Publications

Key Reviews

Srinivasan, S. R., de Gusmao, C. M., Korecka, J. A., & Khurana, V. Repeat expansion disorders. 2023. In Neurobiology of Brain Disorders (pp. 293-312). Academic Press. PDF.

Lam, I,  Hallacli, E,  and Khurana, V. Proteome-scale mapping of perturbed proteostasis in living cells.  Cold Spring Harbor Persp Biol 2019 Mar 25. pii: a034124. doi: 10.1101/cshperspect.a034124. PDF

Jarosz, DF and Khurana, V Specification of Physiologic and Disease States by Distinct Proteins and Protein Conformations. Cell 2017 Nov 16; 171(5):1001-1014. PDF

Khurana, V, Tardiff, DF, Chung, CY, & Lindquist, S. Toward stem cell-based phenotypic screens for neurodegenerative diseases. Nature Reviews Neurology 2015 11(6):339-50. PDF

Khurana V and Lindquist S. Modeling neurodegeneration in S. cerevesiae: Why cook with baker’s yeast? Nature Reviews Neuroscience 2010 11(6):436-49. PDF

Alpha-synuclein biology and mechanisms of toxicity

Lam I*, Ndayisaba A*, Lewis AJ, Fu YH, Zaccagnini L, Sandoe J, Sanz R, Vahdatshoar A, Martin TD, Nader M, Ichihashi T, Tripathi A, Ramalingam N, Oettgen C, Bartels T, Schäbinger M, Jiang X, Verma A,  Yu X, Hyles K, Park C, Theunissen TW, Wang H,  Jaenisch R, Stevens B, Stefanova N, Wenning G, Luk KC, Pernaute RS, Gómez-Esteban JC, Felsky D, Kiyota Y, Sahni N, Yi S, Chung CY,  Stahlberg H, Abizanda IF,  Schöneberg J, Elledge SJ, Dettmer U, Halliday GM, Bartels T, and Khurana V. Rapid iPSC inclusionopathy models shed light on formation, consequence and molecular subtype of proteinaceous alpha-synuclein inclusions. bioRxiv 2022. *Equal contribution.

Hallacli E, Kayatekin C, Nazeen S , Wang X, Sheinkopf Z, Sathyakumar S, Sarkar S, Jiang X, Dong X, Di Maio R, Wang W, Keeney MT, Daniel Felsky, Sandoe J, Vahdatshoar A, Mani DR, Udeshi ND, Carr SA, de Jager P, Myers CL, Greenmyre TJ, Lindquist S, Bartel DP, Sunyaev S, Feany MB, Chung CY and Khurana V. The Parkinson’s disease protein alpha-synuclein is a modulator of Processing-bodies and mRNA stability. Cell 2022 Jun 9;185(12):2035-2056.e33. PDF

Mittal S, Bjørnevik K, Im DS, Flierl A, Dong X, Locascio JJ, Abo KM, Long E, Jin M, Xu B, Xiang YK, Rochet JC, Engeland A, Rizzu P, Heutink P, Bartels T, Selkoe DJ, Caldarone BJ, Glicksman MA, Khurana V, Schüle B, Park DS, Riise T, Scherzer CR. ß2-Adrenoreceptor is a regulator of the a-synuclein gene driving risk of Parkinson’s disease. Science. 2017 09 01; 357(6354):891-898. PDF

Khurana V*º, Chung CY*, Peng J*, Auluck PK, Tardiff DF, Fanning S, Bartels T, Koeva M, Benyamini   H, Lou Y, Nutter-Upham A, Tuncbag N, Baru V, Freyzon Y, Costanzo M, San-Luis B, Schöndorf DC, Barrasa MI, Caraveo G, Ehsani S, Sanjana N, Zhong Q, Gasser T, Vidal M, Deleidi M, Boone C, Berger Bº, Fraenkel Eº, Lindquist S. Genome-scale molecular networks link neurodegenerative disease genes to alpha-synuclein through specific molecular pathways. Cell Systems 2017 4(2): 157-70. PDF*Equal contribution ºCo-corresponding authors

