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Kyung S. Lee, Ph.D.

Kyung S. Lee, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Cancer Innovation Laboratory

RESEARCH SUMMARY

Dr. Kyung Lee carries out pioneering research aimed at understanding the structure and function of centrosomal self-assemblies and their associated regulatory complexes in human cells. He combines cell biology, structural biology, and cryo-EM to investigate how pericentriolar proteins organize themselves and serve as a platform to physicochemically regulate centriole duplication in a three-dimensional space. A failure in this process can result in abnormal centrosome numbers, improper spindle formation, and chromosome missegregation that leads to genomic instability culminating in genetic disorders such as cancer, microcephaly, ciliopathy, and dwarfism. Dr. Lee has also been investigating the function of mammalian polo-like kinase 1 (Plk1) and has been developing small molecule inhibitors that have potential as anti-cancer therapeutics. Through collaborations with Dr. Ken Jacobson at the National Institute of Diabetes and Digestive and Kidney Diseases, as well as multiple teams at the National Center for Advancing Translational Sciences, Dr. Lee has been steering a drug discovery program to develop inhibitors that target the noncatalytic polo-box domain (PBD) of Plk1, a unique protein-protein interaction module critical for substrate recognition. PBD inhibitors could present a new avenue for overcoming the hurdles currently facing anti-Plk1 therapy and may offer improved therapeutic potential.

Areas of Expertise

1) centrosome organization and function, 2) mitotic regulation, 3) protein kinases and cell cycle control, 4) anti-cancer therapy

Publications

Selected Key Publications

Identification of a New Heterocyclic Scaffold for Inhibitors of the Polo-Box Domain of Polo-like Kinase 1

Alverez CN, Park JE, Toti KS, Xia Y, Krausz KW, Rai G, Bang JK, Gonzalez FJ, Jacobson KA, Lee KS
J Med Chem. 63(22): 14087-14117, 2020. [ Journal Article ]

Phase separation of Polo-like kinase 4 by autoactivation and clustering drives centriole biogenesis

Park JE, Zhang L, Bang JK, Andresson T, DiMaio F, Lee KS
Nat Commun. 10(1): 4959, 2019. [ Journal Article ]

Molecular architecture of a cylindrical self-assembly at human centrosomes

Kim TS, Zhang L, Il Ahn J, Meng L, Chen Y, Lee E, Bang JK, Lim JM, Ghirlando R, Fan L, Wang YX, Kim BY, Park JE, Lee KS
Nat Commun. 10(1): 1151, 2019. [ Journal Article ]

Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis

Park SY, Park JE, Kim TS, Kim JH, Kwak MJ, Ku B, Tian L, Murugan RN, Ahn M, Komiya S, Hojo H, Kim NH, Kim BY, Bang JK, Erikson RL, Lee KW, Kim SJ, Oh BH, Yang W, Lee KS.
Nat. Struct. Mol. Biol. 21(8): 696-703, 2014. [ Journal Article ]

Serendipitous alkylation of a Plk1 ligand uncovers a new binding

Liu F, Park JE, Qian WJ, Lim D, Gräber M, Berg T, Yaffe MB, Lee KS*, Burke TR Jr.*
Nat Chem Biol. 7(9): 595-601, 2011. [ Journal Article ]

Job Vacancies

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Team

Postdoctoral Fellow (Visiting)
Jong II Ahn, Ph.D.
Postdoctoral Fellow (Visiting)
Harsha Ravishankar, Ph.D.
Postdoctoral Fellow (Visiting)
Hobin Lee, Ph.D.
Postdoctoral Fellow (Visiting)
Klara Pongorne Kirsch, Ph.D.
Postdoctoral Fellow (Visiting)
Yan Zeng, Ph.D.