Paul Muchowski, PhD

Title(s)Professor, Neurology
SchoolSchool of Medicine
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    The Role of Microglia and the Kynurenine Pathway in Huntington's Disease
    NIH/NINDS R01NS057715Mar 1, 2008 - Feb 28, 2014
    Role: Co-Principal Investigator
    Elucidation of the structures and biological activities of huntingtin oligomers
    NIH/NINDS R01NS054753Apr 1, 2006 - Jan 31, 2013
    Role: Principal Investigator
    Modifiers of Huntingtin and Alpha-synuclein Toxicity
    NIH/NINDS R01NS047237Jan 1, 2004 - Feb 28, 2009
    Role: Principal Investigator

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Chen MZ, Mok SA, Ormsby AR, Muchowski PJ, Hatters DM. N-Terminal Fragments of Huntingtin Longer than Residue 170 form Visible Aggregates Independently to Polyglutamine Expansion. J Huntingtons Dis. 2017; 6(1):79-91. PMID: 28339398.
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    2. Erhardt S, Pocivavsek A, Repici M, Liu XC, Imbeault S, Maddison DC, Thomas MAR, Smalley JL, Larsson MK, Muchowski PJ, Giorgini F, Schwarcz R. Adaptive and Behavioral Changes in Kynurenine 3-Monooxygenase Knockout Mice: Relevance to Psychotic Disorders. Biol Psychiatry. 2017 Nov 15; 82(10):756-765. PMID: 28187857.
      View in: PubMed
    3. Larkin PB, Sathyasaikumar KV, Notarangelo FM, Funakoshi H, Nakamura T, Schwarcz R, Muchowski PJ. Tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase 1 make separate, tissue-specific contributions to basal and inflammation-induced kynurenine pathway metabolism in mice. Biochim Biophys Acta. 2016 11; 1860(11 Pt A):2345-2354. PMID: 27392942.
      View in: PubMed
    4. Oliveira AO, Osmand A, Outeiro TF, Muchowski PJ, Finkbeiner S. aB-Crystallin overexpression in astrocytes modulates the phenotype of the BACHD mouse model of Huntington's disease. Hum Mol Genet. 2016 05 01; 25(9):1677-89. PMID: 26920069.
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    5. Giorgini F, Huang SY, Sathyasaikumar KV, Notarangelo FM, Thomas MA, Tararina M, Wu HQ, Schwarcz R, Muchowski PJ. Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. J Biol Chem. 2013 Dec 20; 288(51):36554-66. PMID: 24189070; PMCID: PMC3868768.
    6. Bouchard J, Truong J, Bouchard K, Dunkelberger D, Desrayaud S, Moussaoui S, Tabrizi SJ, Stella N, Muchowski PJ. Cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of Huntington's disease. J Neurosci. 2012 Dec 12; 32(50):18259-68. PMID: 23238740; PMCID: PMC3753072.
    7. Horne EA, Coy J, Swinney K, Fung S, Cherry AE, Marrs WR, Naydenov AV, Lin YH, Sun X, Keene CD, Grouzmann E, Muchowski P, Bates GP, Mackie K, Stella N. Downregulation of cannabinoid receptor 1 from neuropeptide Y interneurons in the basal ganglia of patients with Huntington's disease and mouse models. Eur J Neurosci. 2013 Feb; 37(3):429-40. PMID: 23167744; PMCID: PMC3699342.
    8. Kwan W, Träger U, Davalos D, Chou A, Bouchard J, Andre R, Miller A, Weiss A, Giorgini F, Cheah C, Möller T, Stella N, Akassoglou K, Tabrizi SJ, Muchowski PJ. Mutant huntingtin impairs immune cell migration in Huntington disease. J Clin Invest. 2012 Dec; 122(12):4737-47. PMID: 23160193; PMCID: PMC3533551.
    9. Sontag EM, Lotz GP, Agrawal N, Tran A, Aron R, Yang G, Necula M, Lau A, Finkbeiner S, Glabe C, Marsh JL, Muchowski PJ, Thompson LM. Methylene blue modulates huntingtin aggregation intermediates and is protective in Huntington's disease models. J Neurosci. 2012 Aug 08; 32(32):11109-19. PMID: 22875942; PMCID: PMC3546821.
    10. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012 Jul; 13(7):465-77. PMID: 22678511; PMCID: PMC3681811.
    11. Green EW, Campesan S, Breda C, Sathyasaikumar KV, Muchowski PJ, Schwarcz R, Kyriacou CP, Giorgini F. Drosophila eye color mutants as therapeutic tools for Huntington disease. Fly (Austin). 2012 Apr-Jun; 6(2):117-20. PMID: 22634544.
