• To elucidate the role of Glycosylation in immune response and cancer progression.
• To develop novel cell and antibody-based immunotherapy.
Our research has focused essentially in the following interconnected areas:
We work on the role of glycosylation – a posttranslational modification of proteins – in the modulation of immune responses to pathogens and cancer. Virtually every cell surface protein is glycosylated and a considerable number of proteins that regulate immune cell development and function bind glycans (i.e. are lectins). The group is devoted to dendritic cells (DC), one of the most important cells of the immune system. DCs are a key link between innate and adaptive immunity. We have shown that sialic acid-containing glycans influence differentiation, maturation and the capacity of DCs to migrate, capture antigens and to prime T lymphocyte responses. One of the main goal of our research concerns the exploration of DC-based immunotherapy, and to learn how to fine tune the immune response, based on the modifications of specific glycosidic structures. This could result in the establishment of enhanced vaccines against unique signatures in tumour cells and bacteria.
It is an exciting time in Glycoimmunology – there are so many open questions and so many potential applications of new knowledge to immune host-pathogen defense and tumour immunology
We also work on the identification of novel glycan-based biomarkers of cancer and in understanding their pathophysiological role. The strong collaboration with clinicians has allowed us to identify novel tumour-associated glycan structures in different cancers. This is achieved both through basic/fundamental as well applied/clinical research, targeted on tumour cells and tissue.
We have been dedicated to bladder, lung, and breast cancer and found that some particular glycan structures are able to suppress immune functions, thus avoiding the detection and elimination of tumour cells by the immune system. We aim to understand how deranged glycosidic changes occur, how they correlate with cancer progression, metastasis and immune tolerance. We are attracted to contribute to the development of groundbreaking immunotherapeutic approaches which exploit the patient’s own immune system to control tumour progression and immune evasion.
Congenital Disorders of Glycosylation are a group of 50 already-identified inborn errors of metabolism also known as CDG syndromes, caused by defects in glycan synthesis and on their attachment to proteins and lipids. CDG patients show multi-systemic involvement, ranging from severe developmental delay and hypotonia to hypoglycemia and protein-losing enteropathy with normal development, where immunological defects are most usually present. We are particularly interested in understanding the mechanisms behind altered immune responses frequently observed in CDG patients. We collaborate with the Portuguese Association CDG and are now forming the first Portuguese Research Network of Professionals and Patients Association for Congenital Disorders of Glycosylation (CDG) – RIPPAD-CDG (http://sindromecdg.orgfree.com/). The synergy between our group and rare Diseases Associations aims to potentiate research projects, to create educational resources, and to raise awareness amongst society, clinicians and researchers.
Um CD uma Vida (https://www.facebook.com/uncdunavida?fref=photo)
Funded Projects and Prizes:
• aDVANCE Desenvolvimento de novas vacinas anticancro, QREN-ADI 2013-2015
• Prémio de Inovação Bluepharma-Universidade de Coimbra 2014
• Prémio de Mérito Científico Santander Totta – Universidade Nova de Lisboa 2012/2013
• The role of sialic acid in the immunobiology of dendritic cells”PTDC/SAUMII/67561/2006 - Fundação para a Ciência e Tecnologia
• Fulbright Commission to P. Videira (2013) and L. Rodrigues (2014)
• Bolsa LPCC/PFIZER 2011
• Improved Dendritic cell-based vaccines for cancer treatment:
Aim: To identify the role of glycans expressed by human dendritic cells and use glycoengineering to improve dendritic cell based vaccines.
• Glycans involved in haematogenous cell migration::
Aim: To identify the role of glycans expressed by human dendritic cells and cancer cells that contribute to transendothelial migration
• Bispecific antibodies for breast cancer treatment::
Aim: To develop therapeutics to treat breast cancer that specifically target cancer cells, and simultaneously engage patient’s immune system to kill these tumor cells
• Host-pathogen interaction - In vitro model based on human dendritic cell functions::
Aim: To address mechanisms of immune evasion by bacteria
• In vivo model of skin/ surgery infection using immunocompetent rats::
Aim: To compare bacteria growth in skin or surgical wounds, to compare immune response after evasion, to test anti-microbial drugs and drug-delivery systems.
