Gefei Chen

Gefei Chen

Principal Researcher
Visiting address: Blickagången 16, 14152 Flemingsberg
Postal address: H2 Biovetenskaper och näringslära, H2 BioNut Johansson Chen, 171 77 Stockholm

About me

  • *Honours*
    Biträdande Lektor position at KI (Stockholm, Sweden), 2019
    *Commissions of trust*
    /Grant review/
    1) Austrian Science Fund (FWF) in the frame of the programme for funding
    patient oriented clinical research (KLIF).
    /Journal editorial board /
    1) Young Editorial Board of /Military Medical Research/
    2) Editorial Board Member for /Scientific Reports/
    3) Editorial Board (Review Editor) for /Frontiers in Molecular Bioscience/
    4) Editorial Board (Review Editor) for /Frontiers in Aging Neuroscience/
    *Funding*
    Our projects are financially supported by Alzheimer's Association Research
    Grant (U.S.), Petrus och Augusta Hedlunds Stiftelse, Åke Wibergs stiftelse,
    Åhlén-stiftelsens Olle Engkvists Stiftelse, Alzheimerfonden, Stiftelsen
    Sigurd och Elsa Goljes Minne, Loo and Hans Osterman Foundation for Medical
    Research, Gun and Bertil Stohne's Foundation, Magnus Bergvalls Stiftelse,
    Karolinska Institutet Research Foundation Grants, Foundation for Geriatric
    Diseases at Karolinska Institutet, and Stiftelsen för Gamla Tjänarinnor.

Research

  • Research group [1]
    Surveillance by molecular chaperones may decline, and proteins misfold and
    self-assemble into amorphous aggregates as well as fibrillar amyloid which
    are linked to cureless human diseases. Our research aims to understand how
    molecular chaperones interfere with different types of protein aggregation
    and alleviate relevant toxicities, and augment specific chaperone capacity
    for novel treatment developments, in particular against cancer and
    neurodegenerative diseases. On the other side, non-pathological amyloid is
    supposed to be shared by spider silk, one of the toughest biomaterials.
    Currently, our understanding of amyloid-like formation during spider silk
    assembly process and underlying mechanisms are largely missing.
    *Selected publications *
    *(*corresponding author, #equal contribution)*
    [40] Qi X, Wang Y, Yu H.
  • Liu R, Leppert A, Zheng Z, Zhong X, Jin Z, Wang H,
    Li X, Wang X, Landreh M, A. Morozova-Roche L, Johansson J, Xiong S,
    Iashchishyn I, *Chen G**. Spider Silk Protein Forms Amyloid-Like Nanofibrils
    through a Non-Nucleation-Dependent Polymerization Mechanism [2]. /Small/,
    2023, 2304031.
    [39] Medina-Vera D, Zhao H, Bereczki E, Rosell-Valle C, Shimozawa M, *Chen
    G*, de Fonseca F.R, Nilsson P, Tambaro S. The Expression of the
    Endocannabinoid Receptors CB2 and GPR55 is Highly Increased during the
    Progression of Alzheimer’s Disease in AppNL-G-F Knock-In Mice
    [3]. /Biology/, 2023, 12, 805.
    [38]* Chen G**, Leppert A, Poska H, Nilsson H, Carlos A, Zhong X, Koeck P,
    Jegerschöld C, Abelein A, Hebert H, Johansson J. Short hydrophobic loop
    motifs in BRICHOS domains determine chaperone activity against amorphous
    protein aggregation but not against amyloid formation [4]. /Communications
    Biology/, 2023, 6, 497.
    [37] Leppert A, *Chen G*, Lama D, Sahin C, Railaite V, Shilkova O, Arndt T,
    Marklund E, Lane D, Rising A, Landreh M. Liquid-liquid phase separation
    primes spider silk proteins for fiber formation via a conditional sticker
    domain [5]. /Nano Letters/, 2023, , 23, 12, 5836–5841.
