J. Paul Taylor, MD, PhD
J. Paul Taylor, MD, PhD

J. Paul Taylor, MD, PhD

Member, St. Jude Faculty

  • Chair, Cell & Molecular Biology Department
  • Associate Director, Basic Research, Comprehensive Cancer Center
  • Edward F. Barry Endowed Chair in Cell and Molecular Biology

Departments

Education

MD, PhD – Jefferson Medical College, Philadelphia, Pennsylvania
Residency (Neurology) – Hospital of the University of Pennsylvania
Fellowship (Neurogenetics) – Neurogenetics Branch, NINDS/NIH

Honors & Awards

  • 2015 Lisa S. Krivickas Lecture, Massachusetts General Hospital Neurology
  • 2014 George Karpati Lecture, Montreal Neurological Institute and McGill University
  • 2014 Vince Kidd Memorial Mentor of the Year Award
  • 2013 Derek Denny-Brown Young Neurological Scholar Award, American Neurological Association
  • 2013 Elected Fellow of the American Neurological Association
  • 2010 Elected to the American Society of Clinical Investigation
  • 2008 Dana Brain Imaging Award, The Dana Foundation
  • 2002 NINDS K22 Career Award
  • 2000 Howard Hughes Medical Institute Fellowship Award for Physician-Scientists

Research Interests

The principal goal of our research is to reduce the morbidity and mortality associated with neurological disease. Toward this end we:

  • Use in vitro and in vivo modeling to elucidate the molecular basis of neuronal dysfunction and neuronal loss in neurological diseases
  • Use the fruit fly Drosophila melanogaster to apply the power of genetics to illuminate the pathogenesis of neurodegeneration
  • Investigate the molecular genetics of amyotrophic lateral sclerosis, frontotemporal dementia, inclusion body myopathy and polyglutamine disease
  • Screen small molecules to identify compounds that can be translated to clinical use

Selected Publications

Taylor JP. G-quadruplex poses a quadruple threat. Nature 507(7491):175-7, 2014.

Alami NH, Smith RB, Carrasco MA, Williams LA, Winborn CS, Han SSW, Kiskinis E, Winborn B, Freibaum BD, Kanagaraj A, Clare AJ, Badders NM, Bilican B, Chaum E, Chandran S, Shaw CE, Eggan KC, Maniatis T and Taylor JP. Microtubule-dependent transport of TDP-43 mRNA granules in neurons is impaired by ALS-causing mutations. Neuron 81(3):536-543, 2014.

Seleen M, Visser AE, Overste DJ, Kim HJ, Palud A,Wong TH, van der Flier WM, van Swieten JC, Scheltens P, Voermans NC, Baas F, de Jong JMBV, van der Kooi AJ, de Visser M, Veldink JH, Taylor JP, Van Es MA, van den Berg LH. No mutations in hnRNPA1 and hnRNPA2B1 in Dutch patients with amyotrophic lateral sclerosis, frontotemporal dementia and inclusion body myositis.Neurobiol Aging 35(8):1956.e9-1956.e11, 2014.

Johnson JO, Pioro EP, Boehringer A, Chia R, Feit H, Renton AE, Pliner HA, Abramzon Y, Marangi G, Winborn BJ, Gibbs JR, Nalls MA, Morgan S, Shoai M, Hardy J, Pittman A, Orrell RW, Malaspina A, Sidle KC, Fratta P, Harms MB, Baloh RH, Pestronk A, Weihl CC, Rogaeva E, Zinman L, Drory VE, Borghero G, Mora G, Calvo A, Rothstein JD, ITALSGEN23, Drepper C, Sendtner M, Singleton AB, Taylor JP, Cookson MR, Restagno G, Sabatelli M, Bowser R, Chiò A, Traynor BJ. Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. Nature Neurosci 17(5):664-6, 2014.

Pinkus JL, Amato AA, Taylor JP, Greenberg SA. Abnormal distribution of heterogeneous nuclear ribonucleoproteins in sporadic inclusion body myositis. Neuromuscular Disorders 24(7):611-6, 2014.

Figley MD, Bieri G, Kolaitis RM, Taylor JP, Gitler AD. Profilin 1 Associates with Stress Granules and ALS-Linked Mutations Alter Stress Granule Dynamics. J Neurosci 34(24):8083-97, 2014.

Pinkus JL, Amato AA, Taylor JP, Greenberg SA. Abnormal distribution of heterogeneous nuclear ribonucleoproteins in sporadic inclusion body myositis. Neuromuscul Disord 24(7):611-6, 2014.

