Bio


My primary goal is to develop an independent research career in hematology. As an African from a family background afflicted by hereditary hematologic disorders, I have longed to be part of research efforts to develop better treatments for blood diseases. My doctoral research focused on sickle cell disease where I conducted a preclinical investigation of a novel derivative of butyrate as a drug candidate for ameliorating the complications of the illness (Oseghale AR et al. Blood Cells Mol Dis. 2019 Jul 9;79:102345). My current focus as a postdoctoral scholar, in the Porteus laboratory, is to use CRISPR/Cas9 for genomic modification of human primary cells for curative therapeutic applications. A major aim of my project is to develop an automated closed system for the manufacturing of CRISPR/Cas9-engineered chimeric antigen receptor-expressing (CAR) T cells.

Stanford Advisors


Lab Affiliations


All Publications


  • High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition. Nature biotechnology Selvaraj, S., Feist, W. N., Viel, S., Vaidyanathan, S., Dudek, A. M., Gastou, M., Rockwood, S. J., Ekman, F. K., Oseghale, A. R., Xu, L., Pavel-Dinu, M., Luna, S. E., Cromer, M. K., Sayana, R., Gomez-Ospina, N., Porteus, M. H. 2023

    Abstract

    Therapeutic applications of nuclease-based genome editing would benefit from improved methods for transgene integration via homology-directed repair (HDR). To improve HDR efficiency, we screened six small-molecule inhibitors of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key protein in the alternative repair pathway of non-homologous end joining (NHEJ), which generates genomic insertions/deletions (INDELs). From this screen, we identified AZD7648 as the most potent compound. The use of AZD7648 significantly increased HDR (up to 50-fold) and concomitantly decreased INDELs across different genomic loci in various therapeutically relevant primary human cell types. In all cases, the ratio of HDR to INDELs markedly increased, and, in certain situations, INDEL-free high-frequency (>50%) targeted integration was achieved. This approach has the potential to improve the therapeutic efficacy of cell-based therapies and broaden the use of targeted integration as a research tool.

    View details for DOI 10.1038/s41587-023-01888-4

    View details for PubMedID 37537500

    View details for PubMedCentralID 3694601