UNC researchers receive $8.2-million grant to study the role of coagulation in pathology of sickle cell disease

A multi-disciplinary team of basic and clinical scientists from the Division of Hematology/Oncology in the Department of Medicine has received a five-year, $8.2-million grant from the NIH-NHLBI to study the role of coagulation in the pathology of sickle cell disease. Kenneth Ataga, MD, Nigel Key, MB, ChB, Nigel Mackman, PhD, and Rafal Pawlinski, PhD, will serve as co-PIs on the grant.

The following doctors will serve as joint principal investigators of the grant: Kenneth Ataga, MD, Associate Professor of Medicine, Director of the UNC Comprehensive Sickle Cell Program; Nigel Key, MB, ChB, FRCP, Harold R. Roberts Distinguished Professor, Chief of the Section of Hematology in the Division of Hematology/Oncology, and the Director of the UNC Hemophilia and Thrombosis Center; Nigel Mackman, PhD, FAHA, John Parker Professor of Medicine; and Rafal Pawlinski, PhD, Associate Professor of Hematology/Oncology. Eugene Orringer, MD, Program Director of UNC MD-PhD Program, professor of medicine, and Director of Education/Training/Career Development Core at NC TraCS Institute will be the leader of the Translational Research Skills Development Core.

Although primarily a hematologic disorder, SCD is associated with a complex vascular pathophysiology that includes activation of coagulation and inflammation. Dr.  Pawlinski’s laboratory, in collaboration with Drs. Key and Mackman, made the exciting discovery that inhibition of tissue factor, the primary cellular initiator of the coagulation cascade, not only reduces coagulation but also inflammation and endothelial cell activation in two mouse models of SCD.

Dr. Pawlinski together with Drs. Key and Mackman will use a combination of genetic and pharmacologic approaches to determine the mechanism by which different coagulation proteases contribute to the thrombotic complications and vascular inflammation in sickle cell mice. These mechanistic studies in mice will be complemented with a human proof-of-concept study, led by Dr. Ataga, to investigate the potential benefits of the recently approved oral anticoagulant Rivaroxaban in attenuating coagulation and inflammation in sickle cell patients.

The proposed studies may lead to the development of new therapies for SCD. Furthermore, the Translational Research Skills Development Core will provide the opportunity for recruitment and career development of young MD and PhD investigators willing to pursue a research career in hemoglobin disorders.