Collaborations

Artur Paiva
Coimbra University Hospital Center (CHUC), Coimbra, Portugal

Bruno Manadas
Center for Neuroscience and Cell Biology, UC Biotech, Cantanhede, Portugal

Carlos B. Duarte
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

Cláudia Lobato da Silva
Instituto Superior Técnico (IST), Lisbon, Portugal

Gonçalo Castelo-Branco
Karolinska Institute, Sweden

João B. Relvas
I3S/IBMC, University of Porto, Porto, Portugal

Joaquim M. Sampaio Cabral
Instituto Superior Técnico (IST), Lisbon, Portugal

José Lopes da Silva
QOPNA, Chemistry Department, University of Aveiro, Aveiro, Portugal

José Pereira da Silva
Coimbra University Hospital Center (CHUC), Coimbra, Portugal

Lino Ferreira
Center for Neuroscience and Cell Biology, UC Biotech, Cantanhede, Portugal

Livia Sousa
Coimbra University Hospital Center (CHUC), Coimbra, Portugal

Ricardo Neves
Center for Neuroscience and Cell Biology, UC Biotech, Cantanhede, Portugal

Our research interests are in the field of mechanotransduction, namely mechanobiology of the cell & mechanosignaling. Specifically, we are currently focused on studying the implications & molecular mechanisms underlying the mechanical modulation of (i) oligodendrocytes and (ii) mesenchymal stem/stromal cells (MSCs).
We develop and produce cell culture platforms with defined biochemical and mechanical features as a model of the extracellular matrix (ECM). Our approach allows us to independently set the extracellular matrix protein composition and the stiffness of the substrates in order to (re)create specific cellular environments. Hence, it is possible to define conditions mimicking physiological and pathological aspects of the ECM.
Despite our primary focus on oligodendrocytes and MSCs, these in vitro platforms can be used for a wide array of cells, conditions and applications, which we are exploring in collaboration with others.

Mechanobiology of oligodendrocytes
Oligodendrocytes (OLs) are specialized myelin-producing neural cells whose processes wrap around axons in the central nervous system (CNS). Myelin wrapping provides trophic support and insulation of axons, supporting structural and functional integrity of the neuronal networks present in the CNS, allowing for efficient saltatory conduction of action potentials (Lourenço and Grãos, Frontiers in Cellular Neuroscience, 2016).
We have shown that OLs are highly mechanosensitive and that the combination of mechanical and biochemical features of synthetic cell culture substrates (mimicking the extracellular matrix) profoundly influence the maintenance of oligodendrocyte progenitors cells and their differentiation into mature OLs (Lourenço et al., Scientific Reports 2016). We are currently elucidating the molecular mechanisms governing this regulation and exploring the potential of this system to contribute to understanding specific aspects of the biology & disease of the CNS (in particular those involving oligodendrocytes) as well as screening for therapeutic agents.

Mechanomodulation of MSCs
Mesenchymal stem/stromal cells (MSCs) are adult progenitor cells with extensive self-renewal capacity and differentiation potential into osteoblasts, chondrocytes and adipocytes, among other cell lineages, although to a lesser extent (Leite et al., Plos One 2014). MSCs hold a great potential in terms of clinical applications in several fields of cell-based therapies. Besides their direct regenerative potential, MSCs also provide important trophic and immunomodulatory factors that can contribute to tissue regeneration and suppression of inflammation & autoimmunity, constituting one of the applications being thoroughly explored at the moment.
We are currently tackling 4 aspects involving the mechanomodulation of MSCs: (i) Implications of mechanomodulation of MSCs during reprogramming, (ii) Elucidation of molecular mechanisms underlying the response of MSCs to mechanical cues, (iii) Influence of mechanical cues in the MSC proteome and its exploitation for future clinical applications and (iv) Effect of mechanical cues on the differentiation capacity of MSCs towards clinically-relevant lineages.
 

