Hyun Kate Lee

Hyun Ok “Kate” Lee was born and raised in South Korea. She became fascinated with cell biology as an undergraduate researcher in Sean Morrison‘s laboratory at the University of Michigan, where she studied how stem cells contribute to repairing damaged tissues in mice. During her graduate research with Bob Duronio at the University of North Carolina, she studied how cell growth, DNA replication and damage are regulated during development, identifying new targets of Cullin4 E3 ubiquitin ligases. She then moved to Dresden, Germany, to begin her postdoctoral research at the Max Planck Institute of Molecular Cell Biology and Genetics. As a fellow in Tony Hyman’s laboratory, she studied how groups of molecules assemble functional organelles without membrane enclosures. Her research showed that these dynamic, liquid-like assemblies can promote the formation of rigid protein clumps that may lead to cell death in neurodegenerative diseases. Dr. Lee has received awards for her research, as well as for her teaching and research mentorship.

The Lee lab studies how non-membrane-bound organelles are regulated and function in cells and how their dysregulation affects cellular health and function. To gain insight into these questions, we use quantitative cell biology techniques in human stem cells and neurons, biochemical and biophysical methods with purified proteins and nucleic acids in vitro, and computational and omics approaches through collaborations.

Cellular response to stress and disease: biomolecular condensates and disordered protein regions

Cells constantly face challenges like UV, toxins, infections, environmental changes, and nutrient shortages that threaten their integrity. To cope, cells activate protective mechanisms that sense stress, initiate repair, and restore normal function. With age or mutations, these mechanisms weaken, allowing damage to accumulate and increasing the risk of diseases such as cancer and neurodegeneration. Our lab studies how cells detect, limit, and repair stress-induced damage, using these insights to develop strategies that promote health and resilience.

A conserved cellular response to stress is the reorganization of internal space to store or repair essential molecules. Within the crowded environment of a cell, many biochemical processes occur within specialized compartments, or organelles. While some, like the endoplasmic reticulum and Golgi apparatus, are enclosed by membranes, many others concentrate and exclude specific molecules without them, including nucleoli and RNA processing bodies. These non-membrane-bound organelles, called biomolecular condensates, arise through interactions between specific molecules that bring them together, much like oil droplets separating from water.

Many organelles, including condensates, change during stress. Certain condensates only form in response to stress, such as stress granules and DNA damage repair foci. This dynamic compartmentalization seems to help cells limit damage and recover more effectively, as defects in their regulation are linked to hallmarks of cancer and neurodegeneration. We want to understand:

1) what mechanisms regulate the assembly, composition, and dynamics of stress-response condensates in healthy cells

2) how condensates support stress resilience and healthy recovery from repeated stress

3) how disease-associated changes in these processes disrupt cellular function

Of particular interest is understanding how intrinsically disordered protein regions contribute to these processes. Unlike structured domains, these regions lack stable secondary structures and instead exist as dynamic ensembles of conformations. They play key roles in regulating the formation, composition, and material properties of biomolecular condensates, influence stress response and tolerance, and are functionally conserved across evolution, even when their linear amino acid sequences are not. We aim to understand the features of these regions that enable them to perform such versatile yet conserved functions.

RNA granules

RNA and RNA-binding proteins organize into several distinct condensates within cells, including RNA processing bodies, stress granules, and RNA transport granules. Disruptions in these structures have been linked to numerous neurological diseases. Notably, many of the proteins that form aggregates in these disorders are RNA-binding proteins that normally reside in RNA granules or interact with them. Mutations or cellular conditions that strengthen these interactions can increase the tendency of these proteins to form stable, non-dynamic assemblies known as aggregates or plaques, which is a hallmark of neurodegenerative disease. Our goal is to identify the mechanisms that prevent protein aggregation around RNA granules, define the molecular features that determine the unique composition of different RNA granules, and uncover their roles in cellular stress response and disease.

DNA damage repair sites

Accumulation of DNA damage is a hallmark of many diseases, including cancer and neurodegeneration. Our research and others have demonstrated that numerous DNA repair proteins assemble into biomolecular condensates. Disease-associated mutations in these proteins can alter the formation or composition of DNA repair foci. These changes can cause either insufficient or excessive repair activity, both of which can disturb normal cell health and function. We seek to understand the mechanisms that control DNA repair foci assembly, disassembly and composition, and how disrupting these factors (e.g., by disease-associated mutations) influences repair reactions.

Cell biology of neuromuscular diseases

Emerging evidence suggests that different cell types in the body vary in how they respond to stress and are affected by stressors. We aim to understand how long-lived, highly metabolic, differentiated cell types, such as neurons and muscle cells, manage stress and how failures in these responses contribute to disease. To address these questions, we combine insights from our in vitro reconstituted systems and studies in cycling immortalized cells with investigations of differentiated cells from induced pluripotent stem cells (iPSCs) derived from patients and healthy individuals.

Courses Taught

BCH2136H Biological Condensates
BCH473Y Advanced Research Project in Biochemistry
BCH455H Organelles in Cell Health and Function