Skip to main content

Gefei Chen

Assistant professor

Research description

Proteins can misfold and self-assemble into highly ordered fibrillar amyloid structures with toxic effects, a phenomenon that is linked to about 40 human diseases, including type-2 diabetes and the neurodegenerative disorders Parkinson disease and Alzheimer's disease (AD). Molecular chaperones play important roles in preventing protein misfolding and its potentially harmful consequences. Deterioration of molecular chaperone systems upon ageing are thought to underlie age-related neurodegenerative diseases and augmenting their activities could have therapeutic potential. 

My research focuses on 1) the molecular mechanisms of dementia relevant chaperone domain BRICHOS against self-assembly of proteins and peptides, e.g. Aβ42 and Tau associated with AD and islet amyloid polypeptide (IAPP) associated with type 2 diabetes, and the augmentation of chaperone activity for clinical applications; 2) the importance of amyloid like structure formation during the fast spider silk assembly process, and the underlying mechanisms of structural transformation. In particular we are interested to produce and study a specific motif in its soluble and fibrillar state; 3) large scale generation of recombinant Aβ42 from E. coli with high-quality and molecular modifications for mechanism study. 

Publications (#equal contributions) 

[1]    Chen G, Andrade-Talavera Y, Tambaro S, Leppert A, Nilsson H, Zhong X, Landreh M, Nilsson P, Hebert H, Biverstål H, Fisahn A, Abelein A, Johansson J. Augmentation of Bri2 molecular chaperone activity against amyloid-β reduces neurotoxicity in mouse hippocampus in vitro. Communications Biology, 2020, 3(1): 32.

[2]    Abelein A, Chen G, Kitoka K, Aleksis R, Oleskovs F, Sarr M, Landreh M, Pahnke J, Nordling K, Kronqvist N, Jaudzems K, Rising A, Johansson J, Biverstål H. High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain. Scientific Reports, 2020, 10(1): 235.

[3]    Kaldmäe M, Leppert A, Chen G, Sarr M, Sahin C, Nordling K, Kronqvist N, Gonzalvo-Ulla M, Fritz N, Abelein A, Laίn S, Biverstål H, Jörnvall H, Lane DP, Rising A, Johansson J, Landreh M. High intracellular stability of the spidroin N-terminal domain in spite of abundant amyloidogenic segments revealed by in-cell hydrogen/deuterium exchange mass spectrometry. The FEBS Journal, 2019.

[4]    Leppert A, Chen G, Johansson J. BRICHOS: a chaperone with different activities depending on quaternary structure and cellular location?[J]. Amyloid, 2019, 26(sup1):152-153.

[5]    Tambaro S, Galan-Acosta L, Leppert A, Chen G, Biverstål H, Presto J, Nilsson P, Johansson J. Blood-brain and blood-cerebrospinal fluid passage of different BRICHOS molecular chaperone domains. The Journal of Biological Chemistry, 2019, 294(8): 2606-2615.

[6]    Balleza-Tapia H, Crux S, Andrade-Talavera Y, Dolz-Gaiton P, Papadia D, Chen G, Johansson J, Fisahn A. TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Aβ-induced impairment in mouse hippocampus in vitro. eLife, 2018, 7: e37703.

[7]    Sarr M, Kronqvist N, Chen G, Aleksis R, Purhonen P, Hebert H, Jaudzems K, Rising A, Johansson J. A spidroin-derived solubility tag enables controlled aggregation of a designed amyloid protein[J]. The FEBS Journal, 2018, 285(10): 1873-1885.

[8]    Chen G#, Abelein A#, Nilsson H, Leppert A, Andrade-Talavera Y, Tambaro S, Hemmingsson L, Roshan F, Landreh M, Biverstål H, Koeck P, Presto J, Hebert H, Fisahn A, Johansson J. Bri2 BRICHOS client specificity and chaperone activity are governed by assembly state[J]. Nature Communications, 2017, 8: 2081.

[9]    Poska H, Haslbeck M, Kurudenkandy FR, Hermansson E, Chen G, Kostallas G, Abelein A, Biverstål H, Crux S, Fisahn A, Presto J, Johansson J. Dementia related Bri2 BRICHOS is a versatile molecular chaperone that efficiently inhibits Abeta42 toxicity in Drosophila[J]. Biochemical Journal, 2016, 473(20): 3683-3704.

[10]    Lin S, Chen G, Liu X, Meng Q. Chimeric spider silk proteins mediated by intein result in artificial hybrid silks[J]. Biopolymers, 2016, 105(7): 385-392.

[11]    Otikovs M#, Chen G#, Nordling K, Landreh M, Meng Q, Jörnvall H, Kronqvist N, Rising A, Johansson J, Jaudzems K. Back Cover: Diversified structural basis of a conserved molecular mechanism for ph-dependent dimerization in spider silk N-terminal domains[J]. ChemBioChem, 2015, 16(12): 1720-1724.

[12]    Andersson M#, Chen G#, Otikovs M, Landreh M, Nordling K, Kronqvist N, Westermark P, Jörnvall H, Knight S, Ridderstråle Y, Holm L, Meng Q, Jaudzems K, Chesler M, Johansson J, Rising A. Carbonic anhydrase generates CO2 and H+ that drive spider silk formation via opposite effects on the terminal domains[J]. PLoS Biology, 2014, 12(8): e100192.

[13]    Kronqvist N, Otikovs M, Chmyrov V, Chen G, Andersson M, Nordling K, Landreh M, Sarr M, Jörnvall H, Wennmalm S, Widengren J, Meng Q, Rising A, Otzen D, Knight SD, Jaudzems K, Johansson J. Sequential pH-driven dimerization and stabilization of the N-terminal domain enables rapid spider silk formation[J]. Nature communications, 2014, 5: 3254.

[14]    Chen G, Liu X, Zhang Y, Lin S, Yang Z, Johansson J, Rising A, Meng Q. Full-length minor ampullate spidroin gene sequence[J]. PLoS ONE, 2012, 7(12): e52293.

 

Loading bibliometrics...