Physiological and pathophysiological roles of DARC (ACKR1) in haematopoiesis

I will study how the expression of the atypical chemokine receptor ACKR1 by erythroid cells affects the steady-state haematopoiesis, including the molecular make-up and functional profiles of stem-, progenitor- and lineage-restricted cells. Furthermore, I will explore the contribution of ACKR1 to the pathomechanisms of experimental diseases that rely in their pathogeneses on haematopoietic cell outputs. Experimental findings in mouse models will be aligned with molecular and cellular parameters of haematopoiesis in individuals of West African origin who carry the hugely prevalent ACKR1 polymorphism FyB(ES) and thus selectively lack ACKR1 in the erythroid lineage.

FyB(ES) is the most predictive ancestry informative marker of African origin and individuals who carry it are recognised to have altered incidences and outcomes of several debilitating diseases, compared to other ACKR1 polymorphisms. I will seek to provide a causative explanation for these findings.