    [36] Leppert A, Poska H, Landreh M, Abelein A, *Chen G*, Johansson J. A new
    kid in the folding funnel: Molecular chaperone activities of the BRICHOS
    domain [6]. /Protein Science/, 2023, e4645.
    [35] Saluri M, Leppert A, Gese G, Sahin C, Lama D, Kaldmäe M, *Chen G*,
    Elofsson A, Allison T, Arsenian-Henriksson M, Johansson J, P. Lane D,
    Hällberg M, Landreh M. A "grappling hook" interaction connects self-assembly
    and chaperone activity of Nucleophosmin 1 [7]. /PNAS Nexus/, 2023, 2(2):
    pgac303.
    [34] Andrade-Talavera Y#, *Chen G#*, Pansieri J#, Arroyo-García L. E,
    Toleikis Z, Smirnovas V, Johansson J, Morozova-Roche L, Fisahn A. S100A9
    amyloid growth and S100A9 fibril-induced impairment of gamma oscillations in
    area CA3 of mouse hippocampus ex vivo is prevented by Bri2 BRICHOS [8].
    /Progress in Neurobiology, // //Progress in Neurobiology/, 2022, 219:102366.
    [33]* Chen G**, Andrade-Talavera Y, Zhong X, Hassan S, Biverstal H, Poska H,
    Abelein A, Leppert A, Kronqvist N, Rising A, Hebert H, Koeck P, Fisahn A,
    Johansson J. Ability of the BRICHOS domain to prevent neurotoxicity and
    fibril formation are dependent on a highly conserved Asp residue [9]. /RSC
    Chemical Biology/, 2022, 3:1342-1358.
    [32] Manchanda S, Galan-Acosta L, Abelein A, Tambaro S, *Chen G*, Nilsson P,
    Johansson J. Intravenous treatment with a molecular chaperone designed
    against amyloid-β toxicity improves features of Alzheimer disease pathology
    in mouse models [10]. /Molecular Therapy/, 2022, S1525-0016(22)00498-1.
    [31] Arndt T, Jaudzems K, Shilkova O, Francis J, Johansson M, Laity P, Sahin
    C, Chatterjee U, Kronqvist N, Barajas-Ledesma E, Kumar R, *Chen G*,
    Strömberg R, Abelein A, Langton M, Landreh M, Barth A, Holland C, Johansson
    J, Rising A. Spidroin N-terminal domain forms amyloid-like fibril based
    hydrogels and provides a protein immobilization platform [11]. /Nature
    Communications/, 2022, 13(1):4695.
    [30] Zhong X, Kumar R, Wang Y, Biverstal H, Jegerschöld C, Koeck P,
    Johansson J, Abelein A, *Chen G**. Amyloid fibril formation of Arctic
    amyloid-β 1–42 peptide is efficiently inhibited by the BRICHOS domain
    [12]. /ACS Chemical Biology/, 2022, 17(8):2201-2211.
    [29] Tang X, Liu L, Miao Z, Zhang J, Cai X, Zhao B-Q, *Chen G*, Schultzberg
    M, Zhao Y, Wang X. Resolution of inflammation is disturbed in acute ischemic
    stroke with diabetes mellitus and rescued by resolvin D2 treatment [13].
    /Free Radical Biology and Medicine/, 2022, 188:194-205.
    [28] Jiang R, Smailovic U, Haytural H, Tijms B, Li H, Haret R, Shevchenko G,
    *Chen G*, Abelein A, Gobom J, Frykman S, Sekiguchi M, Fujioka R, Watamura N,
    Sasaguri H, Nystrom S, Hammarstrom P, Saido T, Jelic V, Syvanen S, Zetterberg
    H, Winblad B
  • Bergquist J, Visser P, Nilsson P. Increased CSF-decorin
    predicts brain pathological changes driven by Alzheimer’s Aβ amyloidosis
    [14]. /Acta Neuropathologica Communications/, 2022, 10(1):96.
