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Active Grants and Sponsored Research

Project Date: September 1, 2015 - August 31, 2020
Sponsoring Organization: Harvard Medical School - Burroughs Wellcome Fund

Functional Characterization of Trait Associated Enhancers

Description of Major Goals
The goals of this research are to synthesize genetics, biology, and technology to test the hypothesis that enhancer variation is a prevailing determinant of human traits. We will systematically disrupt blood cell trait-associated enhancers to investigate impact on blood cell development, the genetic architecture of blood cell traits, and define cis- and trans-acting determinants of hematopoiesis.
Sponsor Grant ID: 2015134 Project Date: September 1, 2015 - August 31, 2018
Sponsoring Organization: Doris Duke Charitable Foundation

High-resolution and High Through-put genome editing to determine minimal repressive sequences within the beta-globin gene cluste

Description of Major Goals
This research is designed to test the hypothesis that NHEJ-mediated targeted indel production itself would be a favorable therapeutic genome editing strategy for sickle cell disease by disruption of endogenous β-globin gene cluster sequences that repress the expression of fetal hemoglobin.
Project Date: July 1, 2015 - June 30, 2018
Sponsoring Organization: American Society of Hematology

Characterization of Enhancers Underlying Human Erythroid Traits

Description of Major Goals
The goal of this project is to explore genetic determinants of human red blood cell traits that modulate erythroid enhancer elements. The aims are: to compare deletion of trait-associated enhancers to non-trait associated enhancers to investigate the genetic architecture of erythroid traits; and to disrupt trait-associated enhancers to identify variants and genes underlying erythroid traits.
Sponsor Grant ID: 1R03DK109232-01 Project Date: June 1, 2016 - May 31, 2018
Sponsoring Organization: National Institutes Of Health (NIH)

Identification of sequences and factors required for HbF repression

Description of Major Goals
The goals of this research are to utilize a high-resolution, high-throughput genome editing approach to identify genetically implicated noncoding sequences (in addition to the GWAS-marked BCL11A enhancer) associated with HbF level and to define trans-acting factors that physically and functionally interact with critical noncoding sequences at BCL11A and HBS1L-MYB.
Sponsor Grant ID: SG-0095-16-00 Project Date: May 1, 2016 - April 30, 2018
Sponsoring Organization: Harvard Stem Cell Institute

Targeted Disruption of the BCL11A Erythroid Enhancer in Hematopoietic Stem Cells for Genetic Therapy of the Beta-Hemoglobinopathies

Description of Major Goals
This research aims to investigate the effects of disrupting the BCL 11 A erythroid enhancer in HSCs and ensure that the modified cells can produce all types of blood cells while also leading to elevated levels of HbF. In addition, we will investigate whether targeting a more specific, enriched HSC population will allow for increased rates of editing and a more effective therapy. The work proposed here will provide important advancements in creating a gene therapy treatment for the 13-hemoglobinopathies as well as improving the use of genome editing technologies in hematopoietic stem cells.
Sponsor Grant ID: 3R03DK109232-01S1 Project Date: July 1, 2016 - June 30, 2017
Sponsoring Organization: National Institutes Of Health (NIH)

Research Supplement to Promote Diversity in Health-Related Research Associated with R03DK109232 Identification of sequences and factors required for HbF repression

Description of Major Goals
The goal of this proposal is to identify mechanisms that regulate HbF level and could serve as rational targets for efforts to re-induce HbF for the β-hemoglobin disorders.
Project Date: July 1, 2016 - June 30, 2017
Sponsoring Organization: Boston Children's Hospital - TRP

Biology studies of hematopoietic stem progenitor cells mobilized by plerixafor from patients with sickle cell disease

Description of Major Goals
The goal of this research is to study various features of the early blood cells that are collected during the plerixafor trial. We will test whether the plerixafor-mobilized cells are suitable for gene therapy and gene editing.
Project Date: July 1, 2016 - June 30, 2017
Sponsoring Organization: Cooley's Anemia Foundation, Inc.

Genome Editing of Beta-Globin Gene Cluster Repressive Elements for Beta-Thalassemia

Description of Major Goals
In 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.
Sponsor Grant ID: 4K08DK093705-05 Project Date: August 06, 2012 - May 31, 2017
Sponsoring Organization: National Institute Diab & Digest & Kid Diseases (NIDDKD)

Epigenetic regulation of BCL11A in hemoglobin switching

Description of Major Goals
The goals of this research are to discover molecular mechanisms underpinning hemoglobin switching. Specific aims include: to investigate mechanisms of BCL11A transcriptional regulation promoting the fetal-to-adult developmental transition; and to functionally evaluate regulatory elements at the BCL11A locus.
Sponsor Grant ID: 601139_FY16-17_Bauer_Seed Project Date: April 1, 2016 - March 31, 2017
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 Goals
The 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.
Sponsor Grant ID: 2015189 Project Date: November 11, 2015 - October 31, 2016
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 Goals
Molecular 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.