Professor David Rubinsztein

David  Rubinsztein

University position

Professor

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

Departments

Department of Medical Genetics

Institutes

Cambridge Institute for Medical Research (CIMR)

Home page

http://www.cimr.cam.ac.uk/investi... (personal home page)

Research Themes

Cellular and Molecular Neuroscience

Clinical and Veterinary Neuroscience

Interests

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

Keywords

Huntington's disease

autophagy

polyglutamine

oculopharyngeal muscular dystrophy

Parkinson's disease

Clinical conditions

Alzheimer's disease

Cerebellar ataxias

Huntington's disease

Parkinson's disease

Spinocerebellar ataxia

Equipment

Cell culture

Confocal microscopy

Fluorescence microscopy

Immunohistochemistry

Recombinant protein expression

Collaborators

Cambridge

Roger Barker

Cahir O'Kane

United Kingdom

Steve Brown Web: http://www.har.mrc.ac.uk/

Publications

2011

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

2010

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

2009

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

2008

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

2007

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

2006

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

2005

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

2004

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