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Department
  • Clinical Neurosciences
    • Institute
  • UK Dementia Research Institute at University of Cambridge
    • Research Theme Neurons, Circuits and Networks Beyond the Neuron Lifelong Brain Development and Brain Ageing
    Research Focus

    Keywords

  • Organelle Interactions
  • Organelle Traffic
  • Cellular Neurophysiology

    • Clinical Conditions

  • Alzheimer's disease
  • Hereditary spastic paraplegia
  • Motor neurone disease

    • Equipment & Techniques

  • Calcium imaging
  • Fluorescence microscopy
  • Recombinant protein expression
  • Computational modelling
  • Intracellular recording

    • Back

    Edward Avezov

    University Position
    Group Leader

    Interests

    Through an in-depth investigation of the neuronal cell biophysical properties, our program aims to Identify new targetable pathways, disrupted in dementia. In particular, we seek understanding of the role Endoplasmic Reticulum, and its structure function regulation, plays in neuronal (patho)physiology, and thus to gain insight into the dementia-underlying dysregulation of ER function. In our quests we develop, implement and combine techniques such as high tempora-spatial resolution light microscopy (super-resolution), genetically encoded biosensors, genetic manipulations of neuronal models (e.g. iPS cells based) and in vitro/in vivo biochemistry.

    Collaborators

    Cambridge
  • Michele Vendruscolo
  • Cahir O'Kane
  • John Skidmore
  • Clemens Kaminski
  • Gabriele Kaminski Schierle
  • David Rubinsztein
  • David Klenerman

    • Key Publications

    Endoplasmic reticulum morphology regulation by RTN4 modulates neuronal regeneration by curbing luminal transport.

    DOI: http://doi.org/10.1016/j.celrep.2024.114357
    Journal: Cell Rep
    E-pub date: 23 Jul 2024
    Authors: T Konno, P Parutto, CC Crapart, V Davì, DMD Bailey, MA Awadelkareem, C Hockings, AI Brown, KM Xiang, A Agrawal, JE Chambers, MJ Vander Werp, KM Koning, LM Elfari, S Steen, E Metzakopian, LM Westrate, EF Koslover, E Avezov

    Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca2+ signals.

    DOI: http://doi.org/10.1073/pnas.2312172121
    Journal: Proc Natl Acad Sci U S A
    E-pub date: 26 Mar 2024
    Authors: CC Crapart, ZC Scott, T Konno, A Sharma, P Parutto, DMD Bailey, LM Westrate, E Avezov, EF Koslover

    Stress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP.

    DOI: http://doi.org/10.1038/s41467-022-30238-2
    Journal: Nature Communications
    E-pub date: 6 May 2022
    Authors: EP Melo, T Konno, I Farace, MA Awadelkareem, LR Skov, F Teodoro, TP Sancho, AW Paton, JC Paton, M Fares, PMR Paulo, X Zhang, E Avezov

    The structure and global distribution of the endoplasmic reticulum network are actively regulated by lysosomes.

    DOI: http://doi.org/10.1126/sciadv.abc7209
    Journal: Sci Adv
    E-pub date: 1 Dec 2020
    Authors: M Lu, FW van Tartwijk, JQ Lin, W Nijenhuis, P Parutto, M Fantham, CN Christensen, E Avezov, CE Holt, A Tunnacliffe, D Holcman, L Kapitein, GSK Schierle, CF Kaminski

    Single particle trajectories reveal active endoplasmic reticulum luminal flow.

    DOI: http://doi.org/10.1038/s41556-018-0192-2
    Journal: Nat Cell Biol
    E-pub date: 1 Oct 2018
    Authors: D Holcman, P Parutto, JE Chambers, M Fantham, LJ Young, SJ Marciniak, CF Kaminski, D Ron, E Avezov

    Publications

    PERK-ATAD3A interaction provides a subcellular safe haven for protein synthesis during ER stress.

