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
Genetic Risk Factors for Clonal Hematopoiesis and Leukemia Development Following Ionizing Radiation and Chemical ExposureDescription of Major Goals
The overall goal of this project is to test the hypothesis that genotoxic stress (ionizing radiation, DNA damaging chemicals, etc.) selects for pre-existing hematopoietic stem/progenitor cells that contain mutations in genes, such as RUNX1, that activate the DNA damage response pathway. This will be tested in a whole animal model. In addition, a CRISPR/Cas9 screen will be used to identify novel genes involved in this pathway.
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.
Regulation of RUNX1 Multiprotein Complex Formation during HematopoiesisDescription of Major Goals
The overall goal of this project is to further understand the mechanisms and signaling pathways that modulate RUNX1 protein-protein interactions during cellular differentiation.
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.
Transcriptional Effectors of Activated RAS Signaling in Juvenile Myelomonocytic LeukemiaDescription of Major Goals
The goal of this project is to test the role of RUNX1 as a dysregulated transcriptional effect target of activated RAS/Shp2 signaling in Juvenile Myelomonocytic Leukemia.
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.