Research Lab

Glycoimmunology

Glycoimmunology
29679
Research Interests

We are focused on the physiological and pathological roles of glycosylation. Glycans are involved in all biological processes, influencing the development, growth and functioning of cells and organisms. Our main goals are to identify novel therapeutic targets and to develop innovative immunotherapies, based on antibodies and dendritic cells. Our studies demonstrated the fundamental roles of cell surface glycans in modulating the potency of dendritic cells and their therapeutically potential against infection and cancer. We are also screening aberrant glycosylation that potentiates cancer progression and metastasis, and suppress immune function for target therapy. We use state-of-the-art methods: immune-based assays, cell and molecular biology, in vitro and in vivo models with human/patient cells.

Research Highlights
Exploring glycosylation to improve anti-tumor immunotherapy

We developed a technology that holds promise to improve dendritic cells (DC)-based vaccines against cancer. The capacity of DCs to boost anti-tumor immunity is affected by cell surface sialic acid containing glycans (Cabral et al, 2013). Our technology shortages sialic acid and enhances the the ability of DCs to activate T cells to speci cally kill tumor cells (Silva et al, 2016; WO 2017002045 A1). While we further investigate this, we are looking for partners to translate our technology into clinics. On the other hand, tumor cells may express the sialyl Tn and sialyl Lewis X glycans, which are associated with increased malignancy. We found that these glycans are aberrantly expressed in de ned proteins and attribute cancer cells capacity to evade immune system and to adhere to endothelial cells, initiating hematogenous metastasis (Carrascal et al, submit). We are interested in glycans and also other biomarkers. e.g. intracelluar stress, that relate with malignancy as potential candidates for antibody based therapy (Loureiro et al, 2015).

Exploring glycosylation to improve anti-tumor immunotherapy
CDG & Allies -PPAIN - Congenital disorders of Glycosylation - Professionals and Patient Associations International Network.

Together with the Portuguese association of CDG (APCDG) we founded an unrivalled international network that joins scientists, physicians, families and patient advocacy groups dedicated to CDG. We are establishing a patient-led unique infrastructure that foments research, awareness and education for CDG (Monticelli et al, 2016; Marques da Silva et al. 2017). Website www.apcdg.com/ research.html. CDG & Allies PPAIN is located at FCT NOVA and directed by V. Ferreira (APCDG) and P. Videira.

2

Representative Projects

  • “Siamab therapeutics research agreement”, Total and Unit funding: €20,000, Paula Videira (PI).
  • “GlyCoCan - exploiting glycosylation of colorectal cancer for the development of improved diagnostics and therapeutics”, Total funding: €3,2M and Unit funding: €476,712, Paula Videira (Collaborator).
  • “Trifunctional antibodies and dendritic cell-based technologies: a combined approach to cancer immunotherapy” Bluepharma | University of Coimbra Award, Total and Unit funding: €20,000, Paula Videira (PI).
  • “ADVANCE - desenvolvimento de novas vacinas anti- cancro a partir de células dendríticas”, FEDER,-QREN, Total funding: €431,012, Unit funding: €215,506 , Paula Videira (co-PI).
  • “Therapeutic targets for triple negative breast cancer: development of mono and bispeci c antibodies against Notch1 ligands”, FCT-MCTES, Total funding: €197,643, Unit funding: €18,000, Paula Videira (Collaborator).

Selected Publications

Chaves, RP; da Silva, SR; Neto, LGN; Carneiro, RF; da Silva, ALC; Sampaio, AH; de Sousa, BL; Cabral, MG; Videira, PA; Teixeira, EH; Nagano, CS. 2018. Structural characterization of two isolectins from the marine red alga Solieria filiformis (Kutzing) PW Gabrielson and their anticancer effect on MCF-7 breast cancer cells. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 107, DOI: 10.1016/j.ijbiomac.2017.09.116
Araújo, JE; López-Fernández, H; Diniz, MS; Baltazar, PM; Pinheiro, LC; da Silva, FC; Carrascal, M; Videira, P; Santos, HM; Capelo, JL. 2018. Dithiothreitol-based protein equalization technology to unravel biomarkers for bladder cancer. TALANTA, 180, DOI: 10.1016/j.talanta.2017.11.063
Viegas, CSB; Costa, RM; Santos, L; Videira, PA; Silva, Z; Araujo, N; Macedo, AL; Matos, AP; Vermeer, C; Simes, DC. 2017. Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: Implications for calcification-related chronic inflammatory diseases. PLoS One, 12, DOI: 10.1371/journal.pone.0177829
Mariana Silva; Ronald Kam Fai Fung; Conor Brian Donnelly; Paula Alexandra Videira; Robert Sackstein. 2017. Cell-Specific Variation in E-Selectin Ligand Expression among Human Peripheral Blood Mononuclear Cells: Implications for Immunosurveillance and Pathobiology. The Journal of Immunology, 198(9), DOI: 10.4049/jimmunol.1601636
Severino, PF; Silva, M; Carrascal, M; Malagolini, N; Chiricolo, M; Venturi, G; Astolfi, A; Catera, M; Videira, PA; Dall'Olio, F. 2017. Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guerin (BCG) and to oxidative damage. Oncotarget, 8, DOI: 10.18632/oncotarget.17138