He F, Krans A, Freibaum BD, Taylor JP, Todd PK. TDP-43 suppresses CGG repeat-induced neurotoxicity through interactions with HnRNP A2/B1. Hum Mol Genet 23(19):5036-51 2014.

Lee JY, Kapur M, Li M, Choi MC, Choi S, Kim HJ, Kim I, Lee E, Taylor JP, Yao TP. MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria. J Cell Sci 2014 (in press).

Gao FB, Taylor JP. RNA metabolism in neurological disease. Brain Res 2014 (in press).

Oskarsson B, Wheelock V, Benatar M, Taylor JP, Joyce N, Chesak D, Jin LW. A case of familial ALS due to multi-system proteinopathy 1 and Huntington disease. Amyotroph Lateral Scler Frontotemporal Degener 2014 (in press).

Ramaswami M*, Taylor JP*, Parker R†. Altered "Ribostasis": RNA-protein granule formation or persistence in the development of degenerative disorders. Cell 154(4):727-36, 2013. *Co-corresponding authors.

Buchan JR, Kolaitis R, Taylor JP* and Parker R*. Eukaryotic stress granules are cleared by granulophagy and Cdc48/VCP function. Cell 153(7):1461-74, 2013. *Co-corresponding authors.

Kim HJ, Kim NC, Wang M, Scarborough EA, Moore J, Diaz Z, Maclea K, Freibaum B, Molliex A, Kanagaraj A, Li S, Pinkus JL, Greenberg SA, Trojanowski J, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Wojtas AM, Boylan KB, Rademakers R, Kottlors M, Kirschner J, Li YR, Gitler AD, Benatar M, King OD, Kimonis V, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495:467-473, 2013.

Shorter J, Taylor JP. Disease mutations in the prion-like domains of hnRNPA1 and hnRNPA2B1 introduce potent steric zippers that drive excess RNP granule assembly. Rare Diseases 25200, 2013. doi: 10.4161/rdis.

Taylor JP. RNA Gets RAN in Neurodegeneration. Science 339:1282-1283, 2013.

Kim NC, Tresse E, Kolaitis RM, Molliex A, Thomas R, Alami N, Wang B, Joshi A, Smith RB, Ritson GP, Winborn BJ, Lee JY, Yao TP, Pallanck L, Kundu M, Taylor JP. VCP is essential for mitochondrial quality control by the PINK1/Parkin pathway and this function is impaired by disease-causing mutations. Neuron 78:65-80, 2013.

Benatar M, Weihl CC, Wuu J, Traynor B, Oskarsson B, Fernandez C, Taylor JP. Motor neuron involvement in multisystem proteinopathy: implications for ALS. Neurology 80(20):1874-1880, 2013.

Fujita K, Nakamura Y, Oka T, Ito H, Tarrua T, Tagawa K, Sasabe T, Katsuta A, Motoki K, Shiwaku H, Sone M, Yoshida C, Katsana M, Eishi Y, Murata M, Taylor JP, Wanker EE, Kono K, Tashiro S, Sobue G, La Spada AR, Okazawa H. A functional deficiency of TERA/VCP/p97 contributes to impaired DNA damage repair in multiple polyglutamine diseases. Nature Communications 4:1816, 2013. doi: 10.1038/ncomms2828.

Todd PK, Oh SY, Krans A, He F, Sellier C, Frazer M, Renoux AJ, Chen KC, Scaglione M, Basrur V, Elenitoba-Johnson K, Vonsattel JP, Louis ED, Sutton MA, Taylor JP, Mills RE, Charlet-Berguerand N, and Paulson HL. CGG Repeat-Associated Translation Mediates Neurodegeneration in Fragile X Tremor Ataxia Syndrome. Neuron 78(3):440-455, 2013.

Gao FB, Taylor JP. RNA-binding proteins in neurological disease. Brain Research 1462:1-2. 2012.

Usenovic M, Tresse E, Taylor JP, Krainc D. Parkinsonism-linked ATP13A2 causes lysosomal dysfunction and α-synuclein accumulation. J Neurosci 32(12):4240-6. 2012.

Messing A, Li R, Naidu S, Taylor JP, van der Knaap MS, Flint D, Brenner M. Novel GFAP mutations in two archetypical Alexander disease families. Archives of Neurology 69(2):208-14. 2012.

Klionsky et al., Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8(4):445-544, 2012.

