Laboratory of Immunoproteasome Chemical Biology
Kim lab’s research interests lie at the interface between chemistry and biology, with a particular focus on the development and the biological and pharmacological profiling of chemical probes of complex biological processes such as the proteasome-ubiquitin pathway. Specifically, there are currently three main themes to the work in Kim lab:
1) Investigation of the roles of the immunoproteasome in cancer: The immunoproteasome, an alternative form of the constitutive proteasome, is highly expressed in some solid and hematologic cancers and may play an important role in cancer cell proliferation and survival. However, the immunoproteasome remains largely untapped for drug discovery and the biology of the immunoproteasome is poorly understood. Recently, we have developed a small molecule (UK-101) that selectively inhibits catalytically active LMP2, a major catalytic subunit of the immunoproteasome. The goals of our research are to determine the role of the immunoproteasome in cancer and to investigate therapeutic potentials of the immunoproteasome-targeting approaches in cancer therapy, by developing and using small molecule probes, such as UK-101 and fluorescently labeled UK-101, which can be used as a non-invasive diagnostic tool.
2) Targeted protein degradation: the PROTAC approach: In the era of systemic proteomics, temporal and spatial control of protein functions has become very important in the investigation of complex biological processes in vitro and in vivo. While manipulation of protein expression levels at the DNA or RNA levels has provided a powerful tool to study protein function, their widespread applications are somewhat limited by the lack of temporal and spatial control. The goal of Kim lab is to study protein functions using small molecule modulators, which easily afford more temporal and spatial control of targeted biological events than the genetic approach. Specifically, Kim lab uses a targeted protein degradation strategy employing small molecules called PROTACs. Kim lab is one of pioneering labs in the PROTAC approach. PROTACs can be used as molecular probes for functional study as well as therapeutic agents by destroying disease-promoting proteins. Our current research efforts are focused on refinement of PROTAC design strategy for in vivo application.