Pharmacologic Enhancement of Residual Wild Type RUNX1 Activity in Familial Platelet Disorder with Propensity to Develop Leukemia (FPD/AML)Description of Major Goals
The goal of this study is test the use of src family kinase inhibitors in preclinical models for use in enhancing the residual wild type RUNX1 activity in patients with heterozygous loss-of-function RUNX1 mutations.
Developing Novel Treatments for Juvenile Myelomonocytic Leukemia (JMML)Description of Major Goals
The major goal of this study is to test the efficacy of a small molecule inhibitor of CBFb-RUNX1 interactions for its ability reduce disease severity in a mouse model of juvenile myelomonocytic leukemia (JMML) as well as in JMML patient sample cellular assays.
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.
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.
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.