• Medical Genetics
  • Research Focus


  • Autophagy
  • Huntington's Disease
  • Parkinson's Disease
  • Dementia
  • Clinical Conditions

  • Huntington's disease
  • Alzheimer's disease
  • Parkinson's disease
  • Equipment & Techniques

  • Cell culture
  • Back

    Professor David Rubinsztein MB ChB, PhD, FMedSci, FRS

    University Position
    Professor David Rubinsztein is pleased to consider applications from prospective PhD students.


    Many of the intracytoplasmic, aggregate-prone, mutant proteins causing movement disorders, like mutant huntingtin (in Huntington’s disease (HD)), alpha-synuclein (in Parkinson’s disease (PD)) and mutant tau (in frontotemporal dementia and Parkinsonism), cause pathology via toxic gain-of-function mechanisms. The factors regulating their clearance are likely to be important for understanding pathogenesis and developing rational therapeutic strategies. The two major intracellular protein degradation pathways are the ubiquitin-proteasome system and (macro)autophagy. My laboratory discovered that these intracytoplasmic proteins are removed by autophagy and that one can lower their levels and ameliorate disease in cell and animal models by boosting autophagosome formation. Our research goal is to understand the links between these diseases and autophagy. We currently focus on: understanding how autophagy is regulated using several cell and animal models; how autophagy may be compromised in neurodegeneration; and possible ways to ramp up this process in order to remove toxic proteins and avoid the development of neurodegenerative disease.

    autophagosomes in a neuron

    Key Publications

    Mammalian autophagosomes form from finger-like phagophores.

    Journal: Dev Cell
    E-pub date: 4 Dec 2023
    Authors: C Puri, MJ Gratian, DC Rubinsztein

    Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration.

    Journal: Neuron
    E-pub date: 5 Jul 2023
    Authors: BP Festa, FH Siddiqi, M Jimenez-Sanchez, H Won, M Rob, A Djajadikerta, E Stamatakou, DC Rubinsztein

    Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance.

    Journal: Nature Communications
    E-pub date: 16 Jul 2022
    Authors: L Wrobel, SM Hill, A Djajadikerta, M Fernandez-Estevez, C Karabiyik, A Ashkenazi, VJ Barratt, E Stamatakou, A Gunnarsson, T Rasmusson, EW Miele, N Beaton, R Bruderer, Y Feng, L Reiter, MP Castaldi, R Jarvis, K Tan, RW Bürli, DC Rubinsztein

    Glucose starvation induces autophagy via ULK1-mediated activation of PIKfyve in an AMPK-dependent manner.

    Journal: Dev Cell
    E-pub date: 12 Jul 2021
    Authors: C Karabiyik, M Vicinanza, SM Son, DC Rubinsztein

    VCP/p97 regulates Beclin-1-dependent autophagy initiation.

    Journal: Nat Chem Biol
    E-pub date: 1 Apr 2021
    Authors: SM Hill, L Wrobel, A Ashkenazi, M Fernandez-Estevez, K Tan, RW Bürli, DC Rubinsztein

    A DNM2 Centronuclear Myopathy Mutation Reveals a Link between Recycling Endosome Scission and Autophagy.

    Journal: Dev Cell
    E-pub date: 20 Apr 2020
    Authors: C Puri, MM Manni, M Vicinanza, C Hilcenko, Y Zhu, G Runwal, E Stamatakou, FM Menzies, K Mamchaoui, M Bitoun, DC Rubinsztein

    Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing.

    Journal: Nat Commun
    E-pub date: 18 Apr 2019
    Authors: FH Siddiqi, FM Menzies, A Lopez, E Stamatakou, C Karabiyik, R Ureshino, T Ricketts, M Jimenez-Sanchez, MA Esteban, L Lai, MD Tortorella, Z Luo, H Liu, E Metzakopian, HJR Fernandes, A Bassett, E Karran, BL Miller, A Fleming, DC Rubinsztein

    Neurodegenerative Diseases and Autophagy

    E-pub date: 1 Aug 2018
    Authors: A Fleming, M Vicinanza, M Renna, C Puri, T Ricketts, J Füllgrabe, A Lopez, SM de Jager, A Ashkenazi, M Pavel, F Licitra, A Caricasole, SP Andrews, J Skidmore, DC Rubinsztein

    The RAB11A-Positive Compartment Is a Primary Platform for Autophagosome Assembly Mediated by WIPI2 Recognition of PI3P-RAB11A.

