pathways may exist that serve to protect the immature lung from severe inflammation, and potentially allow for a greater regeneration after injury. Using a murine model of acute respiratory distress syndrome induced by the administration of systemic lipopolysaccharide, we are exploring the molecular mechanisms that serve to protect the lung against injury, and identify how these mechanisms are distinct in immature and mature animals. We believe that the information learned from these studies will be clinically relevant to a broad number of pulmonary diseases including bronchopulmonary dysplasia, asthma, ARDS, and emphysema.

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