Molecular Hematopoiesis

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.

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Senior Investigator Research Interests

Research Interests

Our research interests span 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 result in bone marrow failure or leukemia. We utilize 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, in both health and disease. For over thirty years, our research group has utilized the rhesus macaque transplantation model to study hematopoiesis and the immune system. This model provides unique predictive insights into human hematopoiesis and blood diseases. Our studies have provided insights into stem cell frequency, lifespan, aging, geographic location, and differentiation. Recently we provided the first direct evidence for self-renewal and long-term persistence of mature natural killer cells, explaining aspects of natural killer cell memory and providing insights into dynamics of these cells following infections or as therapies to fight cancer.

We have also been engaged in more than three decades of efforts to design, optimize and utilize methods to genetically modify or correct hematopoietic stem cells, with direct translation to human gene therapies. We have 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. The rhesus macaque model has been of great utility for assessment of the safety and efficacy of novel gene and cell therapies. These translational studies have provided critical information to improve clinical gene therapies targeting blood diseases such as inherited immunodeficiencies and sickle cell anemia. We have also investigated gene editing technologies, such as CRISPR/Cas9, to correct or modify the genome at specific gene targets, creating macaque models of human hematopoietic stem cell aging and marrow failure disorders, and using gene editing to overcome potential toxicities of CAR-T cells directed against forms of leukemia.

We have expanded our focus to other types of stem cells, particularly induced pluripotent stem cells (iPSC). We were the first to derive rhesus macaque iPSC and have gone on to use the rhesus iPSC model to develop safe and effective approaches for tissue and organ regeneration, particularly focused on the heart, and on methodologies to track cells in vivo long-term following administration, crucial information for optimizing safety and efficacy of clinical cell therapy products.

Clinically, we have led the clinical development of approaches 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, in a trial led by Dr Dunbar at the NIH Clinical Center together with other NHLBI investigators. This resulted in the first FDA approval for new drug to treat aplastic anemia in over 30 years. Ongoing clinical trials focus on testing the utility of this drug in other bone marrow failure syndromes.

Summary of research interests

 

Clinical Trials and Studies

Recruiting
Adult, Older Adult
All Genders
Not Accepting Healthy Volunteers
Are you at least 18 years old with chronic anemia? Researchers in this study are trying to find a better treatment for chronic anemia and are testing a new medication to see if it works well. To participate, you must be at least 18 years old and have chronic anemia. This study is taking place at the National Institutes of Health Clinical Center.

Meet the Team

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Cynthia "Cindy" Dunbar, M.D.

NIH Distinguished Investigator

Chief, Translational Stem Cell Biology Branch, and 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 therapies, 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 290 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 in the laboratory of Dr. Arthur Nienhuis, followed by clinical training in hematology at the University of California, San Francisco. In 1991she returned to the NIH to set up her own research program. She has been elected to the American Society for Clinical Investigation, the American College of Physicians and the National Institute of Medicine. She has been active in major professional societies, including current service as the Secretary of the American Society of Hematology, and as 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, leading the NIH hematology fellowship program for 17 years. She has been a leader in efforts to enhance the research environment and diversity within the intramural NIH through her service as founding co-chair and current officer of the NIH Assembly of Scientists, and member of the NIH Equity Committee. She has received numerous teaching and mentoring awards from NHLBI, NIH and her professional societies.

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Alumni

Richard Lozano

Postbaccalaureate Fellow
2019 - 2021
Richard Lozano is currently a Medical Student at Yale University School of Medicine.

Ryland Mortlock

Postbaccalaureate Fellow
2019 - 2021
Ryland Mortlock is currently a M.D./Ph.D. Student at Yale University School of Medicine.

Stefan Cordes, M.D., Ph.D.

Clinical Fellow
2017 - 2021
Stefan Cordes, M.D., Ph.D. is currently a Assistant Clinical Investigator at National Heart, Lung, and Blood Institute, NIH.

Lauren Truitt

Postbaccalaureate Fellow
2017 - 2019
Lauren Truitt is currently a Medical Student at University of Texas Southwestern School of Medicine, Dallas, TX.

Xavier Guitart, MSE

Postbaccalaureate Fellow
2017 - 2019
Xavier Guitart, MSE is currently a Ph.D. Student at Genome Sciences Program, University of Washington, Seattle, WA.

Shirley Chen

Postbaccalaureate Fellow
2017 - 2019
Shirley Chen is currently a Medical Student at Vanderbilt School of Medicine, Nashville, TN.

Aishia Aljanahi, M.S.

