Guo Research

M. Hayashi, A. Girdhar, Y.-H. Ko, K. M. Kim, J. DePierro, J. Buchler, N. Arunprakash, A. Bajaj, G. Cingolani*, L. Guo*. Engineered NLS-chimera downregulates expression of aggregation-prone endogenous FUS. Nature Communications 2024, 15:7887.

Y.-H. Ko, R. K. Lokareddy, S. G. Doll, D. P. Yeggoni, A. Girdhar, I. Mawn, J. R. Klim, N. F. Rizvi, R. Meyers, R. E. Gillilan, L. Guo* and G. Cingolani*. Single acetylation-mimetic mutation in TDP-43 nuclear localization signal disrupts importin a1/b signaling. Journal of Molecular Biology 2024, 436(20):168751. (*Co-corresponding author). 

​S. Vazquez-Sanchez, B. Tilkin, F. Gasset-Rosa, S. Zhang, D. Piol, M. McAlonis-Downes, J. Artates, N. Govea-Perez, L. Guo, D. W. Cleveland, J. Shorter, and S. Da Cruz. Frontotemporal dementia-like disease progression from age-dependent, seeded aggregation and spread of FUS. Molecular Neurodegeneration 2024, 19(46). 

M. E. Cicardi, V. Kankate, S. Sriramoji, K. Krishnamurthy, S. S. Markandaiah, B. M. Verdone, A. Girdhar, A. Nelson, L. B. Rivas, A. Boehringer, A. R. Haeusler, P. Pasinelli, L. Guo*, and D. Trotti*. The nuclear import receptor Kapβ2 modifies neurotoxicity mediated by poly(GR) in C9orf72-linked ALS/FTD.  Commun Biol. 2024, 7(1):376. (*Co-corresponding authors)

L. Guo*, J.R. Mann, J.C. Mauna, K.E. Copley, H. Wang, J.D. Rubien, H.M. Odeh, J. Lin, B.L. Lee, L. Ganser, E. Robinson, K.M. Kim, A.C. Murthy, T. Paul, B. Portz, A.M. Gleixner, Z. Diaz, J.L. Carey, A. Smirnov, G. Padilla, E. Lavorando, C. Espy, Y. Shang, E.J. Huang, A. Chesi, N.L. Fawzi, S. Myong, C.J. Donnelly*, and J. Shorter*. Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains. bioRxiv. doi:10.1101/2023.09.04.555754. (*Co-corresponding author).

K. Sharma, S. Banerjee, D. Savran, C. Rajes, S. Wiese, A. Girdhar, N. Schwierz, C. Lee, J. Shorter, M. Schmidt, L. Guo, and M. Fändrich. Cryo-EM structure of the full-length hnRNPA1 amyloid fibril. J. Mol. Biol. 2023, 435(18):168211.

J. Gao*, Q. T. Mewborne*, A. Girdhar, U. Sheth, A. N. Coyne Ritika Punathil, B. G. Kang, M. Dasovich, A. Veire, M. D. Hernandez, S Liu, Z Shi, R. Dafinca, E. Fouquerel, K. Talbot, T-I Kam, Y-J Zhang, D. Dickson, L. Petrucelli, M. van Blitterswijk, L. Guo, T. M. Dawson, V. L. Dawson, A. K. L. Leung, T. E. Lloyd, T. F. Gendron, J. D. Rothstein, K. Zhang. Poly(ADP-ribose) promotes toxicity of C9ORF72 arginine-rich dipeptide repeat proteins. Sci. Transl. Med. 2022, 14, eabq3215. (*Co-first author).

​A. Girdhar and L. Guo. Regulating Phase Transition in Neurodegenerative Diseases by Nuclear Import Receptors. Biology, 2022, 11, 1009.

H.J. Kim*, P. Mohassel*, S. Donkervoort, L. Guo, K. O’Donovan, M. Coughlin, X. Lornage, N. Foulds, S.R. Hammans, A.R. Foley, C.M. Fare, A.F. Ford, M. Ogasawara, A. Sato, A. Iida, P. Munot, G. Ambegaonkar, R. Phadke, D.G. O’Donovan, R. Buchert, M. Grimmel, A. Töpf, I.T. Zaharieva, L. Brady, Y. Hu, T.E. Lloyd, A. Klein, M. Steinlin, A. Kuster, S. Mercier, P. Marcorelles, Y. Péréon, E. Fleurence, A. Manzur, S. Ennis, R. Upstill-Goddard, L. Bello, C. Bertolin, E. Pegoraro, L. Salviati, C.E. French, A. Shatillo, F.L. Raymond, T. Haack, S. Quijano-Roy, J. Böhm, I. Nelson, T. Stojkovic, T. Evangelista, V. Straub, N.B. Romero, J. Laporte, F. Muntoni, I. Nishino, M.A. Tarnopolsky, J. Shorter, J.P. Taylor, and C.G. Bönnemann. Specific heterozygous frameshift variants in hnRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy. Nature Comm. 2022, 13(1):2306. (*Co-first author).

