Fanconi Anemia and Bone Marrow Failure Multidisciplinary Clinic

Today, Children's researchers are conducting some of the world's leading-edge studies of bone marrow failure syndromes. We believe research into these conditions offers significant opportunities for improving treatment therapies. Studies are currently underway in the following areas:

Fanconi Anemia
Principal Investigator: Dr. Alan D'Andrea, Department of Radiation Oncology, Dana-Farber Cancer Institute

Dr. D'Andrea's laboratory, located at Dana-Farber Cancer Institute, is a leading research center for Fanconi anemia. Researchers are investigating the molecular basis for Fanconi anemia as well as other chromosomal breakage syndromes such as ataxia-telangiectasia, Nijmegen breakage syndrome, and Seckel syndrome. They are also exploring targeted therapies to treat Fanconi anemia. Investigators in this lab are responsible for identifying important interactions between the biochemical pathway for Fanconi anemia and DNA repair and tumor suppressor pathways. This laboratory is recognized world-wide for its work on the molecular mechanisms that contribute to cancer development and Fanconi anemia.

Principal Investigator: Drs. David A. Williams and Lars Mueller, Division of Hematology and Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute

Dr. Williams' laboratory studies the communication between the bone marrow environment and hematopoetic stem cells. His laboratory has defined Rho GTPases as key molecular switches that regulate the engraftment and retention of stem cells within the bone marrow. In addition, his laboratory has developed new therapies for Fanconi anemia, including the use of gene therapy. Most recently, in collaboration with Dr. George Daley’s laboratory, Dr. Mueller and Dr. Williams are exploring the methods to generate hematopoietic stem cells from other somatic tissues using ‘induced pluripotent stem cells’ or iPS cells.

Principal Investigator: Dr. Benjamin Ebert, Division of Hematology, Brigham and Women's Hospital

Dr. Ebert's laboratory studies both congenital and neoplastic causes of bone marrow failure, including myelodysplastic syndrome and Diamond-Blackfan Anemia.

In recent work, Dr. Ebert and colleagues identified a gene that plays a central role in the pathophysiology of the 5q- syndrome, a subtype of myelodysplastic syndrome, revealing a molecular link between the 5q- syndrome and Diamond-Blackfan Anemia. Dr. Ebert's laboratory also works on the identification and characterization of compounds that alter hematopoietic differentiation that could be useful for the treatment of cancer and non-malignant hematopoietic disorders.

Dr. Lodish's laboratory, located at the Whitehead Institute, is a leading research center for the study of hematopoiesis, cell signaling, and adipocyte biology. Members of his group are investigating signal transduction by the erythropoietin receptor in erythroid progenitor cells, and the regulation of transcription, apoptosis, cell division, and enucleation during erythropoiesis. They are characterizing new marker cell surface proteins for hematopoietic stem cells and new growth factors for their expansion in culture. They are also elucidating the roles of specific microRNAs in regulating hematopoiesis and fat and muscle cell development and metabolism, and the functions of adiponectin, an adipocyte-produced hormone that affects many aspects of metabolism.

Dr. Sieff's laboratory studied the families of many Diamond-Blackfan anemia (DBA) patients to map new DBA genes. This led to the discovery that other ribosomal protein genes, in addition to RPS19, are mutated in DBA. For example, RPS24, RPL5 and RPL11 are mutated in a significant proportion of patients. To investigate why patients with DBA are anemic, the laboratory established a mouse model by decreasing (knocking down) expression of RPS19 in fetal liver cells. This work has led to new insights into the reasons for anemia in DBA. Recent studies include new approaches to diagnosis of DBA that may be particularly useful in non-classical DBA patients and in family members who do not have known mutations but who are being considered as stem cell transplant donors.

Hematopoiesis and Cancer
Principal investigator: Dr. Leonard Zon, Department of Hematology and Oncology, Children's Hospital Boston

Studying blood cell formation in zebra fish, researchers in this laboratory have made important insights into the biology of hematopoietic stem cells and the genetic programs regulating blood cell development.

Stem Cells
Principal investigator: Dr. George Daley, Department of Hematology and Oncology, Children's Hospital Boston

Dr. Daley's lab is using somatic cell reprogramming to model a variety of human genetic diseases of the blood and bone marrow, prominently conditions like Fanconi anemia (with the Williams lab), Dyskeratosis Congenita (with Instructors of Pediatrics Suneet Agarwal and Deborah Chirnomas), Shwachman-Diamond syndrome (with former faculty member Akiko Shimamura), Diamond-Blackfan anemia (with Colin Sieff, Ben Ebert, and Len Zon), and various mitochondrial diseases like Pearson's and Kearns-Sayre's syndrome. Additional studies in murine models include the treatment of thalassemia by combined gene and cell therapy using pluripotent stem cells generated via somatic cell nuclear transfer, parthenogenesis, as well as direct reprogramming. The laboratory is also developing protocols for the directed differentiation of hematopoietic populations including long-term hematopoietic stem cells from mouse and human pluripotent stem cell types.