Ph.D. Student Georgetown/NIH Program
2016 - 2021
Aishia Aljanahi, M.S. is currently a Postdoctoral Fellow at NIAID Vaccine Research Center.

John Ostrominski

Medical Research Scholars Program
2016 - 2017
John Ostrominski is currently a Internal Cardio Fellow at Brigham and Womens’ Hospital, Boston, MA.

Di Yang, M.D.

Visiting Fellow
2015 - 2017
Di Yang, M.D. is currently a Associate Professor at Department of Hematology, Tongji Medical College, Hubei, China.

Vinh Dang

Postbaccalaureate Fellow
2015 - 2017
Vinh Dang is currently a Start Up Founder.

Ravi Yada

Postbaccalaureate Fellow
2015 - 2017
Ravi Yada is currently a M.D./Ph.D. Student at University of Wisconsin, Madison, WI.

Diego Espinoza

Postbaccalaureate Fellow
2015 - 2017
Diego Espinoza is currently a M.D./Ph.D. Student at University of Pennsylvania, Philadelphia, PA.

Kyung-Rok Yu, Ph.D.

Visiting Fellow
2014 - 2018
Kyung-Rok Yu, Ph.D. is currently a Assistant Professor at Seoul National University, Seoul, Korea.

Idalia Yabe

Graduate Student
2014 - 2019
Idalia Yabe is currently a Postdoctoral Fellow at National Institute of Allergy and Infectious Diseases, Bethesda, MD.

Eun Jung Baek, M.D.

Visiting Fellow
2016 - 2017
Eun Jung Baek, M.D. is currently a Associate Professor and Senior Hematologist at Hayang University, Seoul, Republic of Korea.

Sandhya Panch, M.D.

Clinical Fellow
2014 - 2016
Sandhya Panch, M.D. is currently a Assistant Professor at Division of Hematology and Puget Sound Blood Center, University of Washington, Seattle, WA .

Marcus Corat, Ph.D.

Research Fellow
2014 - 2016
Marcus Corat, Ph.D. is currently a Scientist at University of Sao Paolo, Brazil.

Moonjung Jung, M.D.

Clinical Fellow
2013 - 2016
Moonjung Jung, M.D. is currently a Assistant Professor at Johns Hopkins University School of Medicine, Baltimore, MD.

So Gun Hong, D.V.M., Ph.D.

Visiting Fellow then Research Fellow
2010 - 2016
So Gun Hong, D.V.M., Ph.D. is currently a Staff Scientist and Non-Human Primate Program Director at Translational Stem Cell Biology Branch, NHLBI, NIH.

Kyujoo Choi

Postbaccalaureate Fellow
2014 - 2015
Kyujoo Choi is currently a Dental Student at University of Maryland.

Samson Koelle

Postbaccalaureate Fellow
2013 - 2015
Samson Koelle is currently a Ph.D. Student at Statistics Program, University of Washington, Seattle, WA.

Chuanfeng "Joy" Wu, Ph.D.

Visiting Fellow then Research Fellow
2009 - 2015
Chuanfeng "Joy" Wu, Ph.D. is currently a Staff Scientist at Translational Stem Cell Biology Branch, NHLBI, NIH.

Thomas Winkler, M.D.

Visiting Fellow and Clinical Fellow
2007 - 2014
Thomas Winkler, M.D. is currently a Medical Director at Astra-Zeneca, Gaithersburg, MD.

William Hughes

Postbaccalaureate IRTA Fellow
2012 - 2014
William Hughes is currently a Medical Student at University of Georgia/Georgia Regents University School of Medicine, Athens, GA.

Chen Glait-Santar, Ph.D.

Visiting Fellow
2013 - 2014
Chen Glait-Santar, Ph.D. is currently a Visiting Fellow at Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Brian Li

Postbaccalaureate IRTA Fellow
2012 - 2013
Brian Li is currently a Internal Medicine Resident at Beth Israel Hospital, Boston, MA.

Taha Bat, M.D.

Visiting Fellow
2011 - 2013
Taha Bat, M.D. is currently a Assistant Professor at Hematology Division, University of Texas/Southwestern, Dallas, TX.

Cecilia Barese, M.D.

Research Fellow
2008 - 2013
Cecilia Barese, M.D. is currently a Director of Analytics at Avrobio, Cambridge, MA.

Zanetta Chang

Postbaccalaureate IRTA Fellow
2011 - 2012
Zanetta Chang is currently a M.D./Ph.D. Student at Duke University School of Medicine, Durham, NC.

