The Translational Stem Cell Biology Branch focuses on understanding the basic biology and the clinical applications of stem cells, focusing on hematopoietic stem cells responsible for producing all blood cells and on induced pluripotent stem cells able to form a wide variety of tissues and organs. Our mission is to gain a better understanding of the processes that control self-renewal, differentiation and normal and abnormal functioning of hematopoietic and pluripotent stem cells in vivo, focusing on models with direct relevance to human biology and disease. We develop safe and effective gene, cell and small molecule therapies for a wide variety of serious human diseases, focusing on disorders of hematopoiesis and the cardiovascular system.
Hematopoiesis—the development and differentiation of stem cells into multiple types of blood cells—occurs throughout life, and its dysfunction is associated with low blood counts or leukemia. Research in the Laboratory of Molecular Hematopoiesis, led by Dr. Cynthia E. Dunbar, focuses on understanding the process of hematopoiesis in humans and in animal models that closely predict biology and disease in humans. Building on her laboratory’s work to understand these processes, Dr. Dunbar has translated her findings to improve the safety and effectiveness of gene therapies to treat human blood diseases. She is focusing on optimizing gene addition using engineered viruses and, more recently, gene editing using CRISPR/Cas9 approaches to precisely correct or modify specific locations in the genome of hematopoietic stem cells. This work has many applications in the treatment of serious human diseases, including sickle cell anemia and other inherited bone marrow diseases, leukemia, and HIV infection. Dr. Dunbar has built on her knowledge of hematopoietic stem cells in preclinical development of induced pluripotent stem cells for use in regenerative medicine, particularly for the treatment of cardiovascular, blood, bone and liver diseases, and in modeling human inherited diseases in the laboratory. Dr. Dunbar’s recent clinical work has focused on strategies to expand human hematopoietic stem cells in vivo in patients with bone marrow failure, most notably in a trial of the stem cell stimulatory drug eltrombopag for the treatment of patients with severe refractory aplastic anemia. This trial resulted in the first FDA approval for new drug to treat aplastic anemia in over 30 years.