3D Chromatin Interaction Analysis to Accurately Map Cis-Regulatory Elements to Human Megakaryocyte/Platelet GenesDescription of Major Goals
Generate maps that assign distal enhancer elements to their correct target gene(s) in human Mks
Development of Mouse Model to Study RAS-mediated Elevation of Human Fetal Globin LevelsDescription of Major Goals
The goal of this project is to determine whether an inducible mouse model of activated RAS/PTPN11 signaling (PTPN11-lox-stopper-loxD61Y) containing a human beta-globin locus transgene recapitulates the elevated human fetal globin production seen in patients with disorders of activated RAS/PTPN11 signaling.
HSCI FACS Core Facility AwardDescription of Major Goals
This grant is to support a core facility that isolates normal and leukemia stem cells for investigators a Boston Children’s Hospital and the Harvard Stem Cell Institute.
Megakaryocyte Transcription Factor Activation to Enhance In Vitro Platelet Production from Human IPSCsDescription of Major Goals
The overall goal of this project is to investigate signaling pathways that activate megakaryocyte transcription factors as a means to enhance the efficiency of platelet production of human IPS cells.
Pharmacologic Enhancement of Residual Wild Type RUNX1 Protein Activity in FPD/AMLDescription of Major Goals
The goal of this project is to identify small molecules that enhance residual wild type protein in individuals with germline heterozygous RUNX1 inactivating mutations in Familial Platelet Disorder with Propensity to Develop
Clinical Hematology Research Career Development AwardDescription of Major Goals
The major goal of this project is to support training in clinical research for non-malignant hematology. The long-term goal of this career development grant is to attract and retain talented young physician scientists to the field of blood diseases.
Role of GATA2 Dysregulation in Juvenile Myelmonocytic LeukemiaDescription of Major Goals
Juvenile myelomonocytic leukemia is an aggressive blood cancer of young children. The only current curative treatment is bone marrow transplantation, Yet, about 50% of children still die from their disease despite this very aggressive therapy. An improved understanding of the mechanisms that cause JMML is critical to developing new treatments. Based on recent work, we hypothesize that a protein called GATA2, which normally turns on and off white blood cell genes, is erroneously activated in JMML. This proposal is designed to test this hypothesis. Positive results would support development of medicines to inhibit GATA2 for the treatment of JMML.
Developmental Biology of Human Erythropoiesis: Project 4Description of Major Goals
The overall goal of this program project grant is to further understand the molecular regulation of erythroid development in humans. Dr. Cantor’s project involves elucidating the mechanisms by which GATA-1, a master erythroid transcription factor, distinguishes between direct target genes to activate versus repress and how it carries out these opposing transcriptional outputs in a gene context-dependent manner.
Role of RUNX1 (AML1) Dysregulation in Juvenile Myelomonocytic LeukemiaDescription of Major Goals
This proposal aims to further elucidate the molecular pathogenesis of an aggressive cancer of young children, with the goal of identifying improved and less-toxic treatments for this disorder
Runx1 Regulatory Mechanisms in Hematopoietic Stem Cell Ontogeny and MaintenanceDescription of Major Goals
The main goal of this study is to further elucidate the regulatory mechanisms that govern RUNX1’s activity in hematopoietic stem cell ontogeny and maintenance. It examines interactions between RUNX1 and Bmi1, and the role of src-family kinase mediated RUNX1 tyrosine phosphorylation.
Inhibition of Runx1 Tyrosine Phosphorylation in the Treatment of Human LeukemiaDescription of Major Goals
The major goal of this study is to test whether clinically available src family tyrosine kinase inhibitors can block Runx1 tyrosine phosphorylation and enhance its activity.
Runx-1 Centered Transcriptional Pathways as Tools to Discover Novel Genetic Risk Factors for Radiation-Induced Myelodysplastic Syndrome and LeukemiaDescription of Major Goals
The major goal of this study is to identify the genetic cause of families with autosomal dominant thrombocytopenia and propensity to develop leukemia who do not have Runx-1 gene alterations.
Role ASXL1 Mutations in Human Myelodysplastic Syndrome and LeukemiaDescription of Major Goals
The aims of this study are to identify novel ASXL1 interacting proteins to further understand its function in hematopoiesis, and to test the hypothesis that mutant ASXL1 proteins associated with human leukemia have dominant negative activity.
Proteomic Approach to Further Understanding the Role of Runx-1 in MyelodysplasiaDescription of Major Goals
The goals of this study were to purify and characterize Runx-1 containing multiprotein complexes in hematopoietic cells and examine the effects of myelodysplastic syndrome (MDS) associated Runx-1 mutations on observed protein-protein interactions.
Proteomic Study of Megakaryocyte Transcriptional ControlDescription of Major Goals
This goal of this study is to isolate GATA-1 containing multiprotein complexes from megakaryocytes, identify the components, and assess their functional significance in megakaryopoiesis.
Transcriptional Regulation of MegakaryopoiesisDescription of Major Goals
The main goal of this study was to further understand the transcriptional regulation of megakaryopoiesis by identifying novel GATA-1 associated proteins and assessing their functional significance in megakaryopoiesis.
Role of FOG-1 in HematopoiesisDescription of Major Goals
The major goal of this project is to define the mechanism of action of the transcriptional cofactor FOG-1 in hematopoiesis through a structure/function analysis.