Kyung S. Lee, Ph.D.

Life is established through varying degrees of hierarchical self-organization, from individual molecules and complexes to higher-order macromolecular assemblies. Understanding how cells orchestrate these diverse structural entities to induce a specific biological function is a key step to understanding the mystery of life. We have established an interdisciplinary research program aimed at addressing two fundamental questions:

• How are higher-order macromolecular assemblies generated?
• How are they further organized into a macroscale subcellular architecture to lay the foundations for inducing discrete intracellular processes?

The centrosome, which plays a central role as the main microtubule-organizing center for animal cell division, appears to be a particularly attractive model system for studying the formation of higher-order architectures thanks to the presence of multiple scaffold proteins that are concentrically arranged around a centriole in a highly ordered manner. For the past few years, we have been investigating the structure and function of several pericentriolar scaffolds, such as Cep192, Cep152, and Cep63, along with its effector, Polo-like kinase 4 (Plk4), a key regulator for centriole duplication. Our multifaceted approach has brought together wide-ranging fields, including cell biology (e.g., super-resolution microscopy, atomic force microscopy), biophysical chemistry (e.g., analytical ultracentrifugation, circular dichroism, SEC-MALS), structural biology (e.g., X-ray crystallography, NMR spectroscopy, SAXS), electron microscopy (e.g., thin-section TEM, cryo-EM), and nanomaterials science (e.g., nanopillar technology).

Our experience has been enriched by working effectively with supramolecular architectures generated through intricately regulated physicochemical processes. Our long-term goal is to understand the organization and function of the centrosome as a holistic functional entity. This research may offer a new paradigm for investigating the ways in which macroscale supramolecular assemblies are architected to achieve a new level of functional proficiencies, and it may provide a potential roadmap for studying other biological processes orchestrated by higher-order subcellular structures.

Dr. Kyung Lee received his Ph.D. in 1994 from the Department of Biochemistry at Johns Hopkins University in Baltimore. He then worked with Dr. Raymond Erikson at Harvard University as a postdoctoral fellow studying protein kinase and cancer. 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.

Dr. Lee is the recipient of an NCI Intramural Research Award, a Society for Biomedical Research CKD Award, an NCI CCR Synergy Award, and several Federal Technology Transfer Awards for his inventions and patents related to Plk1. He serves as an academic editor for PLoS ONE and an editorial board member for The Journal of Biological Chemistry.