J. L. Carey, L. Guo. Liquid-Liquid Phase Separation of TDP-43 and FUS in Physiology and Pathology of Neurodegenerative Diseases. Front. Mol. Biosci. 2022, 9:826719. doi: 10.3389/fmolb.2022.826719.

L. Gottlieb, L. Guo, J. Shorter, and R. Marmorstein. N-alpha-acetylation of Huntingtin protein increases its propensity to aggregate. J. Biol. Chem. 2021, 297(6):101363.

D. Beijer, *, H. J. Kim*, L. Guo*, K. O’Donovan, I. Mademan, T. Deconinck, K Van Schil, C. M. Fare, L. E. Drake, A. F. Ford, A. Kochański, D. Kabzińska, N. Dubuisson, P. Van den Bergh, N. C. Voermans, R. J. L. F. Lemmers, S. M. van der Maarel, D. Bonner, J. B. Sampson, M. T. Wheeler, A. Mehrabyan, S. Palmer, P. De Jonghe, J. Shorter, J. P. Taylor, and J. Baets. Characterization of HNRNPA1 mutations defines diversity in pathogenic mechanisms and clinical presentation. JCI Insight. 2021, 6(14):e148363. (*Co-first author)

T. Yoshizawa, L. Guo. Karyopherin-βs play a key role as a phase separation regulator. J. Biochem. 2021, 170(1):15-23.

E. Robinson, J. Shorter, L. Guo. Karyopherin-β2 Inhibits and Reverses Aggregation and Liquid-liquid Phase Separation of the ALS/FTD-Associated Protein FUS. Bio-protocol. 2020, 10 (16):e3725-e3725. 

C. Wang*, Y. Duan*, G. Duan*, Q. Wang, K. Zhang, X. Deng, B. Qian, J. Gu, Z. Ma, S. Zhang, L. Guo, C. Liu, Y. Fang. Stress Induces Dynamic, Cytotoxicity-Antagonizing TDP-43 Nuclear Bodies via Paraspeckle LncRNA NEAT1-Mediated Liquid-Liquid Phase Separation. Molecular Cell. 2020, 79(3):443-458. (*Co-first author)

A.G. Niaki*, J. Sarkar*, X. Cai, K. Rhine, V. Vidaurre, B. Guy, M. Hurst, J.C. Lee, H.R. Koh, L. Guo, C.M. Fare, J. Shorter, and S. Myong. (2020). Loss of dynamic RNA interaction and aberrant phase separation induced by two distinct types of ALS/FTD-linked FUS mutations. Mol. Cell. 77(1):82-94. (*Co-first author).

F. Gasset-Rosa, S. Lu, H. Yu, C. Chen, Z. Melamed, L. Guo, J. Shorter, S. Da Cruz, and D.W. Cleveland. Cytoplasmic TDP-43 de-mixing independent of stress granules drives inhibition of nuclear import, loss of nuclear TDP-43, and cell death. Neuron. 2019,doi:10.1016/j.neuron.2019.02.038. 

J.R. Mann, A.M. Gleixner, J.C. Mauna, E. Gomes, M.R. DeChellis-Marks, P.G. Needham, K.E. Copley, B. Hurtle, B. Portz, N.J. Pyles, L. Guo, C.B. Calder, Z.P. Wills, U.B. Pandey, J.K. Kofler, J.L. Brodsky, A. Thathiah, J. Shorter, and C.J. Donnelly. RNA binding antagonizes neurotoxic phase transitions of TDP-43. Neuron. 2019,doi:10.1016/j.neuron.2019.01.048. 

Y-J. Zhang, L. Guo, P.K. Gonzales, T.F. Gendron, Y. Wu, K. Jansen-West, A.D. O’Raw, S.R. Pickles, M. Prudencio, Y. Carlomagno, M.A. Gachechiladze, C. Ludwig, R. Tian, J. Chew, M. DeTure, W-L. Lin, J. Tong, L.M. Daughrity, M. Yue, Y. Song, J.W. Andersen, M. Castanedes-Casey, A. Kurti, A. Datta, G. Antognetti, A. McCampbell, R. Rademakers, B. Oskarsson, D.W. Dickson, M. Kampmann, M.E. Ward, J.D. Fryer, C.D. Link, J. Shorter, and L. Petrucelli. Heterochromatin anomalies and double-stranded RNA accumulation underlie C9orf72 poly(PR) toxicity. Science. 2019,363(6428):eaav2606. 

L. Guo*, C.M. Fare*, and J. Shorter. Therapeutic dissolution of aberrant phases by nuclear-import receptors. Trends. Cell Biol. 2019,doi:10.1016/j.tcb.2018.12.004.  (*Co-first author).

L. McGurk*, E. Gomes*, L. Guo*, J. Shorter, and N.M. Bonini. Poly(ADP-ribose) engages the TDP-43 nuclear-localization sequence to regulate granulo-filamentous aggregation. Biochemistry. 2018, 57(51):6923−6926. (*Co-first author.).

