Dr. Vivien Sheehan is a pediatric and adult hematologist specializing in sickle cell disease (SCD). Her research projects range from clinical research to basic science.
Investigating the effects of hydroxyurea on red cell rheology
Dr. Sheehan’s clinical projects include: investigations into the effects of hydroxyurea on red cell rheology, including red cell density, whole blood viscosity, and oxygen carrying capacity. These investigations are the foundation for a clinical trial of the use of hydroxyurea and phlebotomy in the treatment of Hemoglobin SC disease (HbSC), a sickle cell subtype in which viscosity and red cell density plays a major role in disease pathology. Despite composing 25% of the sickle cell disease population, HbSC patients were excluded from all sickle cell treatment trials, so we currently have no evidence based therapies to offer them.
A phase II trial of hydroxyurea in HbSC patients will open in the fall of 2014.
Developing a transition clinic to help young adult hemoglobinopathies patients transition to adult hematology care
Dr. Sheehan is developing a transition clinic to help our young adult hemoglobinopathies patients successfully move from pediatric to adult hematology care. The period between 18 and 26 years of age is marked by increased mortality and morbidity, often due to loss of subspecialty care. Emergency department utilization increases, and use of chronic maintenance therapy, such as hydroxyurea or chronic transfusions, declines.
It is essential that patients receive support through this difficult period, and assure a smooth, seamless transition to adult care through a transition clinic located in an adult hematology clinic, staffed by dually-trained physicians that are aware of the special needs, both medical and psycho-social, of this chronically ill, vulnerable population.
Whole exome sequencing to study the pharmacogenomics of hydroxyurea
Dr. Sheehan’s translational research project uses whole exome sequencing to study the pharmacogenomics of hydroxyurea, the only drug treatment for sickle cell disease. Clinical and laboratory response to hydroxyurea varies, and the mechanism by which it achieves fetal hemoglobin (HbF) induction is unknown.
Dr. Sheehan has obtained genomic DNA and associated phenotypes from patients in the hematology center and 4 other sickle cell centers across the country to assemble the largest cohort of hydroxyurea-treated sickle cell patients. She will identify variants associated with HbF response to hydroxyurea and confirm the association with functional studies.
This work will add to existing scientific knowledge of drug induction of HbF, and potentially identify new drug targets for patients who do not benefit from hydroxyurea.
Investigating the role of FOXO3 in erythropoiesis and gamma globin regulation
Her basic science project studies gamma globin regulation, a component of HbF. While investigating the pharmacogenomics of hydroxyurea, Dr. Sheehan’s laboratory identified an association between FOXO3 and baseline HbF in sickle cell patients. This association has been confirmed with functional studies in two model systems: an erythroid leukemia cell line and primary erythroid cells. Dr. Sheehan’s laboratory will continue to investigate the role of FOXO3 in erythropoiesis and gamma globin regulation.
Vivien Sheehan, MD, PhD
Yankai Zhang, PhD
Carly Summarell, MS