Cancer & Ageing Group


About the Lab

For over a decade, our research has been directed at exploring the role of FOXO transcription factors in cancer and longevity. Our lab generated cutting edge screening technologies to monitor the activity of the PI3K/AKT/FOXO signaling pathway. Based on these tools we identified and characterized several genetic and pharmacological means to manipulate the activity of FOXO proteins. A major breakthrough has been accomplished with the discovery of the FOXO repressor protein TRIB2 as a novel oncogene in melanoma driving therapy resistance.

A second focus of our research is to explore the pharmacological modulation of FOXO proteins to treat cancer and other age-related diseases. FOXO factors are involved in cellular homeostasis and play a key role in the defense system against cellular stress. Intriguingly, FOXO3 has emerged as a longevity gene consistently associated with extreme human life and health span. We have founded the biotech company Refoxy Pharma GmbH, Berlin ( to explore the therapeutic potential of small molecule FOXO modulating compounds.

The Cancer & Aging Laboratory will take an integrated genomics, biological and proteomic approach to:

  1. To characterize the mechanism underlying TRIB2 mediated resistance in different tumor models (pancreatic, glioblastoma and melanoma);
  2. Identify the key players that aid TRIB2 promoting resistance, thus unveiling new novel therapeutic targets to be exploited;
  3. To correlate TRIB2 expression with clinical data in samples from GBM and low-grade glioma patients.

Team Members

Wolfgang Link
Invited Assistant Professor and Co-PI
Ana Luísa Coelho
Invited Assistant Professor
Bruno Santos
PhD student
Letícia Leite
Master student
Gisela Serrão
Lab Technician
Inês Grenho
Master Student
Alexandra Bento
Master Student

Selected Publications

2021 | Jiménez L., Silva A., Calissi G., Grenho I., Monteiro R., Blanco-Aparicio C., Mayoral-Varo V., Pastor J., Bustos V., Bracher F., Megias D., Ferreira B.I.* and Link W.*. Screening health-promoting compounds for their capacity to induce the activity of FOXO3. Journal of Gerontology doi: 10.1093/gerona/glab265. PMID: 34508571

2021 | Ferreira B.I., Santos B., Link W. and De Sousa-Coelho AL. Tribbles Pseudokinases in Colorectal Cancer. Cancers (Basel) 13, 2825. doi: 10.3390/cancers13112825, PMID: 34070799

2021 | Hazael Pérez-Beltrána C., García-Guzmán J.J., Ferreira B., Estévez-Hernández O., López-Iglesias D., Cubillana-Aguilera L., Link W., Stănicăhe N., dos Santos Rosa da Costa A.M. and Palacios-Santander J.M.. One-minute and green synthesis of magnetic iron oxide nanoparticles assisted by design of experiments and high energy ultrasound: Application to biosensing and immunoprecipitation. Mater Sci Eng C Mater Biol Appl. 123, 112023. doi: 10.1016/j.msec.2021.112023. PMID: 33812640

2020 | Machado S., Silva A., De Sousa-Coelho A.L., Duarte I., Grenho I., Santos B., Mayoral-Varo V., Megias D., Sánchez-Cabo F., Dopazo A., Ferreira B.I. and Link W..  Harmine and Piperlongumine Revert TRIB2-Mediated Drug Resistance. Cancers (Basel) 9, 12 doi: 10.3390/cancers12123689, PMID: 33316942

2020 | Ferreira B.I., Cautain B., Grenho I. and Link W. . Small molecule inhibitors of CRM1. Frontiers in Pharmacology 11, 625. doi: 10.3389/fphar.2020.00625, PMID: 32574233

2020 | Jacinto F.V., Link W., Ferreira B.I.. CRISPR/Cas9-mediated genome editing: from basic research to translational medicine. Journal of Cellular and Molecular Medicine 24, 3766-3778. doi: 10.1111/jcmm.14916.

