Name: Patrícia Maciel

Office: G2.23

School Phone: +351 253 604 824

Email: pmaciel@med.uminho.pt

Keywords: Neurogenetics ▪ Neurodegeneration ▪ Neurodevelopment ▪ Polyglutamine diseases ▪ Ataxia ▪ Intellectual disability ▪ Autism ▪ Epilepsy ▪ Chromatin Remodelling ▪ Ubiquitin Proteasome System ▪ Proteostasis ▪ Aging ▪

About

1. Lopes F*, Barbosa M*, Ameur A, Temudo T, Sá J, Dias AI, Oliveira G, Cabral P, Eulália Calado E, Soares G, Fineza-Cruz I, Vieira JP, Oliveira R, Esteves S, Jonasson I, Pinto D, Gyllensten U, MACIEL P. “Identification of novel genetic causes of Rett syndrome-like phenotypes”. Journal of Medical Genetics, 53(3):190-9, 2016. (Cover and Featured Article of the month)

2. Teixeira-Castro A*, Jalles A*, Esteves S*, Kang S, Silva Santos L, Silva-Fernandes A, Neto MF, Brielmann RM, Bessa C, Duarte-Silva S, Miranda A, Oliveira S, Neves-Carvalho A, Bessa J, Summavielle T, Silverman RB, Oliveira P, Morimoto RI, MACIEL P. “Serotonergic signaling suppresses ataxin-3 aggregation and neurotoxicity in animal models of Machado-Joseph disease”. Brain, 138(Pt 11):3221-37, 2015.

3. Neves-Carvalho A, Logarinho E, Freitas A, Duarte-Silva S, Costa MC, Silva-Fernandes A, MartinsM, Cravino Serra S, Lopes A, Paulson HL, Heutink P, Relvas JB, MACIEL P.“Dominant negative effect ofpolyglutamine expansion perturbs normal function of ataxin-3 in neuronalcells”. Human Molecular Genetics, 24(1):100-17, 2015.

4.  Silva-Fernandes A*, Duarte-Silva S*, Neves-Carvalho A, Amorim M, Soares-Cunha C, Oliveira P,Thirstrup K, Teixeira-Castro A, MACIEL P. “Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado-Joseph disease”. Neurotherapeutics, 11(2):433-449, 2014.

5.   Teixeira-Castro A, Ailion M, Jalles A, Brignull HR, Vilaça JL, Dias N, Rodrigues P, Oliveira JF, Neves-Carvalho A, Morimoto RI, MACIEL P. “Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF1 pathways”. Human Molecular Genetics, 20(15):2996-3009, 2011.

6.   Rodrigues AJ, Neves-Carvalho A, Teixeira-Castro A, Rokka A, Logarinho E, MACIEL P. “Absence of ataxin-3 leads to enhanced stress response in C. elegans”. PLoS One, 19;6(4):e18512, 2011.

7.    Santos M, Summavielle T, Teixeira-Castro A, Silva-Fernandes A, Duarte-Silva S, Marques F, Martins L, Dierssen M, Oliveira P, Sousa N and MACIEL P. “Monoamine deficits in the brain of Mecp2-null mice suggest the involvement of the cerebral cortex in early stages of Rett syndrome”. Neuroscience, 170(2):453-67, 2010.

8.    Silva-Fernandes A*, Costa MC*, Silva S*,Oliveira P, Botelho C,  Martins L, Mariz JA, Ferreira T, Pinto-Ribeiro F, Correia-Neves M, Costa C and MACIEL P. “Genetic instability, motor phenotype and neuropathology in a transgenic mouse model of Machado-Joseph disease in the absence of intranuclear inclusions and ataxin-3 cleavage products”. Neurobiology of Disease, 40(1):163-176, 2010.

9.   Ferro A, Teixeira-Castro A,Almeida C, Tomé RL, Cortes L, Rodrigues AJ, Logarinho E, Sequeiros J, Carvalho AL, Macedo-Ribeiro S and MACIEL P. “NEDD8: a new ataxin-3 interactor” . BiochimicaBiophysica Acta – Molecular Cell Research, 1773(11):1619-27, 2007.

10.   Rodrigues A-J, Coppola G, Santos C, Costa MC, Sequeiros J, Ailion M, Geschwind D, MACIEL P. “Functional genomics and biochemical characterization of the C. elegans orthologue of the Machado-Joseph disease protein ataxin-3”.  FASEB Journal, 21(4):1126-36,2007.

11.   Temudo T, Oliveira P, Santos MJ, Dias K,Vieira JP, Moreira A, Calado E, Carrilho I, Oliveira G, Levy A ,Barbot C,  , Fonseca MJ, Cabral A, DiasA, Lobo Antunes N, Cabral P, Monteiro JP, Borges L, Gomes R, BarbosaC, Santos M, Mira G, Andrada G, Freitas P, Eusébio F, Figueiroa S, Chorão R,Sequeiros J, MACIEL P. “Stereotypies in Rett Syndrome:analysis of 83 Portuguese patients with and without MECP2 mutations” . Neurology,68(15):1183-7, 2007.

12.  Santos M, Silva-Fernandes A, OliveiraP, Sousa N and MACIEL P. “Evidence for abnormal early development in a mouse model of Rett syndrome” . Genes, Brain & Behavior, 6(3):277-286, 2007.

Ataxin-3 and ubiquitin signalling in the nervous system (Leader) 

Clinical and Genetic studies of human neurodevelopmental disorders (Leader) 

Pathogenesis and Therapeutics of Machado-Joseph disease (Leader) 

Chatterjee A, Saha S, Silva-Fernandes A, Mandal SM, Neves-Carvalho A, Liu Y, Pandita RK, Chakraborty A, Hegde ML, Hegde PM, Boldogh I, Ashizawa T, Koeppen AH, Pandita TK, Maciel P, Sarkar P, Hazra TK. The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia Type 3 pathogenesis. PLoS Genetics, 29;11(1):e1004749 (2015).

Gao R, Liu Y, Silva-Fernandes A, Paulucci-Holthauzen A, Chatterjee A, Zhang H, Mattsura T, Fang X, Choudhary S, Ashizawa T, Koeppen A, Maciel P, Hazra TK, Sarkar PS. Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3. PLoS Genetics, 11(1):e1004834 (2015).

Teixeira-Castro A, Ailion M, Jalles A, Brignull HR, Vilaça JL, Dias N, Rodrigues P, Oliveira JF, Neves-Carvalho A, Morimoto RI, Maciel P. Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways. Hum Mol Genet. 2011 Aug 1;20(15):2996-3009. doi: 10.1093/hmg/ddr203. Epub 2011 May 5.

Baptista MS, Duarte CB, Maciel P. Role of the ubiquitin-proteasome system in nervous system function and disease: using C. elegans as a dissecting tool. Cell Mol Life Sci. 2012 Aug;69(16):2691-715. doi: 10.1007/s00018-012-0946-0. Epub 2012 Mar 3.

Torres F, Barbosa M, Maciel P. Recurrent copy number variations as risk factors for neurodevelopmental disorders: critical overview and analysis of clinical implications. J Med Gen, 53(2):73-90 (2016).