Zachary C. Severance

This paper develops CRISPR-MACE, a platform for continuous directed evolution of CRISPR-Cas9 in human cells, generating variants with enhanced DNA binding and resistance to AcrIIA4.

This paper develops a small molecule, BRD8833, that induces BCR-ABL phosphorylation to disrupt its active site electric field, leading to loss of hyperactivity and apoptosis in BCR-ABL-dependent cancer cells.

This study shows induced-proximity inhibitors have orthogonal resistance mechanisms to classical inhibitors, using KRAS as a model system.