Cell and Molecular Neuroscience

Tiago Outeiro

Tiago Fleming Outeiro

Principal Investigator
PhD (2004) at the Whitehead Institute for Biomedical Research, MIT, EUA
Post-doctoral research at Harvard Medical School and at FoldRx Pharmaceuticals, USA
Co-founder of BioEPI Clinical and Translational Research Center, Portugal

CV

Location:

CEDOC
Campus Sant'Ana
Pólo de Investigação, NMS, UNL
Rua Câmara Pestana, nº 6
1150-082 Lisboa, Portugal

Phone: (+351) 218 803 101
E-mail: tiago.outeiro(at)nms.unl.pt

Main Interests:

Logotipo_T F Outeiro LabOur research interests are focused on the understanding of the molecular mechanisms which lead to neurodegeneration in diseases such as Parkinson's, Huntington's, or Alzheimer's disease. These diseases are intimately associated with protein misfolding and aggregation in specific regions of the brain.

Because the molecular pathways involved in protein homeostasis are highly conserved, we employ a wide variety of model organisms, from the simple but powerful budding yeast to mammalian cell culture and mice, to study the origin of the problems.

Our ultimate goals are to develop novel therapeutic approaches for these and other related disorders. We are working closely together with clinicians in order to accelerate drug discovery efforts, translating basic research into clinical applications that will improve the lives of patients.

Projects

2016 - 2019 - Targeting the glycation defenses as a protective strategy for Parkinson’s disease, PTDC/NEU-OSD/5644/2014
(Hugo Vicente Miranda)

2014-2018 - COST Action BM1307 PROTEOSTASIS (http://cost-proteostasis.eu/).
(Sandra Tenreiro: Management Committee Substitute)

2012-2015 - The role and regulation of alpha-synuclein phosphorylation in both pathological and physiological conditions. PTDC/BIA-BCM/117975/2010.
(Sandra Tenreiro)

2013/2014 - Alpha-synuclein as blood biomarker for Parkinson's Disease. Fundação para a Ciência e Tecnologia, EXPL/NEU-OSD/0606/2012
(Hugo Vicente Miranda)

2012-2013 - The role of phosphorylation pathways in the oligomerization and toxicity of mutant huntingtin. Seed Funds, European Huntington's Disease Network (EHDN).
(Federico Herrera/Tiago F. Outeiro)

2009-2011 - Doença de Parkinson de Progressão Lenta e Rápida: Determinantes Moleculares e Biomarcadores. Fundação para a Ciência e a Tecnologia, (PIC/IC/82760/2007).
(Tiago F. Outeiro)

2009-2011 - Axa Research Fund: Doctoral sponsorship agreement. AXA.
(Tiago F. Outeiro)

2009-2011 - EMBO Installation Grant. European Molecular Biology Organization.
(Tiago F. Outeiro)

2008-2009 - Molecular characterization of the Portuguese population affected by neurodegeneratives disorders. Alto Comissariado para a Saúde.
(Tiago F. Outeiro)

2007-2009 - SirT2 as a Drug Target in Parkinson's Disease. Michael J. Fox Foundation.
(Tiago F. Outeiro)

2007-2009 - Unraveling the genetic basis for alpha-synuclein oligomerization in living cells using bimolecular fluorescence complementation. Michael J. Fox Foundation.
(Tiago F. Outeiro)

2007-2009 - Deciphering the Molecular Role of DJ-1 in Parkinson's disease, Fundação Calouste Gulbenkian. Fundação Calouste Gulbenkian.
(Tiago F. Outeiro)

2007-2011 - NEUROFOLD, Uncovering the Molecular Basis of Neurodegenerative Disorders. Marie Curie Program, European Commission. FP7-Comissão Europeia.
(Tiago F. Outeiro)

2007-2009 - The molecular effects of the novel ACE mutation Q1069R. American Portuguese Biomedical Research Fund.
(Tiago F. Outeiro)