    DOI: http://doi.org/10.1126/science.adp7114
    Journal: Science
    E-pub date: 30 Aug 2024
    Authors: KK Brar, DT Hughes, JL Morris, K Subramanian, S Krishna, F Gao, L-S Rieder, S Uhrig, J Freeman, HL Smith, R Jukes-Jones, E Avezov, J Nunnari, J Prudent, AJ Butcher, GR Mallucci

    Non-esterified fatty acid palmitate facilitates oxidative endoplasmic reticulum stress and apoptosis of β-cells by upregulating ERO-1α expression.

    DOI: http://doi.org/10.1016/j.redox.2024.103170
    Journal: Redox Biol
    E-pub date: 1 Jul 2024
    Authors: S Sharifi, T Yamamoto, A Zeug, M Elsner, E Avezov, I Mehmeti

    Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum

    DOI: http://doi.org/10.7554/elife.93518.1
    Journal:
    E-pub date: 10 Apr 2024
    Authors: PH Htet, E Avezov, E Lauga

    Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum

    DOI: http://doi.org/10.1101/2023.01.11.523552
    Journal:
    E-pub date: 1 Aug 2023
    Authors: PH Htet, E Avezov, E Lauga

    Luminal transport rates through intact endoplasmic reticulum limit the magnitude of localized Ca2+signals

    DOI: http://doi.org/10.1101/2023.06.23.546357
    Journal:
    E-pub date: 1 Aug 2023
    Authors: C Crapart, Z Scott, T Konno, A Sharma, D Bailey, E Avezov, E Koslover

    ERnet: a tool for the semantic segmentation and quantitative analysis of endoplasmic reticulum topology.

    DOI: http://doi.org/10.1038/s41592-023-01815-0
    Journal: Nat Methods
    E-pub date: 1 Apr 2023
    Authors: M Lu, CN Christensen, JM Weber, T Konno, NF Läubli, KM Scherer, E Avezov, P Lio, AA Lapkin, GS Kaminski Schierle, CF Kaminski

    Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models.

    DOI: http://doi.org/10.1126/science.abn1366
    Journal: Science
    E-pub date: 31 Mar 2023
    Authors: AS Mukadam, LVC Miller, AE Smith, M Vaysburd, SA Sakya, S Sanford, S Keeling, BJ Tuck, T Katsinelos, C Green, L Skov, SS Kaalund, S Foss, K Mayes, K O'Connell, M Wing, C Knox, J Banbury, E Avezov, JB Rowe, M Goedert, JT Andersen, LC James, WA McEwan

    H2O2/ROS Production, Consumption, and Transport across Organelles

    DOI: http://doi.org/10.1201/9781003160649-6
    Journal:
    E-pub date: 1 Jan 2023
    Authors: T Konno, C Crapart, E Avezov

    High-throughput super-resolution single-particle trajectory analysis reconstructs organelle dynamics and membrane reorganization.

    DOI: http://doi.org/10.1016/j.crmeth.2022.100277
    Journal: Cell Rep Methods
    E-pub date: 22 Aug 2022
    Authors: P Parutto, J Heck, M Lu, C Kaminski, E Avezov, M Heine, D Holcman

    Intracellular Aβ42 aggregation leads to cellular thermogenesis

    DOI: http://doi.org/10.1101/2022.03.30.486355
    Journal:
    E-pub date: 1 Aug 2022
    Authors: CW Chung, A Stephens, T Konno, E Ward, E Avezov, C Kaminski, A Hassanali, G Kaminski Schierle

    ERnet: a tool for the semantic segmentation and quantitative analysis of endoplasmic reticulum topology for video-rate super-resolution imaging

    DOI: http://doi.org/10.1101/2022.05.17.492189
    Journal:
    E-pub date: 1 Aug 2022
    Authors: M Lu, C Christensen, J Weber, T Konno, N Läubli, K Scherer, E Avezov, P Lio, A Lapkin, G Kaminski Schierle, C Kaminski

    Intracellular Aβ42 Aggregation Leads to Cellular Thermogenesis.

