Protein Homeostasis and
Drug Discovery

Our Research

Protein homeostasis (aka, proteostasis) – the equilibrium and optimal biological function of cellular proteins – is crucial for proper cellular functioning; its
imbalance is closely associated with diverse human diseases, including neurodegeneration and cancers.
Maintenance of proteostasis is attained through the coordinated action of the proteolytic machinery that preserve the proteome integrity.
Especially, the critical contribution of ubiquitin-proteasome system(UPS) to cellular proteostasis has been increasingly recognized in recent years.
We strive to understand cellular proteolytic mechanisms and develop new strategies for improving proteostasis by exploiting the UPS.
We are particularly interested in investigating proteasome, the master player in protein degradation,
and critical deubiquitinating enzymes (DUBs) in human pathophysiology.
Our group is trying to develop chemo-genomic methods to modulate the deubiquitinatio n activities acting upstream of and on the proteasome to explore novel deubiquitination biology. By developing new class of chemical proteolytic inducers and DUB inhibitors, we aim to define novel drug targets in protein quality control machinery and ultimately seek for proteolysis-based therapeutic strategies for human health.

Research Interest

Research Interest

  • Profiling deubiquitinating enzymes (DUBs) that are critically involved in human diseases
  • Chemo-genomic screening of DUB activities that are capable of controlling the half-lives of the challenging targets
  • High-throughput small-molecule screening of DUB inhibitors for proteolytically targeting the challenging targets
  • Developing novel chemical strategies to dispose of the "undruggables" or challenging targets by induced proteolysis
  • Elucidating dynamic nature of DUB reactions on the proteasome for proteolytic versatility
  • Deciphering the ‘ubiquitin code’ by discovering novel deubiquitination biology

Selected Publications