    [27] Leppert A, *Chen G*, Lianoudaki D, Williams C, Zhong X, Gilthorpe J,
    Landreh M, Johansson J. ATP-independent molecular chaperone activity
    generated under reducing conditions [15]. /Protein Science/, 2022, 31(8):
    e4378.
    [26] Kaldmäe M, Vosselman T, Zhong X, Lama D, *Chen G*, Saluri M, Kronqvis
    N, Siau J, Seng Ng A, Ghadessy F, Sabatier P, Vojtesek B, Sarr M, Sahin C,
    Österlund N, Ilag L, Väänänen V, Sedimbi S, Arsenian-Henriksson M,
    Zubarev R, Nilsson L, Koeck P, Rising A, Abelein A, Fritz N, Johansson J,
    Lane D, and Landreh M. A “spindle and thread”-mechanism unblocks p53
    translation by modulating N-terminal disorder [16]. /Structure, / 2022,
    30(5):733-742.
    [25] Oliveira D, Svensson J, Zhong X, Biverstål, *Chen G*#*, Karlström H*#.
    Molecular chaperone BRICHOS inhibits CADASIL-mutated NOTCH3 aggregation in
    vitro [17]. /Frontiers in Molecular Biosciences/, 2022, 9:812808.
    [24] Li X, Qi X, Cai Y, Sun Y, Wen R, Zhang R, Johansson J, Meng Q*, *Chen
    G**. Customized flagelliform spidroins form spider silk-like fibers at pH 8.0
    with outstanding tensile strength [18]. /ACS Biomaterials Science &
    Engineering/, 2022, 8(1): 119-127.
    [23] Rising A, Gherardi P, *Chen G*, Johansson J, Oskarsson M, Westermark G,
    Westermark P. AA amyloid in human food chain is a possible biohazard [19].
    /Scientific Reports/, 2021, 11:21069.
    [22] Andrade-Talavera Y, *Chen G*, Kurudenkandy F, Johansson J, Fisahn A.
    Bri2 BRICHOS chaperone rescues impaired fast-spiking interneuron behavior and
    neuronal network dynamics in an AD mouse model in vitro [20]. /Neurobiology
    of Disease/, 2021, 159:105514.
    [21] Schmuck B, *Chen G*, Pelcman J, Kronkvist N, Rising A, Johansson J.
    Expression of the human molecular chaperone domain Bri2 BRICHOS on a gram per
    liter scale with an E. coli fed-batch culture [21]. /Microbial Cell
    Factories/, 2021, 20(1):150.
    [20] Zhao Q, Gong S, Jiang R, Li C, *Chen G*, Luo C, Qiu H, Liu J, Wang L,
    Zhang R. Echocardiographic prognosis relevance of attenuated right heart
    remodeling in idiopathic pulmonary arterial hypertension [22][J]. /Frontiers
    in Cardiovascular Medicine/, 2021, 8:650848.
    [19] Andrade-Talavera Y, Balleza-Tapia H, Dolz-Gaiton P, *Chen G, * Johansson
    J, Fisahn A. Ablation of p75NTR-signaling strengthens gamma-theta rhythm
    interaction and counteracts Aβ-induced degradation of neuronal dynamics in
    mouse hippocampus in vitro [23][J]. /Translational Psychiatry/, 2021, 11:212.
    [18] Tigro H, Kronqvist N, Abelein A, Galan-Acosta L, *Chen G*, Lyashkov A,
    Aon M.A, Ferrucci L, Shimmo R, Johansson J, Moaddel R. The synthesis and
    characterization of Bri2 BRICHOS coated magnetic particles and their
    application to Protein Fishing: Identification of novel binding proteins
    [24][J]. /Journal of Pharmaceutical and Biomedical Analysis/, 2021,
    198:113996.