Chung CY*º, Khurana V*º, Loh K, Yi S, Sahni N, Hill D, Peng J, Vidal M, Ting A, Lindquist S. In situ proteome approaches connect alpha-synuclein directly to endocytic trafficking and mRNA metabolism. Cell Systems 2017 4(2): 242-250. PDF*Equal contribution ºCo-corresponding authors

Chung CY*, Khurana V*, Auluck PK, Tardiff DF, Mazzulli JR, Soldner F, Baru V, Lou Y, Freyzon Y, Cho S, Mungenast A, Muffat J, Mitalipova M, Pluth MD, Jui NT, Schüle B, Lippard SJ, Tsai LH, Krainc D, Buchwald, SL, Jaenisch R, Lindquist S. Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons. Science 2013 342 (6161): 983-87. PDF *Equal contribution

Tardiff DF, Jui NT, Khurana V, Tambe M, Tucci ML, Chung CY, Lancaster AK, Caldwell KA, Caldwell GA, Rochet JC, Buchwald ST, Lindquist S. Phenotypic screening and chemical genetics reveals a “druggable” Rsp5/Nedd4 network that ameliorates α-synuclein toxicity. Science 2013 342 (6161): 979-83 PDF

Soldner F, Laganière J, Cheng AW, Hockemeyer D, Gao Q, Alagappan R, Khurana V, Golbe LI, Myers RH, Lindquist S, Zhang L, Guschin D, Fong LK, Vu BJ, Meng X, Urnov FD, Rebar EJ, Gregory PD, Zhang HS, Jaenisch R. Generation of Isogenic Pluripotent Stem Cells Differing Exclusively at Two Early Onset Parkinson Point Mutations. Cell 2011 146(2):318-31. PDF

Parkinson's Disease/Synucleinopathy: Drug Discovery (including Stearoyl coA desaturase inhibitors)

Raja WK, Neves E, Burke C, Jiang X, Xu P, Rhodes KJ, Khurana V, Scannevin RH, Chung CY. Patient-derived three-dimensional cortical neurospheres to model Parkinson’s disease. PLoS One. 2022 Dec 1;17(12):e0277532. PDF
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Nuber S, Chung CY, Tardiff DF, Bechade PA, McCaffery TD, Shimanaka K, Choi J, Chang B, Raja W, Neves E, Burke C, Jiang X, Xu P, Khurana V, Dettmer U, Fanning S, Rhodes KJ, Selkoe DJ, Scannevin RH. A Brain-Penetrant Stearoyl-CoA Desaturase Inhibitor Reverses α-Synuclein Toxicity. Neurotherapeutics 2022 Apr;19(3):1018-1036. PDF
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Vincent BM, Tardiff DF, Piotrowski JS, Aron R, Lucas MC, Chung CY, Bacherman H, Chen Y, Pires M, Subramaniam R, Doshi DB, Sadlish H, Raja WK, Solís EJ, Khurana V, Le Bourdonnec B, Scannevin RH, Rhodes KJ. Inhibiting Stearoyl-CoA Desaturase Ameliorates α-Synuclein Cytotoxicity. Cell Reports 2018 Dec 4;25(10):2742-2754. PDF
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Mittal S, Bjørnevik K, Im DS, Flierl A, Dong X, Locascio JJ, Abo KM, Long E, Jin M, Xu B, Xiang YK, Rochet JC, Engeland A, Rizzu P, Heutink P, Bartels T, Selkoe DJ, Caldarone BJ, Glicksman MA, Khurana V, Schüle B, Park DS, Riise T, Scherzer CR. ß2-Adrenoreceptor is a regulator of the a-synuclein gene driving risk of Parkinson’s disease. Science 2017 357(6354):891-898. PDF
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Tardiff DF, Jui NT, Khurana V, Tambe M, Tucci ML, Chung CY, Lancaster AK, Caldwell KA, Caldwell GA, Rochet JC, Buchwald ST, Lindquist S. Phenotypic screening and chemical genetics reveals a “druggable” Rsp5/Nedd4 network that ameliorates α-synuclein toxicity. Science 2013 342 (6161): 979-83 Pubmed

Parkinson's Disease/ MSA / Familial Synucleinopathies: Biomarkers and Precision Medicine Clinical Trials

