Cynthia Dunbar

Cynthia E. Dunbar, M.D.

Senior Investigator

Building 10-CRC, Room 5-3332
10 Center Dr
Bethesda, MD 20814
United States

301-443-5414
301-402-0888

Biography

Head, Molecular Hematopoiesis Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD

Dr. Dunbar has pursued a career encompassing clinical investigation and patient care, basic science, and education/administration.  As a translational research scientist, she has made important findings in the areas of hematopoiesis, stem cell biology, leukemogenesis, natural killer cell biology, and gene therapy, focusing on non-human primate models to provide insights not possible using murine or in vitro models. She has also led important clinical trials in gene therapy, transplantation, autoimmune disease, and bone marrow failure.  She has published over 250 articles in peer-reviewed journals, and served as the principle investigator on numerous clinical protocols. She graduated from Harvard College with a degree in History of Science, and from Harvard Medical School. Following internal medicine training at Boston City Hospital, she came to the NIH as a postdoctoral research fellow with Dr. Arthur Nienhuis, and following one further year of clinical training in hematology at University of California, San Francisco, she returned to the NIH to set up her own research program in 1991. She has been elected to the American Society for Clinical Investigation and the American College of Physicians. She has been active in major professional societies, including service on the executive committee of the American Society of Hematology, and is immediate past President of the American Society for Cell and Gene Therapy. She served as Editor-in-Chief of the premier hematology journal BLOOD from 2007-2012, the first woman to serve in this position. She has shown great commitment to education and career development of physician-scientists, running the NIH hematology fellowship program for 17 years, and serving as the chair of the NIH ACGME committee. She has been a leader in efforts to enhance the research environment within the intramural NIH through her service on various committees and as a founding member and current Co-Chair of the NIH Assembly of Scientists.  She has received numerous teaching and mentoring awards from NHLBI, NIH and her professional societies. She lives in Washington, DC with her husband, having recently launched her two daughters onto adulthood, and relaxes by performing and listening to classical music, hiking and rowing.

Cynthia Dunbar CV (PDF, 409KB)

Research

Research Interests
- Cynthia E. Dunbar, M.D.

Dr. Dunbar’s research in the Translational Stem Cell Biology Branch (TSCBB) spans basic laboratory studies through pioneering clinical trials focusing on stem cell biology and hematopoiesis—the development and differentiation of bone marrow stem cells into multiple types of blood cells. Hematopoiesis occurs throughout life, and dysfunction of these processes can be associated with low blood counts, such as in aplastic anemia, or leukemia. Much of the research in the TSCBB focuses on understanding the process of hematopoiesis as it occurs in the body, using cutting edge molecular technologies such as genetic barcoding and single cell gene expression analyses to understand the “family tree” linking stem cells to their daughter cells and eventually to mature circulating blood cells. For over twenty-five years, Dr. Dunbar’s research group has utilized the rhesus macaque transplantation model to study hematopoiesis, with unique relevance to understanding human hematopoiesis. These studies have provided insights into stem cell frequency, lifespan, aging, geographic location, and differentiation.  Recently this research approach yielded the first direct evidence for self-renewal and long-term persistence of mature natural killer cells, a poorly understood cell population able to fight cancer and viral infections, with relevance to the maintenance of NK cell memory. 

The TSCBB is also engaged in designing and optimizing methods to genetically modify or correct hematopoietic stem cells, with direct translation to human gene therapies. The research group has focused on understanding and improving the safety and effectiveness of a variety of gene transfer vectors that integrate into the genome of hematopoietic stem cells, including murine retroviruses, avian retroviruses, and lentiviruses. These translational studies have provided critical information to improve clinical gene therapies targeting blood diseases such as inherited immunodeficiencies and sickle cell anemia. Most recently the group has focused on gene editing technologies, such as CRISPR/Cas9, to correct or modify the genome at specific gene targets with rapid progress, creating models of human hematopoietic stem cell aging and using gene editing to overcome potential toxicities of CAR-T cells directed against leukemia. 

The TSCBB has also focused on other types of stem cells, particularly induced pluripotent stem cells (iPSC), utilizing technologies to transform any adult cell type into a very primitive stem cells able to regenerate all types of tissues and organs. The Dunbar research group was the first to create rhesus macaque iPSC, and have gone on to use the rhesus iPSC model to develop safe and effective approaches for tissue and organ regeneration. Active research directions include testing of in vivo cardiac regeneration from rhesus macaque iPSC following myocardial infarction.

In collaboration with other NHLBI investigators, Dr. Dunbar and her group have led pioneering attempts to stimulate human hematopoietic stem cells in vivo, most notably in patients with severe refractory aplastic anemia. The small molecule oral drug eltrombopag was found to improve blood counts in patients with this condition about 50% of the time, and this NHLBI trial resulted in the first FDA approval for new drug to treat aplastic anemia in over 30 years. 

Publications