2019 - Sandra Isabel Anjo, Isaura Simões, Pedro Castanheira, Mário Grãos, BrunoManadas, ‘Use of recombinant proteins as a simple and robust normalization method for untargeted proteomics screening: exhaustive performance assessment’, Talanta, V. 205, 1 December 2019, 120163; doi: 10.1016/j.talanta.2019.120163

2019 - Heloísa Gerardo, Ana Lima, João Carvalho, João R. D. Ramos, Sofia Couceiro, Rui D. M. Travasso, Ricardo Pires das Neves & Mário Grãos, ‘Soft culture substrates favor stem-like cellular phenotype and facilitate reprogramming of human mesenchymal stem/stromal cells (hMSCs) through mechanotransductio’, Scientific Reports, 9, 9086; doi: 10.1038/s41598-019-45352-3

2019 - Sandra I. Anjo, Matilde N. Melo, Liliana R. Loureiro, Lúcia Sabala, Pedro Castanheira, Mário Grãos, Bruno Manadas, ‘oxSWATH: an integrative method for a comprehensive redox-centered analysis combined with a generic differential proteomics screening’, Redox Biology; DOI: 10.1016/j.redox.2019.101130

2017 - Gomes J.R., Lobo A., Duarte C.B., Grãos M. (2017) BDNF-Induced Intracellular Signaling. In: Neuromethods. Humana Press, DOI 10.1007/7657_2017_6

2016 - Tânia Lourenço and Mário Grãos, ‘Modulation of oligodendrocyte differentiation by mechanotransduction’, Frontiers in Cellular Neuroscience, 10:277; doi: 10.3389/fncel.2016.00277

2016 - Tânia Lourenço, Joana Paes de Faria, João Maia, José A. Lopes-da-Silva, João B. Relvas, Mário Grãos, ‘Modulation of oligodendrocyte differentiation and maturation by combined biochemical and mechanical cues’, Scientific Reports, 6, 21563; doi: 10.1038/srep21563

2015 - Ivana Kostic, Isabel Fidalgo-Carvalho, Sezin Aday, Helena Vazão, Tiago Carvalheiro, Mário Grãos, António Duarte, Carla Cardoso, Lino Gonçalves, Lina Carvalho, Artur Paiva, Lino Ferreira, ‘Lysophosphatidic acid enhances survival of human CD34+ cells in ischemic conditions’, Scientific Reports, 5:16406, DOI: 10.1038/srep16406

2015 - Ana Lopes, Mário Grãos, Artur Paiva, ‘Isolation and Characterization of Mesenchymal Stem Cells from Amniotic Membrane’, Amniotic Membrane, pp 195-207, DOI: 10.1007/978-94-017-9975-1_12

2014 - Cristiana Leite, N. Tatiana Silva, Sandrine Mendes, Andreia Ribeiro, Joana Paes de Faria, Tânia Lourenço, Francisco dos Santos, Pedro Z. Andrade, Carla M.P. Cardoso, Margarida Vieira, Artur Paiva, Cláudia L. da Silva, Joaquim M. S. Cabral, João B. Relvas, Mário Grãos, ‘Differentiation of human umbilical cord matrix mesenchymal stem cells into neural-like progenitor cells and maturation into an oligodendroglial-like lineage’, PLoS ONE 9(10): e111059. doi:10.1371/journal.pone.0111059

2014 - Rita Videira, Pedro Castanheira, Mário Grãos, Rosa Resende, Lígia Salgueiro, Carlos Faro, and Carlos Cavaleiro ‘Dose-Dependent Inhibition of BACE-1 by the Monoterpenoid 2,3,4,4-Tetramethyl-5-methylene-cyclopent-2-enone in Cellular and Mouse Models of Alzheimer’s Disease’, J. Nat. Prod., 2014, 77 (6), pp 1275–1279 (DOI: 10.1021/np400903w)

2013 - Sandro L. Pereira, Mário Grãos, Ana Sofia Rodrigues, Sandra I. Anjo, Rui A. Carvalho, Paulo J. Oliveira, Ernest Arenas, João Ramalho-Santos ‘Inhibition of mitochondrial complex III blocks neuronal differentiation and maintains embryonic stem cell pluripotency’, PLoS ONE 8(12): e82095. doi:10.1371/journal.pone.0082095

2013 - Andreia Ribeiro, Paula Laranjeira, Sandrine Mendes, Isabel Velada, Cristiana Leite, Pedro Andrade, Francisco Santos, Ana Henriques, Mário Grãos, Carla Cardoso, António Martinho, MLuísa Pais, Cláudia Lobato da Silva, Joaquim Cabral, Hélder Trindade and Artur Paiva, ‘Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells’, Stem Cell Research & Therapy, 4:125, doi:10.1186/scrt336

2013 - Videira, R., Castanheira, P., Grãos, M., Salgueiro, L., Faro, C. and Cavaleiro, C., ‘A necrodane monoterpenoid from Lavandula luisieri essential oil as a cell-permeable inhibitor of BACE-1, the -secretase in Alzheimer’s disease’, Flavour Fragr. J., 28 (6), 380–388.