Ndayisaba A, Pitaro AT, Willett AS, Jones KA, de Gusmao CM, Olsen AL, Kim J, Rissanen E, Woods JK, Srinivasan SR, Nagy A, Nagy A, Mesidor M, Cicero S, Patel V, Oakley DH, Tuncali I, Taglieri-Noble K, Clark EC, Paulson J, Krolewski RC, Ho GP, Hung AY, Wills AM, Hayes MT, Macmore JP, Warren L, Bower PG, Langer CB, Kellerman LR, Humphreys CW, Glanz BI, Dielubanza EJ, Frosch MP, Freeman RL, Gibbons CH, Stefanova N, Chitnis T, Weiner HL, Scherzer CR, Scholz SW, Vuzman D, Cox LM, Wenning G, Schmahmann JD, Gupta AS, Novak P, Young GS, Feany MB, Singhal T, Khurana V. Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping. Cerebellum 2022 Oct 3:1-21. doi: 10.1007/s12311-022-01471-8. PDF
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Kim J, Young GS, Willett AS, Pitaro AT, Crotty GF, Mesidor M, Jones KA, Bay C, Zhang M, Feany MB, Xu X, Qin L, Khurana V. Toward More Accessible Fully Automated 3D Volumetric MRI Decision Trees for the Differential Diagnosis of Multiple System Atrophy, Related Disorders, and Age-Matched Healthy Subjects. Cerebellum 2022 Sep 26. doi: 10.1007/s12311-022-01472-7. PDF
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Murueta-Goyena A, Cipriani R, Carmona-Abellán M, Acera M, Ayo N, Del Pino R, Tijero B, Fernández-Valle T, Gabilondo I, Zallo F, Matute C, Sánchez-Pernaute R, Khurana V, Cavaliere F, Capetillo-Zarate E, Gómez-Esteban JC. Characterization of molecular biomarkers in cerebrospinal fluid and serum of E46K-SNCA mutation carriers. Parkinsonism Related Disorders. 2022 Mar;96:29-35. PDF
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Carmona-Abellan M, Gabilondo I, Murueta-Goyena A, Khurana V, Tijero B, Luquin MR, Acera M, Del Pino R, Gardeazabal J, Martínez-Valbuena I, Sanchez-Pernaute R, Gómez-Esteban JC. Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K-SNCA mutation carriers. Parkinsonism Related Disorders. 2019 Aug;65:139-145. PDF
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Walsh RR, Krismer F, Galpern WR, Wenning GK, Low PA, Halliday G, Koroshetz WJ, Holton J, Quinn NP, Rascol O, Shaw LM, Eidelberg D, Bower P, Cummings JL, Abler V, Biedenharn J, Bitan G, Brooks DJ, Brundin P, Fernandez H, Fortier P, Freeman R, Gasser T, Hewitt A, Höglinger GU, Huentelman MJ, Jensen PH, Jeromin A, Kang UJ, Kaufmann H, Kellerman L, Khurana V, Klockgether T, Kim WS, Langer C, LeWitt P, Masliah E, Meissner W, Melki R, Ostrowitzki S, Piantadosi S, Poewe W, Robertson D, Roemer C, Schenk D, Schlossmacher M, Schmahmann JD, Seppi K, Shih L, Siderowf A, Stebbins GT, Stefanova N, Tsuji S, Sutton S, Zhang J. Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting. Neurology 2018 Jan 9;90(2):74-82. PDF

Parkinson's Disease: Gene-Environment Interactions

Paul KC*,Krolewski RC*, Lucumi Moreno E, Blank J, Holton K, Ahfeldt T, Furlong M, Yu Y, Cockburn M, Thompson LK, Bronstein J, Rubin Lx, Khurana Vx, and Ritz Bx. Coupling comprehensive pesticide-wide association study to iPSC dopaminergic screening identifies and classifies Parkinson-relevant pesticides. bioRxiv 2022  *co-first authors; xco-corresponding authors.