Alexander Jares

Postbaccalaureate IRTA Fellow
2011 - 2012
Alexander Jares is currently a M.D./Ph.D. Student at SUNY School of Medicine, Stonybrook, NY.

Ronan Desmond, M.D.

Visiting Fellow
2012 - 2013
Ronan Desmond, M.D. is currently a Senior Consultant Hematologist at Tallaght Hospital and the University of Dublin, Dublin, Ireland.

Brian Ichwan

Postbaccalaureate IRTA Fellow
2010 - 2011
Brian Ichwan is currently a Emergency Medicine Physician at Stanford University Medical Center.

Jean-Yves Metais, Ph.D.

Visiting Fellow then Research Fellow
2006 - 2012
Jean-Yves Metais, Ph.D. is currently a Scientist at Department of Transplantation, St. Jude Children's Research Hospital, Memphis, TN.

Andre LaRochelle, M.D./Ph.D.

Clinical Fellow
2004 - 2010
Andre LaRochelle, M.D./Ph.D. is currently a Tenure-Track Investigator at Hematology Branch, NHLBI, NIH, Bethesda, MD.

Ashley Dunfee

Postbaccalaureate IRTA Fellow
Ashley Dunfee is currently a Clinical Associate Professor at Beth Israel/Deaconess Hospital, Boston, MA.

Amy Cantilena (Deceased 2017)

Postbaccalaureate IRTA Fellow
2008 - 2010

Joshua Clevenger

Postbaccalaureate IRTA Fellow
2007 - 2009
Joshua Clevenger is currently a Cardiology Fellow at University Hospitals, Cleveland, OH.

Jianjun Xi, M.D./Ph.D.

Visiting Fellow
2007 - 2009
Jianjun Xi, M.D./Ph.D. is currently a Senior Clinician/Pediatric Hematologist at Daopei Hospital, Beijing China.

George Aue, M.D.

Acting Clinical Director
2006 - 2009
George Aue, M.D. is currently a Acting Clinical Director at NHLBI, NIH, Bethesda, MD.

Inho Kim, M.D.

Visiting Fellow
2007 - 2008
Inho Kim, M.D. is currently a Professor, Department of Hematology at Catholic University of Daego, Seoul, Korea.

Theo Gomes

Postbaccalaureate IRTA Fellow
2005 - 2008
Theo Gomes is currently a Assistant Professor and Program Director, Med-Peds Program at Western Michigan State University, Kalamazoo, MI.

Yoo-Jin Kim, M.D.

Visiting Fellow
2005 - 2007
Yoo-Jin Kim, M.D. is currently a Professor, Department of Hematology, at Catholic University of Korea, Seoul, South Korea.

Jingqiong Hu, Ph.D.

Visiting Fellow
2007 - 2009
Jingqiong Hu, Ph.D. is currently a Professor, in Stem Cell Center at Wuhan Union Hospital, Hubei, China.

Rima Adler, Ph.D.

Graduate Student
2000 - 2007
Rima Adler, Ph.D. is currently a Technical Consultant at Miltenyi, Bethesda, MD.

Stephen Lemery, M.D.

Clinical Fellow
2002 - 2006
Stephen Lemery, M.D. is currently a Lead Medical Officer at Food and Drug Administration, Rockville, MD.

Ruth Seggewiss, M.D./Ph.D.

Visiting Fellow
2002 - 2005
Ruth Seggewiss, M.D./Ph.D. is currently a Associate Professor and Group Leader at University of Wurzburg, Wurztburg, Germany.

Bum Kee Hong, M.D.

Visiting Fellow
2003 - 2005
Bum Kee Hong, M.D. is currently a Associate Professor, Department of Cardiology at Yongdong Severance Hospital, Seoul, Korea.

Cole Ferguson

Postbaccalaureate IRTA Fellow
2003 - 2005
Cole Ferguson is currently a Assistant Professor, Pathology at University of California, San Diego, CA.

Mikko Laukkanen, Ph.D.

Visiting Fellow
2002 - 2005
Mikko Laukkanen, Ph.D. is currently a Group Leader at IRCCS Research Foundation, Naples, Italy.

Boris Calmels, Ph.D.

Visiting Fellow
2002 - 2004
Boris Calmels, Ph.D. is currently a Director at Centre de Thérapie Cellulaire, Institut Paoli Calmettes, Marseille, France.

Jamie Robyn, M.D., Ph.D.

Clinical Fellow
2001 - 2004
Jamie Robyn, M.D., Ph.D. is currently a Senior Physician at VA Medical Center, Akron, OH.