    Journal: Dev Cell
    E-pub date: 9 Apr 2018
    Authors: C Puri, M Vicinanza, A Ashkenazi, MJ Gratian, Q Zhang, CF Bento, M Renna, FM Menzies, DC Rubinsztein

    Polyglutamine tracts regulate beclin 1-dependent autophagy.

    Journal: Nature
    E-pub date: 4 May 2017
    Authors: A Ashkenazi, CF Bento, T Ricketts, M Vicinanza, F Siddiqi, M Pavel, F Squitieri, MC Hardenberg, S Imarisio, FM Menzies, DC Rubinsztein

    siRNA screen identifies QPCT as a druggable target for Huntington’s disease

    Journal: Nature Chemical Biology
    E-pub date: 6 Apr 2015
    Authors: M Jimenez-Sanchez, W Lam, M Hannus, B Sönnichsen, S Imarisio, A Fleming, A Tarditi, F Menzies, TE Dami, C Xu, E Gonzalez-Couto, G Lazzeroni, F Heitz, D Diamanti, L Massai, VP Satagopam, G Marconi, C Caramelli, A Nencini, M Andreini, GL Sardone, NP Caradonna, V Porcari, C Scali, R Schneider, G Pollio, CJ O’Kane, A Caricasole, DC Rubinsztein


    An open-label study to assess the feasibility and tolerability of rilmenidine for the treatment of Huntington’s disease.

    Journal: J Neurol
    E-pub date: 1 Dec 2017
    Authors: BR Underwood, ZW Green-Thompson, PJ Pugh, SE Lazic, SL Mason, J Griffin, PS Jones, JB Rowe, DC Rubinsztein, RA Barker

    Huntington’s Disease: Mechanisms of Pathogenesis and Therapeutic Strategies.

    Journal: Cold Spring Harb Perspect Med
    E-pub date: 5 Jul 2017
    Authors: M Jimenez-Sanchez, F Licitra, BR Underwood, DC Rubinsztein

    A152T tau allele causes neurodegeneration that can be ameliorated in a zebrafish model by autophagy induction.

    Journal: Brain
    E-pub date: 1 Apr 2017
    Authors: A Lopez, SE Lee, K Wojta, EM Ramos, E Klein, J Chen, AL Boxer, ML Gorno-Tempini, DH Geschwind, L Schlotawa, NV Ogryzko, EH Bigio, E Rogalski, S Weintraub, MM Mesulam, Tauopathy Genetics Consortium, A Fleming, G Coppola, BL Miller, DC Rubinsztein

    The Parkinson’s disease-associated genes ATP13A2 and SYT11 regulate autophagy via a common pathway.

    Journal: Nat Commun
    E-pub date: 9 Jun 2016
    Authors: CF Bento, A Ashkenazi, M Jimenez-Sanchez, DC Rubinsztein

    Autophagy regulates Notch degradation and modulates stem cell development and neurogenesis.

    Journal: Nat Commun
    E-pub date: 3 Feb 2016
    Authors: X Wu, A Fleming, T Ricketts, M Pavel, H Virgin, FM Menzies, DC Rubinsztein

    Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson’s Disease-like Dementia.

    Journal: Cell
    E-pub date: 8 Oct 2015
    Authors: P Ejlerskov, JG Hultberg, J Wang, R Carlsson, M Ambjørn, M Kuss, Y Liu, G Porcu, K Kolkova, C Friis Rundsten, K Ruscher, B Pakkenberg, T Goldmann, D Loreth, M Prinz, DC Rubinsztein, S Issazadeh-Navikas

    Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy.

