Active Grants and Sponsored Research
Sponsoring Organization: NIH
Multiscale exploration of the functional non-coding genome
Description of Major GoalsThe goal of this subproject is to plan, generate and analyze data related to base editing screening, allele enrichment by long-read sequencing and UMI incorporation, as well as single cell RNA sequencing following genome editing studies.
Sponsoring Organization: National Heart, Lung, and Blood Institute
Gene editing ELANE to understand and treat severe congenital neutropenia
Description of Major GoalsThe goal is to apply novel gene editing technologies to develop a highly efficient, simple therapeutic approach to better understand and eventually treat ELANE-associated severe congenital neutropenia.
Sponsoring Organization: National Heart, Lung, and Blood Institute
Rectifying splicing mutations in blood disorders by gene editing
Description of Major GoalsThe goal is to develop innovative gene editing methods that can repair the abnormal genes that cause Beta-thalassemia and Shwachman-Diamond syndrome to restore their normal processing.
Sponsoring Organization: NIH/NNLBI
Lentiviral Gene Therapy For Sickle Cell Disease and Immunodeficiency Disorders
Description of Major GoalsThe goal of this project is to develop improved lentiviral gene therapy vectors for erythroid-specific expression of BCL11A shRNAs. Additionally, this project aims to compare two distinct approaches for de-repressing HbF in adult human red blood cells via genome editing.
Sponsoring Organization: St Jude's Children's Research Hospital
Novel Gene Therapies for Sickle Cell Diseases
Description of Major GoalsHigh-throughput discovery of essential noncoding sequences for erythropoiesis
The goals of this project are to utilize high-throughput genome editing technology and knowledge of human genetic variation associated with erythroid traits to characterize noncoding sequences required for erythropoiesis. The intention is to develop improved models of noncoding sequence function by iterative experimental testing and analytic refinement.
The goals of this project are to utilize high-throughput genome editing technology and knowledge of human genetic variation associated with erythroid traits to characterize noncoding sequences required for erythropoiesis. The intention is to develop improved models of noncoding sequence function by iterative experimental testing and analytic refinement.
Sponsoring Organization: Harvard Medical School
Therapeutic gene editing of ELANE for severe congenital neutropenia
Description of Major GoalsThe goal is to conduct preclinical development enabling a clinical trial of therapeutic gene editing for severe congenital neutropenia. We will: define the most favorable sites in ELANE for Cas9 editing to produce premature termination codons (PTCs); maximize Cas9 editing specifically, including evaluation by genome-wide off-target editing assessment; investigate impact on HSC function as measured by xenograft assay; and compare healthy donor and ELANE mutant CD34+ HSPCs.
Sponsoring Organization: Doris Duke Charitable Foundation
Enhanced nuclease delivery for therapeutic gene editing of hematopoietic stem cells in sickle cell disease
Description of Major GoalsThe goal of this project is to develop improved nucleases for delivery to hematopoietic stem cells for therapeutic gene editing that obviates need for ex vivo cell electroporation.
Sponsoring Organization: National Heart, Lung, and Blood Institute
Therapeutic BCL11A enhancer gene editing to induce fetal hemoglobin in Beta-hemoglobinopathy patients- CureSci
Description of Major GoalsThe goal of this project is to conduct a clinical trial of therapeutic gene editing of the BCL11A erythroid enhancer in patients with sickle cell disease and beta-thalassemia to durably induce fetal hemoglobin.
Sponsoring Organization: National Heart, Lung, and Blood Institute
Developmental Biology of Human Erythropoiesis - Project 4
Description of Major GoalsThe goals of the project “Functional Dissection of Erythroid Super-Enhancers” is to investigate the sequence requirements and trans-acting factors interacting with critical erythroid super-enhancer elements. The proposal integrates genome editing, bioinformatic, and biochemistry methodologies to explore fundamental mechanisms of erythroid gene regulation.
Sponsoring Organization: Harvard Medical School - Burroughs Wellcome Fund
Functional Characterization of Trait Associated Enhancers
Description of Major GoalsThe 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.
Sponsoring Organization: National Heart, Lung, and Blood Institute
High-Throughput Discovery of Essential Noncoding Sequences for Erythtropoiesis
Description of Major GoalsThe goals of this project are to utilize high-throughput genome editing technology and knowledge of human genetic variation associated with erythroid traits to characterize noncoding sequences required for erythropoiesis. The intention is to develop improved models of noncoding sequence function by iterative experimental testing and analytic refinement.