Completed Grants and Sponsored Research

Generate maps that assign distal enhancer elements to their correct target gene(s) in human Mks

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.

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.

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.

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

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.