Sue-Ann Mok

 

Research:

Proteins can be thought of as mini machines or tools that execute the work in the cell. The shape of a protein is a critical factor in determining how well it can perform its tasks. Protein can lose their regular shape (misfold) for many reasons such as activity or cellular stress. In some select cases, proteins can take on alternate shapes that allow them to stack together like building blocks into long fibril structures called amyloids. The buildup of amyloids in cells and tissues is linked to several diseases e.g. Alzheimer’s, Parkinson’s, Huntington’s disease. Our team is trying to understand the biochemical features of proteins that increase their risk of misfolding into amyloids and how this process can be prevented. We also are very interested in understanding our cell’s evolved defense mechanisms against protein misfolding. In particular, we study a group of protective proteins called molecular chaperones that are considered the first line of defense against protein misfolding. We aim to understand how molecular chaperones recognize protein folding problems and why their protection fails when we develop diseases such as Alzheimer’s.

Our team uses biochemical and cellular methods to interrogate tau protein aggregation and aggregate structures associated with neurodegenerative diseases. A main focus in our lab is to develop high-throughput approaches in cloning, protein purification and protein structure and activity assays. Using these novel tools, we aim to systematically define the complex relationships between the factors regulating protein aggregation such as kinetics, phase separation, structure, chaperone recognition, and induced cell stress and damage.

 

Selected Publications:

Native PLGA nanoparticles attenuate Aβ-seed induced tau aggregation under in vitro conditions: potential implication in Alzheimer's disease pathology.
Paul PS, Patel T, Cho J-Y, Yarahmady A, Khalili A, Semencheko V, Wille H, Kulka M, Mok SA, Kar S.
Scientific Reports (2024) 14(1):144.

Disease associated mutations in tau encode for changes in aggregate structure conformation.
Sun KT, Patel T, Kang S-G, Yarahmady A, Julien O, Heras J, Mok SA
ACS Chemical Neuroscience (2023) 14(24):4282-4297.

Tau activation of microglial cGAS–IFN reduces MEF2C-mediated cognitive resilience.
Udeochu J, Amin S, Huang Y, Fan L, Torres E, Liu B, McGurran H, Coronas-Samano G, Kauwe G, Mousa GA, Wong MY, Ye P, Nagiri RK, Lo I, Holtzman J, Corona C, Yarahmady A, Gill M, Raju R, Mok SA, Gong S, Luo W, Tracy TE, Ratan R , Tsai L-H, Sinha S, Gan L.
Nature Neuroscience (2022) 26(5): 737-750.

Streamlined high-throughput cloning protocol to generate arrayed mutant libraries.
Sun KT, Patel TS, Kim J, Tang HSH, Eskandari-Sedighi G, Sureshkumar H, Schieve D, Mok SA.
STAR Protocols (2022) 4(1):101930.

Pathologic tau conformer ensembles induce dynamic, liquid-liquid phase separation events at the nuclear envelope.
Kang SG, Han G, Daude N, McNamara E, Wohlgemuth S, Molina-Porcel L, Safar JG, Mok SA, Westaway D.
BMC Biology (2021) 19(1): 199.

Deciphering network crosstalk: The current status and potential of miRNA regulatory networks on the molecular chaperone targets.
Budrass L, Fahlman RP, Mok SA.
Frontiers in Genetics (2021) 12: 991.

Mapping Interactions with the Chaperone Network Reveals Proteostasis Factors that Protect Against Tau Aggregation.
Mok SA, Condello C, Freilich R, Gillies, A, Arhar T, Oroz J, Kadavath H, Julien O, Assimon VA, Rauch JN, Dunyak BM, Lee J, Tsai FTF, Wilson MR, Zweckstetter M, Dickey CA, Gestwicki JE.
Nature Structural and Molecular Biology (2018) 25(5): 384-393.