Photo of Sovan Sarkar

   Sovan Sarkar, Ph.D.
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Research Associate       
Dept. of Medical Genetics,  
University of Cambridge,
Cambridge Institute for Medical Research,
Wellcome Trust/MRC Building,
Addenbrooke's Hospital, Box 139, Hills Road,
Cambridge CB2 0XY,
United Kingdom
E-mail: ss457@cam.ac.uk                      
 
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Research Fellow
Hughes Hall,
University of Cambridge,
Mortimer Road,                                 
Cambridge CB1 2EW,
United Kingdom



                                           
 
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EGFP-HDQ74 aggregates in PC12 cells
Mutant huntingtin aggregates (green fluorescent aggregated structures) in EGFP-positive stable inducible PC12 cell line expressing EGFP-tagged mutant huntingtin exon 1 with 74 polyglutamine repeats.


EGFP-LC3 stable HeLa cells
Increased autophagosome formation (green punctate structures) in stable HeLa cells expressing EGFP-LC3 after treatment with an autophagy- inducing small molecule.
LC3 staining in COS-7 cells
Accumulation of autophagosomes (red punctate structures) in COS-7 cells treated with a chemical blocker of autophagosome-lysosome fusion, as detected by immunostaining with anti-LC3 antibody. It is important to note that accumulation of LC3-positive vesicles can occur not only due to increased autophagosome synthesis (second image above), but also due to impaired LC3 degradation or autophagosome-lysosome fusion.


RFP-EGFP-LC3 stable HeLa cells
Increased autophagy in stable HeLa cells expressing mRFP-EGFP-LC3 after treatment with an autophagy- inducing small molecule. Enhanced autophagic activity is associated with an increase in the numbers of autophagosomes (which have both mRFP and GFP signals and appear yellow in merged image in the bottom panel) and autolysosomes (which have only mRFP signal due to quenching of GFP signal in the acidic lysosomal environment, and therefore appear red in the merged image). mRFP-EGFP-LC3 is an useful tool to distinguish between an autophagy enhancer and an autophagosome- lysosome fusion blocker.
Research publications

  1. Renna M., Jimenez-Sanchez M., Sarkar S. and Rubinsztein D.C. (2010) Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases. Journal of Biological Chemistry Advanced Online Publication. Access article  

  2. Zheng S., Clabough E.B.D., Sarkar S., Futter M., Rubinsztein D.C. and Zeitlin S.O. (2010) Deletion of huntingtin polyglutamine stretch enhances neuronal autophagy and longevity in mice. PLoS Genetics 6(2): e1000838. Access article Supplementary information

  3. Ravikumar B., Futter M., Jahreiss L., Korolchuk V.I., Lichtenberg M., Luo S., Massey D.C.O., Menzies F.M., Narayanan U., Renna M., Jimenez-Sanchez M., Sarkar S., Underwood B., Winslow A. and Rubinsztein D.C. (2009) Mammalian macroautophagy at a glance. Journal of Cell Science 122(11): 1707-1711. Access article

  4. Rubinsztein D.C., Cuervo A.M., Ravikumar B., Sarkar S., Korolchuk V.I., Kaushik S. and Klionsky D.J. (2009) In search of an "autophagomometer". Autophagy 5(5): 585-589. Access article

  5. Sarkar S., Korolchuk V., Renna M., Winslow A. and Rubinsztein D.C. (2009) Methodological considerations for assessing autophagy modulators: A study with calcium phosphate precipitates. Autophagy 5(3): 307-313. Access article

  6. Sarkar S., Ravikumar B. and Rubinsztein D.C. (2009) Autophagic clearance of aggregate-prone proteins associated with neurodegeneration. Methods in Enzymology Klionsky D.J., editor, Autophagy in disease and clinical applications, Academic Press 453C: 83-110. Access article

  7. Sarkar S., Ravikumar B., Floto R.A. and Rubinsztein D.C. (2009) Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death and Differentiation 16(1): 46-56. Access article

  8. Sarkar S. and Rubinsztein D.C. (2008) Small molecule enhancers of autophagy for neurodegenerative diseases. Molecular BioSystems 4(9): 895-901. Access article

  9. Sarkar S. and Rubinsztein D.C. (2008) Huntington's disease: degradation of mutant huntingtin by autophagy. FEBS Journal 275(17): 4263-4270. Access article

  10. Ravikumar B., Imarisio S., Sarkar S., O'Kane C.J. and Rubinsztein D.C. (2008) Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington's disease. Journal of Cell Science 121(10): 1649-1660. Access article Supplementary information 
    Research Highlight in: Journal of Cell Science

  11. Ravikumar B., Sarkar S. and Rubinsztein D.C. (2008) Clearance of mutant aggregate-prone proteins by autophagy. Methods in Molecular Biology Deretic V.P., editor, Autophagosome and Phagosome, Humana Press 445: 195-211. Access article

  12. Williams A.*, Sarkar S.*, Cuddon P.*, Ttofi E.K., Saiki S., Siddiqi F.H., Jahreiss, L., Fleming A., Pask D., Goldsmith P., O’Kane C.J., Floto R.A. and Rubinsztein D.C. (2008) Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Nature Chemical Biology 4(5): 295-305. Access article Supplementary information Chemical compounds  *Joint first authors                                                                  
    Selected Research Highlights in: Nature Chemical Biology, Featured Article: Nature Signaling Gateway, Nature Reviews Drug Discovery, News & Events: University of Cambridge, Huntington's Disease Lighthouse, Science Daily, Business Weekly, Eurekalert, Medical News Today, Genetic Engineering & Biotechnology News
    Press Releases in: Nature Chemical Biology, Wellcome Trust

