Translational and clinical studies targeting gamma-globin modulationDescription of Major Goals
The goal is to exploit the observation that individuals with propionic acidemia (PA) have enhanced HbF expression, in 3 specific aims, the PI proposes to 1) extend the observation that PA is associated specifically with HbF induction, 2) determine the unique metabolites that may be associated with said induction and 3) examine the effects of candidate metabolites on in vitro erythroid cell cultures. Specific globin gene expression, global gene expression, epigenetic modification of the beta globin locus, and a specific analysis of the effects of these metabolites on HDAC activity are proposed.
Hematopoietic regulators and efficient genome engineeringDescription of Major Goals
The goals of the project are to improve methods for gene engineering of hematopoietic stem cells in mouse and human in order to identify key regulators of blood cell development and self-renewal.