    DOI: http://doi.org/10.1021/jacs.2c03599
    Journal: J Am Chem Soc
    E-pub date: 8 Jun 2022
    Authors: CW Chung, AD Stephens, T Konno, E Ward, E Avezov, CF Kaminski, AA Hassanali, GS Kaminski Schierle

    Z-α1-antitrypsin polymers impose molecular filtration in the endoplasmic reticulum after undergoing phase transition to a solid state.

    DOI: http://doi.org/10.1126/sciadv.abm2094
    Journal: Sci Adv
    E-pub date: 8 Apr 2022
    Authors: JE Chambers, N Zubkov, M Kubánková, J Nixon-Abell, I Mela, S Abreu, M Schwiening, G Lavarda, I López-Duarte, JA Dickens, T Torres, CF Kaminski, LJ Holt, E Avezov, JA Huntington, PS George-Hyslop, MK Kuimova, SJ Marciniak

    THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer.

    DOI: http://doi.org/10.15252/emmm.202114764
    Journal: EMBO Mol Med
    E-pub date: 7 Mar 2022
    Authors: A Blomme, C Peter, E Mui, G Rodriguez Blanco, N An, LM Mason, LE Jamieson, GH McGregor, S Lilla, C Ntala, R Patel, M Thiry, SHY Kung, M Leclercq, CA Ford, LK Rushworth, DJ McGarry, S Mason, P Repiscak, C Nixon, MJ Salji, E Markert, GM MacKay, JJ Kamphorst, D Graham, K Faulds, L Fazli, ME Gleave, E Avezov, J Edwards, H Yin, D Sumpton, K Blyth, P Close, DJ Murphy, S Zanivan, HY Leung

    SPtsAnalysis: a high-throughput super-resolution single particle trajectory analysis to reconstruct organelle dynamics and membrane re-organization

    DOI: http://doi.org/10.1101/2021.09.18.460892
    Journal:
    E-pub date: 1 Aug 2021
    Authors: P Parutto, J Heck, M Lu, C Kaminski, M Heine, E Avezov, D Holcman

    Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum.

    DOI: http://doi.org/10.3390/cells10020233
    Journal: Cells
    E-pub date: 25 Jan 2021
    Authors: T Konno, EP Melo, JE Chambers, E Avezov

    The structure and global distribution of the endoplasmic reticulum network is actively regulated by lysosomes

    DOI: http://doi.org/10.1101/2020.01.15.907444
    Journal:
    E-pub date: 1 Aug 2020
    Authors: M Lu, FW van Tartwijk, JQ Lin, W Nijenhuis, P Parutto, M Fantham, CN Christensen, E Avezov, CE Holt, A Tunnacliffe, D Holcman, LC Kapitein, GK Schierle, CF Kaminski

    Single Particle Trajectories Reveal Active Endoplasmic Reticulum Luminal Flow

    DOI: http://doi.org/10.1016/j.bpj.2018.11.964
    Journal: BIOPHYSICAL JOURNAL
    E-pub date: 1 Aug 2019
    Authors: P Parutto, JE Chambers, M Fantham, L Young, S Marciniak, CF Kaminski, D Ron, D Holcman, E Avezov

    Abstract

    DOI: http://doi.org/10.7554/elife.03421.001
    Journal:
    E-pub date: 23 Aug 2018
    Authors:

    An Optical Technique for Mapping Microviscosity Dynamics in Cellular Organelles.

    DOI: http://doi.org/10.1021/acsnano.8b00177
    Journal: ACS Nano
    E-pub date: 22 May 2018
    Authors: JE Chambers, M Kubánková, RG Huber, I López-Duarte, E Avezov, PJ Bond, SJ Marciniak, MK Kuimova

    ER-resident antioxidative GPx7 and GPx8 enzyme isoforms protect insulin-secreting INS-1E β-cells against lipotoxicity by improving the ER antioxidative capacity.

    DOI: http://doi.org/10.1016/j.freeradbiomed.2017.07.021
    Journal: Free Radic Biol Med
    E-pub date: 1 Nov 2017
    Authors: I Mehmeti, S Lortz, E Avezov, A Jörns, S Lenzen

    A novel signalling screen demonstrates that CALR mutations activate essential MAPK signalling and facilitate megakaryocyte differentiation.