- Lamy M, Ferreira A, Dias JS, Braga S, Silva G, Barbas A. Notch-out for breast cancer therapies. N Biotechnol. 2017 Aug 22. pii: S1871-6784(16)32490-6. doi: 10.1016/j.nbt.2017.08.004. [Epub ahead of print]
- 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 Guérin (BCG) and to oxidative damage.
- Silva M, Fung RK, Donnelly CB, Videira PA, Sackstein R (2017) Cell-Specific Variation in E-Selectin Ligand Expression among Human Peripheral Blood Mononuclear Cells: Implications for Immunosurveillance and Pathobiology. J Immunol. 2017 Mar 22. pii: 1601636. doi: 10.4049/jimmunol.1601636. [Epub ahead of print]
- Casal D, Pais D, Iria I, Mota-Silva E, Almeida MA, Alves S, Pen C, Farinho A, Mascarenhas-Lemos L, Ferreira-Silva J, Ferraz-Oliveira M, Vassilenko V, Videira PA, Gory O'Neill J. (2017) A Model of Free Tissue Transfer: The Rat Epigastric Free Flap. J Vis Exp. 2017 Jan 15;(119). doi: 10.3791/55281. J Inherit Metab Dis. 2017 Jan 20. doi: 10.1007/s10545-016-0012-4. [Epub ahead of print]
- Marques-da-Silva D, Dos Reis Ferreira V, Monticelli M, Janeiro P, Videira PA, Witters P, Jaeken J, Cassiman D. (2017) Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature. J Inherit Metab Dis. 2017 Jan 20. doi: 10.1007/s10545-016-0012-4. [Epub ahead of print]
- Martins M, Baptista PV, Mendo AS, Correia C, Videira P, Rodrigues AS, Muthukumaran J, Santos-Silva T, Silva A, da Silva MF, Gigante J, Duarte A, Gajewska M, Fernandes AR. (2016) In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin(iv) complex. Mol Biosyst. 2016 Mar;12(3):1015-23. doi: 10.1039/c5mb00791g.
- Guadalupe Cabral M, Pereira M, Silva Z, Iria I, Coutinho C, Lopes A, Sá-Correia I, Videira PA.(2016) Using dendritic cells to evaluate how Burkholderia cenocepacia clonal isolates from a chronically infected cystic fibrosis patient subvert immune functions. Med Microbiol Immunol. 2016 Dec 16. [Epub ahead of print]
- Monticelli M, Ferro T, Jaeken J, Dos Reis Ferreira V, Videira PA (2016) Immunological aspects of congenital disorders of glycosylation (CDG): a review. J Inherit Metab Dis. 2016 Jul 8. [Epub ahead of print]
- Silva M, Silva Z, Marques G, Ferro T, Gonçalves M, Monteiro M, van Vliet SJ, Mohr E, Lino AC, Fernandes AR, Lima FA, van Kooyk Y, Matos T, Tadokoro CE, Videira PA. 2016. Sialic acid removal from dendritic cells improves antigen cross-presentation and boosts anti-tumor immune responses. Oncotarget. 2016 May 17. doi: 10.18632/oncotarget.9419. [Epub ahead of print]
- Silva Z, Veríssimo T, Videira PA, Novo C. (2015) Protein disulfide isomerases: Impact of thapsigargin treatment on their expression in melanoma cell lines. Int J Biol Macromol. 2015 Aug;79:44-8. doi: 10.1016/j.ijbiomac.2015.04.029. Epub 2015 Apr 23.
- Carrascal MA, Severino P, Cabral MG, Silva M, Ferreira JA, Quinto H, Pen C, D. Ligeiro, LL Santos, Dall'Olio. Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells. Mol Oncol. 2014;8:753-65.
