Active Grants and Sponsored Research

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 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 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 of this project is to transform management of SCD through the development of new drug candidates specifically targeted to interfere with fetal hemoglobin (HbF) silencing. The aims are: Perform comprehensive, fine-resolution functional CRISPR/Cas9 mapping of NuRD complex components; Develop small molecules targeting the bromodomain of ZMYND8; Assess the consequences of ZMYND8 bromodomain domain inhibitors and directed destruction of ZMYND8 protein for HbF induction; and assess the functional consequences of small molecules directed to ZMYND8 for HbF reactivation, and other gene expression and cellular changes, in both wild-type and SCD-patient derived primary CD34 cells.

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.