    DOI: http://doi.org/10.1038/leu.2016.280
    Journal: Leukemia
    E-pub date: 1 Apr 2017
    Authors: K Kollmann, W Warsch, C Gonzalez-Arias, FL Nice, E Avezov, J Milburn, J Li, D Dimitropoulou, S Biddie, M Wang, E Poynton, M Colzani, MR Tijssen, S Anand, U McDermott, B Huntly, T Green

    TriPer, an optical probe tuned to the endoplasmic reticulum tracks changes in luminal H2O2.

    DOI: http://doi.org/10.1186/s12915-017-0367-5
    Journal: BMC Biol
    E-pub date: 27 Mar 2017
    Authors: EP Melo, C Lopes, P Gollwitzer, S Lortz, S Lenzen, I Mehmeti, CF Kaminski, D Ron, E Avezov

    Investigating State Restriction in Fluorescent Protein FRET Using Time-Resolved Fluorescence and Anisotropy.

    DOI: http://doi.org/10.1021/acs.jpcc.6b11235
    Journal: J Phys Chem C Nanomater Interfaces
    E-pub date: 26 Jan 2017
    Authors: TS Blacker, W Chen, E Avezov, RJ Marsh, MR Duchen, CF Kaminski, AJ Bain

    Mannosidase IA is in Quality Control Vesicles and Participates in Glycoprotein Targeting to ERAD.

    DOI: http://doi.org/10.1016/j.jmb.2016.04.020
    Journal: J Mol Biol
    E-pub date: 14 Aug 2016
    Authors: N Ogen-Shtern, E Avezov, M Shenkman, R Benyair, GZ Lederkremer

    TriPer, an optical probe tuned to the endoplasmic reticulum tracks H2O2 consumption by glutathione

    DOI: http://doi.org/10.1101/088351
    Journal:
    E-pub date: 1 Aug 2016
    Authors: EP Melo, C Lopes, P Gollwitzer, S Lortz, S Lenzen, I Mehmeti, C Kaminski, D Ron, E Avezov

    ERO1-independent production of H2O2 within the endoplasmic reticulum fuels Prdx4-mediated oxidative protein folding.

    DOI: http://doi.org/10.1083/jcb.201506123
    Journal: J Cell Biol
    E-pub date: 26 Oct 2015
    Authors: T Konno, E Pinho Melo, C Lopes, I Mehmeti, S Lenzen, D Ron, E Avezov

    Physiological modulation of BiP activity by trans-protomer engagement of the interdomain linker.

    DOI: http://doi.org/10.7554/eLife.08961
    Journal: Elife
    E-pub date: 16 Oct 2015
    Authors: S Preissler, JE Chambers, A Crespillo-Casado, E Avezov, E Miranda, J Perez, LM Hendershot, HP Harding, D Ron

    A method to quantify FRET stoichiometry with phasor plot analysis and acceptor lifetime ingrowth.

    DOI: http://doi.org/10.1016/j.bpj.2015.01.012
    Journal: Biophys J
    E-pub date: 10 Mar 2015
    Authors: W Chen, E Avezov, SC Schlachter, F Gielen, RF Laine, HP Harding, F Hollfelder, D Ron, CF Kaminski

    Retarded PDI diffusion and a reductive shift in poise of the calcium depleted endoplasmic reticulum.

    DOI: http://doi.org/10.1186/s12915-014-0112-2
    Journal: BMC Biol
    E-pub date: 10 Jan 2015
    Authors: E Avezov, T Konno, A Zyryanova, W Chen, R Laine, A Crespillo-Casado, EP Melo, R Ushioda, K Nagata, CF Kaminski, HP Harding, D Ron

    Fat mass and obesity-related (FTO) shuttles between the nucleus and cytoplasm.