    [17] Cai H#, *Chen G#*, Yu H, Tang Y, Xiong S, Qi X. One-step heating
    strategy for efficient solubilization of recombinant spider silk protein from
    inclusion bodies [25][J]. /BMC Biotechnology/, 2020, 20(1):37. (#equal
    contributions)
    [16] Andrade-Talavera Y, Arroyo-García L, *Chen G*, Johansson J, Fisahn
    A. Modulation of Kv3.1/Kv3.2 promotes gamma oscillations by rescuing
    Aβ-induced desynchronization of fast-spiking interneuron firing in an AD
    mouse model [26][J]. /The Journal of Physiology/, 2020, 598(17):3711-3725.
    [15] Poska H, Leppert A, Tigro H, Zhong X, Kaldmäe M, Nilsson H,
    Hebert H, *Chen G*, Johansson J. Recombinant Bri3 BRICHOS domain is a
    bifunctional molecular chaperone [27][J]. /Scientific Reports/, 2020, 10(1):
    9817.
    [14] *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 [28][J].
    /Communications Biology/, 2020, 3(1): 32.
    [13] 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 [29][J]. /Scientific Reports/, 2020, 10(1):235.
    [12] 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 [30][J]. /The FEBS Journal/, 2020, 287(13):2823-2833.
    [11] Leppert A, *Chen G*, Johansson J. BRICHOS: a chaperone with
    different activities depending on quaternary structure and cellular location?
    [31][J]. /Amyloid/, 2019, 26(sup1):152-153.
    [10] 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 [32][J]. /The
    Journal of Biological Chemistry/, 2019, 294(8): 2606-2615.
    [9] 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 [33][J]. /eLife/, 2018, 7: e37703.
    [8] 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 [34][J]. /The FEBS
    Journal/, 2018, 285(10): 1873-1885.
    [7] *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 [35][J]. /Nature
    Communications/, 2017, 8: 2081.
    [6] 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 [36][J]. /Biochemical
    Journal/, 2016, 473(20): 3683-3704.
    [5] Lin S, *Chen G*, Liu X, Meng Q. Chimeric spider silk proteins
    mediated by intein result in artificial hybrid silks [37][J]. /Biopolymers/,
    2016, 105(7): 385-392.
    [4] 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 [38][J]. /ChemBioChem/, 2015,
    16(12): 1720-1724. (#equal contributions)
    [3] 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 [39][J]. /PLoS Biology/, 2014, 12(8): e100192.(#equal
    contributions)
    [2] 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 [40][J]. /Nature communications/, 2014, 5: 3254.
    [1] *Chen G*, Liu X, Zhang Y, Lin S, Yang Z, Johansson J, Rising A,
    Meng Q. Full-length minor ampullate spidroin gene sequence [41][J]. /PLoS
    ONE/, 2012, 7(12): e52293.
    *Gene and structure deposition*
    /Genes/
    1) /Araneus ventricosus/ clone F29-0811 minor ampullate spidroin gene,
    complete cds (NCBI accession number JX513956). 32513 bp, DNA, 2012.
    2) /A. ventricosus/ clone AvMiSp2 minor ampullate spidroin mRNA, partial cds
    (NCBI accession number JX513955). 239 bp, mRNA, 2012.
    3) /A. ventricosus/ clone AvMiSp1 minor ampullate spidroin mRNA, partial cds
    (NCBI accession number JX513954). 370 bp, mRNA, 2012.
    4) Argiope amoena tubuliform spidroin 1 (TuSp1) mRNA, partial cds. (NCBI
    accession number JQ291306). 1273 bp, mRNA, 2012.
    5) /A. ventricosus/ aciniform spidroin 1 (AcSp1) mRNA, partial cds (NCBI
    accession number HQ008714). 6072 bp, mRNA, 2016.
    6) Argiope amoena aciniform spidroin 1 (AcSp1) mRNA, partial cds. (NCBI
    accession number HQ008715). 3216 bp, mRNA, 2016.
    /Structures/
    1) NMR structure of C-terminal domain from /A. ventricosus/ minor ampullate
    spidroin (MiSp) (PDB ID: 2MFZ). 2014.