Tau biology and mechanisms of toxicity

Khurana V*, Merlo P*, Duboff B, Sharp KA, Fulga TA, Campbell S, Gotz J and Feany MB. A neuroprotective role for the DNA damage checkpoint in tauopathy. Aging Cell 2012 11(2): 360-62 PDF *Equal contribution

Khurana V*, Elson-Schwab I,* Fulga TA*, Sharp KA, Mulkearns E, Loewen CA, Scherzer CR, Tyynelä J and Feany MB. Lysosomal dysfunction promotes cleavage and neurotoxicity of tau in vivo. PLoS Genetics 2010 6(7): e1001026. doi:10.1371/journal.pgen.1001026 PDF *Equal contribution

Fulga TA, Elson-Schwab I, Khurana V, Michelle L Steinhilb, Soires TL, Hyman BT, Feany MB. Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nature Cell Biology 2007 9:139-148.Pubmed

Khurana V, Lu Y, Steinhilb ML, Oldham S, Shulman JM, Feany MB. TOR-mediated cell- cycle activation causes neurodegeneration in a Drosophila tauopathy model. Current Biology 2006 16: 231-241.PDF

Ataxins, Polyglutamine Disorders and Cerebellar Ataxias

Aboud Syriani D, Wong D, Andani S, De Gusmao CM, Mao Y, Sanyoura M, Glotzer G, Lockhart PJ, Hassin-Baer S, Khurana V, Gomez CM, Perlman S, Das S, Fogel BL. Prevalence of RFC1-mediated spinocerebellar ataxia in a North American ataxia cohort. Neurology Genetics 2020 May 20;6(3):e440. PDF.
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Khurana V, de Gusmao CM, Glover M, Helgager J. Case 20-2021: A 69-Year-Old Man with Ataxia. New England Journal of Medicine 2021 Jul 8;385(2):165-175. doi: 10.1056/NEJMcpc2004992. PDF.
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Khurana V*º, Chung CY*, Peng J*, Auluck PK, Tardiff DF, Fanning S, Bartels T, Koeva M, Benyamini   H, Lou Y, Nutter-Upham A, Tuncbag N, Baru V, Freyzon Y, Costanzo M, San-Luis B, Schöndorf DC, Barrasa MI, Caraveo G, Ehsani S, Sanjana N, Zhong Q, Gasser T, Vidal M, Deleidi M, Boone C, Berger Bº, Fraenkel Eº, Lindquist S. Genome-scale molecular networks link neurodegenerative disease genes to alpha-synuclein through specific molecular pathways. Cell Systems 2017 4(2): 157-70. PDF  *Equal contribution ºCo-corresponding authors

Khurana V, Fulga TA, Feany MB. Senseless makes sense for spinocerebellar ataxia-1. Nature Neuroscience 2005 8: 1422-1424. PDF

Systems Biology

Khurana V*º, Chung CY*, Peng J*, Auluck PK, Tardiff DF, Fanning S, Bartels T, Koeva M, Benyamini   H, Lou Y, Nutter-Upham A, Tuncbag N, Baru V, Freyzon Y, Costanzo M, San-Luis B, Schöndorf DC, Barrasa MI, Caraveo G, Ehsani S, Sanjana N, Zhong Q, Gasser T, Vidal M, Deleidi M, Boone C, Berger Bº, Fraenkel Eº, Lindquist S. Genome-scale molecular networks link neurodegenerative disease genes to alpha-synuclein through specific molecular pathways. Cell Systems 2017 4(2): 157-70. PDF*Equal contribution ºCo-corresponding authors

Sidhi N, Yi, S, Taipale M, Fuxman Bass JI, Coulombe-Huntington J, Yang F Peng J Weile J, Karras GI,Kamburov A, Krykbaeva I, Tucker G, Khurana V, Sharma A, Liu Y-Y, Yachie N, Zhong Q, Shen Y, Palagi A, San-Miguel A, Fan C, Balcha D, Dricot A, Jordan DM, Walsh, JM, Shah, AA, Yang X, Stoyanova A, Leighton A, Calderwood MA, Jacob Y, Cusick ME, Salehi-Ashtiani K, Whitesell LJ, Sunyaev S, Charloteaux B, Berger B, Hill DE, Barabási A-L, Hao T, Roth FP, Xia Y, Walhout AJM, Lindquist S, Vidal M. Widespread perturbation of disease-specific macromolecular interactions in human genetic disorders. Cell 2015 161(3):647-60.

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