DBA Foundation

These grants were funded through a request for applications from the National Heart, Lung, and Blood Institute for proposals on the molecular mechanisms underlying Diamond Blackfan Anemia and other congenital bone marrow failure syndromes. Data were obtained from CRISP (Computer Retrieval of Scientific information on projects): http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. Search term: Diamond Blackfan Anemia

Principal Investigator: Dr. Jeffrey M. Lipton, North Shore-Long Island Research Institute
Title: The DBA Registry: A Vital Tool for the Study of DBA
Summary: The goal of this study is to expand and update the DBA registry, a comprehensive database of patients with DBA. The DBA registry is a critical tool that will facilitate investigations into the epidemiology and biology of DBA. The registry will also serve as an important resource to patients and physicians guiding diagnosis, treatment options, and reproductive decisions.

Principal Investigator: Dr. Niklas Dahl, Uppsala University
Title: Molecular Basis of Diamond Blackfan Anemia
Summary: The goal of this study is to obtain a better understanding of the molecular pathology underlying DBA and to develop a novel strategy for treating DBA. Studies on the underlying pathology of DBA will focus on the synthesis and function of ribosomal protein S19. A mouse model for DBA will be used to develop gene therapy as a therapeutic option for DBA patients.

Principal Investigator: Dr. Steven Ellis, University of Louisville
Title: Ribosome Function and Diamond Blackfan Anemia
Summary: The goal of this proposal is to study the role of RPS 19 in ribosome synthesis and function. A detailed understanding the function of RPS 19 can be used to develop improved diagnostic procedures and also lead to the identification other genes involved in DBA pathogenesis. This proposal will also study the relationship between ribosome synthesis and bone marrow failure in a novel transgenic mouse model.

Principal Investigator: Dr. Thomas Glaser, University of Michigan
Title: Modeling Diamond Blackfan Anemia
Summary: The goal of this proposal is to study the effects of
disruption of ribosome synthesis and function on mouse development. A strain of mice has been identified that is defective in a ribosomal protein other than RPS 19. Hematopoietic parameters in this strain of mice will be compared with mice strains defective in RPS 19 to examine the extent to which DBA is linked to a selective effect on RPS 19 or whether defects in other ribosomal proteins can result in related pathologies.

Principal Investigator: Dr. Mohadas Narla, New York Blood Center
Title: Diamond Blackfan Anemia and Ribosomal Protein S19
Summary: The goal of this study is to understand the role of RPS 19 in erythropoiesis and how this function is disrupted in DBA patients. RPS 19 levels in erythroid progenitor cells will be experimentally manipulated and the effects on erythroid differentiation examined. Studies will also address the role of prolactin in regulating
erythropoiesis and the mechanism of metoclopramide action.

Summary of Research Funded by the DBAF

Date Funded: 11/04
A grant of $45,000 was awarded to Stefan Karlsson MD, PhD, of Lund University, Lund, Sweden to assist in the funding of his four-year project titled “Cellular and Murine Models for RPS19 deficient DBA”. The goal of this project is to characterize the effects of RPS19 depletion on erythropoiesis using siRNA lentiviral vectors. Please see the related article in this newsletter for additional information.

Date Funded: 10/04
Dr. Niklas Dahl of Uppsala University Children’s Hospital, Uppsala Sweden has been awarded $50,000 for the second year of a project titled “Identification of the Molecular Basis of DBA and the evaluation of RPS19 gene transfer”. This $165,251 project is also receiving funding from three other Swedish organizations. The long term objective of this study is to better understand the basic molecular pathology behind DBA by identifying factors interacting with RPS19 and/or its messenger RNA, and to develop a novel treatment modality for DBA by studying gene transfer in a DBA mouse model.

