Tager Lab
Dr. Tager's research interestes are in identifying new important pathways in the development of idiopathic pulmonary fibrosis that could become additional therapeutic targets.
Fibrotic diseases such as idiopathic pulmonary fibrosis and scleroderma are associated with high morbidity and mortality, with outcomes largely unaffected by current therapies. Improved understanding of the biologic processes involved in development of fibrosis in these diseases, and more complete identification of the molecular mediators driving these processes, are urgently needed to develop effective new therapies.
Dr. Tager’s research group found that the potent lipid mediators lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) direct multiple processes fundamentally involved in fibrogenic responses to injury, including epithelial cell apoptosis, vascular leak, and fibroblast recruitment and persistence. They found that LPA signaling through one of its receptors, LPA1, is critically required for the development of pulmonary and dermal fibrosis in mice following bleomycin-induced injury of these tissues: LPA1-deficient mice are dramatically protected from fibrosis in these commonly used models of IPF and scleroderma. They also found that LPA levels are increased in the BAL fluid of patients with established IPF, that LPA1 is highly expressed by fibroblasts recovered from IPF BAL, and that pharmacological antagonism of LPA1 markedly reduces fibroblast responses ex vivo to the chemotactic activity of IPF BAL. In their studies of S1P in fibrotic disease, they demonstrated that inhibition of S1P-S1P1 signaling dramatically worsened vascular leak induced by bleomycin lung injury. Mice developing increased leak from S1P1 antagonism also went on to develop markedly increased lung fibrosis following bleomycin injury.
Dr. Tager’s research group is pursuing multiple studies to further define the roles of these important mediators, and potential targets for novel therapies, in both mouse models and translational studies of fibrotic diseases.