The seminar will discuss the single cell approach we are taking to understand how arteries change in pulmonary arterial hypertension (PAH), a disease characterized by profound vascular remodeling. In PAH, pulmonary arteries narrow due to medial thickening and occlusion by neointimal lesions, which leads to elevated pulmonary vascular resistance and ultimately right heart failure. Therapies targeting the neointima would represent a significant advance in PAH treatment, and by understanding of the cellular events driving neointima formation, and the molecular pathways that control them, we hope to open the door to new treatments. Using a wide array of approaches -- genetic lineage tracing, clonal analysis, single cell RNA-sequencing, bioinformatic interaction mapping, multiplexed in situ hybridization, immunostaining, deep confocal imaging and staged pharmacologic inhibition – we are defining the cell behaviors underlying each stage of vascular remodeling, the progenitor populations that operate at each stage, and identifying the pathways that control them.
Maya Kumar, MD
Lea Steffes, MD