Cynthia E. Dunbar, M.D.

Molecular Hematopoiesis Section

Cynthia E. Dunbar, M.D.
Senior Investigator
Molecular Hematopoiesis Section

P: +1 301 402 1363
F: +1 301 594 1290
dunbarc@nhlbi.nih.gov

Scientific Focus Area(s): Cancer Biology, Cell Biology, Clinical Research, Stem Cell Biology, Virology

Background

Cynthia Dunbar earned a B.A. magna cum laude in the history of science from Harvard University in 1980 and a M.D. magna cum laude from Harvard Medical School in 1984. She subsequently completed her internal medicine internship and residency at Boston City Hospital and hematology fellowship training at the University of California, San Francisco. She came to the NHLBI as a postdoctoral fellow in the laboratory of Arthur Nienhuis in 1987, became an Investigator in 1993, and has been Head of the Molecular Hematopoiesis Section since 2000. Dr. Dunbar has received numerous awards for teaching, mentorship, and research, including the NIH Clinical Center Distinguished Clinical Teacher Award, the John Decker Memorial Lectureship, and the Brigham and Women's Hospital Moloney Award and Lectureship. She has authored more than 200 peer-reviewed scientific and review articles, and has given numerous invited lectures and presentations about her work. Dr. Dunbar is the Editor-in-Chief of the journal Blood, the flagship publication of the American Society of Hematology. She is also a member of the American Society for Clinical Investigation, a Master of the American College of Physicians, a founder and board member of the American Society for Cell and Gene Therapy, and served seventeen years as the director of the NIH Hematology Clinical Fellowship training program.

Research Interests

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. Dr. Dunbar’s research focuses on understanding the process of hematopoiesis in vivo, as well as on optimizing and improving the safety of gene transfer into primary hematopoietic cells for therapeutic purposes. Her goals are synergistic: insight into the control of hematopoiesis is required to successfully manipulate and genetically modify hematopoietic cells; conversely, genetic marking of hematopoietic stem and progenitor cells has provided novel insights into lineage relationships, stem cell dynamics, and stem cell numbers in vivo that are applicable to gene therapy, stem cell transplantation, and other clinical interventions.
For over twenty years, Dr. Dunbar’s laboratory has had the privilege of utilizing a rhesus macaque transplantation model. Her facility is one of only a handful worldwide able to successfully support non-human primates through stem cell transplantation. This model provides unique and highly relevant insights into hematopoiesis and has resulted in successful optimization of gene and cell therapy approaches later translated successfully into human clinical trials. Her studies also encompass informative in vitro, murine, and human xenograft models.
Dr. Dunbar and her colleagues have mapped the number, frequency, and output of individual stem and progenitor cells over time, and analyzed the impact of clinically relevant interventions such as cytokines on stem cell dynamics in vivo. They have provided insights into the processes of hematopoietic stem cell mobilization and homing, utilizing molecular and high-resolution novel imaging techniques able to track the output of individual stem cell clones, and have described the biochemistry and functional importance of a polarized membrane domain in these processes.
In addition, Dr. Dunbar’s team has developed a number of new gene therapy vector systems for high efficiency transduction of monkey and human hematopoietic stem and progenitor cells. The growing evidence that integrating gene therapy vectors can activate adjacent proto-oncogenes, both from human clinical trials and from primate studies in Dr. Dunbar’s laboratory, has spurred intense investigation into the process of vector integration into the genome. Dr. Dunbar has been a leader in this research for the past ten years. Her laboratory continues to optimize vector and transduction approaches that can retain the therapeutic potential of stem cell gene therapies while avoiding genotoxic events.
Dr. Dunbar’s laboratory has also developed induced pluripotent stem cells in the rhesus model, and is investigating whether their use in regenerative medicine approaches can be made safe and effective. Her recent clinical work has focused on strategies to expand human hematopoietic stem cells in vivo, most notably in a trial of the stem cell stimulatory cytokine analog eltrombopag for the treatment of patients with severe refractory aplastic anemia.

Selected Publications

Dynamic clonal analysis of murine hematopoietic stem and progenitor cells marked by five fluorescent proteins using confocal and multiphoton microscopy.
Malide D, Metais JY, Dunbar CE.
Blood. 2012 Sep 20;.
[Text Abstract on PubMed]
Thymidine kinase suicide gene-mediated ganciclovir ablation of autologous gene-modified rhesus hematopoiesis.
Barese CN, Krouse AE, Metzger ME, King CA, Traversari C, Marini FC, Donahue RE, Dunbar CE.
Mol. Ther. 2012 Oct;20:1932-43.
[Text Abstract on PubMed]
Eltrombopag and improved hematopoiesis in refractory aplastic anemia.
Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE.
N. Engl. J. Med. 2012 Jul 5;367:11-9.
[Text Abstract on PubMed]
Bone marrow homing and engraftment of human hematopoietic stem and progenitor cells is mediated by a polarized membrane domain.
Larochelle A, Gillette JM, Desmond R, Ichwan B, Cantilena A, Cerf A, Barrett AJ, Wayne AS, Lippincott-Schwartz J, Dunbar CE.
Blood. 2012 Feb 23;119:1848-55.
[Text Abstract on PubMed]
No evidence for clonal selection due to lentiviral integration sites in human induced pluripotent stem cells.
Winkler T, Cantilena A, Métais JY, Xu X, Nguyen AD, Borate B, Antosiewicz-Bourget JE, Wolfsberg TG, Thomson JA, Dunbar CE.
Stem Cells. 2010 Apr;28:687-94.
[Text Abstract on PubMed]
Cynthia E. Dunbar's Full List of Publications