      View in: PubMed
    12. Nucifora LG, Burke KA, Feng X, Arbez N, Zhu S, Miller J, Yang G, Ratovitski T, Delannoy M, Muchowski PJ, Finkbeiner S, Legleiter J, Ross CA, Poirier MA. Identification of novel potentially toxic oligomers formed in vitro from mammalian-derived expanded huntingtin exon-1 protein. J Biol Chem. 2012 May 04; 287(19):16017-28. PMID: 22433867; PMCID: PMC3346083.
    13. Sancenon V, Lee SA, Patrick C, Griffith J, Paulino A, Outeiro TF, Reggiori F, Masliah E, Muchowski PJ. Suppression of a-synuclein toxicity and vesicle trafficking defects by phosphorylation at S129 in yeast depends on genetic context. Hum Mol Genet. 2012 Jun 01; 21(11):2432-49. PMID: 22357655; PMCID: PMC3349423.
    14. Kwan W, Magnusson A, Chou A, Adame A, Carson MJ, Kohsaka S, Masliah E, Möller T, Ransohoff R, Tabrizi SJ, Björkqvist M, Muchowski PJ. Bone marrow transplantation confers modest benefits in mouse models of Huntington's disease. J Neurosci. 2012 Jan 04; 32(1):133-42. PMID: 22219276; PMCID: PMC3571858.
    15. Sontag EM, Lotz GP, Yang G, Sontag CJ, Cummings BJ, Glabe CG, Muchowski PJ, Thompson LM. Detection of Mutant Huntingtin Aggregation Conformers and Modulation of SDS-Soluble Fibrillar Oligomers by Small Molecules. J Huntingtons Dis. 2012; 1(1):119-32. PMID: 24086178; PMCID: PMC3786168.
    16. Larkin PB, Muchowski PJ. Genetic Deficiency of Complement Component 3 Does Not Alter Disease Progression in a Mouse Model of Huntington's Disease. J Huntingtons Dis. 2012; 1(1):107-18. PMID: 23097680; PMCID: PMC3478099.
    17. Miller J, Arrasate M, Brooks E, Libeu CP, Legleiter J, Hatters D, Curtis J, Cheung K, Krishnan P, Mitra S, Widjaja K, Shaby BA, Lotz GP, Newhouse Y, Mitchell EJ, Osmand A, Gray M, Thulasiramin V, Saudou F, Segal M, Yang XW, Masliah E, Thompson LM, Muchowski PJ, Weisgraber KH, Finkbeiner S. Identifying polyglutamine protein species in situ that best predict neurodegeneration. Nat Chem Biol. 2011 Oct 30; 7(12):925-34. PMID: 22037470; PMCID: PMC3271120.
    18. Chen X, Wu J, Luo Y, Liang X, Supnet C, Kim MW, Lotz GP, Yang G, Muchowski PJ, Kodadek T, Bezprozvanny I. Expanded polyglutamine-binding peptoid as a novel therapeutic agent for treatment of Huntington's disease. Chem Biol. 2011 Sep 23; 18(9):1113-25. PMID: 21944750; PMCID: PMC3183433.
    19. Zwilling D, Huang SY, Sathyasaikumar KV, Notarangelo FM, Guidetti P, Wu HQ, Lee J, Truong J, Andrews-Zwilling Y, Hsieh EW, Louie JY, Wu T, Scearce-Levie K, Patrick C, Adame A, Giorgini F, Moussaoui S, Laue G, Rassoulpour A, Flik G, Huang Y, Muchowski JM, Masliah E, Schwarcz R, Muchowski PJ. Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell. 2011 Jun 10; 145(6):863-74. PMID: 21640374; PMCID: PMC3118409.
    20. Campesan S, Green EW, Breda C, Sathyasaikumar KV, Muchowski PJ, Schwarcz R, Kyriacou CP, Giorgini F. The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington's disease. Curr Biol. 2011 Jun 07; 21(11):961-6. PMID: 21636279; PMCID: PMC3929356.
    21. Thevandavakkam MA, Schwarcz R, Muchowski PJ, Giorgini F. Targeting kynurenine 3-monooxygenase (KMO): implications for therapy in Huntington's disease. CNS Neurol Disord Drug Targets. 2010 Dec; 9(6):791-800. PMID: 20942784.
      View in: PubMed
    22. Tauber E, Miller-Fleming L, Mason RP, Kwan W, Clapp J, Butler NJ, Outeiro TF, Muchowski PJ, Giorgini F. Functional gene expression profiling in yeast implicates translational dysfunction in mutant huntingtin toxicity. J Biol Chem. 2011 Jan 07; 286(1):410-9. PMID: 21044956; PMCID: PMC3012999.