Abramzon Y, Johnson JO, Scholz SW, Taylor JP, Brunnetti M, Calvo A, Mandrioli J, Benatar M, Mora G, Restagno G, Chio A and Traynor BJ. Valosin-containing protein mutations in sporadic amyotrophic lateral sclerosis. Neurobiology of Aging 33(9):2231.e1-2231.e6. 2012.

Park YN, Zhao X, Norton M, Taylor JP, Eisenberg E and Greene LE. Huntingtin fragments and SOD1 mutants form soluble oligomers in the cell. PloS One 7(6):e40329, 2012.

Smith RB, Taylor JP. Dissection and staining of active zones in the Drosophila neuromuscular junction. Journal of Visualized Experiments (50):e2676, 2011.

Lanson N, Maltare A, King H, Smith R, Kim JH, Taylor JP, Lloyd TE and Pandey UB. A Drosophila model of FUS-related neurodegeneration reveals genetic interaction between FUS and TDP-43.Human Molecular Genetics 20(13):2510-23, 2011.

Majounie E, Traynor BT, Chio A, Restagno G, Benatar M, Taylor JP, Singleton AB. Mutational analysis of the VCP gene in Parkinson’s disease. Neurobiology of Aging 33(1): 209 2011.

Mammen, AL, Mahoney JA, St. Germain A, Badders N, Taylor JP, Rosen A, and Spinette S. A Novel Conserved Isoform of the Ubiquitin Ligase UFD2a/UBE4B is Expressed Exclusively in Mature Striated Muscle Cells. PloS One 6(12):e28861, 2011.

Show More

Johnson JO, Mandrioli J, Benatar M, Abramzon Y, Van Deerlin VM, Trojanowski JQ, Gibbs JR, Brunetti M, Gronka S, Wuu J, Ding J, McCluskey L, Martinez-Lage M, Falcone D, Hernandezz DG, Arepelli S, Chong S, Schymick JC, Rothstein J, Landi F, Wang M, Calvo A, Mora G, Sabatelli M, Monsurro MR, Battaistini S, Salvi F, Spataro R, Sola P, Borghero G, ITALSGEN, Galassi G, Scholz SW, Taylor JP, Restagno G, Chio A, Traynor BJ. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68(5):857-864, 2010.

Todd PK, Oh SY, Krans A, Pandey U, DiProspero N, Min KT, Taylor JP, and Paulson HL. Histone deacetylases suppress CGG repeat-induced neurodegeneration via transcriptional silencing in models of fragile X tremor ataxia syndrome. PLoS Genetics 6(12):1240, 2010.

Nedelsky NB, Pennuto M, Smith RB, Palazzolo I, Nie Z, Moore J, Neale G and Taylor JP. Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy Neuron 67(6): 936-952, 2010.

Ritson GP, Custer SK, Freibaum BD, Guinto JB, Geffel D, Winton MJ, Neumann M, Trojanowski JQ, Lee VMY, Forman MS, Taylor JP. TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97. J Neurosci 30(22):7729-39, 2010.

Lee JY, Nagano Y, Taylor JP, Lim KL, Yao TP. Parkin controls mitophagy by promoting mitochondrial ubiquitination and aggresome-like mitochondrial aggregate formation. J Cell Biol189(4):671-9, 2010.

La Spada AR, Taylor JP. Repeat expansion disease: progress and puzzles in disease pathogenesis. Nature Reviews Genetics 11, 247-256, 2010.

Batlevi Y, Martin DN, Pandey UB, Simon CR, Powers CM, Taylor JP, Baehrecke EB. Dynein light chain 1 is required for autophagy, protein clearance and cell death in Drosophila. Proc Nat Acad Sci USA 107:742-747, 2010.

Freibaum BD, Chitta R, High AA, Taylor JP. Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery. J Proteome Res 9:1104-1120, 2010.

Lee JY, Kawaguchi Y, Koga H, Tang W, Wong E, Pandey UB, Gao YS, Lu J, Taylor JP, Cuervo AM, Yao TP. HDAC6 controls autophagosome-lysosome fusion in basal homeostatic autophagy critical for protein aggregate clearance and neurodegeneration. EMBO J 29(5):969-980, 2010.

Tresse E, Salomons FA, Yao, TP, Dantuma NP, Taylor JP. VCP is essential for maturation of ubiquitin-containing autophagosomes. Autophagy 6, 217-227, 2010.