2012 - Maia J, Vazão H, Pedroso DC, Jesus CS, Brito RM, Grãos M, Gil MH, Ferreira LS ‘VEGF-functionalized dextran has longer intracellular bioactivity than VEGF in endothelial cells’, Biomacromolecules, 13(9): 2906-2916, doi: 10.1021/bm3009268

2012 - Carlos A Ribeiro, Joana S Fraga, Mário Grãos, Nuno M Neves, Rui L Reis, Jeffrey M Gimble, Nuno Sousa and António J Salgado ‘The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations’, Stem Cell Research & Therapy, 3(3):18, doi:10.1186/scrt109

2012 - João R. Gomes, João T. Costa, Carlos V. Melo, Federico Felizzi, Patrícia Monteiro, Maria J. Pinto, Ana R. Inácio, Tadeusz Wieloch, Ramiro D. Almeida, Mário Grãos, Carlos B. Duarte ‘Excitotoxicity downregulates TrkB.FL signaling and upregulates the neuroprotective truncated TrkB receptors in cultured hippocampal and striatal neurons’, The Journal of Neuroscience, 32(13):4610 – 4622., doi: 10.1523/JNEUROSCI.0374-12.2012

2012 - Helena Vazão, Mário Grãos and Lino Ferreira, ‘Vascular Differentiation of Human Pluripotent Stem Cells’, ADVANCES IN STEM CELL RESEARCH, Stem Cell Biology and Regenerative Medicine, 2012, 97-115, DOI: 10.1007/978-1-61779-940-2_7

2011 - Lourenço A., Baldeiras, I., Grãos, M., Duarte C.B. ‘Proteomics-based technologies in the discovery of biomarkers for multiple sclerosis in the cerebrospinal fluid’ – Review paper, Current Molecular Medicine, 11, 326-349., DOI: 10.2174/156652411795677981

2011 - Vazão, H., Neves, R., Grãos, M., Ferreira, L. ‘Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells’. PLoS ONE 6(3): e17771, doi: 10.1371/journal.pone.0017771

2010 - Mário Grãos*, Ana Paula Simões-Wüst*, Carlos B. Duarte, Rudolf Brenneisen, Matthias Hamburger, Monica Mennet, Mac H. Ramos F., Martin Schnelle, Regula Wächter, Andreas M. Worel and Ursula von Mandach. ‘Juice of Bryophyllum pinnatum (Lam.) Inhibits Oxytocin-Induced Increase of the Intracellular Calcium Concentration in Human Myometrial Cells’, Phytomedicine, 17, 12, 980-986, doi: 10.1016/j.phymed.2010.03.005 * - equal contribution

2009 - Mário Grãos*, Joana P. Gonçalves* and André X. C. N. Valente. ‘Polar Mapper: software tool for integrated visualization of protein interaction networks and mRNA expression data’, Journal of the Royal Society Interface, 6, 881–896, doi: 10.1098/rsif.2008.0407 * - equal contribution

2005 - Grãos, M., Almeida, A. D., and Chatterjee, S. ‘Growth-factor-dependent phosphorylation of Bim in mitosis’. Biochem J, 388, 185-194, doi: 10.1042/BJ20041385

2005 - Almeida, R. D., Manadas, B. J., Melo, C. V., Gomes, J. R., Mendes, C. S., Grãos, M., Carvalho, R. F., Carvalho, A. P., and Duarte, C. B. ‘Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways’. Cell Death Differ, 12, 1329-1343, doi:10.1038/sj.cdd.4401662

Updated list of publications and citations:
https://scholar.google.pt/citations?user=6dlIqxgAAAAJ&hl=en-EN (sorted by citation number)
https://scholar.google.pt/citations?hl=en&user=6dlIqxgAAAAJ&view_op=list_works&sortby=pubdate (sorted by publication year)