    Journal: Nat Commun
    E-pub date: 20 Aug 2015
    Authors: K Moreau, G Ghislat, W Hochfeld, M Renna, E Zavodszky, G Runwal, C Puri, S Lee, F Siddiqi, FM Menzies, B Ravikumar, DC Rubinsztein

    PI(5)P regulates autophagosome biogenesis.

    Journal: Mol Cell
    E-pub date: 22 Jan 2015
    Authors: M Vicinanza, VI Korolchuk, A Ashkenazi, C Puri, FM Menzies, JH Clarke, DC Rubinsztein

    VPS35 Parkinson mutation impairs autophagy via WASH.

    Journal: Cell Cycle
    E-pub date: 1 Aug 2014
    Authors: E Zavodszky, MNJ Seaman, DC Rubinsztein

    Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias.

    Journal: Cerebellum
    E-pub date: 1 Apr 2014
    Authors: A Matilla-Dueñas, T Ashizawa, A Brice, S Magri, KN McFarland, M Pandolfo, SM Pulst, O Riess, DC Rubinsztein, J Schmidt, T Schmidt, DR Scoles, G Stevanin, F Taroni, BR Underwood, I Sánchez

    Complex inhibitory effects of nitric oxide on autophagy.

    Journal: Mol Cell
    E-pub date: 8 Jul 2011
    Authors: S Sarkar, VI Korolchuk, M Renna, S Imarisio, A Fleming, A Williams, M Garcia-Arencibia, C Rose, S Luo, BR Underwood, G Kroemer, CJ O'Kane, DC Rubinsztein

    Regulation of mammalian autophagy in physiology and pathophysiology.

    Journal: Physiol Rev
    E-pub date: 1 Oct 2010
    Authors: B Ravikumar, S Sarkar, JE Davies, M Futter, M Garcia-Arencibia, ZW Green-Thompson, M Jimenez-Sanchez, VI Korolchuk, M Lichtenberg, S Luo, DCO Massey, FM Menzies, K Moreau, U Narayanan, M Renna, FH Siddiqi, BR Underwood, AR Winslow, DC Rubinsztein

    Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease.

    Journal: Hum Mol Genet
    E-pub date: 1 Sep 2010
    Authors: BR Underwood, S Imarisio, A Fleming, C Rose, G Krishna, P Heard, M Quick, VI Korolchuk, M Renna, S Sarkar, M García-Arencibia, CJ O'Kane, MP Murphy, DC Rubinsztein

    Mammalian macroautophagy at a glance.

    Journal: J Cell Sci
    E-pub date: 1 Jun 2009
    Authors: B Ravikumar, M Futter, L Jahreiss, VI Korolchuk, M Lichtenberg, S Luo, DCO Massey, FM Menzies, U Narayanan, M Renna, M Jimenez-Sanchez, S Sarkar, B Underwood, A Winslow, DC Rubinsztein

    Huntington’s disease: from pathology and genetics to potential therapies.

    Journal: Biochemical Journal
    E-pub date: 1 Jun 2008
    Authors: S Imarisio, J Carmichael, V Korolchuk, C-W Chen, S Saiki, C Rose, G Krishna, JE Davies, E Ttofi, BR Underwood, DC Rubinsztein

    Huntington disease patients and transgenic mice have similar pro-catabolic serum metabolite profiles.

    Journal: Brain
    E-pub date: 1 Apr 2006
    Authors: BR Underwood, D Broadhurst, WB Dunn, DI Ellis, AW Michell, C Vacher, DE Mosedale, DB Kell, RA Barker, DJ Grainger, DC Rubinsztein

    Rapamycin alleviates toxicity of different aggregate-prone proteins.

    Journal: Hum Mol Genet
    E-pub date: 1 Feb 2006
    Authors: Z Berger, B Ravikumar, FM Menzies, LG Oroz, BR Underwood, MN Pangalos, I Schmitt, U Wullner, BO Evert, CJ O'Kane, DC Rubinsztein