McCray BA, Skordalakes E, Taylor JP. Disease mutations in Rab7 result in unregulated nucleotide exchange and inappropriate activation. Human Molecular Genetics 19(6):1033-1047, 2010.

Custer SK, Neumann M, Lu H, Wright AC, Taylor JP. Transgenic mice expressing mutant forms of VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone.Human Molecular Genetics 19(9):1741-55, 2010.

Palazzolo I, Natalia Nedelsky NB, Askew C, Harmison G, Kasantsev AG, Taylor JP, Fischbeck KH, Pennuto M. B2 attenuates polyglutamine androgen receptor toxicity in spinal and bulbar muscular atrophy. J Neurosci Res 88(10):2207-16, 2010.

Lloyd T, Taylor JP. Flightless flies: Drosophila models of neuromuscular disease. Annals of the New York Acad Sci 1184:1-20, 2010.

Palazzolo I, Stack C, Kong L, Musaro A, Adachi H, Katsuno M, Sobue G, Taylor JP, Sumner C, Fischbeck KH, Pennuto M. Overexpression of IGF-1 attenuates disease in a mouse model of spinal and bulbar muscular atrophy. Neuron Aug 13;63(3):316-28, 2009.

Mojsilovic-Petrovic J, Nedelsky N, Boccitto M, Mano I, Georgiades SN, Zhou W, Liu Y, Neve RL,Taylor JP, Driscoll M, Clardy J, Merry D, Kalb RG. FOXO3a is broadly neuroprotective in vitro and in vivo against insults implicated in motor neurons diseases. J Neurosci 29(25):8236-47, 2009.

Salajegheh M, Pinkus JL, Taylor JP, Amato AA, Nazareno R, Baloh RH, Greenberg SA. Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis. Muscle and Nerve ­40(1):19-31, 2009.

Salomons FA, Menendez-Benito V, Bottcher C, McCray BA, Taylor JP, Dantuma NP. Selective accumulation of aggregation-prone proteasome substrates in response to proteotoxic stress. Mol Cell Biol 29(7):1774-1785, 2009.

Young J, Garden G, Martinez R, Tanaka F, Sandoval C, Smith A, Sopher B, Lin A, Fischbeck KH,Taylor JP, La Spada AR. Polyglutamine-expanded androgen receptor truncation fragments activate a Bax-dependent apoptotic cascade mediated by DP5/Hrk. J Neurosci 29(7):1987-1997, 2009.

Taylor JPDiagnosis and treatment of cerebellar ataxia in adults. In: UpToDate, Basow, DS, UpToDate, Waltham, MA, 2009.

Nedelsky NB, Todd PK, Taylor JP. Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection. Biochim Biophys Acta 1782(12), 691-699, 2009.

Pandey UB, Nie ZP, Batlevi Y, McCray BA, Ritson GP, Schwartz SL, DiProspero N, Knight M, Schuldiner O, Padmanabhan R, Hild M, Berry D, Garza D, Hubbert CC, Yao TP, Baehrecke EH,Taylor JP. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the ubiquitin-proteasome system. Nature 447, 859-863, 2007.

Guinto, JB, Ritson GP, Taylor JP, Forman MS. Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy Acta Neuropath 114(1):55-61, 2007.

Neumann M, Mackenzie MD, Cairns NJ, Boyer PJ, Markesbery WR, Smith CD, Taylor JP, Kretzschmar HA, Kimonis VE, Forman MS. TDP-43 in ubiquitin pathology of frontotemporal dementia with VCP gene mutations. J Neuropathol Exp Neurol 66:152-7, 2007.

Piccioni F, Romano B, Fischbeck KH, Taylor JP. A screen for drugs that protect against the toxicity of polyglutamine-expanded androgen receptor. Hum Molec Genet 13(4):437-446, 2004.

Taylor JP, Taye AA, Campbell C, Kazemi-Esfarjani P, Fischbeck KH, Min KT.  Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein. Genes Dev 17:1463-1468, 2003.

Taylor JP, Tanaka F, Robitschek J, Markovic-Plese S, Taye AA, Sandoval CM, Fischbeck KH. Aggresomes protect cells by accelerating the degradation of polyglutamine-containing protein. Hum Molec Genet 12(7), 749-757, 2003.

La Spada AR, Taylor JP. Polyglutamines placed into context. Neuron 38:681-684, 2003.

Taylor JP, Hardy J, Fischbeck KH. Toxic proteins in neurodegenerative disease. Science 296(5575):1991-1995, 2002.

Last update: October 2014