Postdoctoral position using X-ray crystallography and cryo-EM to investigate Polo kinase and disease

Investigating how Polo-like kinases Plk4 and Plk1 orchestrate centrosome organization, cell signaling, cell proliferation, and tumorigenesis through integrated cell biological, biochemical, structural, and cryo-EM approaches.

Position Description: A postdoctoral fellowship is available to study the function of mammalian polo-like kinase 4 and 1 (Plk4 and Plk1), which play central roles in regulating various biological events, including centriole duplication, bipolar spindle formation, chromosome segregation, cell division, and proliferation. Dysregulation of Plk4/Plk1-dependent processes, by mutations in their associated cellular components or HIV accessory proteins, is tightly linked to the development of aneuploidy and cancer. During the past several years, we have been taking cell biological, biochemical, biophysical, and structural approaches (e.g., super-resolution imaging, single-molecule tracking, in vitro reconstitution, X-ray crystallography, and cryo-EM) to delineate the molecular bases and structural rules governing the centrosomal architecture and function, the deregulation of which can lead to the development of various human diseases, including cancers, microcephaly, and AIDS. For additional information, please visit https://ccr.cancer.gov/staff-directory/kyung-s-lee.

Fellows with expertise in the biochemical and biophysical characterization of regulatory proteins and structural determination using X-ray crystallography or cryo-EM, and with a strong interest in understanding the organization and function of the centrosome and its relevance to pathophysiological disorders, including cancer and other human diseases, are encouraged to apply. Applicants should hold a Ph.D., M.D., or equivalent degree (or expect to receive the degree before joining the laboratory) and should have received their degree within the past three years.

To apply, please send a CV and three names of references to Dr. Kyung Lee (kyunglee@mail.nih.gov). Starts at $68,544 for fellows with no prior years of postdoc training (+ annual raise) and includes complete health insurance.

Employer Name: National Cancer Institute, NIH.

Position Location: 9000 Rockville Pike, Bethesda, MD 20892, U.S.A.

Selected papers:

1. Ravishankar, H., ....., and Kyung S. Lee. An α-helical conformational switch couples multivalent assembly to drive cylindrical self-assembly and centrosome organization. Submitted.

2. Ahn, J. I., ....., and K. S. Lee. 2026. Dual architectural Cep57: A lynchpin for organizing pericentriolar materials and preventing mosaic variegated aneuploidy in humans. Nat. Commun. 17:11262. PMID: 42957679.

3. Park, J.-E, ….., and K. S. Lee. 2024. Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr-VprBP-Plk4 complex in CD4+ T cells. Nat. Commun. 15:2017. PMID: 38443376.

4. Park, J.-E., K. ….., and K. S. Lee. 2023. Specific inhibition of an anticancer target, polo-like kinase 1, by allosterically dismantling its mechanism of substrate recognition. Proc. Natl. Acad. Sci. USA 120:e2305037120 (Direct submission)

5. Ahn, J. I., ….., and K. S. Lee. 2023. Architectural basis for cylindrical self-assembly governing Plk4-mediated centriole duplication in humans. Commun. Biol. 6:712 PMID:37433832.

6. Lee, K. S. and M. Steinmetz. 2021. Centrosomes in the spotlight: from organization to function and their role in disease. Curr Opin Struct Biol. 66: iii–v. (Invited review). PMID: 33485756.

7. Lee, K. S., et al. 2020. Constructing PCM with architecturally distinct higher-order assemblies. Curr Opin Struct Biol. 66:66-73. (Invited review). PMID: 33176265.

8. Alverez, C. N., ….., and K. S. Lee. 2020. Identification of a new heterocyclic scaffold for inhibitors of the polo-box domain of polo-like kinase 1. J Med Chem. 63:14087-14117. PMID: 33175530.

9. Lee, K. S., et al. 2020. A self-assembled cylindrical platform for Plk4-induced centriole biogenesis. Open Biol. 10:200102 (Invited review). Featured article (Cover art). PMID: 32810424.

10. Park, J. -E., ….., and K. S. Lee. 2019. Phase separation of Plk4 by its autoactivation and noncatalytic clustering drives centriole biogenesis. Nat. Commun. 10: 4959. PMID: 31672968. Featured in “Protein Liquid-Liquid Phase Separation in Diseases” in Nat Commun (2022).

11. Kim, T.-S., ….., and K. S. Lee. 2019. Molecular architecture of a cylindrical self-assembly at human centrosomes. Nat. Commun. 10:1151. PMID: 30858376. Featured article (Editors’ Highlights).

Disclaimer: This position is subject to a background investigation. The NIH is dedicated to building a diverse community in its training and employment programs.