Stem Cell Metabolism

Metabolic modulation




Cell Therapy


Ricardo Neves


Research lines

Metabolic modulation of cancer stem cells

Biophysical modulation of cell state and fate

Metabolic modulation and Immunotherapy


The central directions of RPN's laboratory are to explore the link between metabolism > transcription > alternative splicing > stem cell fate decision/ disease. This central line is explored with an approach grounded on basic biochemistry mechanisms and the emphasis on translational applications in the cell therapy area. Recently RPN´s Lab has shown that the biochemical and physical modulation of chromatin structure can constitute a powerful tool to change transcription and gene expression. Using a simple biochemistry cue, the extracellular osmotic pressure, it it possible to change chromatin structure and transcription. Hyposmotic modulation promotes chromatin loosening and induces changes in RNA polymerase II (Pol II) activity. This constitutes an alternative route to manipulate cell fate decisions. This technology has been tested in model protocols of induced pluripotency and transdifferentiation in cells growing in suspension and adherent to substrates, CD34+ umbilical-cord-blood (UCB), fibroblasts and B-cells, with increased efficiency. Also, when cells are cultured on low-rigidity substrates, show open chromatin nuclear regions and enhanced expression of endogenous pluripotency-related genes facilitating the induction of pluripotency. The group has expertise in the synthesis and delivery of nanoparticles (NPs) with different cargos in primary and stem cells and patented a light-activated NP able to release retinoic acid inside the Leukemic niche and induce the differentiation of leukemia stem cells. In this context the group is exploring the delivery of metabolic intermediates able to modulate stem cell niches and tumour microenvironments for cell therapy in cancer and regenerative medicine.


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Information about journal articles, updated at 22-05-2022, from platform CIÊNCIAVITAE.

Reconstruction of tissue-specific genome-scale metabolic models for human cancer stem cells

Barata, Tânia; Vieira, Vítor; Rodrigues, Rúben; Neves, Ricardo Pires das; Rocha, Miguel, 2022. Computers in Biology and Medicine. 142. 2022. . 10.1016/j.compbiomed.2021.105177 . Computers in Biology and Medicine

Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers?

Almeida-Lousada, Hélder; Mestre, André; Ramalhete, Sara; Price, Aryeh J.; de Mello, Ramon Andrade; Marreiros, Ana D.; Neves, Ricardo Pires das; Castelo-Branco, Pedro, 2021. Current Oncology. 4874 - 4893. 6. 28. 2021. . 10.3390/curroncol28060411 . Current Oncology

Identification of colorectal cancer associated biomarkers: an integrated analysis of miRNA expression

Fonseca, André; Ramalhete, Sara Ventura; Mestre, André; Pires das Neves, Ricardo; Marreiros, Ana; Castelo-Branco, Pedro; Roberto, Vânia Palma, 2021. Aging. 21991 - 22029. 18. 13. 2021. . 10.18632/aging.203556 . Aging

Development of an optimized and scalable method for isolation of umbilical cord blood-derived small extracellular vesicles for future clinical use

Renato M. S. Cardoso; Silvia C. Rodrigues; Claudia F. Gomes; Filipe V. Duarte; Maryse Romao; Ermelindo C. Leal; Patricia C. Freire; Ricardo Neves; Joana Simões-Correia, 2021. STEM CELLS Translational Medicine. 2021. . 10.1002/sctm.20-0376 . STEM CELLS Translational Medicine

Correction to: In vitro mechanistic studies on a-amanitin and its putative antidotes

Daniela Ferreira Rodrigues; Ricardo Pires das Neves; Alexandra T. P. Carvalho; Maria Lourdes Bastos; Vera M. Costa; Félix Carvalho, 2020. Archives of Toxicology. 2020. . 10.1007/s00204-020-02735-0 . Archives of Toxicology

In vitro mechanistic studies on a-amanitin and its putative antidotes

Daniela Ferreira Rodrigues; Ricardo Pires das Neves; Alexandra T. P. Carvalho; Maria Lourdes Bastos; Vera M. Costa; Félix Carvalho, 2020. Archives of Toxicology. 2020. . 10.1007/s00204-020-02718-1 . Archives of Toxicology

Soft culture substrates favor stem-like cellular phenotype and facilitate reprogramming of human mesenchymal stem/stromal cells (hMSCs) through mechanotransduction