L. McGurk, E. Gomes, L. Guo, J. Mojsilovic-Petrovic, V. Tran, R.G. Kalb, J. Shorter, and N.M. Bonini. Poly(ADP-ribose) prevents aberrant phase separation of TDP-43 by promoting liquid demixing and stress-granule localization. Mol Cell. 2018, 71(5):703-717. 

E. Bogaert, S. Boeynaems, M. Kato, L. Guo, T.R. Caulfield, J. Steyaert, W. Scheveneels, N. Wilmans, W. Haeck, N. Hersmus, J. Schymkowitz, F. Rousseau, J. Shorter, P. Callaerts, W. Robberecht, P. Van Damme, and L. Van Den Bosch. Molecular dissection of FUS points at synergistic effect of low-complexity domains in toxicity. Cell Rep. 2018, 24(3):529-537  cover

L. Guo*, H.J. Kim*, H. Wang*, J. Monaghan°, F. Freyermuth°, J.C. Sung°, K. O’Donovan, C.M. Fare, Z. Diaz, N. Singh, Z.C. Zhang, M. Coughlin, E.A. Sweeny, M.E. DeSantis, M.E. Jackrel, C.B. Rodell, J.A. Burdick, O.D. King, A.D. Gitler, C. Lagier-Tourenne, U.B. Pandey, Y.M. Chook, J.P. Taylor, and J. Shorter. Nuclear-import receptors reverse aberrant phase transitions of RNA-binding proteins with prion-like domains. Cell. 2018, 173(3):677-692. (*Co-first author. °Co-second author).

T. Zhang*, Y-C. Wu*, P. Mullane, Y.J. Ji, H. Liu, L. He, A. Arora, H-Y. Hwang, A.F. Alessi, A.G. Niaki, G. Periz, L. Guo, H. Wang, E. Elkayam, L. Joshua-Tor, S. Myong, J.K. Kim, J. Shorter, S-E. Ong, A.K.L. Leung, and J. Wang. FUS regulates activity of microRNA-mediated gene silencing. Mol. Cell. 2018, 69(5):787-801. (*Co-first author).

L. Guo and J. Shorter. Biology and pathobiology of TDP-43 and emergent therapeutic strategies. Cold Spring Harb Perspect Med. 2017, 7(9). pii: a024554. 

L. Guo and J. Shorter. It's raining liquids: RNA tunes viscoelasticity and dynamics of membraneless organelles. Mol. Cell. 2015, 60, 189-192. 

L. Guo and F. Gai. Simple Method to Enhance the Photostability of the Fluorescence Reporter R6G for Prolonged Single-Molecule Studies. J. Phys. Chem. A. 2013, 117, 6164-6170.

D. Chow, L. Guo, F. Gai, and M. Goulian. Fluorescence correlation spectroscopy measurements of the membrane protein TetA in Escherichia coli suggest rapid diffusion at short length scales. PLoS ONE. 2012, 7(10):e48600.

Y-H. Wang, A. Collins, L. Guo, K. B. Smith-Dupont, F. Gai, T. Svitkina and P. A. Janmey. Divalent cation-induced cluster formation by polyphosphoinositides in model membranes. J. Am. Chem. Soc. 2012, 134, 3387-3395.

L. Guo, K. B. Smith-Dupont and F. Gai. Diffusion as a probe of peptide-induced membrane domain formation. Biochemistry. 2011, 50, 2291-2297.

J. M. G. Rogers*, A. Polishchuk*, L. Guo*, J. Wang, W. F. DeGrado and F. Gai. Photoinduced electron transfer and fluorophore motion as a probe of the conformational dynamics of membrane proteins: application to the influenza A M2 proton channel. Langmuir. 2011, 27, 3815-3821. (*Equal Contribution).

L. Guo and F. Gai. Heterogeneous diffusion of a membrane-bound pHLIP peptide. Biophys. J. 2010, 98, 2914-2922.

K. B. Smith-Dupont*, L. Guo* and F. Gai. Diffusion as a probe of the heterogeneity of antimicrobial peptide-membrane interactions. Biochemistry. 2010, 49, 4672-4678. (*Equal Contribution).

L. Guo, J. H. Park, T. Lee, P. Chowdhury, M. Lim and F. Gai. Probing the role of hydration in the unfolding transitions of carbonmonoxy myoglobin and apomyoglobin. J. Phys. Chem. B. 2009, 113, 6158-6163.

S. Mukherjee, M. Waegele, P. Chowdhury, L. Guo and F. Gai. Effect of macromolecular crowding on the folding kinetics of protein secondary structures. J. Mol. Biol. 2009, 393, 227-236.

L. Guo, P. Chowdhury, J. M. Glasscock and F. Gai. Denaturant induced expansion and compaction of a multi-domain protein: IgG. J. Mol. Biol. 2008, 384, 1029-1036.

S. Yang, H. Wang, L. Guo, Y. Liu and A. Cao. Interaction of fullerenol with lysozyme investigated by experimental and computational approaches. Nanotechnology. 2008, 19, 395101-395107.

L. Guo, P. Chowdhury, J. Y. Fang and F. Gai. Heterogeneous and anomalous diffusion inside lipid tubules.  J. Phys. Chem. B. 2007, 111, 14244-14249.