Cells encode the instructions for life within their genomes. But this DNA is under constant assault from a variety of sources. Going outside without sunblock, drinking alcohol, smoking, and exposure to radiation are particularly serious stresses. But even just copying the genome can cause multiple forms of DNA damage. Failure to detect and reverse DNA damage can lead to errors that affect functional sequences and perpetuate from generation to generation.
Multicellular eukaryotes have evolved a wide variety of integrated pathways to sense and repair many 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.
But there is a bright side to DNA damage. Genome engineering systems, from nucleases to prime editors, work by targeting DNA damage and influencing repair to achieve a desired outcome. Genome engineering has revolutionized approaches to fundamental biological discovery and begun to yield cell-based therapies and cures for debilitating genetic disorders. DNA damaging genome engineering tools represent new opportunities to study repair in human cells and intensify the urgency of studying these processes so that we can better control engineering.
Research in the Corn lab seeks to understand the intersection between human DNA repair and genome engineering tools and to develop new approaches to cure human diseases using genome editing. We also use advanced genome editing to uncover the mechanisms by which cells accomplish dramatic transformations, such as the the stimulus-dependent destruction of entire organelles. We take a multidisciplinary approach to tackle these problems that includes genome-wide functional genomics, computational modeling, in vitro biochemistry and biophysics, and mechanistic cellular biochemistry.