Our research is focused on three related areas:
- Engineering programmable nucleases for the targeted cleavage of a single site within a vertebrate genome
- Applying programmable nucleases for therapeutic applications
- Applying programmable nucleases to interrogate gene regulatory networks
We have a strong focus on the application of Cas9 and Cpf1 (Cas12a) systems for the ex vivo genome editing of CD34+ HSPCs for therapeutic applications. In particular, we are working on sickle cell disease, beta-thalassemia, and chronic granulomatous disease (CGD). We also have an active research program focused on Limb Girdle Muscular Dystrophy (LGMD). We are working on improving the delivery of Cas9 reagents for somatic cell genome editing (SCGE). All of these projects are in collaboration with labroatories here at UMMS or outside.
We are currently working to improve the precision and range of sequences that can be targeted by CRISPR/Cas9 systems through protein engineering. One of the goals is to create highly precise nuclease tools for inactivation of HIV provirus in reseroir cells. Besides their use in gene editing, we are also interested in applying these RNA-programmed DNA-binding units as effectors of gene regulation and tags for labeling specific chromosomal sites. We have recently described the first generation Cas9-pDBD platform in Nature Methods. We have an active research program focused on further improving precision and adding temporal regulation to this system.
Our research on protein-DNA recognition is currently focused primarily on two different types of DNA-binding domains for development as artificial transcription factors for therapeutic gene regulation:
We are also using working with the laboratory of Nathan Lawson (UMMS - MCCB) to develop new tools for studying gene function in zebrafish.