A5062784258- RNA modifications and cancer
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Erythrocyte Function and Pathophysiology
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Blood disorders and treatments
- RNA and protein synthesis mechanisms
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Hematological disorders and diagnostics
- Immune Response and Inflammation
- Blood groups and transfusion
- Hemoglobinopathies and Related Disorders
- CAR-T cell therapy research
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Acute Lymphoblastic Leukemia research
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Glycosylation and Glycoproteins Research
- Chronic Lymphocytic Leukemia Research
- Erythropoietin and Anemia Treatment
- Cell Adhesion Molecules Research
Harvard University
2009-2021
Boston Children's Hospital
2009-2021
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2017-2021
Dana-Farber Cancer Institute
2004-2019
Children's Center
2018
Center for Cancer and Blood Disorders
2018
Boston Children's Museum
2016
Harvard University Press
1987-2014
Whitehead Institute for Biomedical Research
2007-2009
Massachusetts Institute of Technology
2005
The process of blood cell formation, by which a small number self-renewing stem cells give rise to lineage committed pro- genitor that subsequently proliferate and differentiate produce the circulating mature cells, is sustained through- out life group glycoprotein hormonal growth factors.These hormones are known collectively as colony-stimulating factors (CSFs)' (1); term derives from in vitro observation CSFs stimulate progenitor different hemato- poietic lineages form discrete colonies...
Mice with monoallelic inactivation of the CBP gene develop highly penetrant, multilineage defects in hematopoietic differentiation and, advancing age, an increased incidence hematologic malignancies. The latter are characterized, at least some cases, by loss heterozygosity (LOH) locus. No such pathology was observed wild-type or p300 heterozygous null mice same age and genetic background. Thus, a full complement CBP, but not p300, is required for normal differentiation. These results also...
Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was tested for its ability to induce colony formation in human bone marrow that had been enriched progenitor cells. In addition expected granulocyte-monocyte activity, the GM-CSF burst-promoting activity erythroid burst-forming units and also stimulated colonies derived from multipotent (mixed) progenitors. contrast, erythroid-potentiating did not stimulate The experiments prove has multilineage activity.
Diamond-Blackfan anemia (DBA) is a hypoplastic characterized by impaired production of red blood cells, with approximately half all cases attributed to ribosomal protein gene mutations. We performed exome sequencing on two siblings who had no known pathogenic mutations for DBA and identified mutation in the encoding hematopoietic transcription factor GATA1. This mutation, which occurred at splice site GATA1 gene, full-length form protein. further an additional patient carrying distinct same...
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to inhibit migration of mature granulocytes and enhance their antibody-dependent cellular cytotoxicity. We found that human recombinant GM-CSF also enhanced granulocyte-granulocyte adhesion increased by two- threefold the surface expression Mo1 LeuM5 (P150, 95), two members a family leukocyte molecules (Leu-CAM). Increased occurred within 15 min at 37 degrees C was maximal inhibitory concentration 500 pM. One-half...
Monokine-stimulated endothelial cells are known to produce both burst- and colony-stimulating activities, but neither the nature of monokine nor hematopoietic growth factor(s) produced is known. We show by mRNA analysis that an immortalized line human constitutively granulocyte-macrophage factor. Furthermore, interleukin 1 tumor necrosis factor induce early passage umbilical same
Diamond-Blackfan anemia (DBA) is an inherited form of pure red cell aplasia that usually presents in infancy or early childhood and associated with congenital malformations ∼30-50% patients. DBA has been mutations nine ribosomal protein (RP) genes about 53% We completed a large-scale screen 79 RP by sequencing 16 (RPL3, RPL7, RPL8, RPL10, RPL14, RPL17, RPL19, RPL23A, RPL26, RPL27, RPL35, RPL36A, RPL39, RPS4X, RPS4Y1, RPS21) 96 probands. identified de novo two-nucleotide deletion RPL26 one...
A stem cell reprogramming approach enables disease modeling and drug discovery for a genetic blood disorder uncovers candidate therapeutic.
Recently, the gene for a novel mammalian hematopoietic growth factor homologous to murine interleukin 3 was isolated from gibbon T cell line and expressed in monkey COS cells. The factor, termed multi-colony stimulating (multi-CSF) or 3, is stimulatory human target We investigated range of enriched bone marrow fetal liver progenitors responsive multi-CSF; compared colony types observed with those obtained presence recombinant granulocyte-macrophage CSF (GM-CSF); analyzed effects on formation...
High-dose estrogen administration induces anemia in mammals. In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation. This is associated with down-regulation many cell-specific genes, including alpha- beta-globin, band 3, 4.1, the histone H5. We show here that also reduce number primary human marrow cultures. To address potential mechanisms by which suppress erythropoiesis, we have examined effects on GATA-1, an transcription...