Hematology Branch

Investigators in the Hematology Branch (HB) study normal and abnormal hematopoiesis—the development and differentiation of stem cells into multiple types of blood cells—in the clinic and in the research laboratory. Patients who have a variety of bone marrow failure syndromes and acute and chronic leukemias attend the HB’s clinic and may be enrolled in clinical research protocols at the NIH Clinical Center. Interventions are intended to reverse marrow failure, cure or ameliorate leukemias by stem cell transplant, and control lymphoproliferative diseases such as chronic lymphocytic leukemia by drug therapy. In the laboratory, basic cellular and molecular biology, immunologic, and genomic techniques and approaches are used to study patient samples, cells, cell lines, and in animal models. The Branch has been an international leader in developing understanding of the pathophysiology of hematologic diseases and improving their outcomes.

Our Labs

Hematopoiesis and Bone Marrow Failure

Research in the Hematopoiesis and Bone Marrow Failure Laboratory, led by Dr. Neal Young, spans the basic sciences, clinical trials, and epidemiology. Bench work involves methods of cell and molecular biology, immunology, and virology. Blood cell production in healthy individuals and especially in patients with bone marrow failure is the main theme. Advanced techniques most recently include single cell RNAseq, CRISPR-Cas9 gene editing, multicolored bar coded flow cytometry, and SomaLogic deep proteomics.


Lymphoid Malignancies

The Laboratory of Lymphoid Malignancies, led by Dr. Adrian Wiestner, aims to improve the treatment of patients with chronic lymphocytic leukemia (CLL). The group combines clinical and laboratory investigations to identify the molecular drivers of the disease. These insights are translated into clinical trials that seek to selectively eliminate tumor cells using targeted therapy. CLL samples donated by patients participating in these clinical trials are in turn used in the laboratory to study the effectiveness of the treatment and the reaction of the tumor cells to drugs, which can provide insights how to further improve the therapy.


Molecular Hematopoiesis

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.


Myeloid Malignancies

While considerable therapeutic advances using targeted therapies have been made for many malignancies, the most common treatment for acute myeloid leukemia (AML) has not changed in nearly 40 years. Although the majority of patients treated with chemotherapy will achieve an initial remission, subsequent treatment with either further chemotherapy or allogeneic stem cell transplantation (SCT) is effective at preventing leukemic relapse in only about half of these individuals. The outlook is often especially suboptimal for those diagnosed with AML but not eligible for this intensive therapy due to advanced age or medical co-morbidity. Despite the lack of progress with conventional treatments, recent advances in the scientific understanding of the genetic diversity of AML, new developments in immunotherapy and the powerful graft-versus-leukemia effect already observed after SCT all offer hope that AML is potentially susceptible to control by the immune system in the non-SCT setting. Research in the Laboratory of Myeloid Malignancies, led by Dr. Christopher Hourigan, focuses on three complementary approaches that are united by an overriding theme of performing translational human immunology research in order to find ways to detect, prevent and treat AML relapse.


Regenerative Therapies for Inherited Blood Disorders

Gene and stem cell-based regenerative therapies hold the promise of replacing lost, damaged, or aging cells and tissues in the human body. Despite substantial strides in understanding stem cell biology in humans, major challenges have slowed the translation this knowledge into medical therapies. The Laboratory of Regenerative Therapies for Inherited Blood Disorders, led by Dr. Andre Larochelle, is investigating novel strategies and stem cell concepts that can help advance the translational regenerative field, with a focus on inherited disorders affecting blood-forming hematopoietic stem cells (HSCs). Dr. Larochelle’s program aims to develop regenerative therapies for inherited HSC disorders by: 1) CRISPR-Cas9 and retroviral mediated-genetic correction of HSCs for clinical applications; 2) derivation of engraftable HSCs from genetically corrected induced pluripotent stem cells (iPSCs); and 3) in vivo and ex vivo expansion of HSCs.