- Lima FA, Gómez-Conde I, Videira PA, Marinho CR, Olivieri DN, Tadokoro CE. 2014 Intravital microscopy technique to study parasite dynamics in the labyrinth layer of the mouse placenta. Parasitol Int. 63:254-9 (doi: 10.1016/j.parint.2013.06.012).
- Crespo HJ, Lau JT, Videira PA. Dendritic cells: a spot on sialic Acid. Front Immunol. 2013. 27;4:491. Review
- Monteiro AS, Almeida J, Cabral G, Severino P, Videira PA, Sousa A, Nunes R, Pereira JD, Francisco AP, Perry MJ, Mendes E. 2013 Synthesis and evaluation of N-acylamino acids derivatives of triazenes. Activation by tyrosinase in human melanoma cell lines. Eur J Med Chem. 70:1-9 (doi: 10.1016/j.ejmech.2013.09.040).
- Marques G, Silva Z. Videira P. Establishing a Cell Biology Platform Isolation and Preservation of Human Blood Products ISBN: 978-3-659-21744-9. LAMBERT Academic Publishing.
- Lima L, Severino PF, Silva M, Miranda A, Tavares A, Pereira S, Fernandes E, Cruz R, Amaro T, Reis CA, Dall'olio F, Amado F, Videira PA, Santos L, Ferreira JA. Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy. Br J Cancer. 2013 Oct 15;109(8):2106-14. doi: 10.1038/bjc.2013.571. Epub 2013 Sep 24.
- Bugalho A, Ferreira D, Eberhardt R, Dias SS, Videira PA, Herth FJ, Carreiro L. Diagnostic value of endobronchial and endoscopic ultrasound-guided fine needle aspiration for accessible lung cancer lesions after non-diagnostic conventional techniques: a prospective study. BMC Cancer. 2013;13:130
- Cabral MG, Silva Z, Ligeiro D, Seixas E, Piteira AR, Videira PA. The phagocytic capacity of human dendritic cell is improved by sialidase. Immunology. 2013;138:235–245
- Ferreira JA, Videira PA, Lima L, Pereira S, Silva M, Carrascal M, Severino PF, Fernandes E, Almeida A, Costa C, Vitorino R, Amaro T, Oliveira MJ, Reis CA, Dall’Olio F, Amado F, Lara Santos L. Overexpression of tumour-associated carbohydrate antigen Sialyl-Tn in advanced bladder tumours. Molecular Oncology. 2013;7:719–731
- Cabral MG, Silva Z, Ligeiro D, Seixas E. Crespo H, Carrascal M, Silva M, Piteira AR, Paixão P, Lau JTY, Videira PA. The phagocytic capacity and immunological potency of human dendritic cells is improved by α2,6-sialic acid deficiency. Immunology 2013, 138:235-45. doi: 10.1111/imm.12025.
- Bugalho A, Martins C, Dias SS, Nunes G, Silva Z, Correia M, Marques Gomes MJ, Videira PA. 2013 Cytokeratin 19, Carcinoembryonic Antigen, and Epithelial Cell Adhesion Molecule Detect Lung Cancer Lymph Node Metastasis in Endobronchial Ultrasound-Guided Transbronchial Aspiration Samples. Clin Lung Cancer. 2013. doi:pii: S1525-7304(13)00132-0. 10.1016/j.cllc.2013.06.004.
- Lima L, Ferreira JA, Tavares A, Oliveira D, Morais A, Videira PA, Medeiros R, Santos L. FASL polymorphism is associated with response to bacillus Calmette-Guérin immunotherapy in bladder cancer. Urol Oncol. 2013 Aug 12. doi:pii: S1078-1439(13)00209-3. 10.1016/j.urolonc.2013.05.009.
- Silva A, Luís D, Santos S, Silva J, Mendo AS, Coito L, Silva TF, da Silva MF, Martins LM, Pombeiro AJ, Borralho PM, Rodrigues CM, Cabral MG, Videira PA, Monteiro C, Fernandes AR. Biological characterization of the antiproliferative potential of Co(II) and Sn(IV) coordination compounds in human cancer cell lines: a comparative proteomic approach. Drug Metabol Drug Interact. 2013 26:1-10. doi: 10.1515/dmdi-2013-0015.
