Professor David Rubinsztein

David  Rubinsztein

University position


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


Department of Medical Genetics


Cambridge Institute for Medical Research (CIMR)

Home page (personal home page)

Research Themes

Cellular and Molecular Neuroscience

Clinical and Veterinary Neuroscience


The pathogenesis of diseases caused by codon reiteration mutations (like Huntington’s disease and oculopharangeal muscular dystrophy).

Description of research:

We are studying the pathogenesis of diseases caused by codon reiteration mutations, like Huntington's disease (HD) and oculopharyngeal muscular dystrophy (OPMD), which result from abnormally elongated polyglutamine and polyalanine codon stretches in the HD and PABPN1 genes, respectively. These diseases are associated with intracellular aggregate formation. We are addressing the following questions:

1. What are the early pathological changes that occur in HD and other codon reiteration diseases?

2. What are the genetic pathways that modify polyglutamine toxicity?

3. Can one attenuate polyglutamine toxicity by inducing autophagy?

4. Are there common mechanisms causing pathology in the different diseases associated with intracellular protein aggregation?

Research Focus


Huntington's disease



oculopharyngeal muscular dystrophy

Parkinson's disease

Clinical conditions

Alzheimer's disease

Cerebellar ataxias

Huntington's disease

Parkinson's disease

Spinocerebellar ataxia


Cell culture

Confocal microscopy

Fluorescence microscopy


Recombinant protein expression



Roger Barker

Cahir O'Kane

United Kingdom

Steve Brown Web:



Fleming A, Noda T, Yoshimori T, Rubinsztein DC (2011), “Chemical modulators of autophagy as biological probes and potential therapeutics.” Nat Chem Biol 7(1):9-17 Details

Korolchuk VI, Saiki S, Lichtenberg M, Siddiqi FH, Roberts EA, Imarisio S, Jahreiss L, Sarkar S, Futter M, Menzies FM, O'Kane CJ, Deretic V, Rubinsztein DC (2011), “Lysosomal positioning coordinates cellular nutrient responses.” Nat Cell Biol 13(4):453-60 Details

Moreau K, Ravikumar B, Renna M, Puri C, Rubinsztein DC (2011), “Autophagosome precursor maturation requires homotypic fusion.” Cell 146(2):303-17 Details

Sarkar S, Korolchuk VI, Renna M, Imarisio S, Fleming A, Williams A, Garcia-Arencibia M, Rose C, Luo S, Underwood BR, Kroemer G, O'Kane CJ, Rubinsztein DC (2011), “Complex inhibitory effects of nitric oxide on autophagy.” Mol Cell 43(1):19-32 Details

Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, Sardiello M, Rubinsztein DC, Ballabio A (2011), “TFEB links autophagy to lysosomal biogenesis.” Science 332(6036):1429-33 Details


Davies JE, Rose C, Sarkar S, Rubinsztein DC (2010), “Cystamine suppresses polyalanine toxicity in a mouse model of oculopharyngeal muscular dystrophy.” Sci Transl Med 2(34):34ra40 Details

Ravikumar B, Moreau K, Jahreiss L, Puri C, Rubinsztein DC (2010), “Plasma membrane contributes to the formation of pre-autophagosomal structures.” Nat Cell Biol 12(8):747-57 Details

van Ham TJ, Holmberg MA, van der Goot AT, Teuling E, Garcia-Arencibia M, Kim HE, Du D, Thijssen KL, Wiersma M, Burggraaff R, van Bergeijk P, van Rheenen J, Jerre van Veluw G, Hofstra RM, Rubinsztein DC, Nollen EA (2010), “Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity.” Cell 142(4):601-12 Details

Winslow AR, Chen CW, Corrochano S, Acevedo-Arozena A, Gordon DE, Peden AA, Lichtenberg M, Menzies FM, Ravikumar B, Imarisio S, Brown S, O'Kane CJ, Rubinsztein DC (2010), “α-Synuclein impairs macroautophagy: implications for Parkinson's disease.” J Cell Biol 190(6):1023-37 Details


Korolchuk VI, Mansilla A, Menzies FM, Rubinsztein DC (2009), “Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates.” Mol Cell 33(4):517-27 Details


Williams A, Sarkar S, Cuddon P, Ttofi EK, Saiki S, Siddiqi FH, Jahreiss L, Fleming A, Pask D, Goldsmith P, O'Kane CJ, Floto RA, Rubinsztein DC (2008), “Novel targets for Huntington's disease in an mTOR-independent autophagy pathway.” Nat Chem Biol 4(5):295-305 Details


Rubinsztein DC, Gestwicki JE, Murphy LO, Klionsky DJ (2007), “Potential therapeutic applications of autophagy.” Nat Rev Drug Discov 6(4):304-12 Details

Sarkar S, Perlstein EO, Imarisio S, Pineau S, Cordenier A, Maglathlin RL, Webster JA, Lewis TA, O'Kane CJ, Schreiber SL, Rubinsztein DC (2007), “Small molecules enhance autophagy and reduce toxicity in Huntington's disease models.” Nat Chem Biol 3(6):331-8 Details


Rubinsztein DC (2006), “The roles of intracellular protein-degradation pathways in neurodegeneration.” Nature 443(7113):780-6 Details


Davies JE, Wang L, Garcia-Oroz L, Cook LJ, Vacher C, O'Donovan DG, Rubinsztein DC (2005), “Doxycycline attenuates and delays toxicity of the oculopharyngeal muscular dystrophy mutation in transgenic mice.” Nat Med 11(6):672-7 Details

Luo S, Vacher C, Davies JE, Rubinsztein DC (2005), “Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity.” J Cell Biol 169(4):647-56 Details

Ravikumar B, Acevedo-Arozena A, Imarisio S, Berger Z, Vacher C, O'Kane CJ, Brown SD, Rubinsztein DC (2005), “Dynein mutations impair autophagic clearance of aggregate-prone proteins.” Nat Genet 37(7):771-6 Details

Sarkar S, Floto RA, Berger Z, Imarisio S, Cordenier A, Pasco M, Cook LJ, Rubinsztein DC (2005), “Lithium induces autophagy by inhibiting inositol monophosphatase.” J Cell Biol 170(7):1101-11 Details


Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, Scaravilli F, Easton DF, Duden R, O'Kane CJ, Rubinsztein DC (2004), “Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.” Nat Genet 36(6):585-95 Details