Date Funded: 10/04
A grant for 106,929 was given to Hanna Gazda, MD, PhD, of Dana Farber Cancer Institute, Boston, MA, for her project “Genetics and Biology of DBA”. This investigation will test the hypothesis that detailed clinical and genetic examination of a large number of patients and careful statistical analysis will reveal a phenotype-genotype in individuals with identified RPS19 mutations. Please see Dr. Gazda’s article in this newsletter for additional information.

Date Funded: 7/04
Steve Ellis, PhD, of the University of Louisville, Kentucky was awarded $26,709 to assume the responsibilities of Research Director. In addition to the responsibilities outlined in a separate article in this newsletter, the grant will cover expenses such as a computer and laboratory supplies for related DBA research.

Date Funded: 7/04
Dr. Sarah Ball of St. George’s Hospital Medical School in London, England was the recipient of a $78,283 grant for her project titled “Enhancement of Steroid Response in DBA: Application of an in vitro two-phase erythroid culture model”. This project will use a peripheral blood in vitro two phase erythroid culture model to study erythroid failure in DBA and the stimulatory effect of steroids. The use of agents that enhance steroid effectiveness and the interactions of other cytokines and hormones (including prolactin) on the production of red blood cells in DBA patients will be investigated, with the aim of identifying potentially therapeutic combinations that enhance the effectiveness of steroids.

Date Funded: 6/04
A grant for $70,771 was awarded to Mahmut Y. Celiker, MD, Jeffrey Lipton MD, PhD, Steven Arkin, MD, and Adrianna Vlachos, MD, of Schneider Children’s Hospital, New Hyde Park, NY for the second year of a project titled “Gene Expression During Erythropoeisis in DBA”. The long-term objective of this study is to apply the information gathered about the pathophysiology of DBA, to develop new treatment modalities, to optimize the current treatment methods, and eventually bring a cure to all DBA patients. Research findings from the first year of this study, also funded by the DBAF, have been submitted for publication in a very prestigious journal, “Experimental Hematology”.

Date Funded: 4/04
The DBAF co-sponsored the Fifth Annual Diamond Blackfan Anemia International Consensus Conference with the Daniella Maria Arturi Conference for $40,000. A separate article detailing the highlights of the conference can be found in this newsletter.

Date Funded: 1/04
Dr. Gil Tchernia of Bicetre Hospital, France received $19,000 as the second year funding of the scientific grant titled “Mechanistic Understanding of DBA Pathophysiology”. The long-term goal of this research project is to decipher the mechanistic understanding of the pathophysiology of DBA, and more specifically, to evaluate the role of ribosomal protein S19 (RPS19) in erythropoeisis and then to define the link between the mutation in RPS19 gene and the occurrence of the disease. New insights generated by this study could help design new therapeutic strategies for DBA patients.

Date Funded: 8/03
Funded To: Professor Gil Tchernia
Project Title: Evaluation of metoclopramide efficacy and toxicity in Diamond-Blackfan Anemia patients
Amount Funded: $63,968.00

Date Funded: 8/03
Funded To: Dr. Niklas Dahl
Project Title: Funded Identification of the molecular basis of Diamond-Blackfan Anemia and evaluation of RPS 19 gene transfer
Amount Funded: $53,000.00

Date Funded: 12/02
Funded To: Mahmut Y. Celiker, MD, Jeffrey Lipton, MD, PhD, Steven Arkin, MD, and Adrianna Vlachos, MD, of Schneider Children’s Hospital, New Hyde Park, New York.
Project Title: Gene Expression During Erythropoiesis in Diamond-Blackfan Anemia
Amount Funded: $82,357.00

Date Funded: 12/02
Funded To: Kathleen M. Sakamoto, MD, of the University of California, Los Angeles
Project Title: AML in Diamond-Blackfan Anemia: Molecular Basis and Therapeutic Strategies.
Amount Funded: $25,000.00

Date Funded: 12/02
Funded To: BioIron Society
Project Title: BioIron 2003 World Congress on Iron Metabolism at the National Institutes of Health, Bethesda, MD
Amount Funded: $10,000.00

