Active Grants and Sponsored Research

The 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.

The 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.

The 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.

The 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.

High-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 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.

The 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.

The 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.

The 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.

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.

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.