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Kyung S. Lee, Ph.D.

Kyung S. Lee, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Senior Investigator
Cancer Innovation Laboratory
Head, Chemistry Section

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

Centrosome Organization and Function
Mitotic Regulation
Protein Kinases and Cell Cycle Control
Anti-Cancer Therapy

Publications

Selected Key Publications

Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4+ T cells

Park JE, Kim TS, Zeng Y, Monnie CM, Alam MS, Zhou M, Mikolaj M, Maldarelli F, Narayan K, Ahn J, Ashwell JD, Strebel K, Lee KS
Nat. Commun. in press: 2024. [ Journal Article ]

Specific inhibition of an anticancer target, polo-like kinase 1, by allosterically dismantling its mechanism of substrate recognition

Park JE, Kirsch K, Lee H, Oliva P, Ahn Jl, Ravishankar H, Zeng Y, Fox SD, Kirby SA, Badwar P, Andresson T, Jacobson KA, Lee KS
Proc Natl Acad Sci U S A. 120(35): e2305037120, 2023. [ 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 ]

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Team

Postdoctoral Fellow (Visiting)
Jong II Ahn, Ph.D.
Postdoctoral Fellow (Visiting)
Harsha Ravishankar, Ph.D.
Visiting Fellow
Pooja Badhwar, Ph.D.

News

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