Lineage Tracing Approach to Dissect Pulmonary Vascular Remodeling
With identification of a novel mouse model with severe PAH, Egln1Tie2Cre mice, we have developed a powerful tool for use to trace different cell populations (such as endothelial cells, smooth muscle cells, fibroblast, etc) in our model system. A major advantage of this model is mincing human PAH pathology, which allows it to study dynamic change of cells contributing to the severe pulmonary vascular remodeling in PAH.
High Throughput Screening Meets with CRISPR/Cas9
We still employ CRISPR/Cas9 genomic editing technology and high throughput screening to identify novel partners of HIF and BMPR2 signaling in the pathogenesis of pulmonary vascular remodeling and PAH.
First PAH Mouse Model
Employing the mice with Tie2Cre-mediated disruption of Egln1 encoding PHD2 (Egln1Tie2), we observed spontaneous severe PAH with extensive pulmonary vascular remodeling including vascular occlusion and plexiform-like lesions and severe right ventricular (RV) hypertrophy and resultant right-sided heart failure.To the best of our knowledge, this is the first mouse model with irreversible obliterative vascular remodeling and pathophysiology as seen in patients with severe PAH including IPAH.