Glycoimmunology

Paula Videira

Paula Videira

Principal Investigator

CV

Location:

CEDOC
Campus Sant'Ana
Pólo de Investigação, NMS, UNL
Rua Câmara Pestana, nº 6, Lab 3.8​
1150-082 Lisboa, Portugal
Phone:(+351) 218 803 100 (ext 26040)
E-mail: paula.videira(at)nms.unl.pt

Main interests

• To elucidate the role of Glycosylation in immune response and cancer progression.
• To develop novel cell and antibody-based immunotherapy.

Research Areas

Our research has focused essentially in the following interconnected areas:

IMMUNOLOGY

Fig. 1 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

ONCOBIOLOGY

Fig. 2 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.

Fig. 3 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.

RARE DISEASES

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)

CELL BIOLOGY

Fig. 4
For more information please check the following:
Cell Biology Service Official Website
Cell Biology Service @ CEDOC website

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

Project details:

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.
Fig. 5

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
Fig. 6

Host-pathogen interaction - In vitro model based on human dendritic cell functions::
Aim: To address mechanisms of immune evasion by bacteria
Fig. 7

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.
Fig. 8

Selected Publications
  • 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.
  • 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.

Collaborations

• 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

Foto de grupo_P Videira