Stem cells for therapeutics discovery in genetic blood disordersDescription of Major Goals
This multi-PI, multi-center component of the Progenitor Cell Translation Consortium exploits animal models of genetic blood disorders (zebrafish, murine, and human iPS cells) to screen and validate genes and small molecules as novel therapeutics and moves them into clinical trials. Co-PIs include Leonard Zon and Akiko Shimamura (BCH) and Adrianna Vlachos and Jeffrey Lipton (Hofstra-Northwell).
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.
Pilot Study of Metformin for Patients with Fanconi AnemiaDescription of Major Goals
This pilot study explores whether Metformin is safe and efficacious in improving hematopoiesis in patients with Fanconi Anemia. We focus on pediatric and young adult patients with FA to determine safety, tolerability, and preliminary efficacy of Metformin in Fanconi Anemia patients. This study also integrates biological correlative studies to glean mechanistic insights which may inform future studies.
Cell-Free Analysis of p53 and the Apoptosis CascadeDescription of Major Goals
This represents the remainder of the V Foundation grant received during in 1997. These are now unobligated funds. Investigate the regulation of apoptosis using a cell-free system. I designed the study and experiments, analyzed the data, and wrote the papers.
Feasibility study randomizing IST vs URD BMT for children with aplastic anemiaDescription of Major Goals
David Williams, PI We propose a pilot study to determine the feasibility of randomizing children with acquired aplastic anemia for either immunosuppression therapy (current standard of care) with highly matched unrelated donor hematopoietic stem cell transplant.
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.