Peiman Hematti, M.D.

Clinical Fellow
2000 - 2004
Peiman Hematti, M.D. is currently a Professor, Department of Medicine and the Stem Cell Institute at University of Wisconsin, Madison, WI.

Ken Kuramoto, M.D., Ph.D.

Visiting Fellow
2001 - 2003
Ken Kuramoto, M.D., Ph.D. is currently a Attending Physician/Hematologist at Chuden Hospital, Hiroshima, Japan.

Natasha Bamji

Postbaccalaureate IRTA Fellow
2001 - 2002
Natasha Bamji is currently a Associate Professor of Pediatrics, Department of Endocrinology at New York Medical College, New York, NY.

K. Allison Hinds, Ph.D.

IRTA Fellow
1999 - 2002
K. Allison Hinds, Ph.D. is currently a Analyst at Department of Defense, Arlington, VA.

Magnus Magnusson, M.D.

Clinical Fellow
1999 - 2002
Magnus Magnusson, M.D. is currently a Professor, Department of Hematology at University of Reykjavik, Reykjavik, Iceland.

Patricia Shi, M.D.

Clinical Fellow
1999 - 2002
Patricia Shi, M.D. is currently a Medical Director at New York Blood Center, New York, NY.

Kristin Meade

Postbaccalaureate IRTA Fellow
1999 - 2000
Kristin Meade is currently a Associate Professor, Department of Palliative Care at Duke University School of Medicine.

Maasaki Takatoku, M.D., Ph.D.

Visiting Fellow
1998 - 2000
Maasaki Takatoku, M.D., Ph.D. is currently a Medical Director at Novartis/Japan, Tokyo, Japan. .

Tong Wu, M.D.

Visiting Fellow
1997 - 2000
Tong Wu, M.D. is currently a Medical Director at Beijing Daopei Hospital, Beijing, China.

Dominik Heim, M.D.

Visiting Fellow
1997 - 2000
Dominik Heim, M.D. is currently a Chief Physician, Hematology at University Hospital, Basel, Switzerland.

Hyeoung Joon Kim, M.D., Ph.D.

Visiting Fellow
1997 - 1999
Hyeoung Joon Kim, M.D., Ph.D. is currently a Chair and Professor, Department of Hematology/Oncology at Chonnam National University Medical School, Gwangju, Korea.

Neelam Giri, M.D.

Clinical Fellow
1997 - 1999
Neelam Giri, M.D. is currently a Staff Clinician at Clinical Genetics Branch, National Cancer Institute, Bethesda, MD.

Richard Huhn, M.D.

Clinical Fellow
1996 - 1998
Richard Huhn, M.D. is currently a Vice-President and Medical Director at Biothera, Eagan, MN.

John Tisdale, M.D.

Clinical Fellow
1995 - 1998
John Tisdale, M.D. is currently a Branch Chief at NHLBI, NIH, Bethesda, MD.

Yutaka Hanazono, M.D., Ph.D.

Visiting Fellow
1995 - 1998
Yutaka Hanazono, M.D., Ph.D. is currently a Director and Professor at Center for Regenerative Medicine, Jichi Medical School, Tochigi, Japan.

Jian Mei Yu, M.D.

Visiting Fellow
1994 - 1997
Jian Mei Yu, M.D. is currently a Research Scientist at Walter Reed Army Medical Center Biotechnology Center/IOMAI Corporation, Washington, DC.

Robert Emmons, M.D.

Clinical Fellow
1993 - 1996
Robert Emmons, M.D. is currently a Medical Director for Hematology-Oncology at Ochsner Health Systems, New Orleans, LA.

Malika Sekhar, M.D.

Visiting Fellow
1994 - 1995
Malika Sekhar, M.D. is currently a Associate Professor at Royal Free Hospital/University College London, London, UK.

Toshihiro Soma, M.D., Ph.D.

Visiting Fellow
1992 - 1994
Toshihiro Soma, M.D., Ph.D. is currently a Professor of Hematology at Hyogo School of Medicine, Osaka, Japan.

Rajni Agarwal-Hashmi, M.D.

Associate Professor of Pediatrics
1992 - 1993
Rajni Agarwal-Hashmi, M.D. is currently a Associate Professor of Pediatrics at Stanford University School of Medicine, Palo Alto, CA.

Aliza Cassel, Ph.D.

Visiting Fellow
1991 - 1992
Aliza Cassel, Ph.D. is currently a Director, Hematology Service at Carmel Hospital, Haifa, Israel.