- Julien S, Videira PA, Delannoy P. Sialyl-Tn in Cancer: (How) Did We Miss the Target? Biomolecules 2012, 2, 435-466; doi:10.3390/biom2040435
- Severino PF, Silva M, Carrascal MA, Calais F, Dall’Olio F, Videira PA. 2012. Bladder Cancer – Glycosylation Insights. Volume 38 In: Specialist Periodical Reports (SPR) Carbohydrate Chemistry. Royal Society of Chemistry, Cambridge, UK.
- Paixão P, Almeida S, Videira PA, Ligeiro D, Marques T. 2012. Screening of congenital cytomegalovirus infection by real-time PCR in urine pools. Eur J Pediatr. 171:125-9
- Carrascal M, Silva Z, Crespo HJ, Cabral MG, Videira PA. 2011. Sialylation and dendritic cells: bridging innate and adaptive immune responses. Volume 37 In: Specialist Periodical Reports (SPR) Carbohydrate Chemistry. Royal Society of Chemistry, Cambridge, UK.
- Fernandes AB, Patarrão RS, Videira PA, Macedo MP. 2011. Understanding Postprandial Glucose Clearance by Peripheral Organs: The Role of the Hepatic Parasympathetic System. J Neuroendocrinol. 23: 1288-95. (doi: 10.1111/j.1365-2826.2011.02226).
- Crespo HJ, Cabral MG, Silva Z, Carrascal M, Videira PA. (2011) Sialic acids in the bridge of the innate and adaptive immune systems: the case of dendritic cells. Volume 37 In: Specialist Periodical Reports (SPR) Carbohydrate Chemistry. Royal Society of Chemistry, Cambridge, UK
- Silva Z, Konstantopoulos K, Videira PA. 2011. The Role of Sugars in Dendritic Cell Trafficking. Annals of Biomedical Engineering (invited review, Special Issue). doi: 10.1007/s10439-011-0448-5.
- Lepper PM, Ott SR, Hoppe H, Schumann C, Stammberger U, Bugalho A, Frese S, Schmücking M, Diehm N, Bals R, Hamacher J. Superior Vena Cava Syndrome in Thoracic Malignancies. Respir Care 2011;56(5):653– 666.
- Garrido PI, Ferreira D, Bugalho A, Salvado G, Carreiro L. Dyspnea after a greasy meal. Chest Disease Reports 2011; 1:e5
- Lima L, Silva J, Amaro T, Morais A, Lopes C, Medeiros R, Videira PA, Santos L. IL-4 and TNF-α Polymorphisms Are Associated with Risk of Multiple Superficial Tumors or Carcinoma in situ Development. Urol Int. 2011 18.
- Silva Z, Tong Z, Cabral MG, Martins C, Castro R, Reis C, Trindade H, Konstantopoulos K, Videira PA. 2011. Sialyl Lewis(x)-dependent binding of human monocyte-derived dendritic cells to selectins. Biochem Biophys Res Commun 409:459-64.
- Videira PA, Piteira AR, Cabral MG, Martins C, Correia M, Severino P, Gouveia H, Carrascal M, Almeida JF, Trindade H, Santos LL. 2011. Effects of bevacizumab on autocrine VEGF stimulation in bladder cancer cell lines. Urol Internationalis, 86:95-101
- Cabral MG, Piteira AR, Ligeiro D, Silva Z, Brossmer R, Videira PA. 2010. Human dendritic cells contain cell surface sialyltransferase activity. Immunol Lett doi:10.1016/j.imlet.2010.02.009.
- Cabral MG, Crespo HJ, Piteira AR, Ligeiro D, Videira PA. 2010. Sialic acids as modulators of endocytosis: the case of dendritic cells. In: Endocytosis: Structural Components, Functions and Pathways. Columbus F (eds), Nova Science Publishers, Inc., NY. In press.
