Dr. Kyung Lee received his Ph.D. in 1994 from the Department of Biochemistry at the Johns Hopkins University in Baltimore. He then worked with Raymond Erikson at Harvard University as a postdoctoral fellow and studied in the fields of cellular proliferation and mitotic controls. In 1998, he joined NIH as a tenure-track investigator in the Laboratory of Metabolism at NCI. In 2005, Dr. Lee became a senior investigator and head of the Chemistry Section, Laboratory of Metabolism, NCI, NIH.
The general research theme of the Chemistry Section (CS) is to understand the mechanisms that regulate various aspects of cellular proliferation and tumorigenesis. Our primary research interest lies in investigating the function of mammalian polo-like kinase 1 (Plk1), a critical mitotic kinase that is frequently overexpressed in a wide spectrum of cancers in humans. Over the years, Plk1 has been the focus of extensive studies because of its strong association with neoplastic transformation of human cells. Plk1 is thought to be an attractive anti-cancer drug target. During M-phase of the cell cycle, Plk1 localizes to the centrosome, kinetochore, spindle, and midbody to regulate diverse cellular processes, such as centrosome maturation, bipolar spindle formation, and cytokinesis. The C-terminal polo-box domain (PBD) appears to play a central role in targeting Plk1 to these locations by interacting with distinct binding proteins at these sites. To gain a deeper understanding of the temporal and spatial regulation of Plk1 and the function of the PBD in normal and cancer cell proliferation, we have isolated several proteins that specifically interact with the PBD. These include hCenexin1, PBIP1 (also called CENP-U/50), and Nedd1 (also called GCP-WD) whose functions appear to be required to properly recruit Plk1 to centrosomes, kinetochores, and mitotic spindles, respectively. Identification of additional PBD-binding proteins and further investigation on the physiological significance of PBD-dependent protein-protein interactions are currently underway. Utilizing the knowledge that we obtain from these studies, we are also interested in designing and developing anti-Plk1 PBD therapeutic agents.
Research in the Lee Laboratory
Regulation of the Nedd1-Augmin Complex
In Vitro HTS and In Vivo Cell-Based Assay
Structure-Based Drug Design and Virtual Screening