Neves, Ricardo, 2019. Scientific Reports. 2019. . 10.1038/s41598-019-45352-3 . Scientific Reports

Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation

Neves, Ricardo, 2018. Scientific Reports. 2018. . 10.1038/s41598-018-25517-2 . Scientific Reports

Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression

Márquez-Jurado, S.; Díaz-Colunga, J.; Das Neves, R.P.; Martinez-Lorente, A.; Almazán, F.; Guantes, R.; Iborra, F.J., 2018. Nature Communications. 1. 9. 2018. . 10.1038/s41467-017-02787-4 . Nature Communications

Validating the RedMIT/GFP-LC3 Mouse Model by Studying Mitophagy in Autosomal Dominant Optic Atrophy Due to the OPA1Q285STOP Mutation

Neves, Ricardo, 2018. Frontiers in Cell and Developmental Biology. 2018. . 10.3389/fcell.2018.00103 . Frontiers in Cell and Developmental Biology

Flexible nanofilms coated with aligned piezoelectric microfibers preserve the contractility of cardiomyocytes

Gouveia, P.J.; Rosa, S.; Ricotti, L.; Abecasis, B.; Almeida, H.V.; Monteiro, L.; Nunes, J.; et al, 2017. Biomaterials. 213 - 228. 139. 2017. . 10.1016/j.biomaterials.2017.05.048 . Biomaterials

Prolonged intracellular accumulation of light-inducible nanoparticles in leukemia cells allows their remote activation

Boto, C.; Quartin, E.; Cai, Y.; Martín-Lorenzo, A.; Cenador, M.B.G.; Pinto, S.; Gupta, R.; et al, 2017. Nature Communications. 8. 2017. . 10.1038/ncomms15204 . Nature Communications

Global variability in gene expression and alternative splicing is modulated by mitochondrial content

Guantes, R.; Rastrojo, A.; Neves, R.; Lima, A.; Aguado, B.; Iborra, F.J., 2015. Genome Research. 633 - 644. 5. 125. 2015. . 10.1101/gr.178426.114 . Genome Research

Boron nitride nanotube-mediated stimulation modulates F/G-actin ratio and mechanical properties of human dermal fibroblasts

Ricotti, L.; Das Neves, R.P.; Ciofani, G.; Canale, C.; Nitti, S.; Mattoli, V.; Mazzolai, B.; Ferreira, L.; Menciassi, A., 2014. Journal of Nanoparticle Research. 2. 16. 2014. . 10.1007/s11051-014-2247-z . Journal of Nanoparticle Research

Efficient pro-survival/angiogenic miRNA delivery by an MRI-detectable nanomaterial

Gomes, R.S.M.; Neves, R.P.D.; Cochlin, L.; Lima, A.; Carvalho, R.; Korpisalo, P.; Dragneva, G.; et al, 2013. ACS Nano. 3362 - 3372. 4. 7. 2013. . 10.1021/nn400171w . ACS Nano

Epigenetic engineering to reverse the Parkinson's expression state

Valente, A.X.C.N.; das Neves, R.P.; Oliveira, P.J., 2012. Parkinsonism and Related Disorders. 717 - 721. 6. 18. 2012. . 10.1016/j.parkreldis.2012.04.018 . Parkinsonism and Related Disorders

Mitochondrial variability as a source of extrinsic cellular noise

Johnston, I.G.; Gaal, B.; das Neves, R.P.; Enver, T.; Iborra, F.J.; Jones, N.S., 2012. PLoS Computational Biology. 3. 8. 2012. . 10.1371/journal.pcbi.1002416 . PLoS Computational Biology

Towards the maturation and characterization of smooth muscle cells derived from human embryonic stem cells

Vazão, H.; das Neves, R.P.; Grãos, M.; Ferreira, L., 2011. PLoS ONE. 3. 6. 2011. . 10.1371/journal.pone.0017771 . PLoS ONE

a-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes

Dalziel, M.; Kolesnichenko, M.; Das Neves, R.P.; Iborra, F.; Goding, C.; Furger, A., 2011. Nucleic Acids Research. 2378 - 2392. 6. 39. 2011. . 10.1093/nar/gkq1125 . Nucleic Acids Research

Nanoparticles for intracellular-targeted drug delivery

Paulo, C.S.O.; Pires Das Neves, R.; Ferreira, L.S., 2011. Nanotechnology. 49. 22. 2011. . 10.1088/0957-4484/22/49/494002 . Nanotechnology

