The Polymorphic Red Blood Cell Surface: For Safer Transfusions and a Role as Regulator of Hematopoiesis, Host-Pathogen Interactions and Hemostasis

Red blood cells (RBCs) constitute >80% of our cells and 118 million blood donations/year are used by healthcare globally. All need to be matched between donor and patient. This project focuses on polymorphic surface molecules on RBCs, i.e. blood group glycoproteins or glycolipids. Such knowledge is key to improve transfusion outcome.

E.g. proactive DNA-based matching beyond routine ABO/RhD is impossible when the underlying gene is unknown.

Also, functions of most blood groups remain obscure, but we noted some regulate RBC formation.The overarching aims are:A.

To elucidate the molecular basis of new blood groups(including use of bacterial enzymes to create ABO-universal RBCs)B. To investigate the functional impact of blood groups by:1. Identifying regulators of erythropoiesis(e.g. in cultures of cells lacking the Vel/SMIM1 or MAM/EMP3 proteins)2. Using a large database to identify functions of blood groups in relation to disease3.

Exploring the emerging role of RBCs in clot formation(e.g. by defining how RBCs interact with platelets and coagulation factors)Project will be performed by PI´s team in 5-years.

Unique human knock-out cell panels and rare antisera combined with advanced biochemistry, molecular biology, imaging and bioinformatics will be used to test hypotheses. Longterm goal is to reveal therapeutic targets for anemia, infection and thrombotic disease. With a strong track record in blood group discovery, this grant will allow the team to pursue these bold projects.