  13. Davies J.E., Sarkar S. and Rubinsztein D.C. (2008) Wild-type PABPN1 is anti-apoptotic and reduces toxicity of the oculopharyngeal muscular dystrophy mutation. Human Molecular Genetics 17(8): 1097-1108. Access article Supplementary information

  14. Sarkar S., Krishna G., Imarisio S., Saiki S., O'Kane C.J. and Rubinsztein D.C. (2008) A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin. Human Molecular Genetics 17(2): 170-178. Access article Supplementary information                                                                 
    Research Highlight in:     Nature Clinical Practice Neurology 

  15. Davies J.E., Sarkar S. and Rubinsztein D.C. (2007) The ubiquitin-proteasome system in Huntington's disease and the spinocerebellar ataxias. BMC Biochemistry 8(Suppl 1): S2. Access article

  16. Chakrabortee S., Boschetti C., Walton L.J., Sarkar S., Rubinsztein D.C. and Tunnacliffe A. (2007) Hydrophilic protein associated with dessication tolerance exhibits broad protein stabilization function. Proceedings of the National Academy of Sciences (PNAS), USA 104(46): 18073-18078. Access article Supplementary information 
    Research Highlights in:     Journal of Cell Biology, Journal of Experimental Biology

  17. Floto R.A.*, Sarkar S.*, Perlstein E.O.*, Kampmann B., Schreiber S.L. and Rubinsztein D.C. (2007) Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy, reduce toxicity in Huntington's disease models and enhance killing of mycobacteria by macrophages. Autophagy 3(6): 620-622. Access article  *Joint first authors          
    Research Highlight in: Huntington's Disease Advocacy Center

  18. Sarkar S.*, Perlstein E.O.*, Imarisio S., Pineau S., Cordenier A., Maglathlin R.L., Webster J.A., Lewis T.A., O’Kane C.J., Schreiber S.L. and Rubinsztein D.C. (2007) Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nature Chemical Biology 3(6): 331-338. Access article Supplementary information Chemical compounds Cover highlight  *Joint first authors                                                      
    Selected Research Highlight in:     News & Views: Nature Chemical Biology, Nature Reviews Drug Discovery,     Nature Signaling Gateway, Nature Neuroscience Gateway, News & Events: University of Cambridge, Faculty of 1000 Biology, Channel 4 News, The Post Chronicle, The Scotsman, United Press International, Science Worlds, The Earth Times, Bluesci, Eurekalert    
    Press Release in: Nature Chemical Biology, Wellcome Trust

  19. Sarkar S., Davies J.E., Huang Z., Tunnacliffe A. and Rubinsztein D.C. (2007) Trehalose, a novel mTOR-independent autophagy inducer, accelerates clearance of mutant huntingtin and alpha-synuclein. Journal of Biological Chemistry 282(8): 5641-5652. Access article Supplementary information 
    Research Highlights in: Huntington's Disease Drug Works, Huntington's Disease Lighthouse

  20. Williams A., Jahreiss L., Sarkar S., Saiki S., Menzies F.M., Ravikumar B. and Rubinsztein D.C. (2006) Aggregate-prone proteins are cleared from the cytosol by autophagy – therapeutic implications. Current Topics in Developmental Biology Schatten G.P., editor, Academic Press 76: 89-101. Access article

  21. Davies J.E., Sarkar S. and Rubinsztein D.C. (2006) Trehalose reduces aggregate formation and delays pathology in a transgenic mouse model of oculopharungeal muscular dystrophy. Human Molecular Genetics 15(1): 23-31. Access article Supplementary information  
    Research Highlight in:     Huntington's Disease Advocacy Center

  22. Sarkar S. and Rubinsztein D.C. (2006) Inositol and IP3 levels regulate autophagy – Biology and therapeutic speculations. Autophagy 2(2): 132-134. Access article

  23. Sarkar S., Floto R.A., Berger Z., Imarisio S., Cordenier A., Pasco M., Cook L.J. and Rubinsztein D.C. (2005) Lithium induces autophagy by inhibiting inositol monophosphatase. Journal of Cell Biology 170(7): 1101-1111. Access article Supplementary information                                                                  
    Research Highlight in:     Science STKE

  24. Bao Y.P., Sarkar S., Uyama E. and Rubinsztein D.C. (2004) Congo Red, doxycycline and HSP70 overexpression reduce aggregate formation and cell death in cell models of oculopharyngeal muscular dystrophy. Journal of Medical Genetics 41(1): 47-51. Access article

  25. Ravikumar B., Sarkar S., Berger Z. and Rubinsztein D.C. (2003) The roles of the ubiquitin-proteasome and autophagy-lysosome pathways in Huntington’s disease and related conditions. Clinical Neuroscience Research 3(3): 141-148. Access article

  26. Sarkar S., Choudhury A. and Avinash T.N. (2002) Untangling the mystery of Alzheimer’s disease: Understanding molecular mechanisms for novel therapeutic approaches. Resonance 7(2): 33-45. Access article