Hyun Kate Lee

Hyun Kate Lee

Assistant Professor

Postdoc, Max Planck Institute of Molecular Cell Biology and Genetics, 2011-2017
PhD, University of North Carolina at Chapel Hill, 2010
BSc, University of Wisconsin - Madison, 2004

Address MaRS, West Tower, Suite 1521
661 University Ave.
Toronto, ON M5G 1M1
Lab Lee Lab
Office Phone 416-946-3813
Email hyunokate.lee-at-utoronto.ca

Hyun Ok “Kate” Lee was born and raised in S. 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 the repair of 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 start 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 that lack membranes. Her study demonstrated that these dynamic, liquid-like assemblies can harden over time, driving the formation of rigid protein clumps that drive cell death and are commonly found in neurodegenerative diseases. She started her lab in the Biochemistry Department at the University of Toronto in 2018.

Dr. Lee has received several awards for her research, as well as for her teaching and research mentorship.

 

Research Lab

The Lee lab studies how non-membranous organelles are regulated in cells and how their dysregulation impacts cellular health and function. We use a combination of quantitative live imaging and biochemical approaches in human stem cells and neurons to gain insight into these questions.

Research Description

Membrane-less Organelles and Neurodegeneration

 

 

Cellular space is compartmentalised into numerous organelles that each serve essential functions: from processing specific enzymatic reactions, producing physical force, to storing molecules under stress or during transport. Many organelles like the ER and Golgi separate their processes from the surrounding cytosol using lipid membranes, but a large class of organelles lack membranes, including nucleoli and RNA processing bodies. Membraneless organelles use transient inter- and intra-molecular interactions to concentrate molecules into dynamic and easily deformable compartments, like oil droplets in water. Defects in membraneless organelles have been linked to cellular anomalies causing cell death, yet it is largely unknown how membraneless organelle formation, composition, and function are regulated in cells.

Our lab uses quantitative live imaging techniques in human stem cells as well as differentiated cells like neurons to study 2 types of membrane-less organelles, RNA granules and DNA damage repair sites.

We want to figure out:
1) how their assembly, composition, and dynamics are regulated in healthy cells and altered in degenerative diseases
2) how their dysregulation impacts organelle function and cell health

Our ultimate goal is to identify strategies to improve diseases associated with membrane-less organelles, like neurodegeneration.

 

RNA granules and protein aggregation

RNA and RNA binding proteins form several distinct organelles in neurons, such as RNA processing bodies, stress granules, and RNA transport granules. A common cellular anomaly observed in neurodegenerative diseases is the accumulation of non-dynamic protein masses called aggregates or plaques. Many of the proteins that aggregate in disease are RNA binding proteins that concentrate in RNA granules. We recently discovered that mutations in RNA granule components cause the dynamic organelles to harden and transform into solid aggregates in vitro. Yet, this liquid-to-solid transition is not readily observed in cells, indicating that there are regulatory mechanisms that prevent protein aggregation inside RNA granules.

We want to understand:
1) What cellular factors ensure that proteins inside RNA granules remain soluble
2) What role RNA plays in the regulation of RNA granules

3) How protein aggregates impact other cellular processes

 

DNA damage repair sites and neurodegeneration

One of the most commonly observed cellular defects in aged cells and in degenerating neurons is the accumulation of unrepaired DNA damage. We and others have shown that RNA binding proteins also localize to damaged DNA and form liquid-like membraneless organelles. Disease-associated mutations in these proteins lead to inefficient DNA repair and accumulation of unresolved DNA damage.

We want to determine:
1) How the assembly and composition of DNA repair sites are regulated
2) How disease-associated mutations on RNA binding proteins affect the function of DNA repair sites
3) How unresolved DNA damage influences neuron health and function

 

Cell biology of neuromuscular diseases

Our goal is to elucidate the development and progression of neuromuscular degeneration, such as Amyotrophic Lateral Sclerosis. To do this, we will first use 2D neuron-muscle co-cultures to examine how neuromuscular connection is altered in patient-derived cells. In parallel, we will engineer a 3D tissue-like system to validate these findings and test repair and regeneration strategies.

 

Publications

View all publications on PubMed

A molecular grammar underlying the driving forces for phase separation of prion-like RNA binding proteins.
Wang J, Choi JM, Holehouse AS, Lee HO, Zhang X, Jahnel M, Maharana S, Lemaitre R, Pozniakovsky A, Drechsel D, Poser I, Pappu R, Alberti S, Hyman A.
Cell. 174(3): 688-699.e16

Isogenic FUS-eGFP iPSC Reporter Lines Enable Quantification of FUS Stress Granule Pathology that Is Rescued by Drugs Inducing Autophagy
Marrone L, Japtok J, Reinhardt P, Janosch A, Andree C, Lee HO, Moebius C, Reinhardt L, Cicardi ME, Hackmann K, Klink B, Poletti A, Alberti S, Bickle M, Hyman AA, Casci I, Pandrey U, Hermann A, Sterneckert J.
Stem Cell Reports. 10(2):375-389

An aberrant phase transition of stress granules triggered by misfolded protein and prevented by chaperone function
Mateju D, Franzmann TM, Patel A, Kopach A, Boczek E, Lee HO, Carra S, Hyman AA, Alberti S.
EMBO Journal. Jun 14;36(12):1669-1687

Intracellular Condensates: Organizers of Cellular Biochemistry.
Banani SF*, Lee HO*, Hyman AA, Rosen MK.
Nature Reviews Molecular Cell Biology. May;18(5):285-298

A Surveillance Function of the HSPB8-BAG3-HSP70 Chaperone Complex Ensures Stress Granule Integrity and Dynamism
Ganassi M, Mateju D, Bigi I, Mediani L, Poser I, Lee HO, Seguin SJ, Morelli FF, Vinet J, Leo G, Pansarasa O, Cereda C, Poletti A, Alberti S, Carra S
Mol Cell. 63(5):796-810.

A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation
Patel A*, Lee HO*, Jawerth L, Maharana S, Jahnel M, Hein MY, Stoynov S, Mahamid J, Saha S, Franzmann TM, Pozniakovski A, Poser I, Maghelli N, Royer LA, Weigert M, Myers EW, Grill S, Drechsel D, Hyman AA, Alberti S
Cell. 162, 1066-77

Interkinetic nuclear migration is centrosome independent and ensures apical cell division to maintain tissue integrity
Strzyz PJ, Lee HO, Sidhaye J, Weber IP, Leung LC, Norden C.
Dev Cell. 32, 203-19.

Mechanisms controlling arrangements and movements of nuclei in pseudostratified epithelia.
Lee HO, Norden C
Trends Cell Biol. 23,141-50.

Cell type-dependent requirement for PIP box-regulated Cdt1 destruction during S phase
Lee HO, Zacharek S, Xiong Y, Duronio RJ.
Mol Bio Cell. 21, 3639-53.

Endoreplication: Polyploidy with Purpose.
Lee HO, Davidson JM, Duronio RJ.
Genes Dev. 23, 2461-77.

CDT1 and Cdc6 are destabilized by rereplication-induced DNA damage.
Hall JR, Lee HO, Bunker BD, Dorn ES, Rogers GC, Duronio RJ, Cook JG.
J Biol Chem. 283, 25356-63.

WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase.
Hu J, Zacharek S, He YJ, Lee H, Shumway S, Duronio RJ, Xiong Y
Genes Dev. 22, 866-71.

Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes.
Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buylla A.
Nature. 425, 968-73.