Role of Red Blood Cells in Pulmonary Artery Hypertension (PAH)

Gene expression studies have shown that SSc-PAH patients have an enrichment of immature red blood cells, and red cell parameters are associated with disease onset and severity.  This project seeks to test the hypothesis that abnormalities in red cell development are a key pathologic factor in SSc-PAH and that myeloid cell phagocytosis of red cells drives pathologic immune dysregulation.  This will be accomplished through flow cytometry assessment of erythrocytes in patients with SSc with and without PAH, single cell RNA sequencing of patient immature RBCs, and experiments in TNF-transgenic mice using drugs to target erythrocyte maturation with assessment of PH histologically, physiologically, and by assessing phagocytic cells in the lung.