In-Kwon Kim

Summary

My research focuses on elucidating the mechanisms of and developing new inhibitors for key enzymes in the ADP-ribosylation cycle and DNA repair that are critical for maintaining genomic stability. As you know, inhibitors of these pathways, such as poly(ADP-ribose) polymerase inhibitors (PARPi), have shown promise in selectively killing cancers that have compromised DNA repair functions. I seek to address important biological and biomedical questions: (1) how writers/readers/erasers of ADP-ribosylation and ADP-ribosyl conjugates specifically recognize and metabolize substrates (e.g., PARG and ARH3), (2) how ADP-ribosylation interplays with other post-translational modifications, such as ubiquitination (e.g., Deltex E3 ligases), and (3) how we can translate our new findings into the development of novel tumor-selective therapeutics. Indeed, our research efforts have successfully led to the identification and a US patent for selective inhibitors of PARG, a predominant poly(ADP-ribose)-degrading enzyme in humans, as promising alternatives to current FDA-approved PARPi.