Publications
  • Menezes R, Tenreiro S, Macedo D, Santos CN, Outeiro TF, (2015) From the baker to the bedside: yeast models of Parkinson’s disease, Microbial Cell, 2: 262 – 279.
  • Mbefo M, Fares MB, Paleologou K, Oueslati A, Yin G, Tenreiro S, Pinto M, Outeiro T, Zweckstetter M, Masliah E, Lashuel HA. (2015) The Parkinson's Disease Mutant E46K Enhances Alpha-Synuclein Phosphorylation in Mammalian Cell-Lines, in Yeast and In Vivo. J Biol Chem. 2015 Feb 5. pii: jbc.M114.610774.
  • Macedo D, Tavares L, McDougall GJ, Vicente Miranda H, Stewart D, Ferreira RB, Tenreiro S, Outeiro TF, Santos CN. (2015) (Poly)phenols protect from α-synuclein toxicity by reducing oxidative stress and promoting autophagy. Hum Mol Genet. 2015 Mar 15;24(6):1717-32. doi: 10.1093/hmg/ddu585. Epub 2014 Nov 28.
  • Tenreiro S, Reimão-Pinto MM, Antas P, Rino J, Wawrzycka D, Macedo D, Rosado-Ramos R, Amen T, Waiss M, Magalhães F, Gomes A, Santos CN, Kaganovich D, Outeiro TF. (2015) Phosphorylation modulates clearance of alpha-synuclein inclusions in a yeast model of Parkinson's disease. PLoS Genet. 2014 May 8;10(5):e1004302. doi: 10.1371/journal.pgen.1004302. eCollection 2014 May.
  • Fernandes JT, Tenreiro S, Gameiro A, Chu V, Outeiro TF, Conde JP. (2014) Modulation of alpha-synuclein toxicity in yeast using a novel microfluidic-based gradient generator. Lab Chip. 2014 Oct 21;14(20):3949-57. doi: 10.1039/c4lc00756e.
  • Zondler L, Miller-Fleming L, Repici M, Gonçalves S, Tenreiro S, Rosado-Ramos R, Betzer C, Straatman KR, Jensen PH, Giorgini F, Outeiro TF. (2014) DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease. Cell Death Dis. 2014 Jul 24;5:e1350. doi: 10.1038/cddis.2014.307.
  • Tenreiro S, Eckermann K, Outeiro TF. (2014) Protein phosphorylation in neurodegeneration: friend or foe? Front Mol Neurosci. 2014 May 13;7:42. doi: 10.3389/fnmol.2014.00042. eCollection 2014. Review.
  • Miller-Fleming L , Antas P, Pais TF, Smalley JL, Giorgini F, and Outeiro TF (2014) Yeast DJ-1 superfamily members are required for diauxic-shift reprogramming and cell survival in stationary phase. PNAS. April 2, 2014.
  • Basso E, Antas P, Marijanovic Z, Gonçalves S, Tenreiro S, Outeiro TF, (2013) PLK2 modulates α-synuclein aggregation in yeast and mammalian cells. Mol Neurobiol. December 2013 48(3), 854-62.
  • Tenreiro S, Munder MC, Alberti S, Outeiro TF. (2013). Harnessing the power of yeast to unravel the molecular basis of neurodegeneration. J Neurochem November 2013 127, 438-52.
  • Sajjad MU, Green EW, Hands S, Miller-Fleming L, Herrera F, Kyriacou CP, Faull R, Morton AJ, Jones L, Outeiro TF, Giorgini F, Wyttenbach A. (2013). DJ-1 modulates aggregation and pathogenesis in models of Huntington’s disease. Hum. Mol. Gen. September 26.Feb 1;23(3):755-66.
  • Vicente Miranda H, Xiang W, de Oliveira RM, Simões T, Pimentel J, Klucken J, Penque D, Outeiro TF, (2013) Heat-mediated enrichment of α-synuclein from cells and tissue for assessing post-translational modifications, J Neurochemistry. September 2013. 126(5), 673-84.
  • Pais TF, Szegõ EM, Marques O, Miller-Fleming L, Antas P, Guerreiro P, de Oliveira RM, Kasapoglu B and Outeiro TF*. (2013). The NAD-dependent deacetylase sirtuin 2 is a suppressor of microglial activation and brain inflammation. The EMBO journal. September 2013. 32(19), 2603-16.