    23. Lotz GP, Legleiter J, Aron R, Mitchell EJ, Huang SY, Ng C, Glabe C, Thompson LM, Muchowski PJ. Hsp70 and Hsp40 functionally interact with soluble mutant huntingtin oligomers in a classic ATP-dependent reaction cycle. J Biol Chem. 2010 Dec 03; 285(49):38183-93. PMID: 20864533; PMCID: PMC2992252.
    24. Sathyasaikumar KV, Stachowski EK, Amori L, Guidetti P, Muchowski PJ, Schwarcz R. Dysfunctional kynurenine pathway metabolism in the R6/2 mouse model of Huntington's disease. J Neurochem. 2010 Jun; 113(6):1416-25. PMID: 20236387; PMCID: PMC3721540.
    25. Legleiter J, Mitchell E, Lotz GP, Sapp E, Ng C, DiFiglia M, Thompson LM, Muchowski PJ. Mutant huntingtin fragments form oligomers in a polyglutamine length-dependent manner in vitro and in vivo. J Biol Chem. 2010 May 07; 285(19):14777-90. PMID: 20220138; PMCID: PMC2863238.
    26. Sathasivam K, Lane A, Legleiter J, Warley A, Woodman B, Finkbeiner S, Paganetti P, Muchowski PJ, Wilson S, Bates GP. Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington's disease. Hum Mol Genet. 2010 Jan 01; 19(1):65-78. PMID: 19825844; PMCID: PMC2792149.
    27. Miller J, Rutenber E, Muchowski PJ. Polyglutamine dances the conformational cha-cha-cha. Structure. 2009 Sep 09; 17(9):1151-3. PMID: 19748335; PMCID: PMC2830152.
    28. Wacker JL, Huang SY, Steele AD, Aron R, Lotz GP, Nguyen Q, Giorgini F, Roberson ED, Lindquist S, Masliah E, Muchowski PJ. Loss of Hsp70 exacerbates pathogenesis but not levels of fibrillar aggregates in a mouse model of Huntington's disease. J Neurosci. 2009 Jul 15; 29(28):9104-14. PMID: 19605647; PMCID: PMC2739279.
    29. Muccioli GG, Sia A, Muchowski PJ, Stella N. Genetic manipulation of palmitoylethanolamide production and inactivation in Saccharomyces cerevisiae. PLoS One. 2009 Jun 16; 4(6):e5942. PMID: 19529773; PMCID: PMC2691958.
    30. Legleiter J, Lotz GP, Miller J, Ko J, Ng C, Williams GL, Finkbeiner S, Patterson PH, Muchowski PJ. Monoclonal antibodies recognize distinct conformational epitopes formed by polyglutamine in a mutant huntingtin fragment. J Biol Chem. 2009 Aug 07; 284(32):21647-58. PMID: 19491400; PMCID: PMC2755888.
    31. Schwarcz R, Guidetti P, Sathyasaikumar KV, Muchowski PJ. Of mice, rats and men: Revisiting the quinolinic acid hypothesis of Huntington's disease. Prog Neurobiol. 2010 Feb 09; 90(2):230-45. PMID: 19394403; PMCID: PMC2829333.
    32. Salazar L, Kashiwada T, Krejci P, Muchowski P, Donoghue D, Wilcox WR, Thompson LM. A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells. Hum Mol Genet. 2009 Jun 01; 18(11):1951-61. PMID: 19286672; PMCID: PMC2902846.
    33. Giorgini F, Muchowski PJ. Exploiting yeast genetics to inform therapeutic strategies for Huntington's disease. Methods Mol Biol. 2009; 548:161-74. PMID: 19521824.
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    34. Trinh K, Moore K, Wes PD, Muchowski PJ, Dey J, Andrews L, Pallanck LJ. Induction of the phase II detoxification pathway suppresses neuron loss in Drosophila models of Parkinson's disease. J Neurosci. 2008 Jan 09; 28(2):465-72. PMID: 18184789.
      View in: PubMed
    35. Muchowski PJ, Ramsden R, Nguyen Q, Arnett EE, Greiling TM, Anderson SK, Clark JI. Noninvasive measurement of protein aggregation by mutant huntingtin fragments or alpha-synuclein in the lens. J Biol Chem. 2008 Mar 07; 283(10):6330-6. PMID: 18167346; PMCID: PMC2650484.
    36. Giorgini F, Möller T, Kwan W, Zwilling D, Wacker JL, Hong S, Tsai LC, Cheah CS, Schwarcz R, Guidetti P, Muchowski PJ. Histone deacetylase inhibition modulates kynurenine pathway activation in yeast, microglia, and mice expressing a mutant huntingtin fragment. J Biol Chem. 2008 Mar 21; 283(12):7390-400. PMID: 18079112.
