Cells must maintain the integrity of their genomes or risk permanent damage to functional sequences. Eukaryotes have evolved a wide variety of integrated pathways to sense and repair multiple types of DNA damage, from bulky lesions to double strand breaks. Deficiencies in these pathways can cause cells to accumulate genomic errors that lead to human diseases, including somatic cancers and Mendelian inherited genetic disorders. Harnessing DNA repair through the development of programmable nucleases such as ZFNs, TALENs, and recently CRISPR-Cas effectors is revolutionizing approaches to fundamental biological discovery and holds great promise for the cure of genetic diseases.
Next-generation gene editing tools, exemplified by CRISPR-Cas effectors such as Cas9, are fundamentally DNA damaging agents that introduce double strand breaks (or nicks if so engineered). Hence, they are inextricably linked to DNA repair in that they represent new opportunities to study DNA repair in human cells and intensify the urgency of studying these processes.
Research in the Corn lab seeks to understand the intersection between human DNA repair and genome editing tools and to develop new approaches to cure human diseases using genome editing. We furthermore use advanced genome editing to uncover the mechanisms by which cells use ubiquitin-based signals to encode information, including the stimulus-dependent destruction of entire organelles. We take a multidisciplinary approach to tackle these problems that includes computational modeling, in vitro biochemistry and biophysics, genome-wide screening, and mechanistic cellular biochemistry.