  • Goncalves S and Outeiro TF (2013) Assessing the subcellular dynamics of alpha-synuclein using photoactivation microscopy. Mol Neurobiol . June 2013. 47(3), 1081-92.
  • Martín V, Sanchez-Sanchez AM, Herrera F, Gomez-Manzano C, Fueyo J, Alvarez-Vega MA, Antolín I, Rodriguez C (2013). Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells. Br J Cancer. May 28 2013.108(10), 2005-12.
  • Amaral M, Levy C, Heyes DJ, Lafite P, Outeiro TF, Giorgini F, Leys D, Scrutton NS (2013) Structural basis of kynurenine 3-monooxygenase inhibition. Nature. April 2013. 496(7445), 382-5.
  • Guerreiro P, Huang Y, Gysbers A, Cheng D, Gai WP, Outeiro TF, Halliday GM (2013) LRRK2 interactions with α-synuclein in Parkinson's disease brains and in cell models. Journal of Molecular Medicine. April 2013. 91(4), 513-22.
  • Lopes da Fonseca T, Correia A, Hasselaar W, van der Linde HC, Willemsen R, Outeiro TF (2013) The zebrafish homologue of Parkinson's disease ATP13A2 is essential for embryonic survival. Brain Res Bull. January 2013; 90, 118-26.
  • Rosa P, Tenreiro S, Chu V, Outeiro TF, Conde JP. (2012) High-throughput study of alpha-synuclein expression in yeast using microfluidics for control of local cellular microenvironment. Biomicrofluidics. 2012 Mar;6(1): 14109-141099.
  • de Oliveira RM, Sarkander J, Kazantsev AG, Outeiro TF. (2012) SIRT2 as a Therapeutic Target for Age-Related Disorders. Front Pharmacol. 2012;3:82. Epub 2012 May 3.
  • Herrera F, Gonçalves S, Outeiro TF. (2012) Imaging protein oligomerization in neurodegeneration using bimolecular fluorescence complementation. Methods Enzymol. 2012;506:157-74.
  • Herrera F, Outeiro TF. (2012) α-Synuclein modifies huntingtin aggregation in living cells. FEBS Lett. 2012 Jan 2;586(1):7-12. Epub 2011 Nov 24.
  • Ribeiro Morais G*, Vicente Miranda H*, Santos IC, Santos I, Outeiro TF, Paulo A. (2011) Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes. Bioorg Med Chem. 2011 Dec 15;19(24):7698-710. Epub 2011 Oct 18.
    *equal contribution
  • Näsström T, Gonçalves S, Sahlin C, Nordström E, Screpanti Sundquist V, Lannfelt L, Bergström J, Outeiro TF, Ingelsson M. (2011) Antibodies against alpha-synuclein reduce oligomerization in living cells. PLoS One. 2011;6(10):e27230. Epub 2011 Oct 31.
  • Badiola N, de Oliveira RM, Herrera F, Guardia-Laguarta C, Gonçalves SA, Pera M, Suárez-Calvet M, Clarimon J, Outeiro TF, Lleó A. (2011) Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. PLoS One. 2011;6(10):e26609.
  • Martins M, Rosa A, Guedes LC, Fonseca BV, Gotovac K, Violante S, Mestre T, Coelho M, Rosa MM, Martin ER, Vance JM, Outeiro TF, Wang L, Borovecki F, Ferreira JJ, Oliveira SA. (2011) Convergence of miRNA expression profiling, α-synuclein interacton and GWAS in Parkinson's disease. PLoS One. 2011;6(10):e25443. Epub 2011 Oct 7.
  • Outeiro TF. (2011) Amyloidogenesis: FlAsH illuminates Aβ aggregation. Nat Chem Biol. 2011 Aug 17;7(9):581-2. doi: 10.1038/nchembio.636.
  • Marques S, Batalha VL, Lopes LV, Outeiro TF. (2011) Modulating Alzheimer's disease through caffeine: a putative link to epigenetics. J Alzheimers Dis. 2011;24 Suppl 2:161-71. Review.
  • Jorge CD, Ventura R, Maycock C, Outeiro TF, Santos H, Costa J. (2011) Assessment of the efficacy of solutes from extremophiles on protein aggregation in cell models of Huntington's and Parkinson's diseases. Neurochem Res. 2011 Jun;36(6):1005-11.
