Preclinical Studies of Marrow Failure and Clonal Evolution in Fanconi Anemia: Project 3Description of Major Goals
Evaluate the effects of small molecule compounds, metformin and TGF-beta receptor kinase inhibitors that improve proliferation, hematopoiesis, and cell survival in Fanconia anemia models.
U2AF1 mutations in myelodysplastic syndromes: from mechanism to therapyDescription of Major Goals
The goal of this study is to determine the mechanistic and functional consequences of U2AF1 spliceosomal mutations in order to identify new therapeutic strategies. The specific aims are: 1) Determine the mechanistic basis and consequences of the observed genetic spectrum of U2AF1 mutations; 2) Determine how U2AF1 mutations dysregulate downstream molecular pathways, contributing to molecular features of dysplastic cells. 3) Identify potential therapeutic opportunities for targeting U2AF1-mutant cells.
Translational Studies of Inherited Marrow Failure and Myelodysplastic SyndromesDescription of Major Goals
This is a resource development and discovery grant investigating inherited marrow failure and familial myelodysplastic syndromes with a focus on gene discovery.
Modeling MDS and Leukemia Predisposition for Novel TherapeuticsDescription of Major Goals
The specific aim of this study is to identify small molecule compounds that target del7q clones in Shwachman Diamond Syndrome.
Modeling Marrow Failure and MDS for Novel TherapeuticsDescription of Major Goals
This will utilize CRISPR/Cas to knock down genes. This approach will address the potential limitations of offtarget effects engendered by siRNA screening approaches.