Dr. Cheryl Hillery is an NIH-funded physician-scientist who treats patients with sickle cell disease (SCD) and has been involved with basic and translational research programs focused on the vascular and organ pathologies in human and mouse models of SCD as well as novel mechanisms of pain. She was recruited to the Division of Pediatric Hematology/Oncology in Pittsburgh in May 2015, and has been working with Dr. Linda McAllister-Lucas to build a strong clinical and translational benign hematology program at the University of Pittsburgh and Children’s Hospital of Pittsburgh; she has also continued her NIH-funded collaborative research activities with scientific colleagues from the Medical College of Wisconsin.
SCD is caused by a genetic disorder of hemoglobin that predisposes sickle hemoglobin to form long crystals that damage the red cell membrane and cause it to block blood vessel flow (vaso-occlusion). The major cause of pain, suffering, and death in SCD is tissue injury and inflammation due to repeated vaso-occlusion that results in progressive organ damage. Much remains unknown regarding exactly how sickle red cells injure the blood vessels and how this leads to the blood vessel and organ damage observed in patients. Because of this, there are currently few choices for effective treatment of this disease. Thus, there is a great need to develop novel therapeutic approaches for the prevention and treatment of vaso-occlusion and resultant complications in SCD.
Role of the Clotting and Inflammatory Pathways in Sickle Cell Disease. Abnormal adhesion of sickle red cells to the blood vessel damages the vessel wall and slows or stops blood flow. Increased activity of the clotting and inflammatory pathways further injures blood vessels and organs in SCD. Hillery’s team studies are trying to discern the exact role of the clotting and inflammatory pathways and to determine whether agents that thin the blood or decrease inflammation may help patients who suffer from SCD.
Novel Mechanisms of Pain in Sickle Cell Disease. Pain is the major cause for urgent medical care and admission to the hospital in children who suffer from SCD. The pain and disability are even more severe in adults. In this project, Hillery and her collaborator, Cheryl Stucky, study the precise nerve cells and pathways that sense the pain and carry the message to the brain so that they can develop new methods to treat SCD more safely and effectively. This study is currently funded by NIH R01 “Nociceptive Mechanisms Underlying Sickle Cell Pain” (multiple PIs Stucky and Hillery) through 2019.
Role of Inflammation in the Morbidities Associated with SCD. SCD is characterized by chronic inflammation. Asthma is an inflammatory comorbid condition that is commonly found in children with SCD and may further contribute to sickle hemoglobin-induced vascular and organ pathologies. A diagnosis of asthma among individuals with SCD is associated with twice the rate of pain and increased mortality when compared to SCD individuals without asthma. The researchers have explored the role of asthma and asthmatic inflammatory pathways in complications of human and mouse SCD. In ongoing studies, Hillery and her collaborator, Kirkwood Pritchard, are now exploring the role of high-mobility group box 1 (HMGB1), a nuclear protein that is important for maintaining DNA structure and function. During inflammation and injury, HMGB1 is released from the cells; once released, it can act as a potent inflammatory agent that increases endothelial cell injury and death. They think SCD increases HMGB1 to increase endothelial cell injury and risk of RBC congestion and crisis. The goal of these studies is to learn how HMGB1 increases inflammation, injures endothelial cells, and increases vaso-occlusive crises in SCD. These studies are funded by NIH R01 “Mechanisms of Inflammation in Sickle Cell Disease” (multiple PIs Pritchard and Hillery) to continue these studies with a focus on HMGB1. Hillery is also a collaborator for ongoing U.S. Food and Drug Administration R01 “Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia” (PI Joshua Field).
Education & Training
- Fellowship-University of North Carolina Hospitals/ Graduate Medical Education, Chapel Hill, NC
- Residency-University of North Carolina Hospitals/ Graduate Medical Education, Chapel Hill, NC
- MD-Washington University School of Medicine St. Louis, MO
- MD-Duke University School of Medicine Graduate Medical Education, Durham, NC
- Nociceptive Mechanisms Underlying Sickle Cell Pain
- Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia
- Role of Substance P in the Pathophysiology of Pain in Patients with Sickle Cell Disease