- Videira PA, Correia M, Malagolini N, Crespo HJ, Ligeiro D, Calais FM, Trindade H, Dall’Olio F. 2009. ST3Gal.I sialyltransferase relevance in bladder cancer tissues and cell lines. BMC Cancer 9:357.
- Videira PA, Calais FM, Correia M, Ligeiro D, Crespo HJ, Calais F, Trindade H, 2009. Efficacy of BCG immunotherapy predicted by the expression of antigen presenting molecules and chemokines. Urology. 74:944-950 (doi:10.1016/j.urology.2009.02.053).
- Crespo HJ, Cabral MG, Teixeira AV, Lau JTY, Trindade H. Videira PA, 2009. Effect of sialic acid loss on dendritic cell maturation. Immunology. 128: e621-31 (doi:10.1111/j.1365-2567.2009.03047.x)
- Borrego LM, Arroz MJ, Videira PA, Martins C, Guimarães H, Trindade H. 2009. Regulatory cells, cytokine pattern and clinical risk factors for asthma in infants and young children with recurrent wheeze. Clinical Experimental Allergy 39:1160–1169 (10.1111/j.1365-2222.2009.03253.x).
- Videira PA, Calais da Silva FM, Correia M, Ligeiro D, Crespo HJ, Calais F, Trindade H. 2009. Associação entre a eficácia da imunoterapia com BCG e a expressão de moléculas apresentadoras de antigénio e quimiocinas. URO 15: 7-13.
- >Borrego LM, Arroz MJ, Videira PA, Martins C, Guimarães H, Trindade H. 2009. Regulatory cells, cytokine pattern and clinical risk factors for asthma in infants and young children with recurrent wheeze. Clinical Experimental Allergy 39:1160–1169 (10.1111/j.1365-2222.2009.03253.x). ).
- Videira PA, Amado IF, Crespo HJ, Alguero MC, Dall’Olio F, Cabral MG, Trindade H. 2008. Surface β2,3- and β2,6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis Glycoconjugate Journal 25:259-68. (DOI 10.1007/s10719-007-9092-6).
- Videira PA, Ligeiro D, Correia M, Trindade H. 2007. Gene expression analysis, normalized with β-actin and/or GAPDH, in superficial bladder cancer. Current Urology (DOI:10.1159/000115377)
- Videira PA, Amado I, Correia M, Calais da Silva FM, Calais da Silva F, Dall’Olio F, Ligeiro D, Trindade H. 2007. Abnormal glycosylation related to bladder cancer: Assessment of its prognostic value. URO 13: 26-32.
- Videira PA, Borrego LM, Trindade H. 2006. A genética da asma. Revista Portuguesa de Pneumologia. XII, 6.
• Joseph Lau, Roswell Park Cancer Institute, Buffalo, NY, USA
• Robert Sackstein, Harvard Institutes of Medicine, Brigham & Women's Hospital, Boston, USA
• Lúcio Lara Santos, I.P.O. – Porto, Portugal
• Isabel Sá-Correia, Instituto Superior Técnico, Universidade de Lisboa, Portugal
• Fabio Dall’Olio, Bologna University, Italy
• Celso Reis, IPATIMUP , Porto, Portugal
• Yvette Van Kooyk, VU University Medical Center, Netherlands
• Laura Cipolla, Università degli Studi di Milano-Bicocca, Lombardy, Italy
• Joy Burchell & Joyce Papadimitrou, King's College London, England, United Kingdom
• CarlosTadokoro, UVV - Centro Universitário Vila Velha, Brazil
• José Capelo e Carlos Lodeiro, Bioscope, FCT-UNL, Monte de Caparica, Portugal
• Pedro Baptista e Alexandra Fernandes, CIGMH, Departamento de Ciências da Vida, FCT-UNL, Monte de Caparica, Portugal
• Crioestaminal, Cantanhede, Portugal
• Bluepharma, Coimbra, Portugal