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Kyung S. Lee, Ph.D.

Portait Photo of Kyung Lee
Laboratory of Metabolism
Head, Chemistry Section
Senior Investigator
Center for Cancer Research
National Cancer Institute
Building 37, Room 3122C
Bethesda, MD 20892


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.


Research Program:
The general research theme of the Chemistry Section is to understand the mechanisms that regulate various mitotic events and cellular proliferation. Our primary focus is to understand the function of mammalian polo-like kinase 1 (Plk1), a critical mitotic kinase that is upregulated in ~ 80% of human cancers. A growing body of evidence suggests that Plk1 plays a critical role in numerous mitotic events and cellular proliferation. As such, down-regulation of Plk1 activity results in mitotic catastrophe and apoptotic cell death, whereas constitutive expression of Plk1 induces oncogenic focus formation and tumors in nude mice. Plk1 has been suggested as a biomarker for several types of human cancers (breast, ovarian, non-small cell lung, head/neck, colon, endometrial and esophageal carcinomas, and leukemias) and is considered an important potential target for anti-cancer therapy. To steer a drug discovery program based on strong basic science and to fulfill the mission of the NCI in eliminating suffering and death from cancer, we are investigating the mechanisms of how Plk1 deregulation leads to the development of cancers in humans. To this end, we have focused on isolating novel Plk1 substrates and binding proteins, two of which have been identified as a kinetochore protein, PBIP1, and a centrosomal protein, hCenexin1. Both of these proteins interact with the polo-box domain (PBD) of Plk1, which is essential for targeting the catalytic activity of Plk1 to specific subcellular structures. The physiological significance of these interactions is currently under investigation. Intriguing early results indicate that Plk1-dependent PBIP1 phosphorylation at T78 induces a high affinity interaction between PBIP1 and Plk1 PBD and as a result p-T78 PBIP1-dependent Plk1 recruitment to the mitotic kinetochores. Absence of the PBIP1-Plk1 interaction leads to chromosome missegregation and aneuploidy, suggesting that PBIP1-dependent Plk1 recruitment to the kinetochores is critical for maintaining chromosome stability. Paradoxically, fully activated Plk1 induces PBIP1 degradation in early mitosis, although the mechanism and the significance of this event are yet to be investigated. Intriguingly, a phospho-T78 peptide specifically bound to Plk1, but not to the related Plk2 or Plk3. Further investigation on the nature of the p-T78 peptide-Plk1 PBD interaction will be important to define the structural determinants for the PBD binding, leading to the isolation and design of anti-Plk1 PBD inhibitors and anti-Plk1 therapeutic agents.

This page was last updated on 6/7/2013.