Vanessa Morais Lab

Biologia Mitocondrial e Neurodegeneração

A mitocôndria é um organelo que funciona como central energética da célula, tendo um papel crítico na regulação da maioria dos processos celulares. Os neurónios têm elevadas exigências energéticas, logo a função da mitocôndria nestas células é vital para o correcto estabelecimento de circuitos neuronais e para o bom funcionamento do cerébro.

Esta linha de investigação visiona identificar quais os mecanismos moleculares existentes nas mitocôndrias sinápticas que são responsáveis pela manutenção e funcionamento característico da sinapse. A compreensão desses novos mecanismos moleculares vai auxiliar a correlação da disfunção mitocondrial com a degeneração do neurónio. Em última análise, vão identificar-se os mecanismos moleculares que causam doenças neurodegenerativas, abrindo assim caminhos para novas abordagens terapêuticas.

Equipa de Investigação

Áreas de Investigação

• Regulation of Mitochondria Quality Control Pathways in Neurons
• Mechanisms of Regulation of Synaptic Mitochondria
• Mitochondria Dysfunction in Neurodegenerative Disorders

Projetos de Investigação em Curso

2018/2021 Mecanismos moleculares que mantêm a Homeostase Mitocondrial no Cérebro. Coordenação: Vanessa Morais. Agência Financiadoray: Fundação para a Ciência e a Tecnologia.

2016/2021 SynapticMitochondria: Quality Control and Maintenance of Synaptic Mitochondria - European Research Council ERC-Starting Grant. Coordenação: Vanessa Morais. Agência Financiadora: Comissão Europeia.

Prémios

2015-2020 Investigator FCT Award

March 2015  ADPD Junior Faculty Award. Awarded bi-annually to selected promising scientists.

2008-2010 Postdoctoral Research fellowship (BPD) FCT, Portugal.

2006 EMBO Short Term fellowship

2006-2008  Marie-Curie foundation Postdoctoral fellowship.

2001-2006 PhD fellowship (BD) from FCT, Portugal.

Publicações Selecionadas

Publications arising from Post Doctoral work:

O'Flanagan, C.H., Morais, V.A., O'Neill, C. (2016) PINK1, cancer and neurodegeneration. Oncoscience. 3(1):1-2.

Aerts, L., Craessaerts, K., De Strooper, B., Morais, V.A. (2016) In Vitro Comparison of the Activity Requirements and Substrate Specificity of Human and Triboleum castaneum PINK1 Orthologues. PLoS One. 11(1):e0146083.

Aerts, L., Craessaerts, K., De Strooper, B.*, Morais, V.A.* (2015). PINK1 Kinase Catalytic Activity Is Regulated by Phosphorylation on Serines 228 and 402. J Biol Chem. 290: 2798-811. Citation: 10 *shared corresponding authors

Aerts, L., De Strooper, B., Morais, V.A.* (2015). PINK1 activation-turning on a promiscuous kinase. Biochem Soc Trans. 43(2):280-6. Citation: 4

O’ Flanagan, C., Morais, V.A., Wurst, W., De Strooper, B., O’ Neill, C. (2014). The Parkinson’s gene PINK1 regulates cell cycle progression and promotes cancer-associated phenotypes, Oncogene, 00:00. Citation: 10

Morais, V.A.*, Haddad, D., Craessaerts, K., De Bock, P., Swerts, J., Vilain, S., Aerts, L., Overbergh, L., Grünewald, A., Seibler, P., Klein, C., Gevaert, K., Verstreken, P., De Strooper, B.* (2014). PINK1 Loss of Function Mutations Affect Mitochondrial Complex I Activity via NdufA10 Ubiquinone Uncoupling, Science, 344 (6180), 203-207. Citation: 66 *shared corresponding authors

Vos, M., Lovisa, B., Geens, A., Morais, V.A., Wagnières, G., van den Bergh, H., Ginggen, A., De Strooper, B., Tardy, Y., Verstreken, P. (2013). Near-Infrared 808 nm Light Boosts Complex IV-Dependent Respiration and Rescues a Parkinson-Related pink1 Model, PLoS One, 8 (11), e78562. Citation: 10

Haddad, D., Vilain, S., Vos, M., Esposito, G., Matta, S., Kalscheuer, V., Craessaerts, K., Leyssen, M., Nascimento, R., Vianna-Morgante, A., De Strooper, B., Van Esch, H., Morais, V.A.*, Verstreken, P.* (2013). Mutations in the Intellectual Disability Gene Ube2a Cause Neuronal Dysfunction and Impair Parkin-Dependent Mitophagy, Molecular Cell, 50 (6), 831-43. Citation: 32 *shared corresponding authors

Mandemakers, W., Abuhatzira, L., Xu, H., Caromile, L., Hébert, S., Snellinx, A., Morais, V.A., Matta, S., Cai, T., Notkins, A., De Strooper, B. (2013). Co-regulation of intragenic microRNA miR-153 and its host gene Ia-2 β: identification of miR-153 target genes with functions related to IA-2β in pancreas and brain, Diabetologia, 56 (7), 1547-56. Citation: 14

Vos, M., Esposito, G., Edirisinghe, J., Vilain, S., Haddad, D., Slabbaert, J., Van Meensel, S., Schaap, O., De Strooper, B., Meganathan, R., Morais, V.A., Verstreken, P. (2012). Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency, Science, 336 (6086), 1306-10. Citation: 129