  • Herrera F, Tenreiro S, Miller-Fleming L, Outeiro TF. (2011) Visualization of cell-to-cell transmission of mutant huntingtin oligomers. PLoS Curr. 2011 Feb 11;3:RRN1210.
  • Hansen C, Angot E, Bergström AL, Steiner JA, Pieri L, Paul G, Outeiro TF, Melki R, Kallunki P, Fog K, Li JY, Brundin P. (2011) α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest. 2011 Feb;121(2):715-25. doi: 10.1172/JCI43366. Epub 2011 Jan 18.
  • Büttner S, Delay C, Franssens V, Bammens T, Ruli D, Zaunschirm S, de Oliveira RM, Outeiro TF, Madeo F, Buée L, Galas MC, Winderickx J. (2010) Synphilin-1 Enhances α-Synuclein Aggregation in Yeast and Contributes to Cellular Stress and Cell Death in a Sir2-Dependent Manner. PLoS One. 2010 Oct 27;5(10):e13700.
  • Tauber E, Miller-Fleming L, Mason RP, Kwan W, Clapp J, Butler NJ, Outeiro TF, Muchowski PJ, Giorgini F. (2010) Functional gene expression profiling in yeast implicates translational dysfunction in mutant huntingtin toxicity. J Biol Chem. 2010 Nov 2.
  • de Oliveira RM, Pais TF, Outeiro TF. (2010) Sirtuins: common targets in aging and in neurodegeneration. Curr Drug Targets. 2010 Oct;11(10):1270-80.
  • Tenreiro S, Outeiro TF. (2010) Simple is good: yeast models of neurodegeneration. FEMS Yeast Res. 2010 Dec;10(8):970-9.
  • Gonçalves SA, Matos JE, Outeiro TF. (2010) Zooming into protein oligomerization in neurodegeneration using BiFC. Trends Biochem Sci. 2010 Nov;35(11):643-51.
  • Vicente Miranda H, Outeiro TF. (2010) The sour side of neurodegenerative disorders: the effects of protein glycation. J Pathol. 2010 May;221(1):13-25.
  • Outeiro TF, Putcha P, Tetzlaff JE, Spoelgen R, Koker M, Carvalho F, Hyman BT, McLean PJ. (2008) Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS One. 2008 Apr 2;3(4):e1867. Erratum in: PLoS One. 2008;3(5).
  • Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, Young AB, Abagyan R, Feany MB, Hyman BT, Kazantsev AG. (2007) Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science. 2007 Jul 27;317(5837):516-9. Epub 2007 Jun 21.
  • Outeiro TF, Lindquist S. (2003) Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science. 2003 Dec 5;302(5651):1772-5.
  • Willingham S, Outeiro TF, DeVit MJ, Lindquist SL, Muchowski PJ. (2003) Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein. Science. 2003 Dec 5;302(5651):1769-72.

Collaborations

International
- Flaviano Giorgini (University of Leicester, UK)
- Aleksey Kazantsev (Massachusetts General Hospital, Harvard Medical School, USA)
- Fran Borovecki (University of Zagreb, Croatia)
- Jia-Yi Li (Lund University, Sweden)
- Hilal Lashuel, EPFL (Switzerland)
- Poul Henning Jensen (University of Arhus, Denmark)
- Donata Wawrzycka (University of Wroclaw, Wroclaw, Poland)

National
- Rune Matthiesen (INSA, Lisboa, PT)
- João Pedro Conde (INESC Microsistemas e Nanotecnologias /IST, Lisbon, PT)
- Cláudia N. Santos (ITQB/IBET, Oeiras, PT)
- Matthias Futschik (Universidade do Algarve, Faro, PT)
- Alexandre Quintas (Instituto Superior de Ciências da Saúde Egas Moniz, Caparica, PT)
- Joaquim Ferreira (IMM/Hospital de Santa Maria, Lisboa, PT)
- António Paulo (IST, Lisboa, PT)
- Luísa V. Lopes (IMM, Lisboa, PT)
- Maria José Diogenes (IMM, Lisboa, PT)

Team photos