the Weaver Lab is centered on the function of the epithelium during normal lung
development and in disease. Current research in the lab is focused to three
- Pathogenesis of interstitial lung diseases: ILDs are a
heterogeneous group of pathologies that include the lethal fibrotic disease
idiopathic pulmonary fibrosis (IPF). The alveolar type II epithelial cell is
strongly implicated in the pathogenesis of IPF. We have generated novel knockin
mouse models to identify molecular pathways in type II cells that are perturbed
during disease progression, including the unfolded protein response (UPR),
autophagy and reactivation of developmental pathways.
- Protein misfolding and lung disease: Mutations that result
in misfolding of surfactant protein C (SP-C) are strongly linked to development
of ILD in infants and children. The goals of this project are to identify
molecular chaperones required for folding of normal SP-C and rapid disposal of the
cytotoxic misfolded protein via the proteasome or autophagy/lysosome.
- Lung epithelial barrier function and allergic disease: The lung epithelium is an important
component of innate host defense, forming a barrier that protects the airways
against inhaled particles, allergens and microorganisms. We have discovered a lipid
transport protein (Stard7) that confers protection against allergic asthma by
enhancing barrier function. Current studies are directed toward uncovering the
molecular mechanism(s) underlying the protective effect of Stard7.