Date Funded: 4/02
Funded To: Jeffrey M. Lipton, M.D., PhD, Schneider Children's Hospital, NY
Project Title: The Diamond-Blackfan Anemia Registry: A Tool for Investigating the Epidemiology of Diamond-Blackfan Anemia
Amount Funded: $38,950.00

Date Funded: 2/02
Funded To: The Diamond-Blackfan Anemia Fourth International Consenus
Project Amount Funded: $25,000.00

Date Funded: 11/02
Funded To: Dr. Gil Tchernia of Bicetre Hospital, France.
Project Title: Study the role of ribosomal protein S19 (RPS19)
Amount Funded: $16,000.00

Date Funded: 12/01
Funded To: Dr. Stefan Karlsson, Lund University, Lund, Sweden
Project Title: Diamond-Blackfan Anemia Hematopoiesis and Gene Therapy
Amount Funded: $41,400.00

Date Funded: 5/01
Funded To: Dr. Niklas Dahl, Uppsala University Children's Hospital, Sweden
Project Title: Continuation of "Functional and therapeutic investigations of the ribosomal protein S19 in Diamond-Blackfan Anemia."
Amount Funded: $28,000.00

Date Funded: 12/00
Funded To: Dr. Stefan Karlsson & Dr. Isao Hamaguchi, Lund University, Lund, Sweden
Project Title: "Development of Gene Therapy for Diamond Blackfan Anemia"
Amount Funded: $39,000.00

Date Funded: 12/00
Funded To: Jeffrey M. Lipton, M.D., PhD, Schneider Children's Hospital, NY
Project Title: "Diamond Blackfan Anemia Registry"
Amount Funded: $48,250.00

Date Funded: 5/00
Funded To: Dr. Niklas Dahl, Uppsala University Children's Hospital. Sweden
Project Title: Continuation of "Functional and therapeutic investigations of the ribosomal protein S19 in Diamond-Blackfan Anemia."
Amount Funded: $28,400.00

Date Funded: 12/99
Funded To: Drs. Narla Mohandas and T.N. Willig, Lawrence Berkeley National Laboratory, Berkeley, CA
Project Title: "Diamond Blackfan Anemia."
Amount Funded:$74,682.00

Date Funded: 8/99
Funded To: Dr. Colin Sieff, Dana Farber Cancer Institute, MA
Project Title: "Identification of Interacting Proteins in Diamond Blackfan Anemia"
Amount Funded: $28,000.00

Date Funded: 3/99
Funded To: Dr. Niklas Dahl, Uppsala University Children's Hospital. Sweden
Project Title: "Functional and therapeutic investigations of the ribosomal protein S19 in Diamond-Blackfan Anemia."
Amount Funded: $28,000.00

Date Funded: 12/98
Funded To: Douglas Templeton, M.D., PhD, University of Toronto, Canada
Project Title: "Influence of iron overload and chelation on gene expression related to cardiac fibrosis"
Amount Funded: $18,375.00

Date Funded: 3/98
Funded To: Dr. Niklas Dahl, Uppsala University Children's Hospital, Sweden
Project Title: "Identification of the gene behind Diamond-Blackfan Anemia"
Amount Funded: $29,300.00

Date Funded: 12/96
Funded To: Jeffrey M. Lipton, M.D., PhD, Mount Sinai Hospital, NY
Project Title: "Diamond Blackfan Anemia Registry"
Amount Funded: $25,000.00

Date Funded: 5/96
Funded To: The University of Texas, Southwestern Medical Center at Dallas
Project Title: "Evaluation of High Dose Oral Methylprednisolone Therapy for Patients with Diamond-Blackfan Anemia Refractory to Conventional Doses of Steroids: A Multi-Institutional International Study"
Amount Funded: $500.00

Date Funded: 12/95
Funded To: Mount Sinai Hospital, Jeffrey M. Lipton, M.D., PhD.
Project Title:" Diamond Blackfan Anemia Registry"
Amount Funded: $25,000.00