2019 | Machado S., Raposo C., Ferreira B.I. and Link W.. Image-based identification of chemical compounds capable of trapping FOXO in the cell nucleus. Methods Mol Biol. 1890, 163-170. doi: 10.1007/978-1-4939-8900-3_14, PMID: 30414153

2019 | Henriques V, Machado S., Link W. and Ferreira B.I.. Monitoring the transcriptional activity of FOXO transcription factors by analyzing their target genes. Methods Mol Biol.  1890:103-113. doi: 10.1007/978-1-4939-8900-3_9, PMID: 30414148

2018 | Link W.. Knowledge-based drug discovery intensifies private appropriation of publicly financed research. The Lancet Oncology 19, 1017-1018. doi: 10.1016/S1470-2045(18)30437-6, PMID: 30102212

2018 | Henriques V., Martins M., Link W. and Ferreira B.I. The emerging therapeutic landscape of advanced melanoma, Current Pharmaceutical Design, 24, 549-558. doi: 10.2174/138161282466618012509335, PMID: 29366407

2017 | Link W. and Fernandez-Marcos P.. FOXO transcription factors at the interface of metabolism and cancer. International Journal of Cancer 141, 2379-2391. doi: 10.1002/ijc.30840. PMID: 28631330 Cover image and story

2017 | Link W.. Mind the gap, see the immuno-connection. Nature Chem. Biol. 13, 572-573.doi: 10.1038/nchembio.2373. PMID: 28437396

2017 | Hill R., Madureira PA, Ferreira, B, Baptista. I, Machado, S, Colaço L., dos Santos M.,  Liu N., Dopazo, A, Ugurel S., Adrienn A., Kiss-Toth E., Isbilen M., Gure AO and Link W.. TRIB2 confers resistance to anti-cancer therapy by activating the serine/threonine protein kinase AKT. Nature Comm. 8, 14687. doi: 10.1038/ncomms14687. PMID: 28276427

2017 | Ferreira BI, Lie MK, Engelsen AST, Machado S, Link W and James B. Lorens. Adaptive mechanisms of resistance to antineoplastic agents. MedChemComm, 8, 53 – 66. DOI: 10.1039/C6MD00394J, PMID: 30108690

2016 | Cautien B., Castillo F, Musso L, de Pedro N, Rodriguez Quesada L, Vicente Pérez F, Dallavalle S and Link W.. Discovery of a novel, specific isothiazolonaphthoquinone-based small molecule activator of FOXO nuclear-cytoplasmic shuttling. PLoS One 11(12):e0167491. doi: 10.1371/journal.pone.0167491, PMID: 27936162

2016 | Florindo, C, Ferreira BI, Serrão SM, Tavares, AA, Hill R, and Link W.. Subcellular protein localization in health and disease. eLS. John Wiley & Sons, Ltd: Chichester DOI: 10.1002/9780470015902.a0026534

2016 | Martins R., Lithgow G.J., Link W.. Long live FOXO: Unravelling the role of FOXO proteins in aging and longevity. Aging Cell 15, 196-207. doi: 10.1111/acel.12427, PMID: 26643314

2013 | Rio-Machin A, Ferreira BI, et al. and Cigudosa JC. “Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype”, Leukemia

2008 | Marcos NT, Magalhães A, Ferreira B, et al., Reis CA.Helicobacter pylori induces beta3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x”, Journal of Clinical Investigation

2008 | Ferreira BI, et al. and Cigudosa JC “Comparative genome profiling across sub-types of low grade B cell lymphoma identifies type-specific and common aberrations that target genes with a role in B-cell neoplasia”. Haematologica

2008 | Ferreira BI, et al. and Cigudosa JC. “Array CGH and gene-expression profiling reveals distinct genomic instability patterns associated with DNA repair and cell-cycle checkpoint pathways in Ewing’s sarcoma.” Oncogene


Project: ENDURING- Overcoming drug resistance in Glioblastoma
Period of execution: April 2021 – Present
Coordinator: Bibiana Ferreira
Funding agency: Fundação para a Ciência e Tecnologia, FCT (PTDC_MED_ONC_4167_2020)

Project: Infrastructure PtCAC
Period of execution: April 2021 – Present
Coordinator: Bibiana Ferreira
Funding agency: Roadmap for the Portuguese Infrastructures of academic clinical centers

Project: VISITOR-VarIants Screen In souThern pORtugal
Period of execution: April 2021 – Present
Coordinator: Bibiana Ferreira
Funding agency: ALG-D2-2021-06

Project: Marie Skłodowska-Curie Individual Fellowships-Reintegration
Period of execution: September 2018 – September 2020
Coordinator: Bibiana Ferreira
Funding agency: Marie Skłodowska-Curie (H2020-MSCA-IF-2016)


2019 | LPCC/Terry Fox 2019, to Bibiana Ferreira

2017 | LPCC/Terry Fox 2017, to Wolfgang Link

Funding Agencies

Events to Disseminate

Additional Info

Principal Investigator

Bld. 2, Lab 3.67, ext: 03302

©2021 Algarve Biomedical Center Research Institute

Made with by Algardata

Soon Available
Press releases and ABC-RI in the news
Come to upcoming science events
Open Positions