Connecting variability in global transcription rate to mitochondrial variability

das Neves, R.P.; Jones, N.S.; Andreu, L.; Gupta, R.; Enver, T.; Iborra, F.J., 2010. PLoS Biology. 12. 8. 2010. . 10.1371/journal.pbio.1000560 . PLoS Biology

MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU

Favaro, E.; Ramachandran, A.; McCormick, R.; Gee, H.; Blancher, C.; Crosby, M.; Devlin, C.; et al, 2010. PLoS ONE. 4. 5. 2010. . 10.1371/journal.pone.0010345 . PLoS ONE

Association between active genes occurs at nuclear speckles and is modulated by chromatin environment

Brown, J.M.; Green, J.; Das Neves, R.P.; Neves, R.P.D.; Wallace, H.A.C.; Smith, A.J.H.; Hughes, J.; et al, 2008. Chemtracts. 411 - 413. 10. 21. 2008. . 10.1083/jcb.200803174 . Chemtracts

Repeated administration of d-amphetamine results in a time-dependent and dose-independent sustained increase in urinary excretion of p-hydroxyamphetamine in mice

Carvalho, F.; Soares, M.E.; Fernandes, E.; Remião, F.; Carvalho, M.; Duarte, J.A.; Pires-das-Neves, R.; Pereira, M.D.L.; Bastos, M.D.L., 2007. Journal of Health Science. 371 - 377. 4. 53. 2007. . 10.1248/jhs.53.371 . Journal of Health Science

Effect of Cr(V) on reproductive organ morphology and sperm parameters: An experimental study in mice

Pereira, M.D.L.; Das Neves, R.P.; Oliveira, H.; Santos, T.M.; De Jesus, J.P., 2005. Environmental Health: A Global Access Science Source. 4. 2005. . 10.1186/1476-069X-4-9 . Environmental Health: A Global Access Science Source

Hypericum androsaemum infusion increases tert-butyl hydroperoxide-induced mice hepatotoxicity in vivo

Valentão, P.; Carvalho, M.; Carvalho, F.; Fernandes, E.; Neves, R.P.D.; Pereira, M.L.; Andrade, P.B.; Seabra, R.M.; Bastos, M.L., 2004. Journal of Ethnopharmacology. 345 - 351. 2-3. 94. 2004. . 10.1016/j.jep.2004.06.012 . Journal of Ethnopharmacology

Protective activity of hesperidin and lipoic acid against sodium arsenite acute toxicity in mice

Pires Das Neves, R.N.; Carvalho, F.; Carvalho, M.; Fernandes, E.; Soares, E.; Bastos, M.D.L.; Pereira, M.D.L., 2004. Toxicologic Pathology. 527 - 535. 5. 32. 2004. . 10.1080/01926230490502566 . Toxicologic Pathology

Effect of 3,4-methylenedioxymethamphetamine ("ecstasy") on body temperature and liver antioxidant status in mice: Influence of ambient temperature

Carvalho, M.; Carvalho, F.; Remião, F.; De Lourdes Pereira, M.; Pires-Das-Neves, R.; De Lourdes Bastos, M., 2002. Archives of Toxicology. 166 - 172. 3. 76. 2002. . 10.1007/s00204-002-0324-z . Archives of Toxicology

Cr(V) involvement in the toxicity pathway of testicular damage

Pereira, M.L.; Santos, T.M.; Pires das Neves, R.; Costa, F.G.; Pedrosa de Jesus, J., 2002. Asian Journal of Andrology. 153 - 155. 2. 4. 2002. . Asian Journal of Andrology

Comparative histological studies on liver of mice exposed to Cr(VI) and Cr(V) compounds

Pires Das Neves, R.; Santos, T.M.; De Lourdes Pereira, M.; Pedrosa De Jesus, J., 2002. Human and Experimental Toxicology. 365 - 369. 7. 21. 2002. . 10.1191/0960327102ht243oa . Human and Experimental Toxicology

Chromium(VI) induced alterations in mouse spleen cells: A short-term assay

Das Neves, R.P.; Santos, T.M.; Pereira, M.D.L.; De Jesus, J.P., 2001. Cytobios. 27 - 34. 1 SUPPL.. 413. 2001. . Cytobios

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