    2) NMR structure of N-terminal domain from /A. ventricosus/ minor ampullate
    spidroin (MiSp) at pH 7.2 (PDB ID: 2MX8). 2015.
    3) NMR structure of N-terminal domain from /A. ventricosus/ minor ampullate
    spidroin (MiSp) at pH 5.5 (PDB ID: 2MX9). 2015.
    4) EM model of recombinant human Bri2 BRICHOS domain, oligomeric state (EMDB
    accession code: EMD-3918). 2017.
    5) EM model of recombinant human Bri2 BRICHOS D148N mutation, oligomeric
    state (EMDB accession code: EMD-13005). 2021.
    6) Cryo-EM structural model of recombinant human Bri2 BRICHOS oligomers
    (EMDB accession code: EMD-13866
  • PDB accession code: 7Q8X). 2022.
    [1] https://ki.se/en/bionut/protein-misfolding-and-prevention-by-molecular-chaperones-in-cancer-and-neurodegenerative
    [2] https://onlinelibrary.wiley.com/doi/10.1002/smll.202304031
    [3] https://www.mdpi.com/2079-7737/12/6/805
    [4] https://www.nature.com/articles/s42003-023-04883-2
    [5] https://pubs.acs.org/doi/10.1021/acs.nanolett.3c00773
    [6] https://onlinelibrary.wiley.com/doi/10.1002/pro.4645
    [7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896144/
    [8] https://www.sciencedirect.com/science/article/pii/S0301008222001526?via%3Dihub
    [9] https://pubs.rsc.org/en/content/articlepdf/2022/CB/D2CB00187J?page=search
    [10] https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(22)00498-1
    [11] https://www.nature.com/articles/s41467-022-32093-7
    [12] https://pubs.acs.org/doi/full/10.1021/acschembio.2c00344
    [13] https://www.sciencedirect.com/science/article/pii/S0891584922004580?via%3Dihub
    [14] https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-022-01398-5
    [15] https://onlinelibrary.wiley.com/doi/10.1002/pro.4378
    [16] https://www.sciencedirect.com/science/article/pii/S0969212622000491
    [17] https://www.frontiersin.org/articles/10.3389/fmolb.2022.812808/full
    [18] https://pubs.acs.org/doi/10.1021/acsbiomaterials.1c01354
    [19] https://www.nature.com/articles/s41598-021-00588-w
    [20] https://www.sciencedirect.com/science/article/pii/S0969996121002631?via%3Dihub
    [21] https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-021-01638-8
    [22] https://www.frontiersin.org/articles/10.3389/fcvm.2021.650848/full
    [23] https://www.nature.com/articles/s41398-021-01332-8
    [24] https://pubmed.ncbi.nlm.nih.gov/33690096/
    [25] https://bmcbiotechnol.biomedcentral.com/articles/10.1186/s12896-020-00630-1
    [26] https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP279718
    [27] https://www.nature.com/articles/s41598-020-66718-y
    [28] https://www.nature.com/articles/s42003-020-0757-z
    [29] https://www.nature.com/articles/s41598-019-57143-x
    [30] https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15169
    [31] https://www.tandfonline.com/doi/abs/10.1080/13506129.2019.1582511?journalCode=iamy20
    [32] https://www.jbc.org/content/294/8/2606.long
    [33] https://elifesciences.org/articles/37703
    [34] https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14451
    [35] https://www.nature.com/articles/s41467-017-02056-4
    [36] https://portlandpress.com/biochemj/article-abstract/473/20/3683/77446/Dementia-related-Bri2-BRICHOS-is-a-versatile?redirectedFrom=fulltext
    [37] https://onlinelibrary.wiley.com/doi/abs/10.1002/bip.22828
    [38] https://onlinelibrary.wiley.com/doi/abs/10.1002/cbic.201500263
    [39] https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001921
    [40] https://www.nature.com/articles/ncomms4254
    [41] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052293

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