New Study to Probe the Mechanisms of Platelet Activation by Hemolysis in Sickle Cell Disease

June 28, 2021

Deirdre Nolfi-Donegan, MD, assistant professor of pediatrics in the Division of Pediatric Hematology/Oncology at UPMC Children's Hospital of Pittsburgh, is the recipient of a 2021 Hemostasis and Thrombosis Research Society (HTRS) Mentored Research Award.

Dr. Nolfi’s research project, “Pathologic Platelet Activation in Sickle Cell Disease,” will investigate the mechanisms driving platelet activation in the context of hemolysis and oxidative stress that lead to thrombosis in sickle cell disease (SCD).

Dr. Nolfi-Donegan’s investigation will focus on mitochondrial bioenergetics, platelet function, and in vivo thrombus formation.  Specifically, she will examine how high mobility group box 1 (HMGB1), a protein released from activated immune cells and necrotic tissues whose level is increased in patients with sickle cell disease, interacts with free hemoglobin to promote platelet mitochondrial reactive oxygen species (ROS) production and platelet activation. This work will contribute novel findings that may lead to new and improved preventive strategies or therapies that guard against thrombo-inflammatory complications in individuals with sickle cell disease. Dr. Nolfi-Donegan’s research may also be applicable to other hemolytic diseases in which thrombus formation is a key factor, conditions such as paroxysmal nocturnal hemoglobinuria and unstable hemoglobinopathies.

Dr. Nolfi-Donegan is mentored in her research by Division colleague Cheryl A. Hillery, MD, professor of pediatrics, clinical director of Hematology, and director of the Comprehensive Pediatric Sickle Cell Program at UPMC Children’s, and Sruti Shiva, PhD, professor in the Department of Pharmacology and Chemical Biology and co-director of the Center for Metabolism and Mitochondrial Medicine at the University of Pittsburgh.

Learn more about Dr. Nolfi-Donegan and explore her published research.