Vilain, S., Esposito, G., Haddad, D., Schaap, O., Dobreva, M., Vos, M., Van Meensel, S., Morais, V.A., De Strooper, B., Verstreken, P. (2012). The yeast complex I equivalent NADH dehydrogenase rescues pink1 mutants, PLoS Genetics, 8 (1), e1002456. Citation: 52

Matta, S., Van Kolen, K., da Cunha, R., van den Bogaart, G., Mandemakers, W., Miskiewicz, K., De Bock, P., Morais, V.A., Vilain, S., Haddad, D., Delbroek, L., Swerts, J., Chávez-Gutiérrez, L., Esposito, G., Daneels, G., Karran, E., Holt, M., Gevaert, K., Moechars, D., De Strooper, B., Verstreken, P. (2012). LRRK2 Controls an EndoA Phosphorylation Cycle in Synaptic Endocytosis, Neuron, 75 (6), 1008-1021. Citation: 121

Morais, V.A., De Strooper, B. (2010). Mitochondria Dysfunction and Neurodegenerative Disorders: Cause or Consequence, Journal of Alzheimer's Disease, 20 Suppl 2, S255-63. Citation: 74

Morais, V.A., Verstreken, P., Roethig, A., Smet, J., Snellinx, A., Vanbrabant, M., Haddad, D., Frezza, C., Mandemakers, W., Vogt-Weisenhorn, D., Van Coster, R., Wurst, W., Scorrano, L., De Strooper, B. (2009). Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function, EMBO Molecular Medicine, 1 (2), 99-111. Citation: 187

Mandemakers, W., Morais, V.A., De Strooper, B. (2007). A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases, Journal of Cell Science, 120, 1707-1716. Citation: 145

Publications arising from PhD work:

Escrevente, C., Morais, V.A., Keller, S., Soares, C., Altevogt, P., Costa, J. (2008). Functional role of N-glycosylation from ADAM10 in processing, localization and activity of the enzyme, Biochimica et Biophysica Acta. General Subjects, 1780 (6), 905-913. Citation: 48

Morais, V.A., Leight, S., Pijak, D., Lee, V., Costa, J. (2008). Cellular localization of Nicastrin affects amyloid beta species production, FEBS Letters, 582 (3), 427-433. Citation: 8

Gouveia, R., Morais, V.A., Peixoto, C., Sousa, M., Regalla, M., Alves, P., Costa, J. (2007). Production and purification of functional truncated soluble forms of human recombinant L1 cell adhesion glycoprotein from Spodoptera frugiperda Sf9 cells, Protein Expression and Purification, 52 (1), 182-193. Citation: 18

Morais, V.A., Brito, C., Pijak, D., Crystal, A., Fortna, R., Li, T., Wong, P., Doms, R., Costa, J. (2006). N-glycosylation of human nicastrin is required for interaction with the lectins from the secretory pathway calnexin and ERGIC-53, Biochimica et Biophysica Acta. Molecular Basis of Disease, 1762 (9), 802-810. Citation: 26

Marcos, N., Pinho, S., Grandela, C., Cruz, A., Samyn-Petit, B., Harduin-Lepers, A., Almeida, R., Silva, F., Morais, V.A., Costa, J., Kihlberg, J., Clausen, H., Reis, C. (2004). Role of the human ST6GalNAc-I and ST6GalNAc-II in the synthesis of the cancer-associated sialyl-Tn antigen, Cancer Research, 64 (19), 7050-7057. Citation: 114

Crystal, A., Morais, V.A., Fortna, R., Carlin, D., Pierson, T., Wilson, C., Lee, V., Doms, R. (2004). Presenilin modulates Pen-2 levels posttranslationally by protecting it from proteasomal degradation, Biochemistry, 43 (12), 3555-3563. Citation: 45

Fortna, R., Crystal, A., Morais, V.A., Pijak, D., Lee, V., Doms, R. (2004). Membrane topology and nicastrin-enhanced endoproteolysis of APH-1, a component of the gamma-secretase complex, Journal of Biological Chemistry, 279 (5), 3685-3693. Citation: 78

Palma, A., Morais, V.A., Coelho, A., Costa, J. (2004). Effect of the manganese ion on human alpha 3/4 fucosyltransferase III activity, Biometals, 17 (1), 35-43. Citation: 14

Morais, V.A., Crystal, A., Pijak, D., Carlin, D., Costa, J., Lee, V., Doms, R. (2003). The transmembrane domain region of nicastrin mediates direct interactions with APH-1 and the gamma-secretase complex, Journal of Biological Chemistry, 278 (44), 43284-43291. Citation: 85

Morais, V.A., Costa, J. (2003). Stable expression of recombinant human alpha 3/4 fucosyltransferase III in Spodoptera frugiperda Sf9 cells, Journal of Biotechnology, 106 (1), 69-75. Citation: 20

Morais, V.A., Costa, M., Costa, J. (2003). N-glycosylation of recombinant human fucosyltransferase III is required for its in vivo folding in mammalian and insect cells, Biochimica et Biophysica Acta. General Subjects, 1619 (2), 133-138. Citation: 26

Crystal, A., Morais, V.A., Pierson, T., Pijak, D., Carlin, D., Lee, V., Doms, R. (2003). Membrane topology of gamma-secretase component PEN-2, Journal of Biological Chemistry, 278 (22), 20117-20123. Citation: 104

Morais, V.A., Serpa, J., Palma, A., Costa, T., Maranga, L., Costa, J. (2001). Expression and characterization of recombinant human alpha-3/4-fucosyltransferase III from Spodoptera frugiperda (Sf9) and Trichoplusia ni (Tn) cells using the baculovirus expression system, Biochemical Journal, 353, 719-725. Citation: 35

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