    DOI: http://doi.org/10.1042/BSR20140111
    Journal: Biosci Rep
    E-pub date: 22 Oct 2014
    Authors: P Gulati, E Avezov, M Ma, R Antrobus, P Lehner, S O'Rahilly, GSH Yeo

    Intact protein folding in the glutathione-depleted endoplasmic reticulum implicates alternative protein thiol reductants.

    DOI: http://doi.org/10.7554/eLife.03421
    Journal: Elife
    E-pub date: 29 Jul 2014
    Authors: S Tsunoda, E Avezov, A Zyryanova, T Konno, L Mendes-Silva, E Pinho Melo, HP Harding, D Ron

    Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

    DOI: http://doi.org/10.1056/NEJMoa1312542
    Journal: N Engl J Med
    E-pub date: 19 Dec 2013
    Authors: J Nangalia, CE Massie, EJ Baxter, FL Nice, G Gundem, DC Wedge, E Avezov, J Li, K Kollmann, DG Kent, A Aziz, AL Godfrey, J Hinton, I Martincorena, P Van Loo, AV Jones, P Guglielmelli, P Tarpey, HP Harding, JD Fitzpatrick, CT Goudie, CA Ortmann, SJ Loughran, K Raine, DR Jones, AP Butler, JW Teague, S O'Meara, S McLaren, M Bianchi, Y Silber, D Dimitropoulou, D Bloxham, L Mudie, M Maddison, B Robinson, C Keohane, C Maclean, K Hill, K Orchard, S Tauro, M-Q Du, M Greaves, D Bowen, BJP Huntly, CN Harrison, NCP Cross, D Ron, AM Vannucchi, E Papaemmanuil, PJ Campbell, AR Green

    Lifetime imaging of a fluorescent protein sensor reveals surprising stability of ER thiol redox.

    DOI: http://doi.org/10.1083/jcb.201211155
    Journal: J Cell Biol
    E-pub date: 15 Apr 2013
    Authors: E Avezov, BCS Cross, GS Kaminski Schierle, M Winters, HP Harding, EP Melo, CF Kaminski, D Ron

    A shared endoplasmic reticulum-associated degradation pathway involving the EDEM1 protein for glycosylated and nonglycosylated proteins.

    DOI: http://doi.org/10.1074/jbc.M112.438275
    Journal: J Biol Chem
    E-pub date: 25 Jan 2013
    Authors: M Shenkman, B Groisman, E Ron, E Avezov, LM Hendershot, GZ Lederkremer

    Mechanisms regulating the secretion of the promalignancy chemokine CCL5 by breast tumor cells: CCL5’s 40s loop and intracellular glycosaminoglycans.

    DOI: http://doi.org/10.1593/neo.111122
    Journal: Neoplasia
    E-pub date: 1 Jan 2012
    Authors: G Soria, Y Lebel-Haziv, M Ehrlich, T Meshel, A Suez, E Avezov, P Rozenberg, A Ben-Baruch

    Pulse-chase analysis of N-linked sugar chains from glycoproteins in mammalian cells.

    DOI: http://doi.org/10.3791/1899
    Journal: Journal of Visualized Experiments
    E-pub date: 1 Apr 2010
    Authors: E Avezov, E Ron, Y Izenshtein, Y Adan, GZ Lederkremer

    Endoplasmic reticulum (ER) mannosidase I is compartmentalized and required for N-glycan trimming to Man5-6GlcNAc2 in glycoprotein ER-associated degradation.

    DOI: http://doi.org/10.1091/mbc.e07-05-0505
    Journal: Mol Biol Cell
    E-pub date: 1 Jan 2008
    Authors: E Avezov, Z Frenkel, M Ehrlich, A Herscovics, GZ Lederkremer

    PERK-dependent compartmentalization of ERAD and unfolded protein response machineries during ER stress.

    DOI: http://doi.org/10.1016/j.yexcr.2007.07.006
    Journal: Exp Cell Res
    E-pub date: 1 Oct 2007
    Authors: M Kondratyev, E Avezov, M Shenkman, B Groisman, GZ Lederkremer