Completed Grants and Sponsored Research
Sponsoring Organization: Cooley's Anemia Foundation, Inc.
Genome Editing of Beta-Globin Gene Cluster Repressive Elements for Beta-Thalassemia
Description of Major GoalsIn this proposal, we will identify minimal sequences at the β-globin gene cluster necessary for BCL11A to repress γ-globin in β-thalassemia erythroid cells; and compare methodologies for safely and effectively performing genome editing of these repressive sequences in primary human β-thalassemia HSCs.
Sponsoring Organization: Harvard Medical School
Identification of NuRD subunit domain(s) necessary for Y-globin silencing by functional CRISPR-Cas9 mutagenesis scanning
Description of Major GoalsThe goal of this project is to explore whether a specific domain(s) of NuRD (Nucleosome Remodeling Deacetylase) subunits is necessary for γ-globin silencing and serves as a potential target for HbF reactivation therapy. The long-term goal of this project is to develop a compound(s) that induces HbF by targeting the epigenetic complex regulating globin switching.
Sponsoring Organization: Doris Duke Charitable Foundation
Molecular identification of Psickle in reticulocytes generated from HUDEP-2 cells gene-edited to express Hemoglobin SS in the absence of HbF
Description of Major GoalsMolecular identification of Psickle in reticulocytes generated from HUDEP-2 cells gene-edited to express HbS. This project is designed to enable production of a human cellular model of HbS expression using gene editing and then initial characterization of Psickle activity in HbA and HbS expressing erythroid cells.
Sponsoring Organization: COOLEY'S ANEMIA FOUNDATION, INC
Genome Editing of Beta-Globin Gene Cluster Repressive Elements for Beta-Thalassemia
Description of Major GoalsSpecific Aim 1. Utilize a custom pooled CRISPR guide RNA library to perform high-resolution mutagenesis to determine minimal non-coding sequences at the B-globin gene cluster necessary for HbF repression.
Specific Aim 2. Determine efficiency and specificity of genome editing human HSOCs by measuring rate of on-and off-target editing and impact on HbF level and henatopolesis.