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    37. Cheng IH, Scearce-Levie K, Legleiter J, Palop JJ, Gerstein H, Bien-Ly N, Puoliväli J, Lesné S, Ashe KH, Muchowski PJ, Mucke L. Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J Biol Chem. 2007 Aug 17; 282(33):23818-28. PMID: 17548355.
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    38. Rosser MF, Washburn E, Muchowski PJ, Patterson C, Cyr DM. Chaperone functions of the E3 ubiquitin ligase CHIP. J Biol Chem. 2007 Aug 03; 282(31):22267-77. PMID: 17545168.
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    39. Finkbeiner S, Cuervo AM, Morimoto RI, Muchowski PJ. Disease-modifying pathways in neurodegeneration. J Neurosci. 2006 Oct 11; 26(41):10349-57. PMID: 17035516.
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    40. Ehrnhoefer DE, Duennwald M, Markovic P, Wacker JL, Engemann S, Roark M, Legleiter J, Marsh JL, Thompson LM, Lindquist S, Muchowski PJ, Wanker EE. Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's disease models. Hum Mol Genet. 2006 Sep 15; 15(18):2743-51. PMID: 16893904.
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    41. Duennwald ML, Jagadish S, Giorgini F, Muchowski PJ, Lindquist S. A network of protein interactions determines polyglutamine toxicity. Proc Natl Acad Sci U S A. 2006 Jul 18; 103(29):11051-6. PMID: 16832049; PMCID: PMC1544172.
    42. Duennwald ML, Jagadish S, Muchowski PJ, Lindquist S. Flanking sequences profoundly alter polyglutamine toxicity in yeast. Proc Natl Acad Sci U S A. 2006 Jul 18; 103(29):11045-50. PMID: 16832050; PMCID: PMC1544171.
    43. Giorgini F, Muchowski PJ. Screening for genetic modifiers of amyloid toxicity in yeast. Methods Enzymol. 2006; 412:201-22. PMID: 17046660.
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    44. Giorgini F, Guidetti P, Nguyen Q, Bennett SC, Muchowski PJ. A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nat Genet. 2005 May; 37(5):526-31. PMID: 15806102; PMCID: PMC1449881.
    45. Giorgini F, Muchowski PJ. Connecting the dots in Huntington's disease with protein interaction networks. Genome Biol. 2005; 6(3):210. PMID: 15774033; PMCID: PMC1088934.
    46. Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005 Jan; 6(1):11-22. PMID: 15611723.
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    47. Wacker JL, Zareie MH, Fong H, Sarikaya M, Muchowski PJ. Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nat Struct Mol Biol. 2004 Dec; 11(12):1215-22. PMID: 15543156.
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    48. Outeiro TF, Muchowski PJ. Molecular genetics approaches in yeast to study amyloid diseases. J Mol Neurosci. 2004; 23(1-2):49-60. PMID: 15126692.
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    49. Willingham S, Outeiro TF, DeVit MJ, Lindquist SL, Muchowski PJ. Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein. Science. 2003 Dec 05; 302(5651):1769-72. PMID: 14657499.
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    50. Miller LC, Swayne LA, Chen L, Feng ZP, Wacker JL, Muchowski PJ, Zamponi GW, Braun JE. Cysteine string protein (CSP) inhibition of N-type calcium channels is blocked by mutant huntingtin. J Biol Chem. 2003 Dec 26; 278(52):53072-81. PMID: 14570907.
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    51. Sherman MY, Muchowski PJ. Making yeast tremble: yeast models as tools to study neurodegenerative disorders. Neuromolecular Med. 2003; 4(1-2):133-46. PMID: 14528057.
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    52. Muchowski PJ. Protein misfolding, amyloid formation, and neurodegeneration: a critical role for molecular chaperones? Neuron. 2002 Jul 03; 35(1):9-12. PMID: 12123602.
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    53. Valdez MM, Clark JI, Wu GJ, Muchowski PJ. Functional similarities between the small heat shock proteins Mycobacterium tuberculosis HSP 16.3 and human alphaB-crystallin. Eur J Biochem. 2002 Apr; 269(7):1806-13. PMID: 11952782.
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    54. Muchowski PJ, Ning K, D'Souza-Schorey C, Fields S. Requirement of an intact microtubule cytoskeleton for aggregation and inclusion body formation by a mutant huntingtin fragment. Proc Natl Acad Sci U S A. 2002 Jan 22; 99(2):727-32. PMID: 11792857; PMCID: PMC117373.