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Zhefeng Guo, Ph.D.

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4155 Reed


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Department / Division Affiliations
Assistant Professor, Neurology
Member, Access Biochemistry, Biophysics, Structural Biology Home Area, ACCESS Program, Access Neuroscience Home Area, Brain Research Institute
Assistant Professor In-Residence, Neuroscience IDP

Research Interest:

Structural biology of amyloid-related neurodegenerative diseases

Our long-term goal is to understand the structural basis of amyloid-related neurodegenerative diseases such as Alzheimer's, Parkinson's, and prion diseases, and to develop structure-based therapeutics. Alzheimer's disease is the most common form of dementia, affecting more than five million Americans. In Alzheimer's disease, amyloid beta (Abeta) protein plays a central role in disease development. Self-association of Abeta leads to the formation of oligomers and fibrils that are toxic to neuronal cells. Elucidating the structures of these oligomers and fibrils would contribute important insights into the mechanism of Alzheimer's disease. Because of the strong aggregation propensity of Abeta, Abeta studies have been hindered by a lack of new research tools. Currently, we are developing new approaches to study the structures of Abeta oligomers and fibrils using electron paramagnetic resonance (EPR) spectroscopy. EPR is a powerful technique for studying protein structure, dynamics, folding, and protein-protein interactions. In the studies of amyloid proteins, EPR has some unique advantages over X-ray crystallography and NMR. We will also employ the new EPR approaches to study other proteins such as tau protein in Alzheimer's disease, alpha-synuclein in Parkinson's disease, huntingtin in Huntington's disease, and prion protein in transmissible spongiform encephalopathies.


Zhefeng Guo is a structural biologist and biochemist who joined the UCLA School of Medicine faculty in 2008. Dr. Guo earned his B.S. in Microbiology (1995) at Shandong University and M.S. in Biochemistry (1998) at Peking University in China. Then Dr. Guo came to the United States for graduate studies and received his Ph.D. in Biochemistry (2003) at UCLA, where he was focused on developing electron paramagnetic resonance (EPR) methods to study protein structure, dynamics, and folding in Wayne Hubbell's laboratory. In 2004, Dr. Guo joined David Eisenberg's research group for postdoc training, working on the structural characterization of amyloid fibrils using the approaches of protein engineering and X-ray crystallography. His laboratory is currently investigating the structure and fibrillization mechanism of amyloid fibrils related to a wide range of human disorders such as Alzheimer's, Parkinson's and prion diseases, with the goal of developing molecular diagnostics and therapeutics for amyloid diseases


Gu, Lei; Liu, Cong & Guo, Zhefeng Structural insights into Aβ42 oligomers using site-directed spin labeling. J. Biol. Chem. 2013; 10.1074/jbc.M113.457739. Selected as JBC "Paper of the Week".
Gu, Lei & Guo, Zhefeng Alzheimer's A?42 and A?40 peptides form interlaced amyloid fibrils. J. Neurochem. 2013; DOI: 10.1111/jnc.12202.
Agopian, Audrey & Guo, Zhefeng Structural origin of polymorphism of Alzheimer's amyloid β-fibrils. Biochem. J. 2012; 447(1): 43-50.
Ngo, Sam; Chiang, Vicky & Guo, Zhefeng Quantitative analysis of spin exchange interactions to identify β strand and turn regions in Ure2 prion domain fibrils with site-directed spin labeling. J Struct. Biol. 2012; 180: 374-381.
Ngo, Sam; Chiang, Vicky; Ho, Elaine; Le, Linh & Guo, Zhefeng Prion domain of yeast Ure2 protein adopts a completely disordered structure: a solid-support EPR study. PLoS ONE 2012; 7: e47248.
Gu, Lei; Ngo, Sam & Guo, Zhefeng Solid-support electron paramagnetic resonance (EPR) studies of Aβ40 monomers reveal a structured state with three ordered segments. J Biol. Chem. 2012; 287(12): 9081-9.
Ngo, Sam & Guo, Zhefeng Key residues for the oligomerization of Aβ42 protein in Alzheimer's disease. Biochem. Biophys. Res. Commun. 2011; 414(3): 512-6.
Ngo, Sam; Gu, Lei & Guo, Zhefeng Hierarchical organization in the amyloid core of yeast prion protein Ure2. J Biol. Chem. 2011; 286(34): 29691-29699.
Lopez, Carlos J; Fleissner, Mark R; Guo, Zhefeng; Kusnetzow, Ana K & Hubbell, Wayne L Osmolyte perturbation reveals conformational equilibria in spin-labeled proteins. Protein Sc. 2009; 18(8): 1637-52.
Guo, Zhefeng; Cascio, Dulio; Hideg, Kalman & Hubbell, Wayne L. Structural determinants of nitroxide motion in spin-labeled proteins: Solvent-exposed sites in helix B of T4 lysozyme. Protein Sci. 2008; 17(2): 228-239.
Guo, Zhefeng & Eisenberg, David The structure of a fibril-forming sequence, NNQQNY, in the context of a globular fold. Protein Sci. 2008; 17: 1617-1623.
Guo, Zhefeng & Eisenberg, David The mechanism of the amyloidogenic conversion of T7 endonuclease I. J. Biol. Chem. 2007; 282(20): 14968-74.
Guo, Zhefeng; Cascio, Dulio; Hideg, Kalman; Kalai, Tamas & Hubbell, Wayne L. Structural determinants of nitroxide motion in spin-labeled proteins: Tertiary contact and solvent-inaccessible sites in helix G of T4 lysozyme. Protein Sci. 2007; 16(6): 1069-1086.
Guo, Zhefeng & Eisenberg, David Runaway domain swapping in amyloid-like fibrils of T7 endonuclease I. Proc. Natl. Acad. Sci. USA. 2006; 103: 8042-7.
Li, Huiying; Guo, Zhefeng & Zhu, Yuxian Molecular cloning and analysis of a pea cDNA that is expressed in darkness and very rapidly induced by gibberellic acid. Mol. Gen. Genet. 1998; 259: 393-397.